Category: Science

Dietary Epigenetics: New Frontiers

By: Austin Perlmutter, MD, Medical Student, Miller School of Medicine

While we may be familiar with the dangers of eating too much sugar, the actual effects of this indulgence may be far more frightening than previously imagined. Certainly, science supports the idea that excess sugar consumption leads to weight gain, increases our chances of diabetes and heart disease, and portends worse health outcomes. But now, new data shows that sugar can harm us in a place we didn’t expect, by actually attacking our DNA.

To properly explain this fascinating research, let’s quickly review some biology basics. The human body is made up of roughly 37 trillion cells, our structural building blocks. The “brain” of the cell is called the nucleus, and the nucleus contains our DNA. For years, we’ve assumed that DNA was a product of our heritage, handed down from mother and father, a rigid pre-determinant of everything from our height to our mathematical skills. However, the revolutionary new field of epigenetics has lead to the discovery that what we do actually changes the way our DNA is used, that the choices we make can forever transform our genetic code

This means that the way we interact with the world changes our DNA, not just the other way around. More intriguing, one of the major ways we can change our DNA is by diet. For example, a study published in 2008 showed that exposing mice brains to as little as 6 hours of high blood sugar led to epigenetic changes that increased risk of vascular damage. These changes lasted even after 6 days of normal blood glucose, representing long-term damage after just a short blast of sugar. The research on long-term effects from short exposures is at the core of epigenetics. It’s furthered by data from another 2008 study published in the journal Diabetes. 

In this work, researchers showed that short periods of high blood glucose led to worse long term vascular changes than did sustained high blood glucose (a scary thought for the carbohydrate binger). Again, the underlying mechanism seems to be modification of the cell’s DNA, leading to the extended duration of this effect.

But there’s more. The most frightening data on this subject shows that high blood glucose may damage our telomeres; the ends of our DNA code. Considering that an undamaged telomere may be protective against cancer, death, and the very act of aging, any process that harms telomeres could put us at substantial risk. Data from the Journal of Nutrition, Health and Aging found that the higher the blood sugar, the more damage caused to the telomere and its associated DNA.

If we know that high levels of circulating glucose are trashing our DNA, it would make sense that diets low in glucose could have the opposite effect. Indeed, this is true. From the journal Science, the article “When Metabolism and Epigenetics Converge” relates the known neuroprotective benefits of a low carbohydrate diet to the epigenetic suppression of toxic oxidative stress. This benefit, which was also seen with calorie restrictive diets, seems to indicate that choosing meals lower in carbohydrates and lower in calories improves our brain cells’ ability to fight off damage, leading to healthier brains.

Reflect for a moment on our current dietary recommendations The US dietary guidelines recommend we get 65% of our daily calories from carbohydrates sources. Beyond the fact that most carbohydrate rich meals are converted into sugar as soon as they’re digested, Americans will average around 13-14% of calories a day from pure added sugar. It would seem we’re advocating for a dietary plan destined to harm our DNA. The good news is that the field of epigenetic has also identified substances capable of undoing DNA damage. Enter the epigenetic diet.

Essentially, the idea of epigenetic diet is to maximize the health of your DNA. This diet emphasizes compounds like the sulforaphane (found in broccoli), curcumin (found in turmeric), epigallocatechin gallate (found in green tea) and resveratrol (found in wine), and is designed to slow or potentially reverse damage to our DNA. The epigenetic activity of these chemicals may both prevent cancer formation and lead to decreased fat cells, as well as generally lower inflammation.3 In contrast to the negative effects of blood sugar on the brain, these chemicals may  actually lower risk of Parkinson’s Disease and cognitive decline, as well as slow the progression of Alzheimer’s disease. While it’s too soon to tell if the benefits of these compounds can ameliorate the toxic effects of high sugar, initial research is impressive.

Moving forward, the field of epigenetics is poised to explode. The more we learn about our genetic makeup, the more we can learn how our environment affects it. It’s rather scary and amazing that the choices we make in life change our DNA, but the power this connotes can also lead to empowerment. Realize that when you eat a food, you are triggering a ripple effect that penetrates all the way to your genetic code. Your silverware can quite literally be a gene-editing tool, for better or worse.


1. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008 Sep 29;205(10):2409-17. doi: 10.1084/jem.20081188. Epub 2008 Sep 22. Erratum in: J Exp Med. 2008 Oct 27;205(11):2683. PubMed PMID: 18809715; PubMed Central PMCID: PMC2556800.

2. Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25. PubMed PMID: 18299315.

