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Remedies: Herbal medicinal products are medicinal products where the active ingredient consists exclusively of herbal substances or herbal preparations. Natural remedies are medicinal products where the active ingredient comes from a natural origin and consists of an animal part, a bacterial culture, a mineral or a salt. El Paso, TX. Chiropractor Dr. Alex Jimenez shows natural medicines and remedies for various ailments without having to resort to prescription medications. The term herbal substance denotes whole or parts of plants, algae, fungi and lichens. The material is usually dried but sometimes fresh, and is defined by specifying the species’ full scientific name and or the plant part used. Herbal preparations, such as powders, extracts, distillates and pressed juices, are products obtained by processing herbal substances. Living things have an innate ability to heal themselves. The vital force promotes self-cleansing, self-repair, and self-healing.  This process can be achieved by focusing on the immune, hormonal, nervous, and detoxification/elimination systems of the body.  Once these systems are in balance, restored health is a possibility. For Answers to any questions you may have please call Dr. Jimenez at 915-850-0900

The Benefits of Chamomile

The Benefits of Chamomile

Do you feel:

  • Anxious or cannot focus on tasks?
  • Do digestive problems subside with rest or relaxation?
  • Stomach pains, burning, or aching 1-4 hours after eating?
  • Redden skin?
  • Nausea or vomiting?

If you are experiencing any of these situations, then you might be experiencing some digestive stress. Try some chamomile to reduce that stress and anxious mind.

Chamomile and its products are well known for promoting a relaxed state of mind and for improving sleep quality for anyone. This white and yellow flower, however, has many more impressive health benefits that are beneficial with anyone that is feeling stressed in their daily, hectic lives.

What is Chamomile?

Chamomile is an ancient medicinal plant from the Asteraceae family and is often referred to as the “star among medicinal species.” Its flowers have unusual properties that can boost a person’s health and provide impressive benefits. This plant is native to southern and eastern Europe and has been around for thousands of years. Chamomile has been used in herbal remedies in Ancient Egypt, Greece, and Rome. The plant has thin spindly shaped roots, erect stem, and a flower head that looks similar to daisies. Since chamomile is a therapeutic and medicinal plant, it contains a wide variety of health-supportive compounds that can combat some of the ailments that a person can get.

Chamomile Benefits

Chamomile’s compounds can act as antioxidants in the body. As a result, consuming chamomile products can help prevent the common cold from coming, hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. The two most common types of chamomile are used for therapeutic purposes are the German chamomile (chamomillarecutita) and Roman chamomile (Chamaemelum Nobile). The flower is processed to create chamomile capsules and chamomile tea, while the plant can be extracted to be used as essential oils. These products can help the individual feel relaxed and eased their anxious minds.

Reducing Pain

The anti-inflammatory effects of the chamomile flower and the essential oil can help to reduce the physical pain that the body has encountered. Since chamomile has been used for hundreds of years, it has helped individuals reduce the pain from headaches, back pain, toothaches, and other inflammatory-related symptoms they might be experiencing.


A 2013 study from the University College in Dublin, stated that individuals drinking a herbal beverage that is composed of chamomile, meadowsweet, and willow bark saw that their mechanical joint functions were improving. Their lower back and knee pain was reduced with chamomile. The flavonoid apigenin is one of the main anti-inflammatory compounds that is found in chamomile that is contributing to reducing pain in the joints and the body.

A 2015 study also stated that chamomile oil had been shown as an increase in physical function when it is used as a topical oil for patients with knee osteoarthritis.

Heals Wounds and Promotes Skin Health

Chamomile can help reduce irritated skin. The essential oil from chamomile can be mixed with carrier lotion or oil and be applied directly to the irritated area. It can also provide a positive effect to reduce breakouts and calm down the red or dry skin, thanks to its anti-inflammatory and antibacterial properties. Chamomile products can also reduce symptoms that may be associated with gout, eczema, hemorrhoids, and ulcers that a person may encounter.


In some instances, research has stated that chamomile is more effective than hydrocortisone cream for healing wounds. A 2011 Iranian study has compared that German chamomile solution that is being applied with a topical steroid on peristomal skin lesions on patients found that the wounds were healing faster with the chamomile solution than with the medical hydrocortisone cream.

A 2016 study that was published in the Journal of Supportive Care in Cancer has compared that water cryotherapy and the cryotherapy made with a chamomile infusion has helped with the prevention and the reduction of oral mucositis. The individuals that took the chamomile infused cryotherapy were presented with less mouth pain and had no ulcerations.

Improving Digestion

Another widespread use for chamomile, especially when it is brewed in a tea, is reducing unwanted symptoms that are associated with poor digestion in the digestive system. With chamomile tea, it can soothe an upset stomach, cramping, flatulence, and diarrhea. The therapeutic compounds that are found in chamomile can act as a digestive relaxant.

Improves Sleep and Relaxation

Chamomile, when it is brewed into a tea, can improve sleep quality and can promote a relaxing state of mind. Many individuals found that drinking chamomile tea before going to bed has helped them relax more and have a better night’s sleep. The sedative effects from chamomile tea are due to the flavonoid, apigenin that is bind with the benzodiazepine receptors in the brain. This effect can help reduce anxiety and promotes a good night’s sleep.


A 2017 study has found that sleep quality from older adults has improved after consuming chamomile extract before going to bed, while another study from the University of Fooyin in Taiwan found that postnatal women that are experiencing difficulty sleeping. They consumed chamomile tea for two weeks, and their sleep quality and mood improved drastically.

Boosting Mental Wellness

Using chamomile products can benefit a person’s mental wellness. Since chamomile can help the individual relax, it can also help reduce the feeling of anxiety and depression. Studies have stated that long term chamomile consumption is safe and can significantly reduce moderate to severe GAD symptoms. Even using chamomile oil for aromatherapy, can be considered as an alternative for antidepressant treatments.


So chamomile is a safe and productive plant that has been used for centuries to support individuals that have been experiencing a variety of unwanted symptoms. Chamomile is excellent for reducing pain, have better skin, healing wounds, improve digestion, sleep, and mental wellness. Whether it is taken in the form of tea, supplements, or used in aromatherapy, chamomile is a natural remedy for the anxious mind. Some products combined with chamomile are designed to offer support to the gastrointestinal tract and make sure that sugar metabolism is functioning properly.

The scope of our information is limited to chiropractic, musculoskeletal, and nervous health issues as well as functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or chronic disorders of the musculoskeletal system. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .


Abdullahzadeh, Mehrdad, et al. “Investigation Effect of Oral Chamomilla on Sleep Quality in Elderly People in Isfahan: A Randomized Control Trial.” Journal of Education and Health Promotion, Medknow Publications & Media Pvt Ltd, 5 June 2017,

Chang, Shao-Min, and Chung-Hey Chen. “Effects of an Intervention with Drinking Chamomile Tea on Sleep Quality and Depression in Sleep Disturbed Postnatal Women: a Randomized Controlled Trial.” Journal of Advanced Nursing, U.S. National Library of Medicine, Feb. 2016,

Charousaei, Firuzeh, et al. “Using Chamomile Solution or a 1% Topical Hydrocortisone Ointment in the Management of Peristomal Skin Lesions in Colostomy Patients: Results of a Controlled Clinical Study.” Ostomy/Wound Management, U.S. National Library of Medicine, May 2011,

Dos Reis, Paula Elaine Diniz, et al. “Chamomile Infusion Cryotherapy to Prevent Oral Mucositis Induced by Chemotherapy: a Pilot Study.” Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, U.S. National Library of Medicine, Oct. 2016,

Drummond, Elaine M, et al. “An in Vivo Study Examining the Antiinflammatory Effects of Chamomile, Meadowsweet, and Willow Bark in a Novel Functional Beverage.” Journal of Dietary Supplements, U.S. National Library of Medicine, Dec. 2013,

Fortier, Cait. “Chamomile Health Benefits: Reduce Pain & More.” Fullscript, 1 Nov. 2019,

Kong, Yingying, et al. “Inhalation of Roman Chamomile Essential Oil Attenuates Depressive-like Behaviors in Wistar Kyoto Rats.” Science China. Life Sciences, U.S. National Library of Medicine, June 2017,

Mao, Jun J, et al. “Long-Term Chamomile (Matricaria Chamomilla L.) Treatment for Generalized Anxiety Disorder: A Randomized Clinical Trial.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, U.S. National Library of Medicine, 15 Dec. 2016,

Miraj, Sepide, and Samira Alesaeidi. “A Systematic Review Study of Therapeutic Effects of Matricaria Recuitta Chamomile (Chamomile).” Electronic Physician, Electronic Physician, 20 Sept. 2016,

Shoara, Ruhollah, et al. “Efficacy and Safety of Topical Matricaria Chamomilla L. (Chamomile) Oil for Knee Osteoarthritis: A Randomized Controlled Clinical Trial.” Complementary Therapies in Clinical Practice, U.S. National Library of Medicine, Aug. 2015,

Singh, Ompal, et al. “Chamomile (Matricaria Chamomilla L.): An Overview.” Pharmacognosy Reviews, Medknow Publications Pvt Ltd, Jan. 2011,

Srivastava, Janmejai K, et al. “Chamomile: A Herbal Medicine of the Past with Bright Future.” Molecular Medicine Reports, U.S. National Library of Medicine, 1 Nov. 2010,


A Functional Approach to Integrative Testing

A Functional Approach to Integrative Testing

Cyrex Laboratories is an advanced clinical laboratory that specializes in the functional approach in environmentally induced autoimmunity.  Cyrex works with the leading experts in medical research and provides arrays that address the cross-connections throughout the body systems. In addition to this, Cyrex strives to deliver the best quality for the patients by always improving and using the most accurate and advanced technology.


Cyrex has multiple arrays they use to test patients depending on their symptoms. These arrays range from Alzheimer’s to Joint auto-immune reactivity screenings. Often times, patients who have issues with their joints or headaches and pain, can be traced back to an underlying issue. When a patient comes to a doctor, the practitioner will evaluate and assess the patient based on the symptoms they bring.  From here, the practitioner can go to Cyrex and order the arrays that best suit their patient’s needs. The Cyrex system revolves around immune function and measures the identifiers that can affect multiple tissues in the body, including the brain, heart, pancreas, nervous system, liver, gastrointestinal system, bones, and joints.  The turn around time for these labs is fairly quick and helps highlight the underlying route of the patient’s symptoms.



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Cyrex arrays use serum (a blood draw) as their main form of testing. No matter the array the doctor orders, the patient will receive the same kit. The requisition form that is inside the kit is what matters to the phlebotomist and lab as this is where the array ordered will be marked.

The kit is a small box labeled Cyrex Laboratories, Serum Collection Kit. On top of the kit held in place by a rubber band will be a shipping label and bag for the sample to go in once collected. Inside the kit is a smaller styrofoam box that includes a serum separator tube, a serum transport tube, tube labels, a biohazard bag, and collection instructions.

As one can see from the above photo, the different arrays test for different reactions/conditions. A doctor may order one or multiple arrays depending on the patient.

Array 2 is one of the most popular, as leaky gut is a condition that affects most Americans. This test screens for IgG, IgA, and IgM of Lipopolysaccharides and Occludin/Zonulin.




Integrative Testing

Often times, practitioners will use multiple lab companies on one patient. This is not because one is superior to the other, but rather because they specialize in different areas. Even though the doctor may order labs from different companies, it is in the patient’s best interest because it allows the practitioner to view multiple areas to truly understand the underlying issue.

Patients who come in with symptoms like aching joints, headaches, trouble falling asleep, difficulty staying asleep, leaky gut, and brain fog will certainly benefit from using multiple lab companies.

Using Cyrex array 2 and DUTCH + CAR the patient will get extremely accurate information in regards to what is occurring in their body. The Cyrex array test will show the practitioner if the patient has a leaky gut and how severe. While the DUTCH + CAR allows the doctor to determine the cortisol patterns in the individual’s body. Sometimes, these levels are not rising and falling at the right times, causing the patient to be tired or having trouble staying asleep.

The patient’s health should always come first, and when doctors are knowledgable enough to use more than one lab, the patient benefits are outstanding. By using the companies together, the doctor is able to check multiple areas, leaving no guesswork when it comes to a treatment protocol. However, it is important to remember that labs vary on patient needs. Some patients are able to use the same company for all labs and obtain the accurate results they need.

Cyrex tests for many conditions and has multiple arrays. Although many


Cyrex labs are a great tool for practitioners and health coaches to use! By using these arrays, it helps the practitioner not only treat the symptoms, but it allows them the insight they need to treat the problem at the route source. The tools that Cyrex provides go a long way in evaluating the complex disorders the human body may have. By using Cyrex and coupling it with other tests from DUTCH or labrix, the patient is able to get proper treatment and get back to the hobbies they used to love and enjoy. These companies are all fantastic and provide specialities in different areas. By using more than one company, the pateint truly gets the best results and the doctors are able to construct a solid treatment protocol with all of the information obtained. – Kenna Vaughn, Senior Health Coach 

*All information was obtained from

The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or chronic disorders of the musculoskeletal system. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900.

5 Foods To Eat During The Cold and Flu Season

5 Foods To Eat During The Cold and Flu Season

The cold and flu season can cause havoc on a person’s body during the colder seasons. An individual can feel overly tired, congested, the body has aches and shivers, and lastly, the immune system will work overtime to help fight off the germs. When this happens, many remedies can help these symptoms when a person feels a little bit under the weather. They help the body give that extra boost to recover from cold and flu symptoms and can provide the body a chance to rest.

When anyone is starting to feel sick, an important note is to try and get as much rest as they possibly can. It can be anything like getting more sleep, scaling down on exercising, or take some time off of work to heal more quickly. In this article, here are some of the top 5 foods to help the body improve and recover from the cold and flu season, with some additional remedies to boost the immune system as well.


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Soups are one of the most excellent sources of feeling better during cold and flu season. They are easily digestible and helps soothe the body by containing ample waters to keep it hydrated. Water-based soups like chicken noodle, Hippocrates soup, and vegetable soup incorporates all the essential nutrients that the body needs when it is the colder season, helping to combat the flu.



Garlic has a wide variety of health benefits that can help the body during the cold and flu season. It can help reduce the risk of heart diseases, improve mental health, and enhance the immune system. Studies have shown that whole garlic contains a compound called alliin. When garlic is chopped, chewed, or crushed, it will help boost the disease-fighting response of white blood cells in the body when they are encountering viruses that cause the common cold or flu.

Studies also stated that garlic helps support neurodegenerative health, cardiovascular health, and compromised liver functioning from excessive alcohol use. Researchers at the Toxicology, School of Public Health, Shandong University in China, have isolated the garlic compound, DADS (diallyl disulfide), as the main compound that helps protects the body from ethanol-induced oxidative stress.

Foods That Are Rich in Vitamin C



Foods that contain vitamin C is highly essential when it comes to battling the cold or flu. Vitamin C is a powerful, potent supplement that has antioxidants and immune system boosters that protects the body from environmental factors like reducing oxidative stress, prevent and treat respiratory and systemic infections. With vitamin C-rich foods, they contain essential minerals, vitamins, and high in flavonoids that help individuals who don’t feel like eating or preferring bland foods to consume when they are sick. Initially, they can eat vitamin C rich food by either juice or soup. Here are some delicious fruits and juices that contain a high amount of vitamin C to combat the cold and flu.

  • Guava
  • Strawberries
  • Tomato juice
  • Oranges and Orange juice

Apple Cider Vinegar


Apple Cider Vinegar can provide many minerals and enzymes that can fight off pathogens that can be caused by the common cold or flu. A 2011 study has shown that the probiotics in apple cider vinegar have an immune-boosting effect that can shorten the duration of a cold when an individual drinks apple cider vinegar. Taking apple cider vinegar with a glass of water can also help the body when it is not cold and flu season. Apple cider vinegar helps inhibits bacterial growth, can support healthy blood pressure levels in the body, as well as an excellent addition to the medicine cabinet during cold and flu season.



Ginger is a medicinal root plant that has been used for thousands of years. This root has been known to relieve motion sickness and nausea in the digestive system. Studies have shown that 70% of the immune system is found in the gut, and so it is highly essential that the digestive system in the body is working efficiently. Since ginger is made up of hundreds of compounds, some of them have potent antioxidants and can help support healthy inflammatory pathways in the body. Ginger can be found as a fresh root, dried, as an extract or oil, tinctures, capsules, and lozenges. Here are some of the foods that contain ginger to help the body fight the common cold or flu.

  • Ginger tea
  • Curry
  • Gingerbread
  • Cookies
  • Gingersnaps
  • Ginger ale

IMG_Dr_Jimenez_300_x_300_FADED“It is highly essential to stay hydrated during the cold and flu season. Ample fluids like water, coconut water, and herbal teas are the first line of defense.

Additionally, getting a good night’s sleep helps the immune system in the body recover faster. It is also essential to avoid eating foods like processed foods, alcohol, soda, fried foods, and dairy when it is cold and flu season. Since it can cause inflammation and aggravate the immune system when the body is trying to recover from being sick.”- Dr. Alex Jimenez D.C., C.C.S.T. Insight – Dr. Alex Jimenez D.C., C.C.S.T. Insight


All in all, when it is cold and flu season, people can start stocking up on these five remedies and taking antibiotics to get a head start on not getting sick. When the body does get sick, taking these remedies, getting lots and lots of rest, staying hydrated, and relaxing can ensure that the body will recover faster. Since food matters to people’s health, it’s vital to give the body the nourishment it needs for the cold and flu season.

October is Chiropractic Health Month. To learn more about it, check out Governor Abbott’s proclamation on our website to get full details on this declaration.

So the mechanisms of an autoimmune disease can be either by genetics or by environmental factors that can cause an individual to have problems in their body. There are many autoimmune diseases, both common and rare, that can affect the body. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. We use functional health protocols to treat injuries or chronic disorders of the musculoskeletal system. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .


Biotics Education Team, Unknown. “5 Foods to Eat During the Cold & Flu Season.” Biotics Research Blog, 16 Sept. 2019,

Borlinghaus, Jan, et al. “Allicin: Chemistry and Biological Properties.” Molecules (Basel, Switzerland), MDPI, 19 Aug. 2014,

Carr, Anitra C, and Silvia Maggini. “Vitamin C and Immune Function.” Nutrients, MDPI, 3 Nov. 2017,

Das, Arabinda, et al. “Garlic Compounds Generate Reactive Oxygen Species Leading to Activation of Stress Kinases and Cysteine Proteases for Apoptosis in Human Glioblastoma T98G and U87MG Cells.” Wiley Online Library, John Wiley & Sons, Ltd, 23 July 2007,

Felman, Adam. “Antibiotics: Uses, Resistance, and Side Effects.” Medical News Today, MediLexicon International, 18 Jan. 2019,

Newman, Tim. “Congestive Heart Failure: Causes, Symptoms, and Treatments.” Medical News Today, MediLexicon International, 3 Jan. 2018,

Song, Fu-Young, et al. “The Activation of HO-1/Nrf-2 Contributes to the Protective Effects of Diallyl Disulfide (DADS) against Ethanol-Induced Oxidative Stress.” Biochimica Et Biophysica Acta (BBA) – General Subjects, Elsevier, 28 June 2013,

Surh, Y J, et al. “Chemoprotective Properties of Some Pungent Ingredients Present in Red Pepper and Ginger.” Mutation Research, U.S. National Library of Medicine, 18 June 1998,

Vighi, G, et al. “Allergy and the Gastrointestinal System.” Clinical and Experimental Immunology, Blackwell Science Inc, Sept. 2008,

Watson, Kathryn. “Apple Cider Vinegar for Colds.” Healthline, 22 Jan. 2018,

West, Helen. “How Garlic Fights Colds and The Flu.” Healthline, 17 Mar. 2016,

Yagnik, Darshna, et al. “Antimicrobial Activity of Apple Cider Vinegar against Escherichia Coli, Staphylococcus Aureus and Candida Albicans; Downregulating Cytokine and Microbial Protein Expression.” Scientific Reports, Nature Publishing Group UK, 29 Jan. 2018,

Fasting and Chronic Pain

Fasting and Chronic Pain

Chronic pain is a common health issue which affects many people in the United States. While several medical conditions, such as fibromyalgia and myofascial pain syndrome, can cause chronic pain, it may also develop due to a variety of other health issues. Research studies have found that widespread inflammation is the leading cause of chronic pain. Inflammation is a natural defense mechanism to injury, illness, or infection. But, if the inflammatory process continues for too long, it can become problematic.

Inflammation signals the immune system to heal and repair damaged tissue as well as to protect itself against bacteria and viruses. As mentioned above, however, chronic inflammation can cause a variety of health issues, including chronic pain symptoms. Healthy lifestyle modifications can help manage chronic pain, but first, let’s understand the common causes of chronic pain.

What is Acute Inflammation?

Acute inflammation, by way of instance, occurs following an injury or something as simple as a sore throat. It is a natural response with adverse effects, meaning it works locally in the region where the health issue is found. The common signs of acute inflammation include swelling, redness, warmth, pain and loss of function, as stated by the National Library of Medicine. When acute inflammation develops, the blood vessels dilate causing blood flow to increase, and white blood cells in the injured region promote recovery.

During severe inflammation, compounds called cytokines are released by the damaged tissue. The cytokines act as “emergency signals” which bring on the human body’s own immune cells, as well as hormones and numerous nutrients to repair the health issue. Additionally, hormone-like substances, known as prostaglandins, cause blood clots to heal damaged tissue, and these may also trigger fever and pain as part of the inflammatory procedure. As the damage or injury recovers, the inflammation subsides.

What is Chronic Inflammation?

Unlike acute inflammation, chronic inflammation has long-term effects. Chronic inflammation, also known as persistent inflammation, produces low-levels of inflammation throughout the human body, as demonstrated by an increase in immune system markers located in blood and cell tissues. Chronic inflammation may also cause the progression of various diseases and conditions. Elevated levels of inflammation may sometimes trigger even if there is no injury, illness, or infection, which may also cause the immune system to react.

As a result, the human body’s immune system could begin attacking healthy cells, tissues, or organs. Researchers are still trying to understand the consequences of chronic inflammation in the human body and the mechanisms involved in this natural defense process. By way of instance, chronic inflammation has been associated with a variety of health issues, such as heart disease, and stroke.

One theory suggests that when inflammation remains in the blood vessels, it can encourage the accumulation of plaque. According to the American Heart Association, or the AHA, if the immune system identifies plaque as a foreign invader, the white blood cells can attempt to wall off the plaque found in the blood flowing through the arteries. This can create a blood clot which may block the blood flow to the heart or brain, causing it to become unstable and rupture. Cancer is another health issue associated with chronic inflammation. Furthermore, according to the National Cancer Institute, DNA damage can also be caused by chronic inflammation.

Persistent, low-grade inflammation frequently doesn’t have any symptoms, but healthcare professionals can check for a C-reactive protein, or CRP, known as lipoic acid, a marker for inflammation found in the blood. Elevated levels of CRP are associated with an increased risk of cardiovascular disease. Elevated CRP levels may be found in chronic disorders like lupus or rheumatoid arthritis.

In the case of other chronic conditions, such as fibromyalgia, the nervous system over-reacts to specific stimulation, however, it’s inflammation which causes chronic pain symptoms. Subjectively, it’s almost impossible to tell the difference between the chronic pain caused by an oversensitive nervous system and the chronic pain caused by widespread inflammation. Apart from searching for clues in the bloodstream, a person’s nutrition, lifestyle habits, and environmental exposures, can also promote chronic inflammation.

Dr Jimenez White Coat

Inflammation is the immune system’s natural defense mechanism against injury, illness, or infection. While this inflammatory response can help heal and repair tissues, chronic, widespread inflammation can cause a variety of health issues, including chronic pain symptoms. A balanced nutrition, including a variety of diets and fasting, can help reduce inflammation. Fasting, also known as caloric restriction, promotes cell apoptosis and mitochondrial recovery. The fasting mimicking diet, which is a part of the longevity diet plan, is a dietary program which “tricks” the human body into a fasting state to experience the benefits of traditional fasting. Before following any of the diets described in this article, make sure to consult a doctor.

Dr. Alex Jimenez D.C., C.C.S.T. Insight

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Nutrition, Diets, Fasting and Chronic Pain

Anti-inflammatory diets mainly consist of eating fresh fruits and vegetables, fish, and fats. The Mediterranean diet plan, by way of instance, is an anti-inflammatory diet which promotes eating moderate amounts of nuts, ingesting very little meat, and drinking wine. Anti-inflammatory food parts, such as omega-3 fatty acids, protect the human body against the damage brought on by inflammation.

An anti-inflammatory diet also involves staying away from foods which could promote inflammation. It is ideal to decrease the amount of foods you eat which are high in trans and saturated fats, such as meats. Additionally, an anti-inflammatory diet limits the consumption of refined carbohydrates and foods, such as bread and rice. These also promote cutting back on the utilization of margarine and oils that are packed with omega-6 fatty acids, such as sunflower, safflower and corn oils.

