What Is Epigenetics

Written by Dr. Steve Chaney on . Posted in current health articles, Food and Health, Nutritiion, Obesity

Can What We Eat Affect Our Kids?

Author: Dr. Stephen Chaney

 

what is epigeneticsWhat is epigenetics?  For me, the first stages of understanding came a while back.  When I was a young graduate student (which is more than just a few years ago), I was taught that all genetic information resided in our DNA. During conception, we picked up some DNA from our dad and some from our mom, and that DNA was what made us a unique individual.

We knew that environmental influences such as diet, lifestyle and exposure to toxic chemicals could affect our health personally. However, we never dreamed that the effects of those environmental influences could actually alter our gene expression, and that those genetic alterations could be passed on to our children.

Today we know that environmental influences can actually modify our DNA and that those modifications can be passed on to our offspring – a process called epigenetics.

What Is Epigenetics & How Does It Affect Gene Expression?

Simply put, epigenetics involves modifications to our DNA. DNA can be methylated or acetylated and the proteins that bind to our DNA can be modified in multiple ways. That is important for two reasons:

  • These alterations can turn genes on and off. That means that epigenetic modifications can alter gene expression.
  • These alterations can be influenced by our environment – diet, lifestyle, and exposure to environmental chemicals

In a previous “Health Tips From the Professor” article titled “Can Diet Alter Your Genetic Destiny?”  I discussed recent research suggesting that a healthy diet and lifestyle causes epigenetic changes in the DNA that may reduce your risk of heart disease, cancer and diabetes.

That alone was a monumental discovery. Even more monumental is the recent discovery that at least some of those epigenetic changes can be passed on to our children, which brings me to the question I posed in the title of this article: “Can what we eat affect our kids?”

Animal Studies Showing That Epigenetic Changes Can Be Inherited

epigenetic changes are inheritedAs is often the case, the first definitive study showed that epigenetic changes were heritable was an animal study. This study was done with a mouse strain called agouti (Waterman and Jirtle, Mol. Cell. Biol. 23: 5193 – 5300, 2003). Agouti mice can have two remarkably distinctive phenotypes. They can either have a yellow coat, become obese as adults and be prone to cancer and diabetes as they age or they can have a brown coat and grow up to be lean and healthy.

It had been known for some time that these phenotypic differences were controlled by the epigenetic methylation of a specific gene called the agouti gene. The agouti gene codes for a genetic regulator that controls coat color, feeding behavior, and body weight set-point, among other things. When the agouti gene is under methylated it is active. As a consequence the mice have yellow coats and are prone to obesity. When the agouti gene is highly methylated it is inactive. The mice have brown coats and are lean and healthy.

Moreover, methylation of the agouti gene is not a purely random event. Mothers with the yellow, obese phenotype tended to produce a preponderance of offspring with the same phenotype and vice-versa. In short, the epigenetic methylation pattern of the agouti gene could be passed from generation to generation. It was heritable.

Waterman and Jirtle’s research broke new ground by showing that the methylation of the agouti gene could be strongly influenced by what the mother ate while the fetal mice were still in the womb.

When they fed agouti mothers a diet with extra folic acid, B12, betaine and choline (all nutrients that favor DNA methylation) during conception and pregnancy the agouti gene of their offspring became highly methylated. A high percentage of those offspring had brown coats and grew up to be lean and healthy.

However, when Waterman and Jirtle put agouti mothers on a diet that was deficient in folic acid, B12, betaine and choline during conception and pregnancy the agouti gene of their offspring was under methylated. Many of those offspring had yellow coats and grew up to be fat and unhealthy.

Subsequent studies from the same laboratory have shown that:

  • Addition of genistein, a phytonutrient from soy, to the maternal diet also favors methylation of the agouti gene and protects against obesity in agouti mice (Dolinoy et al, Environmental Health Perspective, 114: 567-572, 2006).
  • The addition of the environmental toxin bisphenol A to maternal diets causes under methylation of the agouti gene and predisposes to obesity in agouti mice, but this effect can be reversed by also feeding the mother genistein or folic acid and related nutrients during pregnancy (Dolinoy et al, PNAS, 13056-13061, 2007).