3. Maeda T, Oyama JI, Higuchi Y, Arima T, Mimori K, Makino N. The correlation between the telomeric parameters and the clinical laboratory data in the patients with brain infarct and metabolic disorders. J Nutr Health Aging. 2010 Nov;14(9):793-7. PubMed PMID: 21085912.

4. Sassone-Corsi P. Physiology. When metabolism and epigenetics converge. Science. 2013 Jan 11;339(6116):148-50. doi: 10.1126/science.1233423. PubMed PMID: 23307727.

5. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, Consumption of Added Sugars Among U.S. Adults, 2005–2010 R. Bethene Ervin, Ph.D., R.D., and Cynthia L. Ogden, Ph.D., M.R.P.

6. Martin SL, Hardy TM, Tollefsbol TO. Medicinal chemistry of the epigenetic diet and caloric restriction. Curr Med Chem. 2013;20(32):4050–4059.

  • Ward

    would you please give the references to the studies mentioned in this post. Thanks.

    • David Perlmutter

      see above

  • Lynn Dell

    Austin, I was prediabetic. These past few months I’ve been following the diet, and lately have been doing much more intense aerobic conditioning via bike riding. Today, I carried my glucose monitor with me to my daughter’s track meet, where I remained fairly active, walking around. I did skip lunch, but had a normal dinner, during which I felt just very slightly shaky. I also rode the bike after dinner for a half hour. My readings for today are – 1 hour post prandial (breakfast) 97, then around 1PM 76, then around 2PM 63, and now, about 9:25 about 3 hours post dinner and 1 1/2 hours after a vigorous bike ride it is 66. I feel absolutely fine. I expect my blood glucose will rise overnight, but not into the prediabetic range, for which I am grateful.

    My husband, who is totally not diabetic or remotely prediabetic, *really* fasted (36 hours) prior to his MD appointment. His doctor himself called him in the evening, with his hair all on fire because my husband’s glucose reading was 49. My husband is also following the Grain Brain diet. After the phone call, my husband went on, unconcerned about the call, and kept on fixing a broken washing machine that most people would have given up on. My husband can walk fast over an hour, can bike for miles, and does so several times a week. He is not shaky or faint. He’s lost a little weight on this diet and it seems he’s able to sleep better at night.

    Knowing what we now know about blood glucose levels in general, and knowing how my husband and I function at levels most people say are hypoglycemic, I think it’s time for the medical community to set the bar a lot differently as to what constitutes normal blood glucose levels. I seemed to do just fine today with glucose readings in the 60s throughout the day, and I would not be pleased to be told to eat carbs to get it back to over 70. Do you have thoughts on this – I mean, about the traditional glucose ranges that are recommended?

    • TechnoTritcale

      “… think it’s time for the medical community to set the bar a lot
      differently as to what constitutes normal blood glucose levels.”

      Fascinating question. I hope Dr. Perlmutter responds to it.

      As I understand it, consensus “normal” is 70-100 mg/dl. I know Dr. Davis (Wheat Belly) recommends a target of 90 or less, but I can’t quickly find any figure for how low he considers too low.

      There’s a huge amount of context that has to be considered in answering this question, of course.

      For anyone reversing or just managing any insulin disfunction (metabolic syndrome & beyond), hypoglycemia could be risky.

      Then there’s the matter of: what is fueling the cells if not glucose? Those who have converted to being fat metabolizers have something else to run on. The typical hi-gly consumer does not.

      So a more precise set of questions might be:
      * what is normal BG for a full time ketogenic diet?
      * what is normal for a part-time keto diet?
      * what is normal for a full-time low-carb, but infrequently keto diet?

      • Lynn Dell

        Earlier I searched for information on glucose levels on a ketogenic diet and could not come up with any standards. At any rate, I do not feel shaky when my glucose readings are in the 60s. I would add two questions to your list, and that is, what should a normal fasting glucose number be, and what should post prandial readings be.

        • TechnoTritcale

          “… and could not come up with any standards.”

          I flipped through my copy of Grain Brain and came up empty as well.

          “… what should a normal fasting glucose number be …”

          The 70-100 number above is fasting.

          “… what should post prandial readings be.”

          Dr. Davis has said “no rise”, but not over 100 in any case. I tend to read this as 90 max at all times.

          The vocal MD advocates of a sane future human diet may actually be reluctant to issue firm guidelines on this if they suspect, as you do, that once again, the consensus is screwed up (but we don’t have a clear picture of the future that is safely applicable to everyone).