Fasting, or caloric restriction, has long been known to decrease oxidative stress and slow down the mechanisms of aging in various organisms. The effects of fasting involve programmed cell death, or apoptosis, transcription, mobile energy efficiency, mitochondrial biogenesis, antioxidant mechanisms, and circadian rhythm. Fasting also contributes to mitochondrial autophagy, known as mitophagy, where genes in the mitochondria are stimulated to undergo apoptosis, which promotes mitochondrial recovery.

Intermittent fasting can help you fight inflammation, improve digestion, and boost your longevity. The human body is designed to be able to survive for extended periods of time without food. Research studies have demonstrated that intermittent fasting can have positive changes in the overall composition of your gut microbiota. Moreover, intermittent fasting can reduce insulin resistance while increasing the immune system response. Finally, intermittent fasting can promote the production of a substance, known as β-hydroxybutyrate, that blocks a portion of the immune system involved in inflammatory ailments as well as substantially reducing the production of inflammatory markers, such as cytokines and the C-reactive protein, or CRP, previously mentioned above.

The Longevity Diet Plan, presented in the book by Dr. Valter Longo, eliminates the consumption of processed foods which can cause inflammation, promoting well-being and longevity. This unique dietary program, unlike most traditional diets, doesn’t promote weight loss. Although you may experience weight reduction, the emphasis of this unique dietary program is on eating healthier. The Longevity Diet Plan has been demonstrated to help activate stem cell-based renewal, reduce abdominal fat, and prevent age-related bone and muscle loss, as well as build resistance to developing cardiovascular disease, Alzheimer’s disease, diabetes, and cancer.


The fasting mimicking diet, or FMD, allows you to experience the benefits of traditional fasting without depriving your body of food. The main difference of the FMD is that instead of completely eliminating all food for several days or even weeks, you only restrict your calorie intake for five days out of the month. The FMD can be practiced once a month to help promote overall health and wellness.

While anyone can follow the FMD on their own, the ProLon® fasting mimicking diet offers a 5-day meal program which has been individually packed and labeled for each day, that serves the foods you need for the FMD in precise quantities and combinations. The meal program is made up of ready-to-eat or easy-to-prepare, plant-based foods, including bars, soups, snacks, supplements, a drink concentrate, and teas. Before starting the ProLon® fasting mimicking diet, 5-day meal program, or any of the lifestyle modifications described above, please make sure to talk to a healthcare professional to find out which chronic pain treatment is right for you.

The scope of our information is limited to chiropractic, spinal health issues, and functional medicine articles, topics, and discussions. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. Your spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.

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Functional Medicine Part 3: Nutrition

Functional Medicine Part 3: Nutrition

Functional Medicine Doctor Explains Nutrition

Each chemical reaction which occurs in the human body requires enzymes and each one of these processes needs a coenzyme. But what are coenzymes? They are vitamins and minerals. Approximately 37 billion, billion chemical reactions occur in the human body every second.

That is why proper nutrition and a balanced diet rich in whole foods with vitamins and minerals is fundamental towards overall health and wellness. The majority of people in the United States are vitamin and/or mineral deficient. But, how do you know if you’re a part of the 90 percent of individuals with enough deficiencies to develop disease? We will discuss the tests you can utilize to find out if you’re vitamin and/or mineral deficient and what you can do about it.

What is Nutrition?

Hello, welcome to part three of “Taking Control of your Healthcare”. Today, we will discuss one of the fun topics of functional medicine: nutrition. Unfortunately, nutrition is one of the most essential conversations that many doctors aren’t willing to have with their patients. The average medical doctor learns about disease and malnutrition rather than learning how to use nutrition as treatment or even how to use nutritional therapies to achieve optimal health and wellness.

I personally believe that food can be utilized as a form of medicine. That it should be the foundation of medical practice, not an afterthought in medicine. There is no better treatment than proper nutrition. Approximately 90 percent of individuals in the United States aren’t getting the essential nutrients they require for healthy bodily functions. And more than that probably aren’t getting enough nutrients to prevent diseases associated with nutritional deficiencies. However, what is ultimately needed to achieve optimal well-being? More than 98 percent of Americans are deficient in omega-3, 80 percent in vitamin D, 50 percent in magnesium, and 10 percent in vitamin C. Nutrient deficiencies can also continue to cause health issues for years.

Acute diseases, such as rickets, scurvy, beriberi, or iron deficiency anemia, are often the most talked about health issues associated with nutrient deficiency, however, there’s also something known as long latency deficiency diseases. So, how much vitamin D do we need to not get rickets? Not a lot, only 30 units really. And how much do we need to not get osteoporosis? Perhaps about 3,000 to 4,000 units per day. Now, how much folate do we need to not get anemia? Also not very much. But, how much do we need to prevent heart disease, cancer, and dementia? You definitely need a lot more units per day.

Each chemical reaction which occurs in the human body requires enzymes and each one of these processes needs a coenzyme. But what are coenzymes? They are vitamins and minerals. Approximately 37 billion, billion chemical reactions occur in the human body every second.

That is why proper nutrition and a balanced diet rich in whole foods with vitamins and minerals is fundamental towards overall health and wellness. The majority of people in the United States are vitamin and/or mineral deficient. But, how do you know if you’re a part of the 90 percent of individuals with enough deficiencies to develop disease? There are only several nutrients which we are generally tested for. And for a majority of these, doctors aren’t aware of what the optimal values should be which can make correcting the nutrient deficiency so much difficult to do.

Taking Control of Your Nutrition

One of the most fundamental nutrients you need to measure is vitamin D. Although it’s referred to as a vitamin, it’s actually more like a hormone and it’s produced from cholesterol. This is yet another reason why cholesterol is essential. Approximately 80 percent of the population is deficient in vitamin D. Unless you’re in the sun 20 minutes every day between 10:00am and 2:00pm, you might need to take vitamin D supplements. In order to supplement properly, however, we need to know from what level you are starting at first. By way of instance, optimal vitamin D levels should be anywhere between 50 and 80 nanograms per milliliter of blood. The recommended amount of vitamin D we can supplement is about 2,000 to 4,000 units.

If you have lower vitamin D levels or if you have genetic problems, you may actually need to supplement with up to 10,000 units of vitamin D. That’s why it’s fundamental to work with a doctor or functional medicine practitioner who can measure and test your nutrient levels as well as help you optimize them. Most supplements contain about 400 units which is 10 times less than the amount most of us need. The optimal levels are generally just over 20. This is way too low. In one research study, women with vitamin D levels between 45 and 60 experienced reduced preterm labors by up to 60 percent. Vitamin D is also essential to help build strong bones and muscles, to improve immune system function, to prevent cancer, and ultimately, to help you live longer. It’s incredible.

Another measurement or test that’s performed by most doctors but is not always interpreted correctly is referred to as the MCV or mean corpuscular volume. The MCV measurement evaluates the size of your red blood cells in a test called CBC, or complete blood count, which is one of the most common blood panels ordered by healthcare professionals. So, if you are deficient in nutrients, your cells can either become smaller or larger. By way of instance, if your cells are too big, it could be a signs of a folate or vitamin B12 deficiency.

B vitamins are essential in numerous chemical reactions within the human body. They help us produce energy as well as help us regulate gene expression in order to create proteins that will ensure our overall health and wellness. If our B vitamins are too low, we could eventually develop an iron deficiency, anemia, or it could even cause a genetic disorder.

Optimal levels of B vitamins should be between 80 to 90. B complex vitamin supplements can help easily optimize levels of B vitamins. But, why would anyone be deficient in B vitamins? Is their diet not providing them with enough nutrients? Are they vegan? Are they taking any drugs and/or medications that prevent vitamin B12 absorption? Moreover, B vitamins are depleted during times of high stress which, as a practicing chiropractor, I can say it happens frequently to a majority of the population in the United States alone.

MCV is not the only measurement or test which evaluates a patient’s levels of B vitamins. Homocysteine is an alternative marker we will discuss in future articles which demonstrates B6, folate, and B12 levels. However, both the MCV and the homocysteine measurement or test only demonstrates that one or more of these nutrients may be deficient. It doesn’t necessarily tell us which one. Therefore, some additional, follow up evaluations may be required.

The MMA, or methylmalonic acid, measurement or test also shows vitamin B12 levels. Ultimately, vitamin B12 is essential for many processes in the human body, including energy production, gene expression, methylation, nerve function, and mood, among many other processes. Vegans have a higher chance of developing a B12 deficiency because it’s only found in animal products. Folate is another fundamental B vitamin. It can be determined directly in the blood, but, homocysteine is a more precise marker for folate levels.

In this section, we’re also going to discuss genetics because there is a measurement or test which can demonstrate a lot more regarding the status of your B vitamins and your ability to utilize them. Our genes are capable of making proteins. We have approximately 20,000 genes which are designed to create proteins. And one third of all the proteins they make are for our enzymes. Enzymes convert molecules into other molecules. These enzymes are also largely dependent on specific nutrients. One of the most fundamental genes which can be affected is known as MTHFR, or methylenetetrahydrofolate reductase. But you can just call it MTHFR.

MTHFR is essential because it helps regulate methylation, homocysteine, and folate, which are vital towards our overall health and wellness. When you have elevated levels of homocysteine, you should check your methylation status by looking for the MTHFR gene through a simple blood test.

Methylation is a key biochemical process which is fundamental towards the proper function of most of the human body’s systems. It triggers billions of times each second. And it ultimately helps control homocysteine, a substance which can damage blood vessels and has been associated with dementia, heart disease, and cancer, among other health issues. Methylation also helps repair your DNA on a regular basis as it helps recycle molecules necessary for detoxification, or getting rid of toxins. It also helps control your mood and it helps manage inflammation. Methylation is critical.

But, to make sure that methylation is active, the human body needs optimal levels of B vitamins. Without enough B vitamins, the methylation process can break down and the effects can be destructive. This is where we start seeing an increase in birth defects, such as spina bifida, down syndrome, and more miscarriages.

MTHFR is frequently abnormal in approximately 35 percent of the population. Methylation breakdown can also increase the risk of developing health issues like osteoporosis and diabetes, cervical dysplasia or cancer, including colon cancer and lung cancer, and even depression, pediatric cognitive dysfunction as well as mood and behavioral disorders, dementia, and stroke. Methylation is truly a key biochemical process.

When we discuss genetics, we have to understand that our environment can alter our genes. So, what if you have an MTHFR variation in your genes? First of all, not all mutations cause health issues. One mutation, by way of instance, known as C677T, is one version of the gene which is more significant than another version of the gene, known as A1298C. Now there’s no need to worry about these gene variations. They serve as examples to demonstrate you the quality of these mutations and how they function. People with these variations of the gene, by way of instance, might only need more folate or they might need a particular type of folate known as methylfolate. This is where a functional medicine practitioner can help their patients.

A genetic test can let you known if you have one of these gene variations. But, don’t get stressed. There’s a lot you can do to optimize your overall health and wellness. Many patients have visited my office after they find out they have these variations in their genes. And they quickly learn that they do have the option to take control of their well-being. However, what you do control is not your genes, you control your gene expression.

If you alter your healthy eating habits, you alter your nutrients. If you alter your environment, you alter which genes become active and which genes become inactive. And with these mutations, you can do just about the same thing by simply following the proper nutrition. When you find a doctor or functional medicine practitioner that’s willing to work with you, they’re going to tell you what lifestyle modifications you should follow to prevent health issues.

So, we’ve only just discussed the B vitamins. Next, we will discuss another fundamental nutrient in the human body: magnesium. Magnesium is a super essential mineral. Approximately 48 percent of people in the United States consume less than the required amount of magnesium from food. Magnesium is necessary in over 300 chemical reactions in the human body. It is also fundamental in the production of ATP, or the energy the human body utilizes as fuel.

A magnesium level blood measurement or test can help determine if you have a deficiency. Magnesium can also help reduce anxiety, calm the nervous system, and improve sleep. It is also an essential nutrient in the management of blood sugar levels. If you’ve been told by a healthcare professional that you have an average blood sugar level of over five and a half in something known as A1c, then magnesium can help.

Also, it’s very easy to know if you have a magnesium deficiency by looking at your current diet and symptoms. Do you eat enough magnesium rich foods like dark, leafy greens, beans, nuts and seeds? Or do you eat a lot of processed foods? Perhaps you also have symptoms such as anxiety, insomnia, constipation, muscle twitching, muscle cramps, PMS, and/or palpitations. If you have one or more of the symptoms I just mentioned, you may have a magnesium deficiency.

Next, we will talk about zinc, the immune-boosting and testosterone-boosting mineral in the human body. This important nutrient is in charge of maintaining your hair volume as well as repairing your gut lining. It’s also responsible for making sure your thyroid is functioning properly. Zinc can be easily measured or tested in the blood and unfortunately, it’s another nutrient we are highly deficient in, in the United States. Additionally, you can also look at your alkaline phosphatase levels, which can be calculated through a liver function evaluation on a regular blood panel. High levels of alkaline phosphatase may indicate the presence of cancer or bone problems, among other health issues, however, low levels of alkaline phosphatase may indicate a zinc deficiency, because it’s a zinc-dependent enzyme.

Finally, the last fundamental nutrient we are going to discuss is iron. Iron is frequently deficient in vegans and vegetarians, or in women in general due to menstruation. Iron is necessary for transporting oxygen throughout the human body and it’s ultimately essential for brain health and wellness. Iron is also important for hair and nails, sleep, and so many other things.

Ferritin is a stored type of iron and it’s this nutrient which helps you see your iron levels. Optimal ferritin levels should be between 50 to 150 in women and 100 to 300 in men. And many times I’ve seen women visit my office who have ferritin levels of less than 50, or worse, in the single digits. This is because pre-menopausal women lose blood every month due to their menstrual cycles and it becomes so much harder for them to maintain proper ferritin levels. Many women also eat way less than what they’re supposed to be eating every day. High levels of ferritin, on the other hand, could be a sign of inflammation, generally caused by insulin resistance to sugar, or it could be a sign of hemochromatosis or iron storage disease, a very dangerous genetic disorder.

Having decreased levels of ferritin can also make you feel tired, and it can cause hair loss, it can cause insomnia. So, even if your blood count is normal, if your ferritin levels are low or your iron levels are low, it can also cause these symptoms. That’s why if you experience symptoms of fatigue, it’s essential to measure or test your ferritin levels. And it can be easily supplemented.

Aside from ferritin, a low MCV can also determine if you have an iron deficiency. Iron deficiencies can cause red blood cells to become very small and that can be demonstrated in low MCV levels, which evaluate the size of your red blood cells. Additionally, transference saturation, serum iron, TIBC, or total iron binding capacity, and hemoglobin, can provide us with a more in depth look at your iron status to distinguish different causes of anemia. These are included on a regular iron blood panel in a lab test.

We’ve discussed several nutrients which can be ordered by a majority of healthcare professinals with access to conventional lab testing. Furthermore, there’s another test which can tell us more about which type of nutrients we need based on our genes. It’s called the DNA health test and it’s provided by a company called DNAlife. This test evaluates a variety of genetic markers associated with detoxification, lipid metabolism, and inflammation, including the MTHFR gene and other B vitamin markers. Now, DNA Health demonstrates the different genes we evaluate. And most of these are common genes, they’re those we can do something about. We analyze the genes we can change based on your nutrition and other lifestyle factors.

It shows us the MTHFR gene, other B vitamin markers, genes that control B6, folate, and B12 as well as demonstrating how they function and whether you have nutrient deficiencies. Then it tells us which nutrients you will need to supplement and how much we will need to give to you. It’s tremendously helpful.

There was an individual who had two variables of the MTHFR gene. This woman had miscarriage after miscarriage after miscarriage. She visited her doctor for an evaluation and it turns out that she had a folate-regulating mutation. So her doctor then started giving her the proper amount of folate she needed and she started having healthy babies. Sometimes, nutrition can be that powerful towards improving a patient’s overall health and wellness.

The DNA health test can help personalize your approach when optimizing your well-being based on your genetics. What we measure utilizing the DNA health test provide well-established insights about your genes as well as what you can do about them.

A micronutrient test known as the individualized optimized nutrition profile or the ION panel, are alternative test options which can also provide information about your current nutritional status. This test is by Genova. This is a robust test which measures all the essential vitamins and minerals, fatty acids, organic acids, and antioxidants you currently have. Ultimately, this test looks for imbalances, insufficiencies, or deficiencies, rather than looking for a specific disease. It looks for things that a majority of doctors never look at.

Functional medicine practitioners or doctors look at patient’s amino acid levels, mineral levels, and even toxin levels from heavy metals like mercury, lead, arsenic, and many more. We also look at your antioxidant levels, vitamin A and vitamin E levels, as well as your CoQ10 antioxidant and beta carotene status. We can determine if a person eats vegetables or not if, by way of instance, they have low levels of beta carotene. We also look at vitamin D levels, essential fatty acids, including your omega-3 fats and your omega-6 fats. We can tell if a person eats junk food. We can tell if a person is eating fish. And We can tell if a person is eating too much olive oil or saturated fats. It’s all demonstrated in these measurements and tests.

An OAT test, or organic acids test, also looks at what is known as organic acids. This test demonstrates a wide array of parameters associated with your mitochondria, which we will discuss in the next article, your B vitamins, your neurotransmitters, your gut flora, and your detoxification. It’s ultimately a comprehensive test which shows me if a patient is well or sick. It shows me where the imbalances are and where I need to recommend lifestyle modifications. It also helps provide clues about other health issues.

By way of instance, if your mitochondria aren’t functioning correctly because you have decreased levels of essential amino acids or you have increased oxidative stress or if you simply have low levels of selenium and zinc, there’s a possibility that you might have some form of toxic overload due to heavy metals. And that’s precisely what I would go looking for. Signs like these provide a lot of information about what we can do to treat a patient. And an experienced functional medicine practitioner or doctor can determine what’s really going on with a patient or they can help patients discover how to optimize their overall health and wellness.

Dr Jimenez White Coat
Nutrition is the study of nutrients in food and how the human body utilizes nutrients as well as the relationship between diet, disease and overall health and wellness. Nutrients are a source of nourishment, including carbohydrates, proteins, fats, vitamins, minerals, fiber and water. Functional medicine focuses on the use of food as a form of medicine. A balanced nutrition can help prevent as well as treat a variety of health issues. Similarly, nutrition in functional medicine involves how certain diseases and conditions may be associated with dietary factors, such as poor diet or malnutrition, food allergies and food intolerances. Dr. Alex Jimenez D.C., C.C.S.T.

Understanding Your Nutrition

As good functional medicine doctors we’re often left asking ourselves, why is it that so many people in the United States are overfed but undernourished? Or, why is it that Americans eat too many calories and too few nutrients? The leading causes for the widespread nutritional deficiencies are the following: First, humans evolved from eating wild foods which contained tremendously higher levels of nutrients. Second, the soil we currently utilize to grow our crops in has become greatly depleted of nutrients. Hybridization techniques from industrial farming are yielding animals and vegetables to have decreased levels of nutrients. Third, processed foods have absolutely no nutrients, which is why they frequently have to be fortified. And last but not least, exposure to environmental toxins, lack of sunlight, chronic stress, and poor diet, including increased alcohol, caffeine, and sugar consumption, can increase our nutritional needs, much of which we’re already not getting enough from our current nutrition.

Well you might not need any vitamins, however, if you can meet certain conditions. Perhaps if you only hunted and gathered wild food and if you weren’t exposed to environmental toxins. Or maybe if you went to sleep with the sun and woke up with the sun, sleeping nine hours a night. And if you experienced absolutely no amount of chronic stress. Ultimately if you only drank pure, clean water and breathed pure, clean air. Then, you probably wouldn’t need any vitamins. But the rest of us that don’t follow these conditions, we do need them.

And with that thought, we wrap up this article. In the next article, we will talk about hormones. Hormones can affect almost every aspect of our well-being, and many healthcare professionals don’t understand what our optimal hormone levels should be or even when to test them and what to do about it once they do. Measuring and testing hormone levels should be standard practice, and many patients have never had a blood panel to look at their hormones. It’s fundamental to know as well as understand what’s going on inside your own body. And that’s why this next article is so important. You won’t want to miss our next update. See you soon.

The scope of our information is limited to chiropractic and spinal health issues as well as functional medicine topics and discussions. To further discuss the subject matter, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

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XYMOGEN’s Exclusive Professional Formulas are available through select licensed health care professionals. The internet sale and discounting of XYMOGEN formulas are strictly prohibited.

Proudly, Dr. Alexander Jimenez makes XYMOGEN formulas available only to patients under our care.

Please call our office in order for us to assign a doctor consultation for immediate access.

If you are a patient of Injury Medical & Chiropractic Clinic, you may inquire about XYMOGEN by calling 915-850-0900.

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XYMOGEN’s Exclusive Professional Formulas are available through select licensed health care professionals. The internet sale and discounting of XYMOGEN formulas are strictly prohibited.

Proudly, Dr. Alexander Jimenez makes XYMOGEN formulas available only to patients under our care.

Please call our office in order for us to assign a doctor consultation for immediate access.

If you are a patient of Injury Medical & Chiropractic Clinic, you may inquire about XYMOGEN by calling


Xymogen Catalog - El Paso, Texas

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* All the above XYMOGEN policies remain strictly in force.

Ketogenic Diet and Intermittent Fasting

Ketogenic Diet and Intermittent Fasting

Why is it that the ketogenic diet and intermittent fasting always seem to fall within the same topic of conversation? This is simply because intermittent fasting may be utilized as an instrument to achieve ketosis, the metabolic state associated with the keto diet. During intermittent fasting, the human body is depleted of glycogen stores. Once these glycogen stores are eliminated, fat stores are then released into the bloodstream in order to be converted into energy molecules, known as ketones, from the liver.

What is Ketosis?

Ketosis is a metabolic state which uses ketone bodies, or ketones, as fuel for energy. On a normal carbohydrate-based diet, the human body burns glucose as its main fuel source, where excess glucose is subsequently stored as glycogen. If the human body cannot utilize sugar as fuel for energy, it will utilize glycogen as fuel for energy. Once glycogen is depleted, you begin to burn fat. The ketogenic diet generates a metabolic state which enables you to break down fat into ketones, or ketone bodies, in the liver for energy.

There are 3 major types ketone bodies found in the blood, urine, and breath, including:

  • Acetoacetate: The type of ketone which is created first. It may be converted to beta-hydroxybutyrate or flipped into acetone.
  • Acetone: Made spontaneously in the breakdown of acetoacetate. It is a very volatile ketone and it is frequently detectable on the breath once an individual first enters ketosis.
  • Beta-hydroxybutyrate (BHB): The type of ketone which is utilized for energy and is most abundant on the bloodstream as soon as you’re completely into ketosis. It is the kind that is located in exogenous ketones and what blood tests quantify.

Intermittent Fasting in the Keto Diet

Intermittent fasting is composed of eating within a specific feeding window rather than eating throughout the day. Each individual, whether they are conscious of it or not, fasts intermittently from dinner to breakfast. There are lots of methods to intermittent fasting. A few individuals fast for 16-20 hours intervals on alternate days while others follow a 24-hour day fast. The most common intermittent fasting variety is the 16/8 method, in which you eat in an 8-hour window followed by a 16-hour fasting window.

Other fasting programs incorporate the 20/4 or even 14/10 methods. Other people follow 24-hour fasts one or two times each week. Intermittent fasting can get you in ketosis quicker because your cells will immediately absorb your glycogen stores and begin burning fat. However, what about once you get into ketosis? Is intermittent fasting worth following consistently? Following the ketogenic diet and intermittent fasting can be a great addition towards an individual’s overall health and wellness, providing various health benefits.

The keto diet and intermittent fasting can provide the following health benefits, including:

  • Healthy weight-loss
  • Fat reduction, not muscle reduction
  • Balancing cholesterol levels
  • Enhancing insulin sensitivity
  • Maintaining blood glucose levels steady

Health Benefits of the Ketogenic Diet

The ketogenic diet dramatically reduces your caloric intake, forcing your body to burn fat instead of sugar, which makes it a powerful tool for weight reduction. While individual results vary, the keto diet has always resulted in a decrease in body fat in a selection of situations. Within a 2017 study, subjects who followed a very low carbohydrate keto meal program significantly decreased body fat percentage and body fat mass, losing an average of 7.6 lbs and 2.6 percent body fat while preserving lean muscle mass.

Likewise, a 2004 research detecting the long-term consequences of a ketogenic diet in overweight patients discovered that the weight and body mass of those patients diminished dramatically over the span of two decades. Individuals who radically reduced their carb intake saw a substantial decline in LDL (bad) cholesterol, triglycerides, and enhanced insulin sensitivity. In 2012, researchers compared a ketogenic diet to eating fewer calories for overweight kids and adults. The results showed kids after the keto diet lost significantly more body fat. They also revealed a dramatic decline in insulin levels, a biomarker of Type 2 diabetes.

Health Benefits of Intermittent Fasting

Studies have shown that intermittent fasting may be an effective weight loss tool, more powerful than just cutting calories. In one analysis, intermittent fasting has been proven to be as successful as constant calorie restriction in combating obesity. In studies done by the NIH, there was reported weight reduction with over 84 percent of participants, regardless of which fasting program they picked.