The agouti mice studies provide a dramatic example of how diet and environmental exposure during pregnancy can cause epigenetic changes in fetal DNA that have long term health consequences for the offspring. However, they are animal studies. Does the same hold true for humans?

Diet, Epigenetic Changes, and Obesity in Humans

diet-epigenetic-changes-obesityWith humans, it is really difficult to determine whether epigenetic changes that occur during conception and pregnancy affect our children. That is because when you measure an epigenetic effect in a child or adult, it is difficult to sort out how much of that effect was caused by what the mom ate during pregnancy and how much was caused by how the family ate as the kids were growing up.

Unfortunately, there is a tragic human experiment that shows that the same kind of epigenetic changes are heritable in humans. I’m referring to what is known as the “Dutch Hunger Winter”. This was a period of starvation during 1944-1945, the final year of World War II, when the Germans set up a blockade that prevented food from reaching western Holland. During that few months even pregnant women were forced to live on food rations providing a little as 500 calories a day.

This was an event without parallel in human history. Holland is not a third world country. Once the blockade was lifted children born during the Hunger Winter had the same plentiful supply of food as every other Dutch citizen. This has allowed generations of research scientists to ask what were the effects of a brief exposure to malnutrition during conception and pregnancy.

The health consequences were dramatic. 50 years later individuals who were conceived during the Hunger Winter weighed about 14 pounds more, had waists about 1.5 “ larger, and were three times more likely to have heart disease than those born to mothers who were in their second or third trimester of pregnancy during that time. By the time they reached age 63, they experienced a 10% increase in mortality.

What caused those health consequences? Could the cause have been epigenetic? Recent research suggests that the answer might be yes.

A recent study analyzed epigenetic changes in DNA from blood samples of survivors born during the Hunger Winter that had been collected when they were 59 years old (Tobi et al, Int. J. Epidemiology, doi: 10.1093/ije/dyv043, 2015). This study showed:

  • A distinct pattern of DNA methylation was observed in survivors who were conceived during the Hunger Winter. This pattern of DNA methylation was not observed in survivors who were in their second or third trimester during the Hunger Winter. It was also not seen in people who were conceived immediately before or after the Hunger Winter.
  • Some of the genes with distinctive methylation patterns were genes that affected things like cholesterol levels and insulin sensitivity, which have the potential to increase disease risk.
  • Other genes with distinctive methylation patterns were genes that affected metabolism. They were “thrifty” genes that increased the efficiency of metabolism. Increased efficiency of metabolism is beneficial when calories are scarce, but can lead to obesity when calories are plentiful.

That is a truly remarkable finding when you think about it. If these data are true, they suggest that starvation during early pregnancy caused the fetus to make epigenetic changes to its DNA that allowed it to become more efficient at energy utilization, and those epigenetic changes have lasted a lifetime – even when food was abundant throughout the rest of that lifetime.

What Is Epigenetics And Can What We Eat Affect Our Kids?

can what we eat affect our kidsThe studies I featured in this article are powerful “proof of concept” that diet and environmental exposure during conception and pregnancy can result in epigenetic changes to the DNA of the offspring that can persist throughout their life and dramatically affect their health. However, it is not yet clear how they apply to you and me.

  • Agouti mice are a very special strain of mice. It is not yet clear what effect folic acid, genistein and bisphenol A have on epigenetic modification of specific human genes, and whether those epigenetic modifications will have health consequences in humans.
  • The specific circumstances of the Dutch Hunger Winter are unlikely to be repeated on any significant scale. The closest approximation I can envision would be a woman who becomes pregnant while on a very low calorie fad diet.