          • Lynn Dell

            Here is a link:

            The opinion of the authors on that page state while MDs think fasting readings should be 70 – 100, they are of the opinion (like Dr. Davis) that it should be 70 – 92. You can read their reasons why there if you like.

            They claim a healthy reaction to food intake is a reading of less than 100 two hours post eating. I just checked mine (had chicken, ~ 3/4 cup mashed potatoes, big salad w/evoo + balsamic vinegar, chocolate and some almonds for lunch, with milk in the coffee) and it was 89 two hours after starting the meal. I am very pleased with this and feel well and satisfied, and it’s been over two hours since I last ate.

            I observed my husband functioning well at readings around 50. I have had mine drawn at, I think 53, and I had to drive home on very slippery roads after that appointment. I suspect there are many more people such as my husband and I who can tolerate what is typically referred to as hypoglycemia, and I hope somebody is collecting information on this.

            In addition – I am wondering what, if any, are possible negative effects of a ketogenic diet, long term. The only one I could think of was maybe possibly bone issues – osteopenia, but metabolism is so complex I have no idea whether this diet might lead to that or not.

          • Wildman

            Why would there be bone issues for people doing long term nutritional ketosis?

          • Lynn Dell

            On account of any acidosis going on from the diet, even if mild. The body has a process to achieve ph homeostasis by taking calcium from the bones, if it has to.

          • Wildman

            Thanks Lynn

          • Lynn Dell

            That’s why it’s crucial to take in plant nutrition that has an alkalizing effect, also grass fed beef that is strictly grass fed. The subject is very complex, as I’ve read about more acidic foods that, for some reason(s), do not bother blood ph.

          • Wildman

            Interesting. I know someone who follows a ketogenic diet that drinks a mix of 1 tsp baking soda in a glass of water every 3 to 4 days for this purpose. I’ve also noticed that the less I cook meat the less acidic I feel. Obviously this is not a measured fact, just the way I feel

    • David Perlmutter

      I think this question and the added comments below are best answered in the context of what it takes in terms of blood sugar to keep glycation at a low level. That said, we need to get away from considering what is a “normal” glucose level and consider what is “optimal” I try to keep my patient’s glucose levels in the upper 80s to low 90s.

      • Lynn Dell

        My mind has to come back to a very few foundational concepts in this arena, and one of them is AGEs, so yes, this is good advice. I also believe what is normal glucose for each person may have a range, when ketogenic.

        Oh, btw, I’ve taken to water fasting on Mondays as a matter of habit. Yesterday just had coconut oil – ~ 3 teaspoons taken at separate times, and some milk in my coffee. I think I went ketogenic in a big way yesterday, judging by my thirst level and, um, output. It was so pronounced that before I went to bed I broke down and ate about a cup of raw kale, about 1/8 t. of salt, and a magnesium tablet, just to make sure I’d wake up in the morning on earth. Surprisingly, my blood sugar remained in the 70s or 80s the whole day. That made me very happy, except I was a little worried that I might be consuming skeletal muscle. But today I feel well, and am VERY motivated to be as low carb as possible! Thanks for all your work.

  • becky

    What is your recommendation for someone who has mitochondrial disease should they follow the grain brain diet?

    • David Perlmutter

      We treat mitochondrial diseases with this approach. By and large, mitochondria are best served by a diet that provides fat as a calorie source. Also, recognize that we now understand that diseases like Alzheimer’s and Parkinson’s represent mitochondrial disorders.

      • Stella Clary

        Hi Dr. Perlmutter, love the Grain Brain book, and my husband and I have been following your diet since last year. We have an appointment to see you on April 22 for consultation because my husband has Parkinson’s. We are looking forward to meeting you in person.

  • ri

    Thank God for doctors like you Dr Perlmutter who challenge government dietary guidelines and conventional dietary advice. Your book is absolutely life changing and I can not wait for the cook book! I also look forward to your new posts! I always learn something interesting and realized the key to good health is controlling blood sugar levels that’s #1 because even with a lot of aerobic exercise if your diet isn’t right your health will still suffer and be on the decline. I love food and the Perlmutter lifestyle it isn’t about food deprivation. I love that i get to enjoy great foods and be on a high fat diet and see my body hair skin mood and energy levels improve and i honestly dont crave muffins and breads the way i used to to me there just not worth all the damage they do.

  • terri mirarchi

    Dr. Perlmutter, can you tell me if you’ve heard of cognimaxx supplement for memory and if it is safe to take it?