Much like ketosis, intermittent fasting increases fat loss while preserving lean muscle mass. In one study, researchers reasoned that fasting led to greater weight loss compared to a low-carb diet, though the overall caloric consumption was exactly the same. If you are attempting to lose weight, then a keto diet or intermittent fasting can be a massive help. But that is not where the rewards stop.

Intermittent Fasting and the Keto Diet for Mental Health

Both intermittent fasting and the ketogenic diet can provide various mental health advantages. Both have been clinically shown to boost memory, improve mental clarity and focus, as well as prevent the development of neurological disorders like Alzheimer’s and epilepsy. On a carb-based diet, changes in glucose can cause changes in energy levels. During ketosis, your brain employs a more consistent supply of fuel: ketones from the fat stores, leading to better productivity and psychological performance.

Whenever you’ve got a consistent and clean energy source from ketones, the brain works better. In addition to this, ketones are better at protecting your brain. Studies reveal that ketone bodies might have antioxidant properties which protect your brain cells from free radicals and oxidative stress. In one study conducted on adults with diminished memory, the growth of BHB ketones in their own blood helped enhance cognition. Also, when you’ve got difficulty staying focused, your hormones can be to blame.

Your brain has two chief neurotransmitters: glutamate and GABA. Glutamate will help you form new memories, and get your brain cells to communicate with one another. GABA is what helps restrain glutamate. If there is too much glutamate, it can cause brain cells to quit working and finally perish. GABA is there to control and slow down glutamate. If GABA levels are reduced, glutamate reigns free and you experience mental fog. Ketones stop damage to cells by processing surplus glutamate into GABA. Considering that ketones raise GABA and lessen glutamate, they assist in preventing cell damage, preventing cell death and enhancing mental focus.

Researchers believe that intermittent fasting enhances memory, decreases oxidative stress, and conserves learning abilities. Since your cells are under moderate strain whilst fasting, the top cells adapt to the stress by improving their particular ability to deal with these circumstances while the weakest tissues die. This is much like the strain that your body gets when you reach the gym.

Exercise is a kind of stress that your body adjusts to improve and get more powerful. This also applies for intermittent fasting: so long as you are still alternate between routine eating habits and fasting, it is going to continue to benefit you. Implying equally that ketosis and intermittent fasting will help improve your cognitive functioning because of the synergistic and protective effects of ketones.

Dr Jimenez White Coat
The ketogenic diet and intermittent fasting are two different nutritional strategies which provide many common health benefits. According to various research studies, both the keto diet and intermittent fasting can help boost ketones, helping the body burn fat more efficiently than any other nutritional strategy. And when these are utilized together, they definitely form a powerful dietary program. The article above discusses the differences between the ketogenic diet and intermittent fasting as well as demonstrates the health benefits of both of these dietary programs and how they can help improve overall health and wellness. Dr. Alex Jimenez D.C., C.C.S.T. Insight

The Perks of Intermittent Fasting and the Keto Diet

The ketogenic diet and intermittent fasting possess similar health benefits because both approaches involve ketosis. Ketosis has lots of physical and mental advantages, from weight loss to enhanced brain function. People following a ketogenic diet may use intermittent fasting as a tool to achieve ketosis and enhance their general well-being. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

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EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


Keto Diet Health Benefits

Keto Diet Health Benefits

If you are currently thinking about the ketogenic diet, then you might be asking yourself, is the keto diet right for you? While you may have already heard about the benefits of the ketogenic diet, you might still be wondering about whether if it is worth it to completely change your diet to take advantage of these benefits.

The keto diet has many benefits, from weight loss and improved physical health to mental clarity and enhanced physical performance. In the following article, we will dive into the details of some of the ketogenic diet health benefits. These benefits can help with the particular health goal you may be attempting to attain.

Ketogenic Diet and Weight Loss

In comparison to low-fat dieting, a low-carb diet can deliver superior results within a shorter time period in terms of weight loss, and the management of cholesterol, and blood pressure. If you want to shed weight, the ketogenic diet plan provides the following benefits and will get you closer to attaining your objective. There can be many reasons for this, including:

  • Low-carb and ketogenic diets are more satisfying with their low carb content and higher quantities of fats and protein.
  • Going onto a low-carb diet usually makes you lose extra water weight.
  • Most individuals can undergo weight loss fairly quickly, especially within the first week of beginning a ketogenic diet.

Increased HDL Cholesterol

Together with the high consumption of saturated fats and other healthy fats, the ketogenic diet may help raise HDL cholesterol and enhance triglycerides levels. Both of these are considerably significant towards promoting heart health.

Ketogenic Diet and Physical Health


Following the ketogenic diet has been demonstrated to also be able to help reduce inflammation and lesions of the skin like those found in acne. This is believed to occur due to the effects of ketosis, or the state in which the cells use ketones instead of glucose for energy.

IBS Support

Moreover, several research studies have also associated a link between the reduced consumption of glucose, or sugar, and an improvement in symptoms of irritable bowel syndrome, or IBS. As a matter of fact, one research study demonstrated that following a ketogenic diet may improve bowel movement habits and help reduce abdominal pain, improving quality of life in people with IBS.

Ketogenic Diet and Physical Performance

Balanced Energy Levels

Do not be surprised if you’re ready to stop drinking coffee every day after adapting to the keto diet. Achieving and maintaining ketosis involves benefits like no day slumps, no mood swings, and reducing changes in energy levels that you might experience otherwise.

In addition, you’ll likely find it much easier to remain longer periods of time without feeling hungry. This is what ultimately helps with weight loss, steady blood sugar levels, and extended periods of fasting, which is one of the best ways to get into ketosis.

Enhanced Workouts

Adjusting to the ketogenic diet may take time, however, once your body gets used to burning fat for fuel rather than sugar, or glucose, from carbohydrates, you will likely notice a difference in your physical performance and endurance, such as more energy and focus for workouts. This makes sense because being in ketosis “instructs” the entire human body to burn fat for fuel more efficiently.

The most important first step in case you start the ketogenic diet and notice limitations in your physical performance is to give your body some time to adapt from utilizing carbohydrates as its primary fuel to utilizing ketones as a source of energy. For individuals who participate in a lot of physical activities and exercise as well as athletes may benefit from a cyclical or targeted ketogenic diet.

Fat Loss / Muscle Gain

The amount of protein intake on a ketogenic diet makes it excellent for building muscle mass. Results might seem to come more gradually than for someone fueling their workouts but that is usually because you’re building lean mass together with fat reduction. By way of instance, when documenting a keto fast for four days, the individual gained 2.4 lbs of muscle with 1.1 lbs of fat reduction.

Ketogenic Diet and Mental Clarity

Several research studies have demonstrated that a ketogenic diet may have the ability to support mental clariy as well as help boost productivity, support better memory, and also, have positive effects in regard to moderate cognitive impairment.

Neurological Support

Early usage of the ketogenic diet has been used as a treatment for reducing seizures in people with epilepsy, especially children. Additionally, it has been shown to benefit people with Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative disorders. This is likely because ketone bodies created through the keto diet can have neuroprotective effects.

Dr Jimenez White Coat
Weight loss is one of the most well-known advantages of the ketogenic diet, however, this nutritional plan can have many other health benefits. By reducing the consumption of carbohydrates, the cells will go into a state of ketosis and instead utilize ketones created from fats, providing a steadier supply of energy than that of glucose, or sugar. Furthermore, research studies have also demonstrated the ketogenic diet’s possible role in disease prevention, such as for people with epilepsy. Dr. Alex Jimenez D.C., C.C.S.T. Insight

The benefits of the ketogenic diet are essential, not just for weight loss, but for overall health and wellness. When you are eating more fats and proteins with fewer carbohydrates, you are more likely to end up eating fewer calories. With this, you also don’t experience a change of energy levels but instead maintain a level of energy that lets you remain focused on your everyday tasks.

Regardless of the health goal you have in mind, the ketogenic, or keto, offers many benefits to improve your quality of life. Being aware of the proper foods you should eat on the keto diet is also important. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

blog picture of cartoon paper boy

EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


Essential Fats on the Ketogenic Diet

Essential Fats on the Ketogenic Diet

Have you started following the ketogenic diet? Are you confused with what type of fats you should eat to achieve and maintain ketosis? In the following article, we will list the different types of essential fats which are vital in the ketogenic diet.

Fats are crucial in the ketogenic diet. To promote the breaking down of fat rather than protein or carbohydrates, you need to consume fat, a process known as ketosis. However, the value of the healthy fats you eat is fundamental. Fat is satiating and it tastes good. Simply, be sure to eat the ideal kind of fat. There are four categories of fat permitted on the ketogenic, or keto, diet:

  • Polyunsaturated fats
  • Monounsaturated fats (MUFAs)
  • Polyunsaturated fats (PUFAs), which comprises omega 3
  • Only naturally-occurring trans fats

Remember that a balance of omega-3s and omega-6s can help maintain overall health and wellness, improving brain and nerve function and decreasing the risk of cardiovascular disease, Alzheimer’s disease, and type-2 diabetes. While omega-6 is vital, however, too much of it can cause inflammation in the human body, therefore, avoid eating high amounts of omega-6 from sources like peanuts and vegetable oils, such as corn oil or sunflower oil.

Instead, focus largely on the intake of omega-3s from fish sources like trout, salmon, tuna, and mackerel or take a high-quality fish oil supplement. Additionally, be cautious of seeds and nuts since they do include some carbohydrates, particularly pistachios and almonds. Make certain that the fat you eat is currently coming out of nutrient-dense foods, such as fatty cuts of meat. Below is a food listing of the major types of fat in the ketogenic diet.

Dr Jimenez White Coat
Fats are the basis of the ketogenic diet. The high fat intake and the low fat intake helps achieve and maintain ketosis, or the creation of ketones. Utilizing ketones for fuel, the human body can burn fat instead of sugar or glucose from carbohydrates. Getting and keeping your body in the state of ketosis can provide many health benefits, including weight loss and overall health and wellness. The quality of fats you consume while on the keto diet is essential towards reaching ketosis. The following article discusses the different types of fats you can eat while on the ketogenic diet and which ones you should avoid. Dr. Alex Jimenez D.C., C.C.S.T. Insight

Fats and Oils in the Ketogenic Diet

The value of your dietary fat on keto creates a massive difference in the results that you’ll see. If you are taking an unhealthy approach for your new low-carb diet program, then you will quickly discover reverse health consequences. That is why it’s vital to understand which sources of fat are actually considered safe and healthy to consume on while on the ketogenic diet.

The very first sort of healthy fat to begin including on your keto diet plan is saturated fat. Saturated fat was analyzed and proven to enhance HDL and LDL cholesterol levels, both good and bad cholesterol markers, and it may also strengthen bone density and improve the function of your immune system as well as promote the production of important hormones in the human body.

Saturated fats include:

  • Grass-fed and organic red meats
  • High fat dairy like ghee, grass-fed butter, and heavy cream
  • Lard, tallow, and eggs

These are animal-based saturated fats but there are also plant-based selections like olive oil and MCT oil that could provide you with the wholesome dose of saturated fats that you need to maintain your well-being. Branching out of healthy unsaturated fats, both monounsaturated fatty acids and polyunsaturated fatty acids can help you accomplish your ketosis objectives. Take a look at the graph below to get a visual of these wholesome oils and fats to focus on if following a ketogenic diet.

Monounsaturated fats include:

  • Virgin olive oil, avocado oil, and macadamia nut oil (eating avocados and olives also helps you reap these healthy fats)
  • Certain nuts and seeds

Polyunsaturated fats include:

  • Nuts and seeds such as walnuts, flaxseeds, chia seeds, sunflower, and pumpkin seeds
  • Flaxseed oil, sesame oil, fish oil, avocado oil, and krill oil
  • Fatty fish like trout, mackerel, salmon, and tuna

Fats and Oils to Avoid in the Keto Diet

You will also have to learn that some dietary fats should be avoided altogether. Simply because you are after a high-fat ketogenic diet does not mean that you ought to indulge in each fat you encounter. All fats aren’t created equal. Stay away from unhealthy fats like:

Hydrogenated and partially hydrogenated oils. These fats can be present in packaged foods. They may also increase your risk of developing higher cholesterol, cancer, obesity, and heart disease along with inflammation. If you are relying on packaged foods to get you through the ketogenic diet, check the tag and ditch any foods with them.

Highly processed vegetable oils. Peanut oil, corn oil, canola oil, soybean oil, sunflower oil, and grapeseed oil are fats which seem healthier than they are. These fats are generally created with genetically modified seeds which are possible allergens. Extreme heat can also make these oils go rancid. Additionally, they may leave fatty deposits on your body that may result in heart attacks and premature death. Finally, these oils contain higher levels of omega 6 fatty acids which can lead to chronic inflammation.

Nuts and Seeds in the Ketogenic Diet

Another simple and gratifying way to sneak healthy fats into the ketogenic diet would be to reach for uncooked seeds and nuts. These nutrient powerhouses are packed with essential nutrients, such as magnesium, selenium, and manganese. Seeds and nuts may enhance brain health, fortify your immune system, and assist with digestion and blood sugar control.

They are also high in healthy fats, have a moderate quantity of protein, and are usually low carb, based on the kind you select. Nuts and seeds are also simple to carry, which makes them among the best snacks when on a keto diet. Some nuts and seeds, however, are better than others. In keto, this implies that they have more fat and less carbohydrates.

The five best nuts in the ketogenic diet include:

  • Macadamia nuts
  • Pecans
  • Brazil nuts
  • Walnuts
  • Hazelnuts

Pine nuts, almonds, cashews, and pistachios are also great nuts to include into the ketogenic diet. However, because they have more carbohydrates compared to the top five, they need to be consumed in moderation so that you don’t accidentally tip on your carbohydrate count daily. Consuming one or more one of these nuts as nut butter is a handy way to receive a spoonful of nourishment during snack time. However, you are going to want to practice portion control too since the serving size is really small.

The following best seeds in the ketogenic diet include: 

  • Pumpkin seeds
  • Sesame seeds
  • Sunflower seeds and sunflower seed butter
  • Tahini (sesame seed paste)
  • Chia seeds
  • Flaxseeds

Nuts and Seeds to Avoid in the Keto Diet

Are you wondering why peanuts and peanut butter is not part of the list of ketogenic diet foods? The majority of us have grown up eating and snacking on peanut butter. But a lot of us don’t recognize that peanut butter isn’t really made out of nuts; peanuts are a legume, which is part of the exact same family as peas, soybeans, and lentils. While the macro dysfunction and low-fat level of a serving of peanuts might be like other nuts, that is where their healthy comparison stops.

Peanuts and peanut butter are:

  • Packed with unnecessary added sugars
  • Loaded with hydrogenated oils (essentially harmful trans fats)
  • Low in fat and filled with junk as a replacement
  • Hard to digest
  • Covered in pesticides
  • High in oxalates (which prevent proper nutrient absorption and can lead to kidney stones)
  • High in inflammatory omega-6 fatty acids

Dairy in the Ketogenic Diet

Most dairy products fit into the “fat” and “protein” category but they are accepted as part of the ketogenic diet as long as you’re not lactose intolerant. Simply make sure you eat the full-fat version and preferably choose organic and raw options, if possible. Dairy is not an extremely important element of a keto diet. If you are lactose intolerant, you may safely omit it.

For people with dairy sensitivities:

  • Find hard and long-aged dairy
  • Use ghee, a butter alternative without the irritating milk solids
  • Get checked for a casein sensitivity to rule out the other common irritant found in dairy

Other dairy choices can include:

  • Unflavored greek yogurt, fermented yogurt, and kefir
  • Hard cheeses like blue cheese, gouda, and parmesan
  • Semi-hard cheese such as Colby, provolone, and swiss cheese
  • Softer cheeses like mozzarella, brie, muenster, and Monterey Jack
  • Cream cheese, mascarpone, creme fraiche, and cottage cheese, which are also okay on a high-fat diet

Dairy to Avoid in the Keto Diet

Very similar to healthy versus unhealthy fats, these dairy things are packed using the wrong ingredients and aren’t good if you are trying to achieve and maintain ketosis. To reach ketosis, avoid these 3 dairy products on the ketogenic diet.

Low fat, reduced fat, and fat-free milk. When fat is removed from dairy, sugar is added to fill in the gaps and make these taste much better. The sugar in these products will prevent you from going into ketosis. Whole milk is not much better, however, with 12.8 grams of carbohydrates per glass, you’re much better off enjoying low carb cheese over a glass of milk.

Half and half. Do not go with this particular half milk/half cream mix either. You are still getting a dose of sugar and less fat, two of which is not ideal for a keto diet. Reach for heavy whipping cream and you won’t hav carbohydrates or sugar to contend with.

Evaporated and condensed milk. Before incorporating these canned milk choices for your next recipe, you need to know these are essentially a cooked down variation of milk syrup and sugar in disguise. Luckily, it is simple to substitute this cooking staple with unsweetened, full-fat, canned coconut milk. Plus, as it is made from coconuts, you also receive healthy saturated fats.

Fats are ultimately essential in the ketogenic diet. Recognizing the different types of fats you can eat while on the keto diet is important in order to help you achieve and maintain ketosis. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

blog picture of cartoon paper boy

EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


What Fats To Eat On The Ketogenic Diet

What Fats To Eat On The Ketogenic Diet

Fats are an essential part of the ketogenic diet since they constitute approximately 70 percent of your dietary calories. However, the type of fat you eat on the ketogenic diet is also important and there may be some confusion regarding good fats and bad fats. The following article discusses exactly what fats you need to include and what fats you must avoid while on the keto diet.

Good Fats on the Ketogenic Diet

The type of “good” fats included while on the ketogenic diet are divided into four groups: saturated fats, monounsaturated fats (MUFAs), polyunsaturated fats (PUFAs), and naturally-occurring trans fats. All fats can be classified into more than one group, however, we classify them according to the most dominant of these mixtures. It’s essential to be able to recognize what type of fat you are eating on the ketogenic diet. Below, we will describe each group of good fat so you can properly implement them into your own food choices.

Saturated Fats

For many years, saturated fats were considered to be detrimental for heart health and we were advised to limit their consumption as much as possible. However, recent research studies have demonstrated no substantial connection between saturated fats and the increased risk of cardiovascular disease. As a matter of fact, including healthy saturated fats into your diet can have many benefits.

One type of saturated fat contains medium-chain triglycerides (MCTs), which can be largely found in coconut oil, or in small quantities in butter and palm oil, and it may be digested quite easily by the human body. Medium-chain triglycerides pass through the liver for immediate use as energy when consumed. MCTs are beneficial towards promoting weight loss and improving athletic performance.

Health benefits of saturated fats on the keto diet can include:

  • Improved HDL and LDL cholesterol levels
  • Maintenance of bone density
  • Boosting of immune system health
  • Support in creation of important hormones like cortisol and testosterone
  • Raising of HDL (good) cholesterol in the blood to prevent buildup of LDL in the arteries
  • Improved HDL to LDL ratio

Recommended types of saturated fats while on the ketogenic diet include:

  • Butter
  • Red meat
  • Cream
  • Lard
  • Coconut oil
  • Eggs
  • Palm oil
  • Cocoa butter

Monounsaturated Fats

Unlike saturated fats, monounsaturated fats, also referred to as monounsaturated fatty acids or MUFAs, have been approved as a healthy source of fat for several years. A variety of research studies have connected them to numerous health benefits associated with improved levels of “good” cholesterol and better insulin resistance, among other health benefits, as described below.

Health benefits of MUFAs on the keto diet can include:

  • Increased HDL cholesterol
  • Lowered blood pressure
  • Lowered risk for heart disease
  • Reduced belly fat
  • Reduced insulin resistance

Recommended types of MUFAs while on the ketogenic diet include:

  • Extra virgin olive oil
  • Avocados and avocado oil
  • Macadamia nut oil
  • Goose fat
  • Lard and bacon fat

Healthy Polyunsaturated Fats

The most important point to keep in mind about eating polyunsaturated fats, also referred to as polyunsaturated fatty acids or PUFAs, on the ketogenic diet is that the specific type you consume actually matters. When heated, some polyunsaturated fats may produce substances that can cause inflammation in the human body, increasing the risk of cardiovascular disease and even cancer.

Many PUFAs must be consumed cold and they should never be utilized for cooking. PUFAs can be found both in very processed oils and in very healthy sources. The right types can additionally provide many health benefits on the ketogenic diet, particularly because several of these include omega 3s and omega 6s, both of which are essential nutrients in a healthy and balanced diet.

Health benefits of PUFAs on the keto diet can include:

  • Reduced risk of heart disease
  • Reduced risk of stroke
  • Lowered risk of autoimmune disorders and other inflammatory diseases
  • Improved symptoms of depression
  • Improved symptoms of ADHD

Recommended types of PUFAs while on the ketogenic diet include:

  • Extra virgin olive oil
  • Flaxseeds and flaxseed oil
  • Walnuts
  • Fatty fish and fish oil
  • Sesame oil
  • Chia seeds
  • Nut oils
  • Avocado oil

Naturally-Occurring Trans Fats

Many people might be confused to see trans fats classified as “good” fats. While most trans fats are considered to be extremely unhealthy and even harmful, one type of trans fat, known as vaccenic acid, can be found naturally in various kinds of food, such as in grass-fed animal products and dairy fats. These naturally-occurring trans fats also provide several health benefits on the keto diet.

Health benefits of naturally-occurring trans fats on the keto diet include:

  • Reduced risk of heart disease
  • Reduced risk of diabetes and obesity
  • Possible protection against cancer risk

Recommended types of naturally-occurring trans fats while on the ketogenic diet include:

  • Grass-fed animal products
  • Dairy fats like butter and yogurt
Dr Jimenez White Coat
When following a ketogenic diet, or any other low carb diet, eating the right type of fat is essential, especially since these make up about 70 percent of your daily caloric intake. The type of fat you eat is classified into various groups depending on the dominant amount found in the mixture. Extra Virgin Olive Oil, for example, is approximately 73 percent monounsaturated fat, therefore, it is considered a monounsaturated fat. Butter is about 65 percent saturated fat and thus, is a saturated fat. It’s essential to be able to recognize what type of fat you are eating on the ketogenic diet in order to enjoy its health benefits. Dr. Alex Jimenez D.C., C.C.S.T. Insight

Bad Fats on the Ketogenic Diet

One of the greatest advantages of the ketogenic diet is the capacity to eat lots of satisfying dietary fats such as those mentioned previously. However, we have to also cover the kinds of fats that you should reduce or eliminate from your diet in order to prevent damaging your well-being. On the keto diet, the quality of food you eat is especially important to achieve ketosis.

Unhealthy Polyunsaturated Fats and Processed Trans Fats

Processed trans fats are the group of fat which most people as the “bad” fats and the truth is, they can actually be quite damaging to your overall health and wellness.  Artificial trans fats are made during food production via the processing of polyunsaturated fats. That is the reason why it’s very important to choose PUFAs which are unprocessed and not overheated or modified. The consumption of unhealthy PUFAs can create harmful free radicals where processed trans fats often contain genetically modified seeds.

Health risks of unhealthy polyunsaturated fats and processed trans fats include:

  • Increased risk of heart disease
  • Increased risk of cancer
  • Reduced HDL cholesterol and increased LDL cholesterol
  • Pro-inflammatory
  • Bad for the health of your gut

Examples of unhealthy polyunsaturated fats and processed trans fats to avoid include:

  • Hydrogenated and partially hydrogenated oils found in processed products like cookies, crackers, margarine, and fast food
  • Processed vegetable oils like cottonseed, sunflower, safflower, soybean, and canola oils

In conclusion, it’s essential to recognize what type of fat you are eating while on the ketogenic diet. In the end, the function of the ketogenic diet will always be to enhance your health, which includes eating the appropriate amount of fat, protein, and carbohydrate ratio as well as picking food resources which promote health and wellness. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

blog picture of cartoon paper boy

EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


What Are Exogenous Ketones?

What Are Exogenous Ketones?

Ketones serve as a source of energy for the mitochondria found inside the cells of the human body. These are an alternative fuel to sugar. Ketones are basic substances with a simple molecular structure. Ketones are natural, or carbon-based, chemicals made up of a central carbon atom double-bonded into an oxygen atom and two carbon-containing substituents, denoted by”R”.

Genetic Ketone Structure

In humans, there are 3 distinct ketones created by the mitochondria. These are referred to as ketone bodies. The 3 ketones are:

  1. Acetone
  2. Acetoacetate, also known as Acetoacetic Acid
  3. Beta-Hydroxybutyric Acid, also known as Beta Hydroxybutyrate or BHB. Additional compound names include 3-hydroxybutyric acid or 3-hydroxybutyrate.

BHB isn’t particularly considered a ketone because it comprises a reactive OH-group rather than a double-bonded oxygen which would generally function as demonstrated in the diagram below. However, BHB continues to function much like a ketone because it transforms into energy, such as acetone and acetoacetate. The following is demonstrated in the diagram below.

Structures of Ketone Bodies

Ketogenesis is the metabolism of fatty acids through β-oxidation. This procedure provides acetyl CoA which converts to β-hydroxy-β-methyglutaryl-CoA, or HMG-CoA, as shown below. HMG-CoA turns into Acetoacetone which may change back-and-forth to BHB. The conversion of Acetoacetate into Acetone is irreversible (as seen on the bottom left). Acetoacetate and BHB, through acetoacetate, are utilized to make energy when converted into acetyl-CoA in the cell’s mitochondria whilst Acetone is excreted in the breath and urine.