There are, of course, many other examples of heritable epigenetic modifications. For example:

  • When female rats are maintained on a “junk-food diet” high in fat and sugar during pregnancy and lactation their offspring show a marked preference for high fat foods (Ong & Muhlhausler, FASB J, 25: 2167-2179, 2011). They also show epigenetic alterations of the central reward pathways that may pre-condition them to require higher intakes of fat to experience pleasure from eating.
  • When rats are fed diets deficient in omega-3 fatty acids, adolescent rats from the second and subsequent generations display marked increases in hyperactivity and anxiety (For more details, see my “Health Tips from the Professor” article titled “The Seventh Generation Revisited”.
  • In a clinical trial of 162 obese Canadian mothers who had children before and after weight loss surgery, the children born after weight loss surgery were half as likely to grow up overweight or obese as the children born before the weight loss surgery (Smith et al, Journal of Clinical Endocrinology & Metabolism 94: 4275-4283, 2009), and this correlated with epigenetic modification of genes that play a role in obesity, diabetes, cancer and heart disease (Guernard et al, PNAS 110: 11439-11443, 2013).

Taken together, the existing data suggest that our diet and environmental exposure during conception and pregnancy can cause epigenetic changes to our children’s DNA that may affect their future health in ways that we can only begin to understand at present. It is a sobering thought.

 

The Bottom Line

 

  • The term epigenetics describes modifications to our DNA that turn our genes off and on.
  • In this article I discussed two powerful “proof of concept” studies, one in rats and the other in humans, showing that diet and environmental exposure during conception and pregnancy can result in epigenetic changes to the DNA of the offspring that can persist throughout their life and dramatically affect their health.
  • The health consequences of these epigenetic modifications include obesity, diabetes, cancer, heart disease, hyperactivity, anxiety and many more.
  • This is a new paradigm. Most prenatal nutrition advice is currently based on what it takes to have a healthy baby – not on what it might take for your child to experience better health throughout their life.
  • Of course, the science of epigenetics is relatively new. It will be many years before we will be able to make specific recommendations as to what your diet should be like during pregnancy and lactation if you wish to make beneficial modifications to your baby’s DNA.
  • However, you should be aware that what you eat during pregnancy & lactation may influence the health of your children – not just at the time of their birth – but throughout their life, and that a high calorie, “junk-food” diet or a fad weight loss diet just may not be your best choice.

*The agouti mice picture is by Randy Jirtle and Dana Dolinoy (E-mailed by author) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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Comments (1)

  • Mary Butler

    |

    I have long wondered why a beautiful, gifted mom and wife of 5 gifted children, is morbidly obese. She is in her 40’s and struggling for life from cancer. Doctors have given up on her…..so very tragic! This may be the answer, her mom is also morbidly obese. Her one sibling is moderately overweight. Thank you for all you do.

    Reply

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Latest Article

Should We Use Supplements For Cardiovascular Health?

Posted July 10, 2018 by Dr. Steve Chaney

Are You Just Wasting Your Money On Supplements?

Author: Dr. Stephen Chaney

 

supplements for cardiovascular health wast moneyYou’ve seen the headlines. “Recent Study Finds Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.”  You are being told that supplements are of no benefit to you. They are a waste of money. You should follow a healthy diet instead. Is all of this true?

If I were like most bloggers, I would give you a simple yes or no answer that would be only partially correct. Instead, I am going to put the study behind these headlines into perspective. I am going to give you a deeper understanding of supplementation, so you can make better choices for your health.

 Should we use supplements for cardiovascular health?

In today’s article I will give you a brief overview of the subject. Here are the topics I will cover today:

  • Is this fake news?
  • Did the study ask the right questions?
  • Is this a question of “Garbage In – Garbage Out?
  • Reducing Heart Disease Risk. What you need to know.

All these topics are covered in much more detail (with references) in my book “Slaying The Supplement Myths”, which will be published this fall.

 

How Was This Study Done?

supplements for cardiovascular healthThis study (D.J.A. Jenkins et al, Journal of the American College Of Cardiology, 71: 2540-2584, 2018 ) was a meta-analysis. Simply put, that means the authors combined the results of many previous studies into a single database to increase the statistical power of their conclusions. This study included 127 randomized control trials published between 2012 and December 2017. These were all studies that included supplementation and looked at cardiovascular end points, cancer end points or overall mortality.