  • BetterCakesByDesign

    Our family just started reading Grain Brain last week and spent the other day completely cleaning out our pantry, cupboards, fridge and freezers – then went shopping for all organic, gluten free, non-GMO foods. Expensive, but well worth it … this is the first week ridding our home of glutenous-gmo hazards and toxins (stuff “they” call food) and ALL of us are truly feeling more energetic and with more well-being of mind and body, even our four dogs! Really! Recipes are just blooming (will share some soon-chef in the family-even making dog foods and treats) making new dishes, beverages, snacks, and now even our own condiments! In one week – yes, it can be done! Now I must ask if the ingredients mentioned in Chapter 3 can be eliminated completely, as even our communion elements at Church Services are tainted … this is just a crime! What, and where can one go for the household and personal items which are free of these Glutenous and GMO toxins and hazards? Does anyone have experience with these issues just yet and know where to purchase trusted products from responsible manufacturers? We have been on a search and have found that even lip balms, vitamins, personal care products – just everything are pretty much infested and tainted … all garbage! We’re a bit perplexed but want to go all the way with this. Any help or advice will be greatly appreciated and we will reciprocate absolutely everything and anything that we find helpful as well.

    • David Perlmutter

      I’m so glad to hear of the success your family is experiencing, and I’m glad you came to this community with your questions. The individuals here are a great resource.

    • Alyssa

      Coconut oil is a great skin moisturizer. You can even mix it with 100% essential oils for a natural deodorant (not antiperspirant). I like Shea Moisture hair and lotion products. All natural and even organic ingredients. You can find them at Target, Walgreens, etc. Read the labels, nothing questionable in them.

      • BetterCakesByDesign

        Hi, thanks so much! We just found, this morning as a matter of fact, the many resources on the Celiac Disease Foundation website and the Gluten Free Resource Directory. Would you like to know something VERY shocking we just were given information on? GMO foods … our nations’s food supply is at risk, our family’s are at risk, our future as a nation is at risk. I have taken the last several days off researching the horrors of the diseases, toxins, the poisons we have been sold to consume as safe … just horrible facts on the GMO scams going on with the food growers and farmers, suppliers, USDA, FDA … these are the very people we pay, we elect to help set policies to protect us. This is a crime against every American, every citizen on this planet, including the planet we live -which is the only one we have! I have now made this issue my mission and have actually left my previous employ to help get this major, major health issue and concern to everyone, actually ANYONE who will listen. It saddens me to see how our country has been hijacked by the corruption, lies, deceit, thieves, politicians and, yes – I am going to call it attempted murderers and MURDERERS of our way of life, our families and planet! We all as Americans MUST wake up and stand up to this outrageous and blatant corruption that has been going on for so long. Thanks for letting me rant, but it IS SO IMPORTANT we get everyone on-board to say NO GMO, NO GLUTEN and NO HAZARDS, TOXINS AND POISONS ON OUR PLATES! I am rounding EVERY SINGLE product that is infected and poisoned and taking them back to the stores that sold them, demand my money back and let them trash the returns to lose money. They DO have a satisfaction guarantee, SO I’M USING IT and TAKING ADVANTAGE OF THEM FOR ONCE. PLEASE EVERYONE, DO THE SAME AND LET’S HAVE OUR VOICE HEARD! Thanks again. I’ll be posting some of the many safe and healthful recipes I have been writing over the last couple of days for everyone. Thanks again.

        • BetterCakesByDesign

          We encourage everyone to look up on YouTube: 1) Genetic Roulette The Gamble Of Our Lives. 2) SPECIAL REPORT- What’s in Your Food. 3) ANY report on GMO foods and supplies, organic eating and gluten free diets. IF we all say no, they will not sell it because there will be no buyers, no profits, they will have to listen if they want to stay in business.

        • Getittoo

          Calm down. I get it, but really…..
          Take a breath, slow and steady progress. Easy does it.

          • BetterCakesByDesign

            Yes, sure … You’re right … of course. Let’s all just stop and take a breath, and very slowly continue to kill our families with the lies and corruption of the government and big business in the name of making a buck! We’ll all “easy does it” to death … while choking down the garbage they continue to tell us is safe, all the while …. whatever dude. “We The Sheeple” …

      • Nanrunner

        Just use a fresh lime for deodorant! No need to make a mixture of anything! Use one small lime for several days…just know which one it is in the refrigerator. 🙂 After a couple days, I slice off the exposed end for a fresh “applicator”. REALLY works!! (And I’m a runner!)

    • Katherine Chapman Colbert

      Gluten free communion wafers can be purchased from the Benedictine Sisters of Perpetual Adoration in Clyde Missouri.