Formation of Ketone Bodies from Acetyl-CoA2

Understanding Exogenous Ketone Bodies

Exogenous ketone bodies are simply ketone bodies which are consumed via a nutritional supplement. Ketone bodies created in the liver are more correctly referred to as endogenous ketone bodies. The following is described below.

Most nutritional supplements depend on BHB as the origin of the exogenous ketone bodies. BHB transforms into acetoacetic acid where a small amount is turned into acetone via an acetoacetate decarboxylase waste pathway. A percentage of that acetoacetic acid may enter the energy pathway utilizing beta-ketothialase, which transforms acetoacetic acid into 2 Acetyl-CoA molecules.

Ketosis Pathway Before Entering the Krebs (Energy) Pathway

The Acetyl-CoA will then enter the Krebs cycle and creates ATP. Exogenous ketone body nutritional supplements provide an instantaneous supply of ketones to consumers. Even when you’re not in the state of ketosis before eating, such as when ingesting a higher-carb diet. These also increase blood ketones even in the presence of insulin, which inhibits ketogenesis.

Researchers do not completely comprehend what the long-term ramifications of combining a non-ketogenic diet with exogenous ketone bodies nutritional supplements really are. Research studies are at their first phases and much more information is required. A standard issue involves why BHB is the ketone body to receive exogenous ketone nutritional supplements. The explanation is a mixture in the simplicity of its formula and its conversion to energy. it is simpler to devise BHB into a nutritional supplement.

Are “Raspberry Ketones” Similar to “Ketone Bodies”?

Raspberry ketones are a common ingredient used in weight-loss nutritional supplements. However, despite their title, they don’t have any connection. This has generated some confusion for individuals considering ketone nutritional supplements that are exogenous.

Raspberry ketones are in reality phenolic compounds that provide raspberries their pleasant odor. They are similar to the stimulant synephrine. Regardless of the research studies, raspberry ketones don’t seem to have much impact on weight loss.

Ketone Salts vs. Ketone Esters

Exogenous ketones of all beta-hydroxybutyrate can be found in two kinds:

  1. Ketone Salts are naturally-derived chemicals which blend sodium as well as potassium and/or calcium with BHB to boost absorption. Commercially available nutritional supplements are all created from ketone salts now (contains KetoForce, KetoCaNa and Keto OS). These are also occasionally called “Ketone Mineral Salts” or “BHB Mineral Salts”.
  2. Ketone Esters are Synthetically-made chemicals that connect an alcohol to a ketone body, where this can be metabolized in the liver as a ketone. Ketone esters are used primarily in search for testing their effectiveness on improving ketone body levels. Below is a standard arrangement of a BHB ester. The very first Ketone Ester beverage is currently accessible by HVMN. Research esters are very unpleasant tasting, something which HVMN expects to modify soon.
Structure of a Beta-Hydroxybutyrate Ester

Ketone Esters increase blood levels of beta-hydroxybutyrate to greater levels compared to Ketone Salts. There’s strong evidence supporting that esters are more powerful than Ketone Salts, so much as their advantages proceed. It’s not apparent why this occurs, but it might be from the gastrointestinal, or GI, tract due to a gap in the absorption rate.

However, esters are normally somewhat tougher to endure because of gut distress after intake and they do not have the most agreeable taste, as stated previously in the article. Figure 1 below demonstrates the difference between eating equivalent quantities of BHB in the kind of a Ketone ester and Ketone salts on bloo BHB. The supplements contained are:

  • BMS (Beta-hydroxybutyrate Mineral Salt) — sodium/ potassium established (KetoForce)
  • KE (Ketone Ester) — (R- 3-hydroxybutyl-R-1,3-hydroxybutyrate) (HVMN)
Figure 1: Blood BHB level after consuming a ketone ester vs a ketone salt drink.

What are the Benefits of Exogenous Ketones?

Exogenous ketone nutritional supplements can offer a great number of benefits. These include more effective weight reduction, athletic performance improvement, cancer prevention, cognitive advancement, and anti-inflammatory properties.

Weight Loss Goals

  • Appetite suppression: Appetite was quantified in 10 males and 5 females after taking a ketone ester, abbreviated as KE, or a dextrose, abbreviated as DEXT, beverage. The wish to consume and perception of appetite dropped after both supplements, however, the KE was 50 percent more successful for 1.5 to 4 hours. Insulin levels rose with both supplements but were 3 times lower with the KE beverage after 30 minutes, according to Figure 2. The desire hormone, ghrelin, was considerably lower between 2 to 4 hours after ingesting the KE, as seen on Figure 2. Ketone esters lower the urge and delays appetite.
Figure 2: Perceived hunger, fullness, and satiety after consuming a dextrose or ketone ester drink over time. Effects of ketone ester or dextrose drink on plasma insulin and ghrelin levels over time.
  • Extra ketones: In case someone has an inordinate number of ketones in the bloodstream, the human body, especially the kidneys, will function as swiftly as possible to filter out ketones via urine instead of converting them into adipose tissue. This isn’t to say you can not gain fat with exogenous ketones, however, they are not as inclined to be converted into fat than other nourishment.
  • More tolerable compared to MCT oil: MCT oil was known to cause gastrointestinal distress in consumers, particularly when taken in high quantities. Exogenous ketones as ketone salts are well-tolerated. They prevent adverse GI events while supplying similar kinds of benefits. Figure 2 demonstrates how Ketone esters may be capable of reducing hunger. A combo of exogenous ketones and MCT oil can help with weight loss and permit a loading of nutritional supplements, with no GI distress.

Athletic Performance Goals

  • Athletic enhancem: The development of energy and fuel pairing mechanisms. Exogenous ketone supplementation may boost these components of athletic performance. There’s a promising prognosis in this area for many different motives:
  1. Exogenous ketones induce severe ketosis, lasting for many hours. This is without having to possess depleted muscle glycogen stores. Low muscle nourishment is well-known to inhibit sustained physical functionality.
  2. The “carb-sparing” impact from BHB inhibits the breakdown of muscle glycogen. This contributes to reduced lactate levels. When raising exercise intensity, fat oxidation, or burning, reaches a limit. Carbohydrates are then burned for energy. But when swallowing Ketone esters, the body doesn’t make this change. This implies ketones are used instead.
  3. Exogenous ketones induce your system to rely on fat as fuel, as seen in Figure 3. Fat takes longer to metabolize compared to muscle glycogen for vitality. That is because fatty acids aren’t the fuel that is favored by the human body under exercise. This might be useful for athletes performing resistance training or cardiovascular exercises. This is especially helpful for athletes that would like to experience cardiovascular or resistance training.
  4. Ketone esters boost free carnitine whilst exercising which appears to enhance physical performance.
  5. Exogenous ketones decrease the usage of Branched-chain amino acids, or BCAAs, as energy, a process known as deamination. The growth was decreased by consumption of a ester beverage by 50 percent during exercise in muscle BCAAs.
Figure 3: Plasma free fatty acid (FFA) and glycerol concentrations after consuming high fat, carbohydrate, or ketone ester drink.
  • Increased cognition: Elevated plasma ketone concentrations divert the brain to use ketone bodies for the synthesis of phospholipids, which drives growth and myelination. Sugar is often the preferred fuel for this process, which is not as efficient. BHB appears to work as a signal for pathways. These improve cognition, plasticity and stress immunity. In rat research studies, ingestion of a ketone ester for 5 days enhanced memory and their learning.

Health & Longevity

  • Anti-carcinogenic properties: Statistics appears to imply that exogenous ketones are a powerful anti-carcinogen. The motive for this is that cancer cells cannot utilize ketone bodies efficiently. In fact ketone supplementation was demonstrated to improve survival rates of mice with cancer.
  • Neuroprotection: As people age, the brain becomes more prone to neurodegeneration and following conditions like Alzheimer’s and Parkinson’s disease. Ketone supplementation seems to ameliorate the decline. The mechanism is that ketone bodies decrease hyperexcitability and the redness that’s ordinarily shown as sugar metabolism declines from the brain.
  • Anti-Inflammatory attributes: There’s proof that ketone bodies play an essential part in reducing inflammation by inhibiting a particular class of proteins known as inflammasones.
  • Gene regulation profile alterations: There’s proof that gene sets could be regulated with an alteration in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, or mHS, as see in rats on a ketogenic diet.
Dr Jimenez White Coat
Ketones are a source of energy which is produced when there is not enough sugar or glucose for the human body to burn as fuel. They serve as an alternative fuel source to glucose. Ketogenesis, the metabolism of fatty acids through ketosis, can have a variety of health benefits. Many people achieve these benefits by following the ketogenic diet, however, these advantages can be achieved without the keto diet as well. Exogenous ketone bodies are simply ketones which are consumed through a nutritional supplement. Although the over-consumption of any supplement can have risks, exogenous ketone bodies can provide similar benefits to ketosis. Dr. Alex Jimenez D.C., C.C.S.T. Insight

How Exogenous Ketones Function

Exogenous ketones possess many different physiological effects soon after ingestion:

  • For starters, ingesting ketones, particularly ketone esters, is an effective approach to Boost BHB from the bloodstream above 2 mMol for almost 8 hours. Ketone salts do not seem to elevate BHB from the bloodstream as efficiently or significantly where ketone esters do, however.
  • Exogenous ketone supplementation induces blood sugar to reduce significantly, likely as a result of an intense increase in insulin sensitivity. Exogenous ketones may pose a possible treatment.
  • Exogenous ketones additionally improve oxygen use, particularly in the central nervous system, or CNS. This effect reduces the odds of oxygen reaching potentially hazardous levels in the CNS, which then has a variety of additional favorable health effects like the ones discussed in the prior section.

Potential Downsides to Ketone Supplementation

Like any other nutritional supplement, side effects and drawbacks are possible after consuming exogenous ketones. As ketone supplementation becomes more notable, they are generally quite benign and will improve. The most frequent side effects to know about when using exogenous ketones consist of:

  • Electrolyte Imbalance: The physiological rationale supporting electrolytes during a state of ketosis is a result of the absence of water retention and frequent urination. The frequency of urination will increase when supplementing exogenous ketones, but it will not deplete glycogen stores. It could be handy after taking ketones if you’re urinating a lot to drink an electrolyte solution, but it is dependent upon the way you are feeling.
  • Halitosis or bad breath: If you are on a ketogenic diet, you’re most likely aware that since the body begins to metabolize fat, ketones may cause bad breath. There is little one can do about this. This may arise when utilizing exogenous ketones, but it is not quite as durable as when on the ketogenic diet. If it turns into a problem, chewing gum or mints is the best choice. This issue may occur due to the over-consumption of this nutritional supplement, tailoring extra BHB.
  • Potential GI distress (flatulence) at exceptionally substantial doses: Exogenous ketones taken in massive doses sometimes lead to GI distress, particularly flatulence. On the other hand, this cause can be hypothesized to be a result of how ketones were blended in a fluid which was palatable. If you are taking a balanced dose of ketones GI distress can be avoided. If some GI distress is widespread, it must improve as you become accustomed to carrying ketones.
  • Hypoglycemia: Accepting exogenous ketones can induce blood sugar levels to become very low, but you’re unlikely to feel the normal signs of hypoglycemia. That is because if levels are large enough, they control energy in the brain; despite having low blood sugar, therefore, you may feel just fine. A research by George Cahill, discovered that if they had been administered insulin to induce hypoglycemia, ketone levels can protect fasted participants.

Future Research Studies

Research studies on exogenous ketones concentrates on the advantages of their use. Research studies will also concentrate more on their therapeutic use. The information on all those applications is currently limited. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

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EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


Ketogenic Diet in Cancer Treatment

Ketogenic Diet in Cancer Treatment

Cancer is the second leading cause of death in the United States. Research studies have estimated that approximately 595,690 Americans die from cancer every year, that’s about 1,600 deaths every day, on average. Cancer is frequently treated utilizing a combination of surgery, chemotherapy, and radiation. Recent research studies have analyzed a variety of nutritional strategies for cancer treatment. Early research studies suggest that the ketogenic diet may help treat cancer.

What is the Ketogenic Diet?

The ketogenic diet is a very low-carb, high-fat diet which is often compared with the Atkins diet and other low carb diets. Also commonly known as the keto diet, this nutritional strategy entails drastically reducing your consumption of carbohydrates and instead substituting them with fat. This dietary shift is what causes the human body to enter a state of ketosis, the well-known metabolic state associated with the keto diet. Ketosis utilizes fat as the cell’s main source of energy, rather than sugar or glucose.

Ketosis causes a considerable increase in the levels of ketones. In general, a ketogenic diet used for weight loss consists of about 60 to 75 percent of calories from fat, with 15 to 30 percent of calories from protein and 5 to 10 percent of calories from carbohydrates. However, when a ketogenic diet is used therapeutically to treat cancer, the fat content might be significantly higher, up to 90 percent of calories from fat, and the protein content will also be considerably lower, up to 5 percent of calories from protein.


The Role of Blood Sugar in Cancer

Many cancer treatments are designed to target the biological differences between cancer cells and normal cells. Nearly all cancer cells share one common characteristic: they feed off of blood sugar or glucose in order to grow and multiply. During the ketogenic diet, several conventional metabolic processes are modified and blood sugar levels decrease, “starving” cancer cells. As a result, cancer cells have been demonstrated to grow much slower, often decreasing in size or even dying.

This nutritional strategy as a form of cancer treatment was first proposed by Otto Heinrich Warburg, a leading cell biologist. Otto Warburg led to the discovery that cancer cells are unable to flourish using energy produced from cellular respiration but instead from glucose fermentation. The Warburg effect developed from the role of glycolysis and lactic acid fermentation to transfer energy, compensating for lower dependence on oxidative phosphorylation and limited mitochondrial respiration.

Benefits of the Keto Diet for Cancer

The ketogenic diet provides other benefits in cancer treatment. Primarily, reducing carbohydrates from your diet can quickly lower calorie intake, reducing the energy available to the cells. In turn, this may slow down tumor development and the progression of cancer. Additionally, the ketogenic diet may help lower insulin levels. Insulin is an anabolic hormone which promotes cell growth, including cancerous cells. Therefore, lower insulin may help slow down tumor development.

The Ketogenic Diet and Cancer in Animals

Researchers have analyzed the ketogenic diet as an alternative cancer treatment for many decades. Until recently, most research studies were performed in animals. A big number of these animal research studies have demonstrated that the ketogenic diet can reduce tumor growth and improve survival levels in mice.

One research study in mice reviewed the cancer-fighting effects of the ketogenic diet along with other diets. Strikingly, the researchers found that 60 percent of mice following the ketogenic diet survived. This increased to 100 percent in mice that received a ketone supplement while on the keto diet. None lived on a standard diet.

The Ketogenic Diet and Cancer in Humans

Despite the promising evidence of the benefits of the ketogenic diet as a form of cancer treatment in animals, research studies in humans have only just started. At present, the limited research studies does seem to demonstrate that a ketogenic diet may decrease tumor size and decrease the progression of certain cancers. One of the few documented cases was conducted on a 65-year-old woman with brain cancer. Following surgery, she followed a ketogenic diet and the tumor’s progression decreased.

However, 10 weeks after returning to a normal diet, she experienced a substantial increase in tumor growth. Similar case reports analyzed the reactions to a ketogenic diet in two women who were undergoing therapy for advanced brain cancer. Researchers discovered that glucose uptake was decreased from the tumors of both patients. One of the women reported improved quality of life and stayed on the diet for 12 weeks. During that time her disease showed no further progression.

One research study tracked tumor growth in response to a high-carbohydrate diet versus a ketogenic diet in 27 patients with gastrointestinal cancer. Tumor growth increased by 32.2 percent in patients who received the high-carb diet while tumor growth decreased by 24.3 percent in patients on the ketogenic diet. In a different research study, three out of five patients on a ketogenic diet combined with radiation or chemotherapy experienced complete remission.

Can the Ketogenic Diet Help Prevent Cancer?

A variety of research studies have also demonstrated that the ketogenic diet can help prevent cancer in the first place. Primarily, it can help reduce several risk factors for cancer. The keto diet may help decrease IGF-1 levels. Insulin-like growth factor 1, or IGF-1, is a hormone that’s essential for cell growth while reducing programmed cell death. This hormone can play a part in the evolution and progression of cancer. The ketogenic diet is thought to decrease IGF-1 levels, thereby decreasing the effects insulin has on cell growth, reducing the risk of cancer.

The ketogenic diet can also help lower blood sugar levels and decrease the risk of diabetes. Other evidence indicates that people with elevated glucose and diabetes have an increased risk of developing cancer. Research studies show that a ketogenic diet can be extremely effective at lowering blood sugar levels and handling diabetes. The keto diet can reduce obesity. Obesity can be a risk factor for cancer. Since the ketogenic diet is a powerful weight loss tool, it may also help reduce the chance of cancer by fighting obesity.

Dr Jimenez White Coat
Emerging research studies continue to demonstrate that sugar or glucose is the main source of fuel for cancer. Researchers have attempted to demonstrate that regulating the metabolic functions within the human body is the real solution towards treating cancer. The ketogenic diet can help treat cancer because it limits the amount of sugar in the body and instead replaces it with ketones, “starving” cancer cells and decreasing cell growth and cancer progression. Dr. Alex Jimenez D.C., C.C.S.T. Insight


A ketogenic diet offers many health advantages. Based on animal and early research studies in humans, it may also serve as a cancer treatment. However, it’s important to keep in mind that further research studies are still required to conclude the effects of the ketogenic diet on cancer. You shouldn’t avoid conventional cancer therapy in favor of an alternative treatment option like the keto diet. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

Green Call Now Button H .png

Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

blog picture of cartoon paper boy

EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


Multi-Dimensional Roles of Ketone Bodies

Multi-Dimensional Roles of Ketone Bodies

Ketone bodies are created by the liver and utilized as an energy source when glucose is not readily available in the human body. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. Ketogenesis is the biochemical process by which organisms produce ketone bodies through the breakdown of fatty acids and ketogenic amino acids.

Ketone bodies are mainly generated in the mitochondria of liver cells. Ketogenesis occurs when there are low glucose levels in the blood, particularly after other cellular carbohydrate stores, such as glycogen, have been exhausted. This mechanism can also occur when there is insufficient amounts of insulin. The production of ketone bodies is ultimately initiated to make available energy which is stored in the human body as fatty acids. Ketogenesis occurs in the mitochondria where it is independently regulated.


Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient remains and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.


Ketone bodies are a vital alternative metabolic fuel source for all the domains of life, eukarya, bacteria, and archaea (Aneja et al., 2002; Cahill GF Jr, 2006; Krishnakumar et al., 2008). Ketone body metabolism in humans has been leveraged to fuel the brain during episodic periods of nutrient deprivation. Ketone bodies are interwoven with crucial mammalian metabolic pathways such as β-oxidation (FAO), the tricarboxylic acid cycle (TCA), gluconeogenesis, de novo lipogenesis (DNL), and biosynthesis of sterols. In mammals, ketone bodies are produced predominantly in the liver from FAO-derived acetyl-CoA, and they are transported to extrahepatic tissues for terminal oxidation. This physiology provides an alternative fuel that is augmented by relatively brief periods of fasting, which increases fatty acid availability and diminishes carbohydrate availability (Cahill GF Jr, 2006; McGarry and Foster, 1980; Robinson and Williamson, 1980). Ketone body oxidation becomes a significant contributor to overall energy mammalian metabolism within extrahepatic tissues in a myriad of physiological states, including fasting, starvation, the neonatal period, post-exercise, pregnancy, and adherence to low carbohydrate diets. Circulating total ketone body concentrations in healthy adult humans normally exhibit circadian oscillations between approximately 100–250 µM, rise to ~1 mM after prolonged exercise or 24h of fasting, and can accumulate to as high as 20 mM in pathological states like diabetic ketoacidosis (Cahill GF Jr, 2006; Johnson et al., 1969b; Koeslag et al., 1980; Robinson and Williamson, 1980; Wildenhoff et al., 1974). The human liver produces up to 300 g of ketone bodies per day (Balasse and Fery, 1989), which contribute between 5–20% of total energy expenditure in fed, fasted, and starved states (Balasse et al., 1978; Cox et al., 2016).

Recent studies now highlight imperative roles for ketone bodies in mammalian cell metabolism, homeostasis, and signaling under a wide variety of physiological and pathological states. Apart from serving as energy fuels for extrahepatic tissues like brain, heart, or skeletal muscle, ketone bodies play pivotal roles as signaling mediators, drivers of protein post-translational modification (PTM), and modulators of inflammation and oxidative stress. In this review, we provide both classical and modern views of the pleiotropic roles of ketone bodies and their metabolism.

Overview of Ketone Body Metabolism

The rate of hepatic ketogenesis is governed by an orchestrated series of physiological and biochemical transformations of fat. Primary regulators include lipolysis of fatty acids from triacylglycerols, transport to and across the hepatocyte plasma membrane, transport into mitochondria via carnitine palmitoyltransferase 1 (CPT1), the β-oxidation spiral, TCA cycle activity and intermediate concentrations, redox potential, and the hormonal regulators of these processes, predominantly glucagon and insulin [reviewed in (Arias et al., 1995; Ayte et al., 1993; Ehara et al., 2015; Ferre et al., 1983; Kahn et al., 2005; McGarry and Foster, 1980; Williamson et al., 1969)]. Classically ketogenesis is viewed as a spillover pathway, in which β-oxidation-derived acetyl-CoA exceeds citrate synthase activity and/or oxaloacetate availability for condensation to form citrate. Three-carbon intermediates exhibit anti-ketogenic activity, presumably due to their ability to expand the oxaloacetate pool for acetyl-CoA consumption, but hepatic acetyl-CoA concentration alone does not determine ketogenic rate (Foster, 1967; Rawat and Menahan, 1975; Williamson et al., 1969). The regulation of ketogenesis by hormonal, transcriptional, and post-translational events together support the notion that the molecular mechanisms that fine-tune ketogenic rate remain incompletely understood (see Regulation of HMGCS2 and SCOT/OXCT1).

Ketogenesis occurs primarily in hepatic mitochondrial matrix at rates proportional to total fat oxidation. After transport of acyl chains across the mitochondrial membranes and β-oxidation, the mitochondrial isoform of 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) catalyzes the fate committing condensation of acetoacetyl-CoA (AcAc-CoA) and acetyl-CoA to generate HMG-CoA (Fig. 1A). HMG-CoA lyase (HMGCL) cleaves HMG-CoA to liberate acetyl-CoA and acetoacetate (AcAc), and the latter is reduced to d-β-hydroxybutyrate (d-βOHB) by phosphatidylcholine-dependent mitochondrial d-βOHB dehydrogenase (BDH1) in a NAD+/NADH-coupled near-equilibrium reaction (Bock and Fleischer, 1975; LEHNINGER et al., 1960). The BDH1 equilibrium constant favors d-βOHB production, but the ratio of AcAc/d-βOHB ketone bodies is directly proportional to mitochondrial NAD+/NADH ratio, and thus BDH1 oxidoreductase activity modulates mitochondrial redox potential (Krebs et al., 1969; Williamson et al., 1967). AcAc can also spontaneously decarboxylate to acetone (Pedersen, 1929), the source of sweet odor in humans suffering ketoacidosis (i.e., total serum ketone bodies > ~7 mM; AcAc pKa 3.6, βOHB pKa 4.7). The mechanisms through which ketone bodies are transported across the mitochondrial inner membrane are not known, but AcAc/d-βOHB are released from cells via monocarboxylate transporters (in mammals, MCT 1 and 2, also known as solute carrier 16A family members 1 and 7) and transported in the circulation to extrahepatic tissues for terminal oxidation (Cotter et al., 2011; Halestrap and Wilson, 2012; Halestrap, 2012; Hugo et al., 2012). Concentrations of circulating ketone bodies are higher than those in the extrahepatic tissues (Harrison and Long, 1940) indicating ketone bodies are transported down a concentration gradient. Loss-of-function mutations in MCT1 are associated with spontaneous bouts of ketoacidosis, suggesting a critical role in ketone body import.