Before looking at the results, it is instructive to look at the strengths and weaknesses of the study. Rather than giving you my interpretation, let me summarize what the authors said about strengths and weaknesses of their own study.

The strengths are obvious. Randomized control trials are considered the gold standard of evidence-based medicine, but they have their weaknesses. Here is what the authors said about the limitations of their study:

  • “Randomized control trials are of shorter duration, whereas longer duration studies might be required to fully capture chronic disease risk.”
  • “Dose-response data were not usually available [from the randomized control studies included in their analysis]. However, larger studies would allow the effect of dose to be assessed.”

There are some other limitations of this study, which I will point out below.

Is This Fake News?

supplements for cardiovascular health fake newsWhen I talk about “fake news” I am referring to the headlines, not to the study behind the headlines. The headlines were definitive: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” However, when you read the study the reality is quite different:

  • In contrast to the negative headlines, the study reported:
    • Folic acid supplementation decreased stroke risk by 20% and overall heart disease risk by 17%.
    • B complex supplements containing folic acid, B6, and B12 decreased stroke risk by 10%.
    • That’s a big deal, but somehow the headlines forgot to mention it.
  • The supplements that had no significant effect on heart disease risk (multivitamins, vitamin D, calcium, and vitamin C) were ones that would not be expected to lower heart disease risk. There was little evidence from previous studies of decreased risk. Furthermore, there is no plausible mechanism for supposing they might decrease heart disease risk.
  • The study did not include vitamin E or omega-3 supplements, which are the ones most likely to prove effective in decreasing heart disease risk when the studies are done properly (see below).

Did The Study Ask The Right Question?

Most of the studies included in this meta-analysis were asking whether a supplement decreased heart disease risk or mortality for everyone. Simply put, the studies started with a group of generally healthy Americans and asked whether supplementation had a significant effect on disease risk for everyone in that population.

That is the wrong question. We should not expect supplementation to benefit everyone equally. Instead, we should be asking who is most likely to benefit from supplementation and design our clinical studies to test whether those people benefit from supplementation.

supplements for cardiovascular health diagramI have created the graphic on the right as a guide to help answer the question of “Who is most likely to benefit from supplementation?”. Let me summarize each of the points using folic acid as the example.

 

Poor Diet: It only makes sense that those people who are deficient in folate from foods are the most likely to benefit from folic acid supplementation. Think about it for a minute. Would you really expect people who are already getting plenty of folate from their diet to obtain additional benefits from folic acid supplementation?

The NIH estimates that around 20% of US women of childbearing age are deficient in folic acid. For other segments of our population, dietary folate insufficiency ranges from 5-10%. Yet, most studies of folic acid supplementation lump everyone together – even though 80-95% of the US population is already getting enough folate through foods, food fortification, and supplementation. It is no wonder most studies fail to find a beneficial effect of folic acid supplementation.

The authors of the meta-analysis I discussed above said that the beneficial effects of folic acid they saw might have been influenced by a very large Chinese study, because a much higher percentage of Chinese are deficient in folic acid. They went on to say that the Chinese study needed to be repeated in this country.

In fact, the US study has already been done. A large study called “The Heart Outcomes Prevention Evaluation (HOPE)” study reported that folic acid supplementation did not reduce heart disease risk in the whole population. However, when the study focused on the subgroup of subjects who were folate-deficient at the beginning of the study, folic acid supplementation significantly decreased their risk of heart attack and cardiovascular death.  This would seem to suggest using supplements for cardiovascular health is a good idea.

Increased Need: There are many factors that increase the need for certain nutrients. However, for the sake of simplicity, let’s only focus on medications. Medications that interfere with folic acid metabolism include anticonvulsants, metformin (used to treat diabetes), methotrexate and sulfasalazine (used to treat severe inflammation), birth control pills, and some diuretics. Use of these medications is not a concern when the diet is adequate. However, when you combine medication use with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial.