  • Otto Janke, DC

    One of my two favorite words: Epigenetics, and Neuroplasticity. Keep the good stuff coming.

  • Catherine Mikkola

    I very much enjoyed Grain Brain. My family was already eating gluten-free and I found the book an encouragement to keep on keeping on. 🙂

    My question is, what would the results be of eating gluten-free, using healthy saturate fats, like coconut oil, animal fats, etc, but also eating grains like quinoa? I’m wondering if the problem with “high carb” diets could have more to do with the “low fat” part of those diets, and less to do with the carbs, as long as one stays away from gluten? Has anyone studied a high-fat, gluten-free, moderate-carb diet?


    • David Perlmutter

      A very fair question Catherine. If folks want to enjoy non-gluten grains like rice or quinoa, I do allow for consumption of those, but in strict moderation.

      • BetterCakesByDesign

        Is Buckwheat acceptable (in moderation of course) as it is not actually wheat, but a grain …. as long as it is 100% Organic and Non-GMO of course!

        • David Perlmutter

          Another gluten-free grain that could be consumed in strict moderation.

  • Gale

    I’ve been enjoying a fruit smoothie in the afternoon made from 1/4 cup orange juice, 1/4 cup unsweetened almond milk, a few frozen peaches slices and/or mangos, a half banana and a couple ice cubes smoothed in a Vitamix. Is this too much sugar to be having on an almost daily basis? Other than that, I’ve been following the gluten free diet, and am also lactose free. I eat mostly protein, veggies, and a glass of wine each day. Thoughts?

  • DrC

    May I be so bold to suggest (as others have done before me) that the debate that “overweight people are less intelligent” (paraphrased version) holds truth. If poor diet also influences our DNA.then it would explain a decline in brain function as weight increases. Dr Perlumutter, I am a huge fan of your work!

  • Stephan

    Fascinating article and nice to see that your son(?) is following in your footsteps.

    • David Perlmutter


  • JaneGrace Bowman

    I love your book. I am a retired RN, and I am always on the search for cutting edge nutritional research and information. Your book is changing my life and those around me. I sent several books to friends and family because I feel it is one of the most important and up to date books on health. It is horrifying to read the truth and research and knowing what the public is exposed to in terms of carbohydrates, synthetic vitamins and GMO. Thank you for this book.

    The one rub is the resveratrol. We know it is found in red wine. However the amount one would have to drink in order to get a therapeutic dose is beyond anyone’s ability (as I understand it). Besides, wine is metabolized into sugar. Can you speak to this? Thank you again.

    • David Perlmutter

      I do suggest that people look to a resveratrol supplement.

  • BetterCakesByDesign

    We are professional chefs 30+ years, NO longer making cakes & pastries, but now good, healthy meals, 100% Organic, NoGMO, sugars, gluten and junk. Will help you re-invent YOUR old favorite recipes free, no charge. Same name, att gmail at the end, contact us and we will be glad to help.

  • Wayne

    Dr. Perlmutter,
    I have been low carb/ high fat for over 5
    months now, due to reading Grain Brain. I am 25 y/o and have a
    hereditary condition known as Charcot-Marie-Tooth (CMT) that, as I
    understand it, is a neurological disorder that may be linked to issues
    with the myelin sheath; hence the reason for starting the diet. Grain
    Brain notes that cholesterol aids in the repair of the myelin sheath
    (forgive me if I misquote) and that carbs oxidize cholesterol basically
    rendering it useless. I figure that, in theory, the diet would
    seemingly aid my familie’s condition to improvement, but how effective
    can it be with something that one is born with? And if effective, how
    long could one expect to see any minor improvements? I have not been to
    a neurologist since I was a child, but I know that the only recommended
    treatment is surgery that I would rather avoid, or possibly a sort of
    stem cell treatment as a hopeful last resort. I am currently in the
    earlier stages of the condition, but have noticed it worsening in my
    lower limbs over the last 2 yrs or so; however, I am mostly concerned
    about how this diet may aid my children in the case that they may be
    diagnosed with CMT in the future. In any case, all the best!

    Thank you very kindly,

  • Vahe

    Hey does anyone know if eating fat with sweet foods like honey or carbs like potatoes reduce the effect it has on raising the average blood sugar?
    I tested 5.4 and I want to retest in 3 months to bring it down wondering if I can have the odd bit of honey with sour cream or maybe some fermented dairy which has fat with carbs and sugar wondering if the dairy and the bit of honey will compromise my effort.

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