  With the exception of potential diversion of ketone bodies into non-oxidative fates (see Non-oxidative metabolic fates of ketone bodies), hepatocytes lack the ability to metabolize the ketone bodies they produce. Ketone bodies synthesized de novo by liver are (i) catabolized in mitochondria of extrahepatic tissues to acetyl-CoA, which is available to the TCA cycle for terminal oxidation (Fig. 1A), (ii) diverted to the lipogenesis or sterol synthesis pathways (Fig. 1B), or (iii) excreted in the urine. As an alternative energetic fuel, ketone bodies are avidly oxidized in heart, skeletal muscle, and brain (Balasse and Fery, 1989; Bentourkia et al., 2009; Owen et al., 1967; Reichard et al., 1974; Sultan, 1988). Extrahepatic mitochondrial BDH1 catalyzes the first reaction of βOHB oxidation, converting it to back AcAc (LEHNINGER et al., 1960; Sandermann et al., 1986). A cytoplasmic d-βOHB-dehydrogenase (BDH2) with only 20% sequence identity to BDH1 has a high Km for ketone bodies, and also plays a role in iron homeostasis (Davuluri et al., 2016; Guo et al., 2006). In extrahepatic mitochondrial matrix, AcAc is activated to AcAc-CoA through exchange of a CoA-moiety from succinyl-CoA in a reaction catalyzed by a unique mammalian CoA transferase, succinyl-CoA:3-oxoacid-CoA transferase (SCOT, CoA transferase; encoded by OXCT1), through a near equilibrium reaction. The free energy released by hydrolysis of AcAc-CoA is greater than that of succinyl-CoA, favoring AcAc formation. Thus ketone body oxidative flux occurs due to mass action: an abundant supply of AcAc and rapid consumption of acetyl-CoA through citrate synthase favors AcAc-CoA (+ succinate) formation by SCOT. Notably, in contrast to glucose (hexokinase) and fatty acids (acyl-CoA synthetases), the activation of ketone bodies (SCOT) into an oxidizable form does not require the investment of ATP. A reversible AcAc-CoA thiolase reaction [catalyzed by any of the four mitochondrial thiolases encoded by either ACAA2 (encoding an enzyme known as T1 or CT), ACAT1 (encoding T2), HADHA, or HADHB] yields two molecules of acetyl-CoA, which enter the TCA cycle (Hersh and Jencks, 1967; Stern et al., 1956; Williamson et al., 1971). During ketotic states (i.e., total serum ketones > 500 µM), ketone bodies become significant contributors to energy expenditure and are utilized in tissues rapidly until uptake or saturation of oxidation occurs (Balasse et al., 1978; Balasse and Fery, 1989; Edmond et al., 1987). A very small fraction of liver-derived ketone bodies can be readily measured in the urine, and utilization and reabsorption rates by the kidney are proportionate to circulating concentration (Goldstein, 1987; Robinson and Williamson, 1980). During highly ketotic states (> 1 mM in plasma), ketonuria serves as a semi-quantitative reporter of ketosis, although most clinical assays of urine ketone bodies detect AcAc but not βOHB (Klocker et al., 2013).

Ketogenic Substrates and their Impact on Hepatocyte Metabolism

Ketogenic substrates include fatty acids and amino acids (Fig. 1B). The catabolism of amino acids, especially leucine, generates about 4% of ketone bodies in post-absorptive state (Thomas et al., 1982). Thus the acetyl-CoA substrate pool to generate ketone bodies mainly derives from fatty acids, because during states of diminished carbohydrate supply, pyruvate enters the hepatic TCA cycle primarily via anaplerosis, i.e., ATP-dependent carboxylation to oxaloacetate (OAA), or to malate (MAL), and not oxidative decarboxylation to acetyl-CoA (Jeoung et al., 2012; Magnusson et al., 1991; Merritt et al., 2011). In liver, glucose and pyruvate contribute negligibly to ketogenesis, even when pyruvate decarboxylation to acetyl-CoA is maximal (Jeoung et al., 2012).

Acetyl-CoA subsumes several roles integral to hepatic intermediary metabolism beyond ATP generation via terminal oxidation (also see The integration of ketone body metabolism, post-translational modification, and cell physiology). Acetyl-CoA allosterically activates (i) pyruvate carboxylase (PC), thereby activating a metabolic control mechanism that augments anaplerotic entry of metabolites into the TCA cycle (Owen et al., 2002; Scrutton and Utter, 1967) and (ii) pyruvate dehydrogenase kinase, which phosphorylates and inhibits pyruvate dehydrogenase (PDH) (Cooper et al., 1975), thereby further enhancing flow of pyruvate into the TCA cycle via anaplerosis. Furthermore, cytoplasmic acetyl-CoA, whose pool is augmented by mechanisms that convert mitochondrial acetyl-CoA to transportable metabolites, inhibits fatty acid oxidation: acetyl-CoA carboxylase (ACC) catalyzes the conversion of acetyl-CoA to malonyl-CoA, the lipogenic substrate and allosteric inhibitor of mitochondrial CPT1 [reviewed in (Kahn et al., 2005; McGarry and Foster, 1980)]. Thus, the mitochondrial acetyl-CoA pool both regulates and is regulated by the spillover pathway of ketogenesis, which orchestrates key aspects of hepatic intermediary metabolism.

Non-Oxidative Metabolic Fates of Ketone Bodies

The predominant fate of liver-derived ketones is SCOT-dependent extrahepatic oxidation. However, AcAc can be exported from mitochondria and utilized in anabolic pathways via conversion to AcAc-CoA by an ATP-dependent reaction catalyzed by cytoplasmic acetoacetyl-CoA synthetase (AACS, Fig. 1B). This pathway is active during brain development and in lactating mammary gland (Morris, 2005; Robinson and Williamson, 1978; Ohgami et al., 2003). AACS is also highly expressed in adipose tissue, and activated osteoclasts (Aguilo et al., 2010; Yamasaki et al., 2016). Cytoplasmic AcAc-CoA can be either directed by cytosolic HMGCS1 toward sterol biosynthesis, or cleaved by either of two cytoplasmic thiolases to acetyl-CoA (ACAA1 and ACAT2), carboxylated to malonyl-CoA, and contribute to the synthesis of fatty acids (Bergstrom et al., 1984; Edmond, 1974; Endemann et al., 1982; Geelen et al., 1983; Webber and Edmond, 1977).

While the physiological significance is yet to be established, ketones can serve as anabolic substrates even in the liver. In artificial experimental contexts, AcAc can contribute to as much as half of newly synthesized lipid, and up to 75% of new synthesized cholesterol (Endemann et al., 1982; Geelen et al., 1983; Freed et al., 1988). Because AcAc is derived from incomplete hepatic fat oxidation, the ability of AcAc to contribute to lipogenesis in vivo would imply hepatic futile cycling, where fat-derived ketones can be utilized for lipid production, a notion whose physiological significance requires experimental validation, but could serve adaptive or maladaptive roles (Solinas et al., 2015). AcAc avidly supplies cholesterogenesis, with a low AACS Km-AcAc (~50 µM) favoring AcAc activation even in the fed state (Bergstrom et al., 1984). The dynamic role of cytoplasmic ketone metabolism has been suggested in primary mouse embryonic neurons and in 3T3-L1 derived-adipocytes, as AACS knockdown impaired differentiation of each cell type (Hasegawa et al., 2012a; Hasegawa et al., 2012b). Knockdown of AACS in mice in vivo decreased serum cholesterol (Hasegawa et al., 2012c). SREBP-2, a master transcriptional regulator of cholesterol biosynthesis, and peroxisome proliferator activated receptor (PPAR)-γ are AACS transcriptional activators, and regulate its transcription during neurite development and in the liver (Aguilo et al., 2010; Hasegawa et al., 2012c). Taken together, cytoplasmic ketone body metabolism may be important in select conditions or disease natural histories, but are inadequate to dispose of liver-derived ketone bodies, as massive hyperketonemia occurs in the setting of selective impairment of the primary oxidative fate via loss of function mutations to SCOT (Berry et al., 2001; Cotter et al., 2011).

Regulation of HMGCS2 and SCOT/OXCT1

The divergence of a mitochondrial from the gene encoding cytosolic HMGCS occurred early in vertebrate evolution due to the need to support hepatic ketogenesis in species with higher brain to body weight ratios (Boukaftane et al., 1994; Cunnane and Crawford, 2003). Naturally occurring loss-of-function HMGCS2 mutations in humans cause bouts of hypoketotic hypoglycemia (Pitt et al., 2015; Thompson et al., 1997). Robust HMGCS2 expression is restricted to hepatocytes and colonic epithelium, and its expression and enzymatic activity are coordinated through diverse mechanisms (Mascaro et al., 1995; McGarry and Foster, 1980; Robinson and Williamson, 1980). While the full scope of physiological states that influence HMGCS2 requires further elucidation, its expression and/or activity is regulated during the early postnatal period, aging, diabetes, starvation or ingestion of ketogenic diet (Balasse and Fery, 1989; Cahill GF Jr, 2006; Girard et al., 1992; Hegardt, 1999; Satapati et al., 2012; Sengupta et al., 2010). In the fetus, methylation of 5’ flanking region of Hmgcs2 gene inversely correlates with its transcription, and is partially reversed after birth (Arias et al., 1995; Ayte et al., 1993; Ehara et al., 2015; Ferre et al., 1983). Similarly, hepatic Bdh1 exhibits a developmental expression pattern, increasing from birth to weaning, and is also induced by ketogenic diet in a fibroblast growth factor (FGF)-21-dependent manner (Badman et al., 2007; Zhang et al., 1989). Ketogenesis in mammals is highly responsive to both insulin and glucagon, being suppressed and stimulated, respectively (McGarry and Foster, 1977). Insulin suppresses adipose tissue lipolysis, thus depriving ketogenesis of its substrate, while glucagon increases ketogenic flux through a direct effect on the liver (Hegardt, 1999). Hmgcs2 transcription is stimulated by forkhead transcriptional factor FOXA2, which is inhibited via insulin-phosphatidylinositol-3-kinase/Akt, and is induced by glucagon-cAMP-p300 signaling (Arias et al., 1995; Hegardt, 1999; Quant et al., 1990; Thumelin et al., 1993; von Meyenn et al., 2013; Wolfrum et al., 2004; Wolfrum et al., 2003). PPARα (Rodriguez et al., 1994) together with its target, FGF21 (Badman et al., 2007) also induce Hmgcs2 transcription in the liver during starvation or administration of ketogenic diet (Badman et al., 2007; Inagaki et al., 2007). Induction of PPARα may occur before the transition from fetal to neonatal physiology, while FGF21 activation may be favored in the early neonatal period via βOHB-mediated inhibition of histone deacetylase (HDAC)-3 (Rando et al., 2016). mTORC1 (mammalian target of rapamycin complex 1) dependent inhibition of PPARα transcriptional activity is also a key regulator of Hmgcs2 gene expression (Sengupta et al., 2010), and liver PER2, a master circadian oscillator, indirectly regulates Hmgcs2 expression (Chavan et al., 2016). Recent observations indicate that extrahepatic tumor-induced interleukin-6 impairs ketogenesis via PPARα suppression (Flint et al., 2016). Despite these observations, it is important to note that physiological shifts in Hmgcs2 gene expression have not been mechanistically linked to HMGCS2 protein abundance or to variations of ketogenic rate.

HMGCS2 enzyme activity is regulated through multiple PTMs. HMGCS2 serine phosphorylation enhanced its activity in vitro (Grimsrud et al., 2012). HMGCS2 activity is allosterically inhibited by succinyl-CoA and lysine residue succinylation (Arias et al., 1995; Hegardt, 1999; Lowe and Tubbs, 1985; Quant et al., 1990; Rardin et al., 2013; Reed et al., 1975; Thumelin et al., 1993). Succinylation of HMGCS2, HMGCL, and BDH1 lysine residues in hepatic mitochondria are targets of the NAD+ dependent deacylase sirtuin 5 (SIRT5) (Rardin et al., 2013). HMGCS2 activity is also enhanced by SIRT3 lysine deacetylation, and it is possible that crosstalk between acetylation and succinylation regulates HMGCS2 activity (Rardin et al., 2013; Shimazu et al., 2013). Despite the ability of these PTMs to regulate HMGCS2 Km and Vmax, fluctuations of these PTMs have not yet been carefully mapped and have not been confirmed as mechanistic drivers of ketogenesis in vivo.

SCOT is expressed in all mammalian cells that harbor mitochondria, except those of hepatocytes. The importance of SCOT activity and ketolysis was demonstrated in SCOT-KO mice, which exhibited uniform lethality due to hyperketonemic hypoglycemia within 48h after birth (Cotter et al., 2011). Tissue-specific loss of SCOT in neurons or skeletal myocytes induces metabolic abnormalities during starvation but is not lethal (Cotter et al., 2013b). In humans, SCOT deficiency presents early in life with severe ketoacidosis, causing lethargy, vomiting, and coma (Berry et al., 2001; Fukao et al., 2000; Kassovska-Bratinova et al., 1996; Niezen-Koning et al., 1997; Saudubray et al., 1987; Snyderman et al., 1998; Tildon and Cornblath, 1972). Relatively little is known at the cellular level about SCOT gene and protein expression regulators. Oxct1 mRNA expression and SCOT protein and activity are diminished in ketotic states, possibly through PPAR-dependent mechanisms (Fenselau and Wallis, 1974; Fenselau and Wallis, 1976; Grinblat et al., 1986; Okuda et al., 1991; Turko et al., 2001; Wentz et al., 2010). In diabetic ketoacidosis, the mismatch between hepatic ketogenesis and extrahepatic oxidation becomes exacerbated by impairment of SCOT activity. Overexpression of insulin-independent glucose transporter (GLUT1/SLC2A1) in cardiomyocytes also inhibits Oxct1 gene expression and downregulates ketones terminal oxidation in a non-ketotic state (Yan et al., 2009). In liver, Oxct1 mRNA abundance is suppressed by microRNA-122 and histone methylation H3K27me3 that are evident during the transition from fetal to the neonatal period (Thorrez et al., 2011). However, suppression of hepatic Oxct1 expression in the postnatal period is primarily attributable to the evacuation of Oxct1-expressing hematopoietic progenitors from the liver, rather than a loss of previously existing Oxct1 expression in terminally differentiated hepatocytes. In fact, expression of Oxct1 mRNA and SCOT protein in differentiated hepatocytes are extremely low (Orii et al., 2008).

SCOT is also regulated by PTMs. The enzyme is hyper-acetylated in brains of SIRT3 KO mice, which also exhibit diminished AcAc dependent acetyl-CoA production (Dittenhafer-Reed et al., 2015). Non-enzymatic nitration of tyrosine residues of SCOT also attenuates its activity, which has been reported in hearts of various diabetic mice models (Marcondes et al., 2001; Turko et al., 2001; Wang et al., 2010a). In contrast, tryptophan residue nitration augments SCOT activity (Brégère et al., 2010; Rebrin et al., 2007). Molecular mechanisms of residue-specific nitration or de-nitration designed to modulate SCOT activity may exist and require elucidation.

Controversies in Extrahepatic Ketogenesis

In mammals the primary ketogenic organ is liver, and only hepatocytes and gut epithelial cells abundantly express the mitochondrial isoform of HMGCS2 (Cotter et al., 2013a; Cotter et al., 2014; McGarry and Foster, 1980; Robinson and Williamson, 1980). Anaerobic bacterial fermentation of complex polysaccharides yields butyrate, which is absorbed by colonocytes in mammalians for terminal oxidation or ketogenesis (Cherbuy et al., 1995), which may play a role in colonocyte differentiation (Wang et al., 2016). Excluding gut epithelial cells and hepatocytes, HMGCS2 is nearly absent in almost all other mammalian cells, but the prospect of extrahepatic ketogenesis has been raised in tumor cells, astrocytes of the central nervous system, the kidney, pancreatic β cells, retinal pigment epithelium (RPE), and even in skeletal muscle (Adijanto et al., 2014; Avogaro et al., 1992; El Azzouny et al., 2016; Grabacka et al., 2016; Kang et al., 2015; Le Foll et al., 2014; Nonaka et al., 2016; Takagi et al., 2016a; Thevenet et al., 2016; Zhang et al., 2011). Ectopic HMGCS2 has been observed in tissues that lack net ketogenic capacity (Cook et al., 2016; Wentz et al., 2010), and HMGCS2 exhibits prospective ketogenesis-independent ‘moonlighting’ activities, including within the cell nucleus (Chen et al., 2016; Kostiuk et al., 2010; Meertens et al., 1998).

Any extrahepatic tissue that oxidizes ketone bodies also has the potential to accumulate ketone bodies via HMGCS2 independent mechanisms (Fig. 2A). However, there is no extrahepatic tissue in which a steady state ketone body concentration exceeds that in the circulation (Cotter et al., 2011; Cotter et al., 2013b; Harrison and Long, 1940), underscoring that ketone bodies are transported down a concentration gradient via MCT1/2-dependent mechanisms. One mechanism of apparent extrahepatic ketogenesis may actually reflect relative impairment of ketone oxidation. Additional potential explanations fall within the realm of ketone body formation. First, de novo ketogenesis may occur via reversible enzymatic activity of thiolase and SCOT (Weidemann and Krebs, 1969). When the concentration of acetyl-CoA is relatively high, reactions normally responsible for AcAc oxidation operate in the reverse direction (GOLDMAN, 1954). A second mechanism occurs when β-oxidation-derived intermediates accumulate due to a TCA cycle bottleneck, AcAc-CoA is converted to l-βOHB-CoA through a reaction catalyzed by mitochondrial 3-hydroxyacyl-CoA dehydrogenase, and further by 3-hydroxybutyryl CoA deacylase to l-βOHB, which is indistinguishable by mass spectrometry or resonance spectroscopy from the physiological enantiomer d-βOHB (Reed and Ozand, 1980). l-βOHB can be chromatographically or enzymatically distinguished from d-βOHB, and is present in extrahepatic tissues, but not in liver or blood (Hsu et al., 2011). Hepatic ketogenesis produces only d-βOHB, the only enantiomer that is a BDH substrate (Ito et al., 1984; Lincoln et al., 1987; Reed and Ozand, 1980; Scofield et al., 1982; Scofield et al., 1982). A third HMGCS2-independent mechanism generates d-βOHB through amino acid catabolism, particularly that of leucine and lysine. A fourth mechanism is only apparent because it is due to a labeling artifact and is thus termed pseudoketogenesis. This phenomenon is attributable to the reversibility of the SCOT and thiolase reactions, and can cause overestimation of ketone body turnover due to the isotopic dilution of ketone body tracer in extrahepatic tissue (Des Rosiers et al., 1990; Fink et al., 1988). Nonetheless, pseudoketogenesis may be negligible in most contexts (Bailey et al., 1990; Keller et al., 1978). A schematic (Fig. 2A) indicates a useful approach to apply while considering elevated tissue steady state concentration of ketones.

  Kidney has recently received attention as a potentially ketogenic organ. In the vast majority of states, the kidney is a net consumer of liver-derived ketone bodies, excreting or reabsorbing ketone bodies from the bloodstream, and kidney is generally not a net ketone body generator or concentrator (Robinson and Williamson, 1980). The authors of a classical study concluded that minimal renal ketogenesis quantified in an artificial experimental system was not physiologically relevant (Weidemann and Krebs, 1969). Recently, renal ketogenesis has been inferred in diabetic and autophagy deficient mouse models, but it is more likely that multi-organ shifts in metabolic homeostasis alter integrative ketone metabolism through inputs on multiple organs (Takagi et al., 2016a; Takagi et al., 2016b; Zhang et al., 2011). One recent publication suggested renal ketogenesis as a protective mechanism against ischemia-reperfusion injury in the kidney (Tran et al., 2016). Absolute steady state concentrations of βOHB from extracts of mice renal tissue were reported at ~4–12 mM. To test whether this was tenable, we quantified βOHB concentrations in renal extracts from fed and 24h fasted mice. Serum βOHB concentrations increased from ~100 µM to 2 mM with 24h fasting (Fig. 2B), while renal steady state βOHB concentrations approximate 100 µM in the fed state, and only 1 mM in the 24h fasted state (Fig. 2C–E), observations that are consistent with concentrations quantified over 45 years ago (Hems and Brosnan, 1970). It remains possible that in ketotic states, liver-derived ketone bodies could be renoprotective, but evidence for renal ketogenesis requires further substantiation. Compelling evidence that supports true extrahepatic ketogenesis was presented in RPE (Adijanto et al., 2014). This intriguing metabolic transformation was suggested to potentially allow RPE-derived ketones to flow to photoreceptor or Müller glia cells, which could aid in the regeneration of photoreceptor outer segment.

βOHB as a Signaling Mediator

Although they are energetically rich, ketone bodies exert provocative ‘non-canonical’ signaling roles in cellular homeostasis (Fig. 3) (Newman and Verdin, 2014; Rojas-Morales et al., 2016). For example, βOHB inhibits Class I HDACs, which increases histone acetylation and thereby induces the expression of genes that curtail oxidative stress (Shimazu et al., 2013). βOHB itself is a histone covalent modifier at lysine residues in livers of fasted or streptozotocin induced diabetic mice (Xie et al., 2016) (also see below, The integration of ketone body metabolism, post-translational modification, and cell physiology, and Ketone bodies, oxidative stress, and neuroprotection).


βOHB is also an effector via G-protein coupled receptors. Through unclear molecular mechanisms, it suppresses sympathetic nervous system activity and reduces total energy expenditure and heart rate by inhibiting short chain fatty acid signaling through G protein coupled receptor 41 (GPR41) (Kimura et al., 2011). One of the most studied signaling effects of βOHB proceeds through GPR109A (also known as HCAR2), a member of the hydrocarboxylic acid GPCR sub-family expressed in adipose tissues (white and brown) (Tunaru et al., 2003), and in immune cells (Ahmed et al., 2009). βOHB is the only known endogenous ligand of GPR109A receptor (EC50 ~770 µM) activated by d-βOHB, l-βOHB, and butyrate, but not AcAc (Taggart et al., 2005). The high concentration threshold for GPR109A activation is achieved through adherence to a ketogenic diet, starvation, or during ketoacidosis, leading to inhibition of adipose tissue lipolysis. The anti-lipolytic effect of GPR109A proceeds through inhibition of adenylyl cyclase and decreased cAMP, inhibiting hormone sensitive triglyceride lipase (Ahmed et al., 2009; Tunaru et al., 2003). This creates a negative feedback loop in which ketosis places a modulatory brake on ketogenesis by diminishing the release of non-esterified fatty acids from adipocytes (Ahmed et al., 2009; Taggart et al., 2005), an effect that can be counterbalanced by the sympathetic drive that stimulates lipolysis. Niacin (vitamin B3, nicotinic acid) is a potent (EC50 ~ 0.1 µM) ligand for GRP109A, effectively employed for decades for dyslipidemias (Benyo et al., 2005; Benyo et al., 2006; Fabbrini et al., 2010a; Lukasova et al., 2011; Tunaru et al., 2003). While niacin enhances reverse cholesterol transport in macrophages and reduces atherosclerotic lesions (Lukasova et al., 2011), the effects of βOHB on atherosclerotic lesions remain unknown. Although GPR109A receptor exerts protective roles, and intriguing connections exist between ketogenic diet use in stroke and neurodegenerative diseases (Fu et al., 2015; Rahman et al., 2014), a protective role of βOHB via GPR109A has not been demonstrated in vivo.

Finally, βOHB may influence appetite and satiety. A meta-analysis of studies that measured the effects of ketogenic and very low energy diets concluded that participants consuming these diets exhibit higher satiety, compared to control diets (Gibson et al., 2015). However, a plausible explanation for this effect is the additional metabolic or hormonal elements that might modulate appetite. For example, mice maintained on a rodent ketogenic diet exhibited increased energy expenditure compared to chow control-fed mice, despite similar caloric intake, and circulating leptin or genes of peptides regulating feeding behavior were not changed (Kennedy et al., 2007). Among proposed mechanisms that suggest appetite suppression by βOHB includes both signaling and oxidation (Laeger et al., 2010). Hepatocyte specific deletion of circadian rhythm gene (Per2) and chromatin immunoprecipitation studies revealed that PER2 directly activates the Cpt1a gene, and indirectly regulates Hmgcs2, leading to impaired ketosis in Per2 knockout mice (Chavan et al., 2016). These mice exhibited impaired food anticipation, which was partially restored by systemic βOHB administration. Future studies will be needed to confirm the central nervous system as a direct βOHB target, and whether ketone oxidation is required for the observed effects, or whether another signaling mechanism is involved. Other investigators have invoked the possibility of local astrocyte-derived ketogenesis within the ventromedial hypothalamus as a regulator of food intake, but these preliminary observations also will benefit from genetic and flux-based assessments (Le Foll et al., 2014). The relationship between ketosis and nutrient deprivation remains of interest because hunger and satiety are important elements in failed weight loss attempts.

Integration of Ketone Body Metabolism, Post-Translational Modification, and Cell Physiology

Ketone bodies contribute to compartmentalized pools of acetyl-CoA, a key intermediate that exhibits prominent roles in cellular metabolism (Pietrocola et al., 2015). One role of acetyl-CoA is to serve as a substrate for acetylation, an enzymatically-catalyzed histone covalent modification (Choudhary et al., 2014; Dutta et al., 2016; Fan et al., 2015; Menzies et al., 2016). A large number of dynamically acetylated mitochondrial proteins, many of which may occur through non-enzymatic mechanisms, have also emerged from computational proteomics studies (Dittenhafer-Reed et al., 2015; Hebert et al., 2013; Rardin et al., 2013; Shimazu et al., 2010). Lysine deacetylases use a zinc cofactor (e.g., nucleocytosolic HDACs) or NAD+ as co-substrate (sirtuins, SIRTs) (Choudhary et al., 2014; Menzies et al., 2016). The acetylproteome serves as both sensor and effector of the total cellular acetyl-CoA pool, as physiological and genetic manipulations each result in non-enzymatic global variations of acetylation (Weinert et al., 2014). As intracellular metabolites serve as modulators of lysine residue acetylation, it is important to consider the role of ketone bodies, whose abundance is highly dynamic.