Genetic Predisposition: The best known genetic defect affecting folic acid metabolism is MTHFR. MTHFR deficiency does not mean you have a specific need for methylfolate. However, it does increase your need for folic acid. Again, this is not a concern when the diet is adequate. However, when you combine MTHFR deficiency with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial. I cover this topic in great detail in my upcoming book, “Slaying The Supplement Myths”. In the meantime, you might wish to view my video, “The Truth About Methyl Folate.”

Diseases: An underlying disease or predisposition to disease often increases the need for one or more nutrients that help reduce disease risk. The best examples of this are two major studies on the effect of vitamin E on heart disease risk in women. Both studies found no effect of vitamin E on heart disease risk in the whole population. However, one study reported that vitamin E reduced heart disease risk in the subgroup of women who were post-menopausal (when the risk of heart disease skyrockets). The other study found that vitamin E reduced heart attack risk in the subgroup of women who had pre-existing heart disease at the beginning of the study.

Finally, if you look at the diagram closely, you will notice a red circle in the middle. When two or three of these factors overlap, that is the “sweet spot” where supplementation is almost certain to make a difference and it may be a good idea to use supplements for cardiovascular health.

Is This A Question Of “Garbage In, Garbage Out”?

supplements for cardiovascular health garbage in outUnfortunately, most clinical studies focus on the “Does everyone benefit from supplementation question?” rather than the “Who benefits from supplementation?” question.

In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.

Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.

 

Should We Use Supplements For Cardiovascular Health?

 

If you want to know whether supplements decrease heart disease risk for everyone, this meta-analysis is clear. Folic acid may decrease the risk of stroke and heart disease. A B complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but the analysis did not include vitamin E and/or omega-3s.

However, if you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.

I would be remiss, however, if I failed to point out that we know healthy diets can decrease heart disease risk. In the words of the authors: “The recent science-based report of the U.S. Dietary Guidelines Advisory Committee, also concerned with [heart disease] risk reduction, recommended 3 dietary patterns: 1) a healthy American diet low in saturated fat, trans fat, and meat, but high in fruits and vegetables; 2) a Mediterranean diet; and 3) a vegetarian diet. These diets, with their accompanying recommendations, continue the move towards more plant-based diets…” I cover the effect of diet on heart disease risk in detail in my book, “Slaying The Food Myths”.

 

The Bottom Line

 

You have probably seen the recent headlines proclaiming: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” The study behind the headlines was a meta-analysis of 127 randomized control trials looking at the effect of supplementation on heart disease risk and mortality.

  • The headlines qualify as “fake news” because:
    • The study found that folic acid decreased stroke and heart disease risk, and B vitamins decreased stroke risk. Somehow the headlines forgot to mention that.
    • The study found that multivitamins, vitamin D, calcium, and vitamin C had no effect on heart disease risk. These are nutrients that were unlikely to decrease heart disease risk to begin with.
    • The study did not include vitamin E and omega-3s. These are nutrients that are likely to decrease heart disease risk when the studies are done properly.
  • The authors of the study stated that a major weakness of their study was that that randomized control studies included in their analysis were short term, whereas longer duration studies might be required to fully capture chronic disease risk.
  • The study behind the headlines is of little use for you as an individual because it asked the wrong question.
  • Most clinical studies focus on the “Does everyone benefit from supplementation question?” That is the wrong question. Instead we need more clinical studies focused on the “Who benefits from supplementation?” question. I discuss that question in more detail in the article above.
  • In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.
  • Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.
  • If you want to know whether supplements decrease heart disease risk for everyone, this study is clear. Folic acid may decrease the risk of stroke and heart disease. A B-complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but they did not include vitamin E and/or omega-3s in their analysis.
  • If you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.
  • However, we do know that healthy, plant-based diets can decrease heart disease risk. I cover heart healthy diets in detail in my book, “Slaying The Food Myths.”

 

For more details, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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