βOHB is an epigenetic modifier through at least two mechanisms. Increased βOHB levels induced by fasting, caloric restriction, direct administration or prolonged exercise provoke HDAC inhibition or histone acetyltransferase activation (Marosi et al., 2016; Sleiman et al., 2016) or to oxidative stress (Shimazu et al., 2013). βOHB inhibition of HDAC3 could regulate newborn metabolic physiology (Rando et al., 2016). Independently, βOHB itself directly modifies histone lysine residues (Xie et al., 2016). Prolonged fasting, or steptozotocin-induced diabetic ketoacidosis increased histone β-hydroxybutyrylation. Although the number of lysine β-hydroxybutyrylation and acetylation sites was comparable, stoichiometrically greater histone β-hydroxybutyrylation than acetylation was observed. Distinct genes were impacted by histone lysine β-hydroxybutyrylation, versus acetylation or methylation, suggesting distinct cellular functions. Whether β-hydroxybutyrylation is spontaneous or enzymatic is not known, but expands the range of mechanisms through ketone bodies dynamically influence transcription.

Essential cell reprogramming events during caloric restriction and nutrient deprivation may be mediated in SIRT3- and SIRT5-dependent mitochondrial deacetylation and desuccinylation, respectively, regulating ketogenic and ketolytic proteins at post-translational level in liver and extrahepatic tissues (Dittenhafer-Reed et al., 2015; Hebert et al., 2013; Rardin et al., 2013; Shimazu et al., 2010). Even though stoichiometric comparison of occupied sites does not necessarily link directly to shifts in metabolic flux, mitochondrial acetylation is dynamic and may be driven by acetyl-CoA concentration or mitochondrial pH, rather than enzymatic acetyltransferases (Wagner and Payne, 2013). That SIRT3 and SIRT5 modulate activities of ketone body metabolizing enzymes provokes the question of the reciprocal role of ketones in sculpting the acetylproteome, succinylproteome, and other dynamic cellular targets. Indeed, as variations of ketogenesis reflect NAD+ concentrations, ketone production and abundance could regulate sirtuin activity, thereby influencing total acetyl-CoA/succinyl-CoA pools, the acylproteome, and thus mitochondrial and cell physiology. β-hydroxybutyrylation of enzyme lysine residues could add another layer to cellular reprogramming. In extrahepatic tissues, ketone body oxidation may stimulate analogous changes in cell homeostasis. While compartmentation of acetyl-CoA pools is highly regulated and coordinates a broad spectrum of cellular changes, the ability of ketone bodies to directly shape both mitochondrial and cytoplasmic acetyl-CoA concentrations requires elucidation (Chen et al., 2012; Corbet et al., 2016; Pougovkina et al., 2014; Schwer et al., 2009; Wellen and Thompson, 2012). Because acetyl-CoA concentrations are tightly regulated, and acetyl-CoA is membrane impermeant, it is crucial to consider the driver mechanisms coordinating acetyl-CoA homeostasis, including the rates of production and terminal oxidation in the TCA cycle, conversion into ketone bodies, mitochondrial efflux via carnitine acetyltransferase (CrAT), or acetyl-CoA export to cytosol after conversion to citrate and release by ATP citrate lyase (ACLY). The key roles of these latter mechanisms in cell acetylproteome and homeostasis require matched understanding of the roles of ketogenesis and ketone oxidation (Das et al., 2015; McDonnell et al., 2016; Moussaieff et al., 2015; Overmyer et al., 2015; Seiler et al., 2014; Seiler et al., 2015; Wellen et al., 2009; Wellen and Thompson, 2012). Convergent technologies in metabolomics and acylproteomics in the setting of genetically manipulated models will be required to specify targets and outcomes.

Anti- and Pro-Inflammatory Responses to Ketone Bodies

Ketosis and ketone bodies modulate inflammation and immune cell function, but varied and even discrepant mechanisms have been proposed. Prolonged nutrient deprivation reduces inflammation (Youm et al., 2015), but the chronic ketosis of type 1 diabetes is a pro-inflammatory state (Jain et al., 2002; Kanikarla-Marie and Jain, 2015; Kurepa et al., 2012). Mechanism-based signaling roles for βOHB in inflammation emerge because many immune system cells, including macrophages or monocytes, abundantly express GPR109A. While βOHB exerts a predominantly anti-inflammatory response (Fu et al., 2014; Gambhir et al., 2012; Rahman et al., 2014; Youm et al., 2015), high concentrations of ketone bodies, particularly AcAc, may trigger a pro-inflammatory response (Jain et al., 2002; Kanikarla-Marie and Jain, 2015; Kurepa et al., 2012).

Anti-inflammatory roles of GPR109A ligands in atherosclerosis, obesity, inflammatory bowel disease, neurological disease, and cancer have been reviewed (Graff et al., 2016). GPR109A expression is augmented in RPE cells of diabetic models, human diabetic patients (Gambhir et al., 2012), and in microglia during neurodegeneration (Fu et al., 2014). Anti-inflammatory effects of βOHB are enhanced by GPR109A overexpression in RPE cells, and abrogated by pharmacological inhibition or genetic knockout of GPR109A (Gambhir et al., 2012). βOHB and exogenous nicotinic acid (Taggart et al., 2005), both confer anti-inflammatory effects in TNFα or LPS-induced inflammation by decreasing the levels of pro-inflammatory proteins (iNOS, COX-2), or secreted cytokines (TNFα, IL-1β, IL-6, CCL2/MCP-1), in part through inhibiting NF-κB translocation (Fu et al., 2014; Gambhir et al., 2012). βOHB decreases ER stress and the NLRP3 inflammasome, activating the antioxidative stress response (Bae et al., 2016; Youm et al., 2015). However, in neurodegenerative inflammation, GPR109A-dependent βOHB-mediated protection does not involve inflammatory mediators like MAPK pathway signaling (e.g., ERK, JNK, p38) (Fu et al., 2014), but may require COX-1-dependent PGD2 production (Rahman et al., 2014). It is intriguing that macrophage GPR109A is required to exert a neuroprotective effect in an ischemic stroke model (Rahman et al., 2014), but the ability of βOHB to inhibit the NLRP3 inflammasome in bone marrow derived macrophages is GPR109A independent (Youm et al., 2015). Although most studies link βOHB to anti-inflammatory effects, βOHB may be pro-inflammatory and increase markers of lipid peroxidation in calf hepatocytes (Shi et al., 2014). Anti- versus pro-inflammatory effects of βOHB may thus depend on cell type, βOHB concentration, exposure duration, and the presence or absence of co-modulators.

Unlike βOHB, AcAc may activate pro-inflammatory signaling. Elevated AcAc, especially with a high glucose concentration, intensifies endothelial cell injury through an NADPH oxidase/oxidative stress dependent mechanism (Kanikarla-Marie and Jain, 2015). High AcAc concentrations in umbilical cord of diabetic mothers were correlated with higher protein oxidation rate and MCP-1 concentration (Kurepa et al., 2012). High AcAc in diabetic patients was correlated with TNFα expression (Jain et al., 2002), and AcAc, but not βOHB, induced TNFα, MCP-1 expression, ROS accumulation, and diminished cAMP level in U937 human monocyte cells (Jain et al., 2002; Kurepa et al., 2012).

Ketone body dependent signaling phenomena are frequently triggered only with high ketone body concentrations (> 5 mM), and in the case of many studies linking ketones to pro- or anti-inflammatory effects, through unclear mechanisms. In addition, due to the contradictory effects of βOHB versus AcAc on inflammation, and the ability of AcAc/βOHB ratio to influence mitochondrial redox potential, the best experiments assessing the roles of ketone bodies on cellular phenotypes compare the effects of AcAc and βOHB in varying ratios, and at varying cumulative concentrations [e.g., (Saito et al., 2016)]. Finally, AcAc can be purchased commercially only as a lithium salt or as an ethyl ester that requires base hydrolysis before use. Lithium cation independently induces signal transduction cascades (Manji et al., 1995), and AcAc anion is labile. Finally, studies using racemic d/l-βOHB can be confounded, as only the d-βOHB stereoisomer can be oxidized to AcAc, but d-βOHB and l-βOHB can each signal through GPR109A, inhibit the NLRP3 inflammasome, and serve as lipogenic substrates.

Ketone Bodies, Oxidative Stress, and Neuroprotection

Oxidative stress is typically defined as a state in which ROS are presented in excess, due to excessive production and/or impaired elimination. Antioxidant and oxidative stress mitigating roles of ketone bodies have been widely described both in vitro and in vivo, particularly in the context of neuroprotection. As most neurons do not effectively generate high-energy phosphates from fatty acids but do oxidize ketone bodies when carbohydrates are in short supply, neuroprotective effects of ketone bodies are especially important (Cahill GF Jr, 2006; Edmond et al., 1987; Yang et al., 1987). In oxidative stress models, BDH1 induction and SCOT suppression suggest that ketone body metabolism can be reprogrammed to sustain diverse cell signaling, redox potential, or metabolic requirements (Nagao et al., 2016; Tieu et al., 2003).

Ketone bodies decrease the grades of cellular damage, injury, death and lower apoptosis in neurons and cardiomyocytes (Haces et al., 2008; Maalouf et al., 2007; Nagao et al., 2016; Tieu et al., 2003). Invoked mechanisms are varied and not always linearly related to concentration. Low millimolar concentrations of (d or l)-βOHB scavenge ROS (hydroxyl anion), while AcAc scavenges numerous ROS species, but only at concentrations that exceed the physiological range (IC50 20–67 mM) (Haces et al., 2008). Conversely, a beneficial influence over the electron transport chain’s redox potential is a mechanism commonly linked to d-βOHB. While all three ketone bodies (d/l-βOHB and AcAc) reduced neuronal cell death and ROS accumulation triggered by chemical inhibition of glycolysis, only d-βOHB and AcAc prevented neuronal ATP decline. Conversely, in a hypoglycemic in vivo model, (d or l)-βOHB, but not AcAc prevented hippocampal lipid peroxidation (Haces et al., 2008; Maalouf et al., 2007; Marosi et al., 2016; Murphy, 2009; Tieu et al., 2003). In vivo studies of mice fed a ketogenic diet (87% kcal fat and 13% protein) exhibited neuroanatomical variation of antioxidant capacity (Ziegler et al., 2003), where the most profound changes were observed in hippocampus, with increase glutathione peroxidase and total antioxidant capacities.

Ketogenic diet, ketone esters (also see Therapeutic use of ketogenic diet and exogenous ketone bodies), or βOHB administration exert neuroprotection in models of ischemic stroke (Rahman et al., 2014); Parkinson’s disease (Tieu et al., 2003); central nervous system oxygen toxicity seizure (D’Agostino et al., 2013); epileptic spasms (Yum et al., 2015); mitochondrial encephalomyopathy, lactic acidosis and stroke-like (MELAS) episodes syndrome (Frey et al., 2016) and Alzheimer’s disease (Cunnane and Crawford, 2003; Yin et al., 2016). Conversely, a recent report demonstrated histopathological evidence of neurodegenerative progression by a ketogenic diet in a transgenic mouse model of abnormal mitochondrial DNA repair, despite increases in mitochondrial biogenesis and antioxidant signatures (Lauritzen et al., 2016). Other conflicting reports suggest that exposure to high ketone body concentrations elicits oxidative stress. High βOHB or AcAc doses induced nitric oxide secretion, lipid peroxidation, reduced expression of SOD, glutathione peroxidase and catalase in calf hepatocytes, while in rat hepatocytes the MAPK pathway induction was attributed to AcAc but not βOHB (Abdelmegeed et al., 2004; Shi et al., 2014; Shi et al., 2016).

Taken together, most reports link βOHB to attenuation of oxidative stress, as its administration inhibits ROS/superoxide production, prevents lipid peroxidation and protein oxidation, increases antioxidant protein levels, and improves mitochondrial respiration and ATP production (Abdelmegeed et al., 2004; Haces et al., 2008; Jain et al., 1998; Jain et al., 2002; Kanikarla-Marie and Jain, 2015; Maalouf et al., 2007; Maalouf and Rho, 2008; Marosi et al., 2016; Tieu et al., 2003; Yin et al., 2016; Ziegler et al., 2003). While AcAc has been more directly correlated than βOHB with the induction of oxidative stress, these effects are not always easily dissected from prospective pro-inflammatory responses (Jain et al., 2002; Kanikarla-Marie and Jain, 2015; Kanikarla-Marie and Jain, 2016). Moreover, it is critical to consider that the apparent antioxidative benefit conferred by pleiotropic ketogenic diets may not be transduced by ketone bodies themselves, and neuroprotection conferred by ketone bodies may not entirely be attributable to oxidative stress. For example during glucose deprivation, in a model of glucose deprivation in cortical neurons, βOHB stimulated autophagic flux and prevented autophagosome accumulation, which was associated with decreased neuronal death (Camberos-Luna et al., 2016). d-βOHB induces also the canonical antioxidant proteins FOXO3a, SOD, MnSOD, and catalase, prospectively through HDAC inhibition (Nagao et al., 2016; Shimazu et al., 2013).

Non-Alcoholic Fatty Liver Disease (NAFLD) and Ketone Body Metabolism

Obesity-associated NAFLD and nonalcoholic steatohepatitis (NASH) are the most common causes of liver disease in Western countries (Rinella and Sanyal, 2016), and NASH-induced liver failure is one of the most common reasons for liver transplantation. While excess storage of triacylglycerols in hepatocytes >5% of liver weight (NAFL) alone does not cause degenerative liver function, the progression to NAFLD in humans correlates with systemic insulin resistance and increased risk of type 2 diabetes, and may contribute to the pathogenesis of cardiovascular disease and chronic kidney disease (Fabbrini et al., 2009; Targher et al., 2010; Targher and Byrne, 2013). The pathogenic mechanisms of NAFLD and NASH are incompletely understood but include abnormalities of hepatocyte metabolism, hepatocyte autophagy and endoplasmic reticulum stress, hepatic immune cell function, adipose tissue inflammation, and systemic inflammatory mediators (Fabbrini et al., 2009; Masuoka and Chalasani, 2013; Targher et al., 2010; Yang et al., 2010). Perturbations of carbohydrate, lipid, and amino acid metabolism occur in and contribute to obesity, diabetes, and NAFLD in humans and in model organisms [reviewed in (Farese et al., 2012; Lin and Accili, 2011; Newgard, 2012; Samuel and Shulman, 2012; Sun and Lazar, 2013)]. While hepatocyte abnormalities in cytoplasmic lipid metabolism are commonly observed in NAFLD (Fabbrini et al., 2010b), the role of mitochondrial metabolism, which governs oxidative disposal of fats is less clear in NAFLD pathogenesis. Abnormalities of mitochondrial metabolism occur in and contribute to NAFLD/NASH pathogenesis (Hyotylainen et al., 2016; Serviddio et al., 2011; Serviddio et al., 2008; Wei et al., 2008). There is general (Felig et al., 1974; Iozzo et al., 2010; Koliaki et al., 2015; Satapati et al., 2015; Satapati et al., 2012; Sunny et al., 2011) but not uniform (Koliaki and Roden, 2013; Perry et al., 2016; Rector et al., 2010) consensus that, prior to the development of bona fide NASH, hepatic mitochondrial oxidation, and in particular fat oxidation, is augmented in obesity, systemic insulin resistance, and NAFLD. It is likely that as NAFLD progresses, oxidative capacity heterogenity, even among individual mitochondria, emerges, and ultimately oxidative function becomes impaired (Koliaki et al., 2015; Rector et al., 2010; Satapati et al., 2008; Satapati et al., 2012).

Ketogenesis is often used as a proxy for hepatic fat oxidation. Impairments of ketogenesis emerge as NAFLD progresses in animal models, and likely in humans. Through incompletely defined mechanisms, hyperinsulinemia suppresses ketogenesis, possibly contributing to hypoketonemia compared to lean controls (Bergman et al., 2007; Bickerton et al., 2008; Satapati et al., 2012; Soeters et al., 2009; Sunny et al., 2011; Vice et al., 2005). Nonetheless, the ability of circulating ketone body concentrations to predict NAFLD is controversial (Männistö et al., 2015; Sanyal et al., 2001). Robust quantitative magnetic resonance spectroscopic methods in animal models revealed increased ketone turnover rate with moderate insulin resistance, but decreased rates were evident with more severe insulin resistance (Satapati et al., 2012; Sunny et al., 2010). In obese humans with fatty liver, ketogenic rate is normal (Bickerton et al., 2008; Sunny et al., 2011), and hence, the rates of ketogenesis are diminished relative to the increased fatty acid load within hepatocytes. Consequently, β-oxidation-derived acetyl-CoA may be directed to terminal oxidation in the TCA cycle, increasing terminal oxidation, phosphoenolpyruvate-driven gluconeogenesis via anaplerosis/cataplerosis, and oxidative stress. Acetyl-CoA also possibly undergoes export from mitochondria as citrate, a precursor substrate for lipogenesis (Fig. 4) (Satapati et al., 2015; Satapati et al., 2012; Solinas et al., 2015). While ketogenesis becomes less responsive to insulin or fasting with prolonged obesity (Satapati et al., 2012), the underlying mechanisms and downstream consequences of this remain incompletely understood. Recent evidence indicates that mTORC1 suppresses ketogenesis in a manner that may be downstream of insulin signaling (Kucejova et al., 2016), which is concordant with the observations that mTORC1 inhibits PPARα-mediated Hmgcs2 induction (Sengupta et al., 2010) (also see Regulation of HMGCS2 and SCOT/OXCT1).


Preliminary observations from our group suggest adverse hepatic consequences of ketogenic insufficiency (Cotter et al., 2014). To test the hypothesis that impaired ketogenesis, even in carbohydrate-replete and thus ‘non-ketogenic’ states, contributes to abnormal glucose metabolism and provokes steatohepatitis, we generated a mouse model of marked ketogenic insufficiency by administration of antisense oligonucleotides (ASO) targeted to Hmgcs2. Loss of HMGCS2 in standard low-fat chow-fed adult mice caused mild hyperglycemia and markedly increased production of hundreds of hepatic metabolites, a suite of which strongly suggested lipogenesis activation. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation. These findings support the central hypotheses that (i) ketogenesis is not a passive overflow pathway but rather a dynamic node in hepatic and integrated physiological homeostasis, and (ii) prudent ketogenic augmentation to mitigate NAFLD/NASH and disordered hepatic glucose metabolism is worthy of exploration.

How might impaired ketogenesis contribute to hepatic injury and altered glucose homeostasis? The first consideration is whether the culprit is deficiency of ketogenic flux, or ketones themselves. A recent report suggests that ketone bodies may mitigate oxidative stress-induced hepatic injury in response to n-3 polyunsaturated fatty acids (Pawlak et al., 2015). Recall that due to lack of SCOT expression in hepatocytes, ketone bodies are not oxidized, but they can contribute to lipogenesis, and serve a variety of signaling roles independent of their oxidation (also see Non-oxidative metabolic fates of ketone bodies and βOHB as a signaling mediator). It is also possible that hepatocyte-derived ketone bodies may serve as a signal and/or metabolite for neighboring cell types within the hepatic acinus, including stellate cells and Kupffer cell macrophages. While the limited literature available suggests that macrophages are unable to oxidize ketone bodies, this has only been measured using classical methodologies, and only in peritoneal macrophages (Newsholme et al., 1986; Newsholme et al., 1987), indicating that a re-assessment is appropriate given abundant SCOT expression in bone marrow-derived macrophages (Youm et al., 2015).

Hepatocyte ketogenic flux may also be cytoprotective. While salutary mechanisms may not depend on ketogenesis per se, low carbohydrate ketogenic diets have been associated with amelioration of NAFLD (Browning et al., 2011; Foster et al., 2010; Kani et al., 2014; Schugar and Crawford, 2012). Our observations indicate that hepatocyte ketogenesis may feedback and regulate TCA cycle flux, anaplerotic flux, phosphoenolpyruvate-derived gluconeogenesis (Cotter et al., 2014), and even glycogen turnover. Ketogenic impairment directs acetyl-CoA to increase TCA flux, which in liver has been linked to increased ROS-mediated injury (Satapati et al., 2015; Satapati et al., 2012); forces diversion of carbon into de novo synthesized lipid species that could prove cytotoxic; and prevents NADH re-oxidation to NAD+ (Cotter et al., 2014) (Fig. 4). Taken together, future experiments are required to address mechanisms through which relative ketogenic insufficiency may become maladaptive, contribute to hyperglycemia, provoke steatohepatitis, and whether these mechanisms are operant in human NAFLD/NASH. As epidemiological evidence suggests impaired ketogenesis during the progression of steatohepatitis (Embade et al., 2016; Marinou et al., 2011; Männistö et al., 2015; Pramfalk et al., 2015; Safaei et al., 2016) therapies that increase hepatic ketogenesis could prove salutary (Degirolamo et al., 2016; Honda et al., 2016).

Ketone Bodies and Heart Failure (HF)

With a metabolic rate exceeding 400 kcal/kg/day, and a turnover of 6–35 kg ATP/day, the heart is the organ with the highest energy expenditure and oxidative demand (Ashrafian et al., 2007; Wang et al., 2010b). The vast majority of myocardial energy turnover resides within mitochondria, and 70% of this supply originates from FAO. The heart is omnivorous and flexible under normal conditions, but the pathologically remodeling heart (e.g., due to hypertension or myocardial infarction) and the diabetic heart each become metabolically inflexible (Balasse and Fery, 1989; BING, 1954; Fukao et al., 2004; Lopaschuk et al., 2010; Taegtmeyer et al., 1980; Taegtmeyer et al., 2002; Young et al., 2002). Indeed, genetically programmed abnormalities of cardiac fuel metabolism in mouse models provoke cardiomyopathy (Carley et al., 2014; Neubauer, 2007). Under physiological conditions normal hearts oxidize ketone bodies in proportion to their delivery, at the expense of fatty acid and glucose oxidation, and myocardium is the highest ketone body consumer per unit mass (BING, 1954; Crawford et al., 2009; GARLAND et al., 1962; Hasselbaink et al., 2003; Jeffrey et al., 1995; Pelletier et al., 2007; Tardif et al., 2001; Yan et al., 2009). Compared to fatty acid oxidation, ketone bodies are more energetically efficient, yielding more energy available for ATP synthesis per molecule of oxygen invested (P/O ratio) (Kashiwaya et al., 2010; Sato et al., 1995; Veech, 2004). Ketone body oxidation also yields potentially higher energy than FAO, keeping ubiquinone oxidized, which raises redox span in the electron transport chain and makes more energy available to synthetize ATP (Sato et al., 1995; Veech, 2004). Oxidation of ketone bodies may also curtail ROS production, and thus oxidative stress (Veech, 2004).

Preliminary interventional and observational studies indicate a potential salutary role of ketone bodies in the heart. In the experimental ischemia/reperfusion injury context, ketone bodies conferred potential cardioprotective effects (Al-Zaid et al., 2007; Wang et al., 2008), possibly due to the increase mitochondrial abundance in heart or up-regulation of crucial oxidative phosphorylation mediators (Snorek et al., 2012; Zou et al., 2002). Recent studies indicate that ketone body utilization is increased in failing hearts of mice (Aubert et al., 2016) and humans (Bedi et al., 2016), supporting prior observations in humans (BING, 1954; Fukao et al., 2000; Janardhan et al., 2011; Longo et al., 2004; Rudolph and Schinz, 1973; Tildon and Cornblath, 1972). Circulating ketone body concentrations are increased in heart failure patients, in direct proportion to filling pressures, observations whose mechanism and significance remains unknown (Kupari et al., 1995; Lommi et al., 1996; Lommi et al., 1997; Neely et al., 1972), but mice with selective SCOT deficiency in cardiomyocytes exhibit accelerated pathological ventricular remodeling and ROS signatures in response to surgically induced pressure overload injury (Schugar et al., 2014).

Recent intriguing observations in diabetes therapy have revealed a potential link between myocardial ketone metabolism and pathological ventricular remodeling (Fig. 5). Inhibition of the renal proximal tubular sodium/glucose co-transporter 2 (SGLT2i) increases circulating ketone body concentrations in humans (Ferrannini et al., 2016a; Inagaki et al., 2015) and mice (Suzuki et al., 2014) via increased hepatic ketogenesis (Ferrannini et al., 2014; Ferrannini et al., 2016a; Katz and Leiter, 2015; Mudaliar et al., 2015). Strikingly, at least one of these agents decreased HF hospitalization (e.g., as revealed by the EMPA-REG OUTCOME trial), and improved cardiovascular mortality (Fitchett et al., 2016; Sonesson et al., 2016; Wu et al., 2016a; Zinman et al., 2015). While the driver mechanisms behind beneficial HF outcomes to linked SGLT2i remain actively debated, the survival benefit is likely multifactorial, prospectively including ketosis but also salutary effects on weight, blood pressure, glucose and uric acid levels, arterial stiffness, the sympathetic nervous system, osmotic diuresis/reduced plasma volume, and increased hematocrit (Raz and Cahn, 2016; Vallon and Thomson, 2016). Taken together, the notion that therapeutically increasing ketonemia either in HF patients, or those at high risk to develop HF, remains controversial but is under active investigation in pre-clinical and clinical studies (Ferrannini et al., 2016b; Kolwicz et al., 2016; Lopaschuk and Verma, 2016; Mudaliar et al., 2016; Taegtmeyer, 2016).


Ketone Bodies in Cancer Biology

Connections between ketone bodies and cancer are rapidly emerging, but studies in both animal models and humans have yielded diverse conclusions. Because ketone metabolism is dynamic and nutrient state responsive, it is enticing to pursue biological connections to cancer because of the potential for precision-guided nutritional therapies. Cancer cells undergo metabolic reprogramming in order to maintain rapid cell proliferation and growth (DeNicola and Cantley, 2015; Pavlova and Thompson, 2016). The classical Warburg effect in cancer cell metabolism arises from the dominant role of glycolysis and lactic acid fermentation to transfer energy and compensate for lower dependence on oxidative phosphorylation and limited mitochondrial respiration (De Feyter et al., 2016; Grabacka et al., 2016; Kang et al., 2015; Poff et al., 2014; Shukla et al., 2014). Glucose carbon is primarily directed through glycolysis, the pentose phosphate pathway, and lipogenesis, which together provide intermediates necessary for tumor biomass expansion (Grabacka et al., 2016; Shukla et al., 2014; Yoshii et al., 2015). Adaptation of cancer cells to glucose deprivation occurs through the ability to exploit alternative fuel sources, including acetate, glutamine, and aspartate (Jaworski et al., 2016; Sullivan et al., 2015). For example, restricted access to pyruvate reveals the ability of cancer cells to convert glutamine into acetyl-CoA by carboxylation, maintaining both energetic and anabolic needs (Yang et al., 2014). An interesting adaptation of cancer cells is the utilization of acetate as a fuel (Comerford et al., 2014; Jaworski et al., 2016; Mashimo et al., 2014; Wright and Simone, 2016; Yoshii et al., 2015). Acetate is also a substrate for lipogenesis, which is critical for tumor cell proliferation, and gain of this lipogenic conduit is associated with shorter patient survival and greater tumor burden (Comerford et al., 2014; Mashimo et al., 2014; Yoshii et al., 2015).

Non-cancer cells easily shift their energy source from glucose to ketone bodies during glucose deprivation. This plasticity may be more variable among cancer cell types, but in vivo implanted brain tumors oxidized [2,4-13C2]-βOHB to a similar degree as surrounding brain tissue (De Feyter et al., 2016). ‘Reverse Warburg effect’ or ‘two compartment tumor metabolism’ models hypothesize that cancer cells induce βOHB production in adjacent fibroblasts, furnishing the tumor cell’s energy needs (Bonuccelli et al., 2010; Martinez-Outschoorn et al., 2012). In liver, a shift in hepatocytes from ketogenesis to ketone oxidation in hepatocellular carcinoma (hepatoma) cells is consistent with activation of BDH1 and SCOT activities observed in two hepatoma cell lines (Zhang et al., 1989). Indeed, hepatoma cells express OXCT1 and BDH1 and oxidize ketones, but only when serum starved (Huang et al., 2016). Alternatively, tumor cell ketogenesis has also been proposed. Dynamic shifts in ketogenic gene expression are exhibited during cancerous transformation of colonic epithelium, a cell type that normally expresses HMGCS2, and a recent report suggested that HMGCS2 may be a prognostic marker of poor prognosis in colorectal and squamous cell carcinomas (Camarero et al., 2006; Chen et al., 2016). Whether this association requires or involves ketogenesis, or a moonlighting function of HMGCS2, remains to be determined. Conversely, apparent βOHB production by melanoma and glioblastoma cells, stimulated by the PPARα agonist fenofibrate, was associated with growth arrest (Grabacka et al., 2016). Further studies are required to characterize roles of HMGCS2/SCOT expression, ketogenesis, and ketone oxidation in cancer cells.

Beyond the realm of fuel metabolism, ketones have recently been implicated in cancer cell biology via a signaling mechanism. Analysis of BRAF-V600E+ melanoma indicated OCT1-dependent induction of HMGCL in an oncogenic BRAF-dependent manner (Kang et al., 2015). HMGCL augmentation was correlated with higher cellular AcAc concentration, which in turn enhanced BRAFV600E-MEK1 interaction, amplifying MEK-ERK signaling in a feed-forward loop that drives tumor cell proliferation and growth. These observations raise the intriguing question of prospective extrahepatic ketogenesis that then supports a signaling mechanism (also see βOHB as a signaling mediator and Controversies in extrahepatic ketogenesis). It is also important to consider independent effects of AcAc, d-βOHB, and l-βOHB on cancer metabolism, and when considering HMGCL, leucine catabolism may also be deranged.

The effects of ketogenic diets (also see Therapeutic use of ketogenic diet and exogenous ketone bodies) in cancer animal models are varied (De Feyter et al., 2016; Klement et al., 2016; Meidenbauer et al., 2015; Poff et al., 2014; Seyfried et al., 2011; Shukla et al., 2014). While epidemiological associations among obesity, cancer, and ketogenic diets are debated (Liskiewicz et al., 2016; Wright and Simone, 2016), a meta-analysis using ketogenic diets in animal models and in human studies suggested a salutary impact on survival, with benefits prospectively linked to the magnitude of ketosis, time of diet initiation, and tumor location (Klement et al., 2016; Woolf et al., 2016). Treatment of pancreatic cancer cells with ketone bodies (d-βOHB or AcAc) inhibited growth, proliferation and glycolysis, and a ketogenic diet (81% kcal fat, 18% protein, 1% carbohydrate) reduced in vivo tumor weight, glycemia, and increased muscle and body weight in animals with implanted cancer (Shukla et al., 2014). Similar results were observed using a metastatic glioblastoma cell model in mice that received ketone supplementation in the diet (Poff et al., 2014). Conversely, a ketogenic diet (91% kcal fat, 9% protein) increased circulating βOHB concentration and diminished glycemia but had no impact on either tumor volume or survival duration in glioma-bearing rats (De Feyter et al., 2016). A glucose ketone index has been proposed as a clinical indicator that improves metabolic management of ketogenic diet-induced brain cancer therapy in humans and mice (Meidenbauer et al., 2015). Taken together, roles of ketone body metabolism and ketone bodies in cancer biology are tantalizing because they each pose tractable therapeutic options, but fundamental aspects remain to be elucidated, with clear influences emerging from a matrix of variables, including (i) differences between exogenous ketone bodies versus ketogenic diet, (ii) cancer cell type, genomic polymorphisms, grade, and stage; and (iii) timing and duration of exposure to the ketotic state.

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Ketogenesis is created by ketone bodies through the breakdown of fatty acids and ketogenic amino acids. This biochemical process provides energy to various organs, specifically the brain, under circumstances of fasting as a response to an unavailability of blood glucose. Ketone bodies are mainly produced in the mitochondria of liver cells. While other cells are capable of carrying out ketogenesis, they are not as effective at doing so as liver cells. Because ketogenesis occurs in the mitochondria, its processes are regulated independently. Dr. Alex Jimenez D.C., C.C.S.T. Insight

Therapeutic Application of Ketogenic Diet and Exogenous Ketone Bodies

The applications of ketogenic diets and ketone bodies as therapeutic tools have also arisen in non-cancerous contexts including obesity and NAFLD/NASH (Browning et al., 2011; Foster et al., 2010; Schugar and Crawford, 2012); heart failure (Huynh, 2016; Kolwicz et al., 2016; Taegtmeyer, 2016); neurological and neurodegenerative disease (Martin et al., 2016; McNally and Hartman, 2012; Rho, 2015; Rogawski et al., 2016; Yang and Cheng, 2010; Yao et al., 2011); inborn errors of metabolism (Scholl-Bürgi et al, 2015); and exercise performance (Cox et al., 2016). The efficacy of ketogenic diets has been especially appreciated in therapy of epileptic seizure, particularly in drug-resistant patients. Most studies have evaluated ketogenic diets in pediatric patients, and reveal up to a ~50% reduction in seizure frequency after 3 months, with improved effectiveness in select syndromes (Wu et al., 2016b). The experience is more limited in adult epilepsy, but a similar reduction is evident, with better response in symptomatic generalized epilepsy patients (Nei et al., 2014). Underlying anti-convulsant mechanisms remain unclear, although postulated hypotheses include reduced glucose utilization/glycolysis, reprogrammed glutamate transport, indirect impact on ATP-sensitive potassium channel or adenosine A1 receptor, alteration of sodium channel isoform expression, or effects on circulating hormones including leptin (Lambrechts et al., 2016; Lin et al., 2017; Lutas and Yellen, 2013). It remains unclear whether the anti-convulsant effect is primarily attributable to ketone bodies, or due to the cascade metabolic consequences of low carbohydrate diets. Nonetheless, ketone esters (see below) appear to elevate the seizure threshold in animal models of provoked seizures (Ciarlone et al., 2016; D’Agostino et al., 2013; Viggiano et al., 2015).

Atkins-style and ketogenic, low carbohydrate diets are often deemed unpleasant, and can cause constipation, hyperuricemia, hypocalcemia, hypomagnesemia, lead to nephrolithiasis, ketoacidosis, cause hyperglycemia, and raise circulating cholesterol and free fatty acid concentrations (Bisschop et al., 2001; Kossoff and Hartman, 2012; Kwiterovich et al., 2003; Suzuki et al., 2002). For these reasons, long-term adherence poses challenges. Rodent studies commonly use a distinctive macronutrient distribution (94% kcal fat, 1% kcal carbohydrate, 5% kcal protein, Bio-Serv F3666), which provokes a robust ketosis. However, increasing the protein content, even to 10% kcal substantially diminishes the ketosis, and 5% kcal protein restriction confers confounding metabolic and physiological effects. This diet formulation is also choline depleted, another variable that influences susceptibility to liver injury, and even ketogenesis (Garbow et al., 2011; Jornayvaz et al., 2010; Kennedy et al., 2007; Pissios et al., 2013; Schugar et al., 2013). Effects of long-term consumption of ketogenic diets in mice remain incompletely defined, but recent studies in mice revealed normal survival and the absence of liver injury markers in mice on ketogenic diets over their lifespan, although amino acid metabolism, energy expenditure, and insulin signaling were markedly reprogrammed (Douris et al., 2015).

Mechanisms increasing ketosis through mechanisms alternative to ketogenic diets include the use of ingestible ketone body precursors. Administration of exogenous ketone bodies could create a unique physiological state not encountered in normal physiology, because circulating glucose and insulin concentrations are relatively normal, while cells might spare glucose uptake and utilization. Ketone bodies themselves have short half-lives, and ingestion or infusion of sodium βOHB salt to achieve therapeutic ketosis provokes an untoward sodium load. R/S-1,3-butanediol is a non-toxic dialcohol that is readily oxidized in the liver to yield d/l-βOHB (Desrochers et al., 1992). In distinct experimental contexts, this dose has been administered daily to mice or rats for as long as seven weeks, yielding circulating βOHB concentrations of up to 5 mM within 2 h of administration, which is stable for at least an additional 3h (D’Agostino et al., 2013). Partial suppression of food intake has been observed in rodents given R/S-1,3-butanediol (Carpenter and Grossman, 1983). In addition, three chemically distinct ketone esters (KEs), (i) monoester of R-1,3-butanediol and d-βOHB (R-3-hydroxybutyl R-βOHB); (ii) glyceryl-tris-βOHB; and (iii) R,S-1,3-butanediol acetoacetate diester, have also been extensively studied (Brunengraber, 1997; Clarke et al., 2012a; Clarke et al., 2012b; Desrochers et al., 1995a; Desrochers et al., 1995b; Kashiwaya et al., 2010). An inherent advantage of the former is that 2 moles of physiological d-βOHB are produced per mole of KE, following esterase hydrolysis in the intestine or liver. Safety, pharmacokinetics, and tolerance have been most extensively studied in humans ingesting R-3-hydroxybutyl R-βOHB, at doses up to 714 mg/kg, yielding circulating d-βOHB concentrations up to 6 mM (Clarke et al., 2012a; Cox et al., 2016; Kemper et al., 2015; Shivva et al., 2016). In rodents, this KE decreases caloric intake and plasma total cholesterol, stimulates brown adipose tissue, and improves insulin resistance (Kashiwaya et al., 2010; Kemper et al., 2015; Veech, 2013). Recent findings indicate that during exercise in trained athletes, R-3-hydroxybutyl R-βOHB ingestion decreased skeletal muscle glycolysis and plasma lactate concentrations, increased intramuscular triacylglycerol oxidation, and preserved muscle glycogen content, even when co-ingested carbohydrate stimulated insulin secretion (Cox et al., 2016). Further development of these intriguing results is required, because the improvement in endurance exercise performance was predominantly driven by a robust response to the KE in 2/8 subjects. Nonetheless, these results do support classical studies that indicate a preference for ketone oxidation over other substrates (GARLAND et al., 1962; Hasselbaink et al., 2003; Stanley et al., 2003; Valente-Silva et al., 2015), including during exercise, and that trained athletes may be more primed to utilize ketones (Johnson et al., 1969a; Johnson and Walton, 1972; Winder et al., 1974; Winder et al., 1975). Finally, the mechanisms that might support improved exercise performance following equal caloric intake (differentially distributed among macronutrients) and equal oxygen consumption rates remain to be determined. Clues may emerge from animal studies, as temporary exposure to R-3-hydroxybutyl R-βOHB in rats was associated with increased treadmill time, improved cognitive function, and an apparent energetic benefit in ex vivo perfused hearts (Murray et al., 2016).

Future Perspective

Once largely stigmatized as an overflow pathway capable of accumulating toxic emissions from fat combustion in carbohydrate restricted states (the ‘ketotoxic’ paradigm), recent observations support the notion that ketone body metabolism serves salutary roles even in carbohydrate-laden states, opening a ‘ketohormetic’ hypothesis. While the facile nutritional and pharmacological approaches to manipulate ketone metabolism make it an attractive therapeutic target, aggressively posed but prudent experiments remain in both the basic and translational research laboratories. Unmet needs have emerged in the domains of defining the role of leveraging ketone metabolism in heart failure, obesity, NAFLD/NASH, type 2 diabetes, and cancer. The scope and impact of ‘non-canonical’ signaling roles of ketone bodies, including regulation of PTMs that likely feed back and forward into metabolic and signaling pathways, require deeper exploration. Finally, extrahepatic ketogenesis could open intriguing paracrine and autocrine signaling mechanisms and opportunities to influence co-metabolism within the nervous system and tumors to achieve therapeutic ends.



In conclusion, ketone bodies are created by the liver in order to be used as an energy source when there is not enough glucose readily available in the human body. Ketogenesis occurs when there are low glucose levels in the blood, particularly after other cellular carbohydrate stores have been exhausted. The purpose of the article above was to discuss the multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

Referenced from:

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

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EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


The Function Of Ketones In Ketosis

The Function Of Ketones In Ketosis

Ketosis is a natural procedure the human body goes through on a regular basis. This method provides the cells with energy from ketones if sugar isn’t readily available. A moderate degree of ketosis occurs when we skip a meal or two, do not consume many carbohydrates throughout the day or exercise for an extended amount of time. When there is an increased demand for energy and carbohydrates are not immediately available to meet that need, the human body will subsequently begin to raise its ketone levels.

If carbohydrates continue to be limited for a considerable amount of time, ketone levels may increase further. These deeper degrees of ketosis provide many favorable effects throughout the entire body. These benefits can be taken advantage of by following the ketogenic diet. However, the majority of people are seldom in ketosis since the human body prefers to utilize sugar, or glucose, as its principal fuel supply. Below, we will discuss ketosis, ketones, and how these procedures work together to keep the cells healthy.

How Nutrients are Converted into Energy

The human body processes several kinds of nutrients to produce the energy it requires. Carbohydrates, proteins, and fats can be converted to energy in order to fuel various metabolic processes. If you consume high-carbohydrate foods or excessive amounts of protein, your cells will break these down into a simple sugar called glucose. This occurs because sugar provides the cells with the fastest source of ATP, which one of the main energy molecules required to fuel virtually every system within the human body.

By way of instance, more ATP means more cell energy and more calories result in more ATP. As a matter of fact, each calorie consumed from carbohydrates, proteins, and fats may be utilized to maximize ATP levels. The human body consumes a lot of these nutrients to maintain the proper function of all its structures. If you consume more than sufficient food, nevertheless, there’ll be too much sugar which your system does not need. But, considering this, what does the human body do with all this excess sugar? Instead of eliminating excess calories which the body does not need, it will store them as fat where it can be used later once the cells require energy.

The human body stores energy in two ways:

  • Glycogenesis. Through this procedure, excess glucose is converted into glycogen, or the stored form of glucose, which is stored in the liver and muscles. Researchers estimate that the entire human body stores about 2000 calories in the shape of muscle and liver glycogen. This generally means that glycogen levels will be used within 6 to 24 hours if no additional calories are consumed. An alternate system of energy storage may help sustain the human body when glycogen levels are reduced: lipogenesis.
  • Lipogenesis. When there are sufficient amounts of glycogen in the muscles and liver, any excess glucose is converted into fats and stores through a procedure called lipogenesis. Compared to our limited glycogen stores, our fat stores are almost infinite. These supply us with the capability to sustain ourselves for weeks to even months without enough food being available.

When food is limited and the intake of nutrients like carbohydrates are restricted, glycogenesis and lipogenesis is no longer active. Rather, these procedures are replaced with glycogenolysis and lipolysis which free energy from glycogen and fat stores throughout the human body. However, something unexpected occurs when the cells no longer have stored sugar, fat or glycogen. Fat will continue to be used as fuel but an alternate fuel source known as ketones is produced as well. Because of this, the process of ketosis occurs.

Why Does Ketosis Occur?

When you don’t have any access to foods, such as when you’re sleeping, fasting, or following the ketogenic diet, then the human body will convert some of its stored fat into exceptionally efficient energy molecules known as ketones. Ketones are synthesized following the entire breakdown of fats into fatty acids and glycerol, where we can thank our cell’s capacity to change metabolic pathways for this. Although fatty acids and glycerol are turned into fuel throughout the entire body, they’re not utilized as energy by brain cells.

Because these nutrients are converted into energy too slowly to support the function of the brain, sugar is still considered to be the principal source of fuel for the brain. This process also helps us understand why we create ketones. Without an alternate energy supply, the brain would be exceedingly vulnerable if we don’t consume enough calories. Our muscles would be broken down instantly and converted into sugar to feed our hungry brains. Without ketones, the human race would have most probably been extinct.

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Low-carbohydrate modified ketogenic diets have been demonstrated to have many health benefits, including weight loss and the increased ability to help fight diabetes. These type of diets have a remarkable way of providing energy for the brain. Research studies have discovered that entering ketosis has the ability to reduce insulin levels, freeing fat from fat cells. Researchers have also shown that the ketogenic diet can have a significant metabolic advantage, which leads to more calories burned than with any other diet. Dr. Alex Jimenez D.C., C.C.S.T. Insight

The Way Ketones are Produced

The human body breaks down fat into fatty acids and glycerol which may be utilized for fuel in the cells directly but not by the brain. To fulfill the requirements of the brain, the fatty acids from fats and glycerol go through the liver where they’re then converted into glucose, or sugar, and ketones. Glycerol undergoes a process called gluconeogenesis, which transforms it into glucose, where fatty acids are converted to ketone bodies through a procedure called ketogenesis. As a consequence of ketogenesis, a ketone body called acetoacetate is generated. Acetoacetate is then converted to two different types of ketone bodies:

  • Beta-hydroxybutyrate (BHB). After being keto-adapted for several weeks, the cells will start to convert acetoacetate into BHB because it’s a more efficient source of fuel where it destroys an extra chemical reaction which provides more energy to the cell compared to acetoacetate. Research studies have demonstrated that the human body and brain favor utilizing BHB and acetoacetate for energy because the cells can utilize it 70 percent better than they can sugar or glucose.
  • Acetone. This substance can occasionally be metabolized into glucose, however, it is largely eliminated as waste. This is what specifically provides the distinctly smelling breath which many ketogenic dieters have learned to understand.

Over time, the human body will release less surplus ketone bodies, or acetone, and, should you utilize keto sticks to monitor your degree of ketosis, you might believe it’s slowing down. As the brain burns off BHB as fuel, the cells attempt to present the brain with as much effective energy as they can. This is why long-term low-carbohydrate users won’t show profound levels of ketosis in their urine tests. As a matter of fact, long-term keto dieters can endure around 50 percent of their basal energy demands and 70 percent of their brain’s energy demands from ketones. Therefore, you shouldn’t allow the urine tests to fool you.

The Significance of Gluconeogenesis

Regardless of how keto-adapted the human body may become, the cells will still require glucose to function properly. To satisfy the energy demands of the human mind and body which can’t be fulfilled by ketones, the liver will initiate a process called gluconeogenesis. Amino acids in proteins and lactate in the muscles may also be transformed into glucose.

By converting amino acids, glycerol, and lactate into glucose, the liver can satisfy the glucose demands of the human body and brain during times of fasting and carbohydrate limitation. That is the reason why there’s not any crucial requirement for carbohydrates to be included in our diet. The liver will, generally, make sure to have sufficient sugar in the blood for your own cells to survive.

It’s important to remember, however, that certain variables, such as eating too much protein, may get in the way of ketosis and boost the demand for gluconeogenesis. Insulin levels and ketone production are closely connected. Protein sources, which are generally consumed on the ketogenic diet, can also increase insulin levels. In response to a rise in insulin levels, ketogenesis is downregulated, which raises the demand for gluconeogenesis to generate more sugar.

This is the reason why eating too much protein may impair your ability to enter ketosis. But this doesn’t necessarily mean you ought to limit your protein intake either. By restricting protein intake, your muscle cells will be employed to generate the sugar your body and brain demand for fuel. With proper guidance, you can consum the perfect quantity of protein your body needs to maintain muscle mass and fulfill your glucose needs when you’re on the road to ketosis.

Recognizing the Path to Ketosis

Almost all of our understanding behind ketosis originates from research studies on people who have fasted from all foods, not only from ketogenic dieters. However, we could make many inferences concerning the ketogenic diet out of what the researchers discovered from the research studies on fasting. First, let us look at the phases the body goes through during fasting:

Stage 1 – The glycogen depletion phase – 6 to 24 hours of fasting

In this phase, most energy is produced by glycogen. During this time, hormone levels begin to change, causing increases in gluconeogenesis and fat burning, however, ketone generation isn’t active yet.

Stage 2 – The gluconeogenic stage – 2 to 10 days of fasting

In this phase, glycogen is totally depleted and gluconeogenesis supplies the cells with energy. Ketones begin to be generated at reduced levels. You will notice you have keto breath and are urinating more frequently due to greater acetone levels in your blood. The timeframe for this phase is so extensive (two to ten days) since it is dependent upon who is fasting. By way of instance, healthy men and obese people have a tendency to remain in the gluconeogenic phase for extended periods of time compared to healthy women.

Stage 3 – The ketogenic stage – after 2 days of fasting or more

This phase is characterized by a decrease in protein breakdown for energy through an increase in fat and ketone usage. At this phase, you will surely be in ketosis. Every individual can enter this point at various rates based on lifestyle and genetic variables, their physical activity levels, and the number of times they fasted and/or restricted carbohydrates before. Whether you’re following the ketogenic diet or fasting, you may go through these phases, but this doesn’t guarantee the same benefits fasting as you do from the keto diet.

Ketogenic Diet Ketosis vs Starvation Ketosis

The ketosis which you experience on the ketogenic diet is considered to be a lot safer and healthier compared to the ketosis you get to when fasting. During the time you’re fasting, the human body doesn’t have any food resources, therefore it begins converting the protein from your muscles into sugar. This induces rapid muscle reduction.

The ketogenic diet, on the other hand, provides us with the healthiest and safest way to experience the advantages of ketosis. Limiting carbohydrates while keeping sufficient caloric intake from protein and fat permits the ketogenic procedure to sustain muscle tissue by employing ketosis and the ketone bodies we generate for fuel without having to utilize valuable muscle mass. Many research studies have discovered that ketones can also have an array of beneficial effects throughout the entire body too.

Ketoacidosis: The Bad Side of Ketosis

Ketoacidosis is a potentially lethal condition which occurs when excessive ketones accumulate in the blood. Some healthcare professionals may advise against increasing your ketone levels with the ketogenic diet because they fear you could enter ketoacidosis. The practice of ketosis is closely governed by the liver, and also the entire body infrequently generates more ketones then it requires for fuel. That is the reason why the ketogenic diet has been referred to as a safe and effective way to enter ketosis.

Ketoacidosis, on the other hand, is more likely to occur in type 1 and type 2 diabetics who don’t have their glucose under control. The mix of insulin deficiency and higher glucose levels, which are generally found in people with diabetes, produce a vicious cycle which causes ketones to build up in the blood. By limiting carbohydrates, nevertheless, healthy people and patients with diabetes may continue to keep their glucose under control and also experience the advantages of utilizing ketones for fuel.

Putting It All Together

Ketogenesis takes fatty acids from stored fat and transforms it into ketones. The ketones are subsequently released into the bloodstream. The procedure where the body burns off ketones for fuel is known as ketosis. However, not all cells can utilize ketones as fuel. Some cells will always utilize glucose to function accordingly. To satisfy the energy requirements which can’t be fulfilled by ketones, your liver utilizes a process called gluconeogenesis. Gluconeogenesis is the procedure where the liver converts glycerol from fatty acids, amino acids from proteins, and lactate from muscles, into glucose. Collectively, ketogenesis and gluconeogenesis produce the ketones and glucose which fulfill all the body’s energy demands when food is not available or when carbohydrates are limited.

Though ketones are well-known for being an alternate fuel supply, they supply us with several unique advantages too. The best and safest way to receive all the advantages of ketosis is by simply adhering to the ketogenic diet. In that way, you won’t encounter the chance of losing valuable muscle mass or inducing the potentially lethal condition of ketoacidosis. But, the ketogenic diet is somewhat more nuanced than a lot of men and women think. It is not just about restricting carbohydrates, it’s about making sure sufficient fat, protein, and overall calorie intake are consumed, which are ultimately vital. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 .

Curated by Dr. Alex Jimenez

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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  

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EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor


What Are The Risks Of Nrf2 Overexpression?

What Are The Risks Of Nrf2 Overexpression?

The nuclear erythroid 2-related factor 2 signaling pathway, best known as Nrf2, is a protective mechanism which functions as a “master regulator” of the human body’s antioxidant response. Nrf2 senses the levels of oxidative stress within the cells and triggers protective antioxidant mechanisms. While Nrf2 activation can have many benefits, Nrf2 “overexpression” can have several risks. It appears that a balanced degree of NRF2 is essential towards preventing the overall development of a variety of diseases in addition to the general improvement of these health issues. However, NRF2 can also cause complications. The main cause behind NRF2 “overexpression” is due to a genetic mutation or a continuing chronic exposure to a chemical or oxidative stress, among others. Below, we will discuss the downsides of Nrf2 overexpression and demonstrate its mechanisms of action within the human body.


Research studies found that mice that don’t express NRF2 are more inclined to develop cancer in response to physical and chemical stimulation. Similar research studies, however, showed that NRF2 over-activation, or even KEAP1 inactivation, can result in the exacerbation of certain cancers, particularly if those pathways have been interrupted. Overactive NRF2 can occur through smoking, where continuous NRF2 activation is believed to be the cause of lung cancer in smokers. Nrf2 overexpression might cause cancerous cells not to self-destruct, while intermittent NRF2 activation can prevent cancerous cells from triggering toxin induction. Additionally, because NRF2 overexpression increases the human body’s antioxidant ability to function beyond redox homeostasis, this boosts cell division and generates an unnatural pattern of DNA and histone methylation. This can ultimately make chemotherapy and radiotherapy less effective against cancer. Therefore, limiting NRF2 activation with substances like DIM, Luteolin, Zi Cao, or salinomycin could be ideal for patients with cancer although Nrf2 overactivation should not be considered to be the only cause for cancer. Nutrient deficiencies can affect genes, including NRF2. This might be one way as to how deficiencies contribute to tumors.


The overactivation of Nrf2, can also affect the function of specific organs in the human body. NRF2 overexpression can ultimately block the production of the insulin-like growth factor 1, or IGF-1, from the liver, which is essential for the regeneration of the liver.


While the acute overexpression of Nrf2 may have its benefits, continuous overexpression of NRF2 may cause long-term harmful effects on the heart, such as cardiomyopathy. NRF2 expression can be increased through high levels of cholesterol, or the activation of HO-1. This is believed to be the reason why chronic elevated levels of cholesterol might cause cardiovascular health issues.


NRF2 overexpression has also been demonstrated to inhibit the capability to repigment in vitiligo as it might obstruct Tyrosinase, or TYR, action which is essential for repigmentation through melaninogenesis. Research studies have demonstrated that this process may be one of the primary reasons as to why people with vitiligo don’t seem to activate Nrf2 as efficiently as people without vitiligo.

Why NRF2 May Not Function Properly


NRF2 has to be hormetically activated in order to be able to take advantage of its benefits. In other words, Nrf2 shouldn’t trigger every minute or every day, therefore, it’s a great idea to take breaks from it, by way of instance, 5 days on 5 days off or every other day. NRF2 must also accomplish a specific threshold to trigger its hormetic response, where a small stressor may not be enough to trigger it.

DJ-1 Oxidation

Protein deglycase DJ-1, or just DJ-1, also called the Parkinson’s disease protein, or PARK7, is a master regulator and detector of the redox status in the human body. DJ-1 is essential towards regulating how long NRF2 can perform its function and produce an antioxidant response. In the case that DJ-1 becomes overoxidized, the cells will make the DJ-1 protein less accessible. This process induces NRF2 activation to expire too fast since DJ-1 is paramount for maintaining balanced levels of NRF2 and preventing them from being broken down in the cell. In case the DJ-1 protein is non-existent or overoxidized, NRF2 expression will probably be minimal, even using DIM or alternative NRF2 activators. DJ-1 expression is imperative to restore impaired NRF2 action.

Chronic Illness

If you have a chronic illness, including CIRS, chronic infections/dysbiosis/SIBO, or heavy metal build up, such as mercury and/or that from root canals, these can obstruct the systems of NRF2 and phase two detoxification. Rather than oxidative stress turning NRF2 into an antioxidant, NRF2 will not trigger and oxidative stress can remain in the cell and cause damage, meaning, there is no antioxidant response. This is a significant reason why many people with CIRS have several sensitivities and reach to numerous factors. Some people believe they may be having a herx response, however, this reaction may only be damaging the cells farther. Treating chronic illness, however, will permit the liver to discharge toxins into the bile, gradually developing the hormetic response of NRF2 activation. If the bile remains toxic and it’s not excreted from the human body, it will reactivate NRF2’s oxidative stress and cause you to feel worse once it’s reabsorbed from the gastrointestinal, or GI, tract. For example, ochratoxin A may block NRF2. Aside from treating the problem, histone deacetylase inhibitors can block the oxidative reaction from a number of the factors which trigger NRF2 activation but it might also prevent NRF2 from triggerring normally, which might ultimately fail to serve its purpose.

Fish Oil Dysregulation

Cholinergics are substances which boost acetylcholine, or ACh, and choline in the brain through the increase of ACh, particularly when inhibiting the breakdown of ACh. Patients with CIRS often have problems with the dysregulation of acetylcholine levels in the human body, especially in the brain. Fish oil triggers NRF2, activating its protective antioxidant mechanism within the cells. People with chronic illnesses might have problems with cognitive stress and acetylcholine excitotoxicity, from organophosphate accumulation, which might cause fish oil to create inflammation within the human body. Choline deficiency additionally induces NRF2 activation. Including choline into your diet, (polyphenols, eggs, etc.) can help enhance the effects of cholinergic dysregulation.

What Decreases NRF2?

Decreasing NRF2 overexpression is best for people that have cancer, although it may be beneficial for a variety of other health issues.

Diet, Supplements, and Common Medicines:

  • Apigenin (higher doses)
  • Brucea javanica
  • Chestnuts
  • EGCG (high doses increase NRF2)
  • Fenugreek (Trigonelline)
  • Hiba (Hinokitiol / β-thujaplicin)
  • High Salt Diet
  • Luteolin (Celery, green pepper, parsley, perilla leaf, and chamomile tea – higher doses may increase NRF2 – 40 mg/kg luteolin three times per week )
  • Metformin (chronic intake)
  • N-Acetyl-L-Cysteine (NAC, by blocking the oxidative response, esp at high doses)
  • Orange Peel (have polymethoxylated flavonoids)
  • Quercetin (higher doses may increase NRF2 – 50 mg/kg/d quercetin)
  • Salinomycin (drug)
  • Retinol (all-trans retinoic acid)
  • Vitamin C when combined with Quercetin
  • Zi Cao (Purple Gromwel has Shikonin/Alkannin)

Pathways and Other:

  • Bach1
  • BET
  • Biofilms
  • Brusatol
  • Camptothecin
  • DNMT
  • DPP-23
  • EZH2
  • Glucocorticoid Receptor signaling (Dexamethasone and Betamethasone as well)
  • GSK-3β (regulatory feedback)
  • HDAC activation?
  • Halofuginone
  • Homocysteine (ALCAR can reverse this homocysteine induce low levels of NRF2)
  • IL-24
  • Keap1
  • MDA-7
  • NFκB
  • Ochratoxin A(aspergillus and pencicllium species)
  • Promyelocytic leukemia protein
  • p38
  • p53
  • p97
  • Retinoic acid receptor alpha
  • Selenite
  • SYVN1 (Hrd1)
  • STAT3 inhibition (such as Cryptotanshinone)
  • Testosterone (and Testosterone propionate, although TP intranasally may increase NRF2)
  • Trecator (Ethionamide)
  • Trx1 (via reduction of Cys151 in Keap1 or of Cys506 in the NLS region of Nrf2)
  • Trolox
  • Vorinostat
  • Zinc Deficiency (makes it worse in the brain)

Nrf2 Mechanism Of Action

Oxidative stress triggers through CUL3 where NRF2 from KEAP1, a negative inhibitor, subsequently enters the nucleus of these cells, stimulating the transcription of the AREs, turning sulfides into disulfides, and turning them into more antioxidant genes, leading to the upregulation of antioxidants, such as GSH, GPX, GST, SOD, etc.. The rest of these can be seen in the list below:
  • Increases AKR
  • Increases ARE
  • Increases ATF4
  • Increases Bcl-xL
  • Increases Bcl-2
  • Increases BDNF
  • Increases BRCA1
  • Increases c-Jun
  • Increases CAT
  • Increases cGMP
  • Increases CKIP-1
  • Increases CYP450
  • Increases Cul3
  • Increases GCL
  • Increases GCLC
  • Increases GCLM
  • Increases GCS
  • Increases GPx
  • Increases GR
  • Increases GSH
  • Increases GST
  • Increases HIF1
  • Increases HO-1
  • Increases HQO1
  • Increases HSP70
  • Increases IL-4
  • Increases IL-5
  • Increases IL-10
  • Increases IL-13
  • Increases K6
  • Increases K16
  • Increases K17
  • Increases mEH
  • Increases Mrp2-5
  • Increases NADPH
  • Increases Notch 1
  • Increases NQO1
  • Increases PPAR-alpha
  • Increases Prx
  • Increases p62
  • Increases Sesn2
  • Increases Slco1b2
  • Increases sMafs
  • Increases SOD
  • Increases Trx
  • Increases Txn(d)
  • Increases UGT1(A1/6)
  • Increases VEGF
  • Reduces ADAMTS(4/5)
  • Reduces alpha-SMA
  • Reduces ALT
  • Reduces AP1
  • Reduces AST
  • Reduces Bach1
  • Reduces COX-2
  • Reduces DNMT
  • Reduces FASN
  • Reduces FGF
  • Reduces HDAC
  • Reduces IFN-γ
  • Reduces IgE
  • Reduces IGF-1
  • Reduces IL-1b
  • Reduces IL-2
  • Reduces IL-6
  • Reduces IL-8
  • Reduces IL-25
  • Reduces IL-33
  • Reduces iNOS
  • Reduces LT
  • Reduces Keap1
  • Reduces MCP-1
  • Reduces MIP-2
  • Reduces MMP-1
  • Reduces MMP-2
  • Reduces MMP-3
  • Reduces MMP-9
  • Reduces MMP-13
  • Reduces NfkB
  • Reduces NO
  • Reduces SIRT1
  • Reduces TGF-b1
  • Reduces TNF-alpha
  • Reduces Tyr
  • Reduces VCAM-1
  • Encoded from the NFE2L2 gene, NRF2, or nuclear erythroid 2-related factor 2, is a transcription factor in the basic leucine zipper, or bZIP, superfamily which utilizes a Cap’n’Collar, or CNC structure.
  • It promotes nitric enzymes, biotransformation enzymes, and xenobiotic efflux transporters.
  • It is an essential regulator at the induction of the phase II antioxidant and detoxification enzyme genes, which protect cells from damage caused by oxidative stress and electrophilic attacks.
  • During homeostatic conditions, Nrf2 is sequestered in the cytosol through bodily attachment of the N-terminal domain of Nrf2, or the Kelch-like ECH-associated protein or Keap1, also referred to as INrf2 or Inhibitor of Nrf2, inhibiting Nrf2 activation.
  • It may also be controlled by mammalian selenoprotein thioredoxin reductase 1, or TrxR1, which functions as a negative regulator.
  • Upon vulnerability to electrophilic stressors, Nrf2 dissociates from Keap1, translocating into the nucleus, where it then heterodimerizes with a range of transcriptional regulatory protein.
  • Frequent interactions comprise with those of transcription authorities Jun and Fos, which can be members of the activator protein family of transcription factors.
  • After dimerization, these complexes then bind to antioxidant/electrophile responsive components ARE/EpRE and activate transcription, as is true with the Jun-Nrf2 complex, or suppress transcription, much like the Fos-Nrf2 complex.
  • The positioning of the ARE, which is triggered or inhibited, will determine which genes are transcriptionally controlled by these variables.
  • When ARE is triggered:
  1. Activation of the synthesis of antioxidants is capable of detoxifying ROS like catalase, superoxide-dismutase, or SOD, GSH-peroxidases, GSH-reductase, GSH-transferase, NADPH-quinone oxidoreductase, or NQO1, Cytochrome P450 monooxygenase system, thioredoxin, thioredoxin reductase, and HSP70.
  2. Activation of this GSH synthase permits a noticeable growth of the GSH intracellular degree, which is quite protective.
  3. The augmentation of this synthesis and degrees of phase II enzymes like UDP-glucuronosyltransferase, N-acetyltransferases, and sulfotransferases.
  4. The upregulation of HO-1, which is a really protective receptor with a potential growth of CO that in conjunction with NO allows vasodilation of ischemic cells.
  5. Reduction of iron overload through elevated ferritin and bilirubin as a lipophilic antioxidant. Both the phase II proteins along with the antioxidants are able to fix the chronic oxidative stress and also to revive a normal redox system.
  • GSK3β under the management of AKT and PI3K, phosphorylates Fyn resulting in Fyn nuclear localization, which Fyn phosphorylates Nrf2Y568 leading to nuclear export and degradation of Nrf2.
  • NRF2 also dampens the TH1/TH17 response and enriches the TH2 response.
  • HDAC inhibitors triggered the Nrf2 signaling pathway and up-regulated that the Nrf2 downstream targets HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit, or GCLC, by curbing Keap1 and encouraging dissociation of Keap1 from Nrf2, Nrf2 nuclear translocation, and Nrf2-ARE binding.
  • Nrf2 includes a half-life of about 20 minutes under basal conditions.
  • Diminishing the IKKβ pool through Keap1 binding reduces IκBα degradation and might be the elusive mechanism by which Nrf2 activation is proven to inhibit NFκB activation.
  • Keap1 does not always have to be downregulated to get NRF2 to operate, such as chlorophyllin, blueberry, ellagic acid, astaxanthin, and tea polyphenols may boost NRF2 and KEAP1 at 400 percent.
  • Nrf2 regulates negatively through the term of stearoyl CoA desaturase, or SCD, and citrate lyase, or CL.




  • C allele – showed a significant risk for and a protective effect against drug resistant epilepsy (DRE)

rs11085735 (I’m AC)

  • associated with rate of decline of lung function in the LHS



  • T allele – protective allele for Parkinsonian disorders – had stronger NRF2/sMAF binding and was associated with the higher MAPT mRNA levels in 3 different regions in brain, including cerebellar cortex (CRBL), temporal cortex (TCTX), intralobular white matter (WHMT)


rs10183914 (I’m CT)

  • T allele – increased levels of Nrf2 protein and delayed age of onset of Parkinson’s by four years

rs16865105 (I’m AC)

  • C allele – had higher risk of Parkinson’s Disease

rs1806649 (I’m CT)

  • C allele – has been identified and may be relevant for breast cancer etiology.
  • associated with increased risk of hospital admissions during periods of high PM10 levels

rs1962142 (I’m GG)

  • T allele – was associated with a low level of cytoplasmic NRF2 expression (P = 0.036) and negative sulfiredoxin expression (P = 0.042)
  • A allele – protected from forearm blood flow (FEV) decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)

rs2001350 (I’m TT)

  • T allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)

rs2364722 (I’m AA)

  • A allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)


  • C allele – associated with significantly reduced FEV in Japanese smokers with lung cancer


  • G allele – showed a significant risk for and a protective effect against drug resistant epilepsy (DRE)
  • AA alleles – showed significantly reduced KEAP1 expression
  • AA alleles – was associated with an increased risk of breast cancer (P = 0.011)

rs2886161 (I’m TT)

  • T allele – associated with Parkinson’s Disease


  • A allele – was associated with low NRF2 expression (P = 0.011; OR, 1.988; CI, 1.162–3.400) and the AA genotype was associated with a worse survival (P = 0.032; HR, 1.687; CI, 1.047–2.748)

rs35652124 (I’m TT)

  • A allele – associated with higher associated with age at onset for Parkinson’s Disease vs G allele
  • C allele – had increase NRF2 protein
  • T allele – had less NRF2 protein and greater risk of heart disease and blood pressure

rs6706649 (I’m CC)

  • C allele – had lower NRF2 protein and increase risk for Parkinson’s Disease

rs6721961 (I’m GG)

  • T allele – had lower NRF2 protein
  • TT alleles – association between cigarette smoking in heavy smokers and a decrease in semen quality
  • TT allele – was associated with increased risk of breast cancer [P = 0.008; OR, 4.656; confidence interval (CI), 1.350–16.063] and the T allele was associated with a low extent of NRF2 protein expression (P = 0.0003; OR, 2.420; CI, 1.491–3.926) and negative SRXN1 expression (P = 0.047; OR, 1.867; CI = 1.002–3.478)
  • T allele – allele was also nominally associated with ALI-related 28-day mortality following systemic inflammatory response syndrome
  • T allele – protected from FEV decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
  • G allele – associated with increased risk of ALI following major trauma in European and African-Americans (odds ratio, OR 6.44; 95% confidence interval
  • AA alleles – associated with infection-induced asthma
  • AA alleles – exhibited significantly diminished NRF2 gene expression and, consequently, an increased risk of lung cancer, especially those who had ever smoked
  • AA alleles – had a significantly higher risk for developing T2DM (OR 1.77; 95% CI 1.26, 2.49; p = 0.011) relative to those with the CC genotype
  • AA alleles – strong association between wound repair and late toxicities of radiation (associated with a significantly higher risk for developing late effects in African-Americans with a trend in Caucasians)
  • associated with oral estrogen therapy and risk of venous thromboembolism in postmenopausal women

rs6726395 (I’m AG)

  • A allele – protected from FEV1 decline (forced expiratory volume in one second) in relation to cigarette smoking status (p = 0.004)
  • A allele – associated with significantly reduced FEV1 in Japanese smokers with lung cancer
  • GG alleles – had higher NRF2 levels and decreased risk of macular degeneration
  • GG alleles – had higher survival with Cholangiocarcinoma

rs7557529 (I’m CT)

  • C allele – associated with Parkinson’s Disease
Dr Jimenez White Coat
Oxidative stress and other stressors can cause cell damage which may eventually lead to a variety of health issues. Research studies have demonstrated that Nrf2 activation can promote the human body’s protective antioxidant mechanism, however, researchers have discussed that Nrf2 overexpression can have tremendous risks towards overall health and wellness. Various types of cancer can also occur with Nrf2 overactivation. Dr. Alex Jimenez D.C., C.C.S.T. Insight

Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More

Isothiocyanates are some of the most important plant compounds you can get in your diet. In this video I make the most comprehensive case for them that has ever been made. Short attention span? Skip to your favorite topic by clicking one of the time points below. Full timeline below. Key sections:
  • 00:01:14 – Cancer and mortality
  • 00:19:04 – Aging
  • 00:26:30 – Brain and behavior
  • 00:38:06 – Final recap
  • 00:40:27 – Dose
Full timeline:
  • 00:00:34 – Introduction of sulforaphane, a major focus of the video.
  • 00:01:14 – Cruciferous vegetable consumption and reductions in all-cause mortality.
  • 00:02:12 – Prostate cancer risk.
  • 00:02:23 – Bladder cancer risk.
  • 00:02:34 – Lung cancer in smokers risk.
  • 00:02:48 – Breast cancer risk.
  • 00:03:13 – Hypothetical: what if you already have cancer? (interventional)
  • 00:03:35 – Plausible mechanism driving the cancer and mortality associative data.
  • 00:04:38 – Sulforaphane and cancer.
  • 00:05:32 – Animal evidence showing strong effect of broccoli sprout extract on bladder tumor development in rats.
  • 00:06:06 – Effect of direct supplementation of sulforaphane in prostate cancer patients.
  • 00:07:09 – Bioaccumulation of isothiocyanate metabolites in actual breast tissue.
  • 00:08:32 – Inhibition of breast cancer stem cells.
  • 00:08:53 – History lesson: brassicas were established as having health properties even in ancient Rome.
  • 00:09:16 – Sulforaphane’s ability to enhance carcinogen excretion (benzene, acrolein).
  • 00:09:51 – NRF2 as a genetic switch via antioxidant response elements.
  • 00:10:10 – How NRF2 activation enhances carcinogen excretion via glutathione-S-conjugates.
  • 00:10:34 – Brussels sprouts increase glutathione-S-transferase and reduce DNA damage.
  • 00:11:20 – Broccoli sprout drink increases benzene excretion by 61%.
  • 00:13:31 – Broccoli sprout homogenate increases antioxidant enzymes in the upper airway.
  • 00:15:45 – Cruciferous vegetable consumption and heart disease mortality.
  • 00:16:55 – Broccoli sprout powder improves blood lipids and overall heart disease risk in type 2 diabetics.
  • 00:19:04 – Beginning of aging section.
  • 00:19:21 – Sulforaphane-enriched diet enhances lifespan of beetles from 15 to 30% (in certain conditions).
  • 00:20:34 – Importance of low inflammation for longevity.
  • 00:22:05 – Cruciferous vegetables and broccoli sprout powder seem to reduce a wide variety of inflammatory markers in humans.
  • 00:23:40 – Mid-video recap: cancer, aging sections
  • 00:24:14 – Mouse studies suggest sulforaphane might improve adaptive immune function in old age.
  • 00:25:18 – Sulforaphane improved hair growth in a mouse model of balding. Picture at 00:26:10.
  • 00:26:30 – Beginning of brain and behavior section.
  • 00:27:18 – Effect of broccoli sprout extract on autism.
  • 00:27:48 – Effect of glucoraphanin on schizophrenia.
  • 00:28:17 – Start of depression discussion (plausible mechanism and studies).
  • 00:31:21 – Mouse study using 10 different models of stress-induced depression show sulforaphane similarly effective as fluoxetine (prozac).
  • 00:32:00 – Study shows direct ingestion of glucoraphanin in mice is similarly effective at preventing depression from social defeat stress model.
  • 00:33:01 – Beginning of neurodegeneration section.
  • 00:33:30 – Sulforaphane and Alzheimer’s disease.
  • 00:33:44 – Sulforaphane and Parkinson’s disease.
  • 00:33:51 – Sulforaphane and Hungtington’s disease.
  • 00:34:13 – Sulforaphane increases heat shock proteins.
  • 00:34:43 – Beginning of traumatic brain injury section.
  • 00:35:01 – Sulforaphane injected immediately after TBI improves memory (mouse study).
  • 00:35:55 – Sulforaphane and neuronal plasticity.
  • 00:36:32 – Sulforaphane improves learning in model of type II diabetes in mice.
  • 00:37:19 – Sulforaphane and duchenne muscular dystrophy.
  • 00:37:44 – Myostatin inhibition in muscle satellite cells (in vitro).
  • 00:38:06 – Late-video recap: mortality and cancer, DNA damage, oxidative stress and inflammation, benzene excretion, cardiovascular disease, type II diabetes, effects on the brain (depression, autism, schizophrenia, neurodegeneration), NRF2 pathway.
  • 00:40:27 – Thoughts on figuring out a dose of broccoli sprouts or sulforaphane.
  • 00:41:01 – Anecdotes on sprouting at home.
  • 00:43:14 – On cooking temperatures and sulforaphane activity.
  • 00:43:45 – Gut bacteria conversion of sulforaphane from glucoraphanin.
  • 00:44:24 – Supplements work better when combined with active myrosinase from vegetables.
  • 00:44:56 – Cooking techniques and cruciferous vegetables.
  • 00:46:06 – Isothiocyanates as goitrogens.
According to research studies, Nrf2, is a fundamental transcription factor which activates the cells’ protective antioxidant mechanisms to detoxify the human body. The overexpression of Nrf2, however, can cause health issues. The scope of our information is limited to chiropractic and spinal health issues. To discuss the subject matter, please feel free to ask Dr. Jimenez or contact us at 915-850-0900 . Curated by Dr. Alex Jimenez
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Additional Topic Discussion: Acute Back Pain

Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. The spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.  
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EXTRA EXTRA | IMPORTANT TOPIC: Recommended El Paso, TX Chiropractor