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.

Trackback from your site.

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

Leave a comment

Recent Videos From Dr. Steve Chaney

READ THE ARTICLE
READ THE ARTICLE

Latest Article

A Low Carb Diet and Weight Loss

Posted January 15, 2019 by Dr. Steve Chaney

Do Low-Carb Diets Help Maintain Weight Loss?

Author: Dr. Stephen Chaney

 

low carb dietTraditional diets have been based on counting calories, but are all calories equal? Low-carb enthusiasts have long claimed that diets high in sugar and refined carbs cause obesity. Their hypothesis is based on the fact that high blood sugar levels cause a spike in insulin levels, and insulin promotes fat storage.

The problem is that there has been scant evidence to support that hypothesis. In fact, a recent meta-analysis of 32 published clinical studies (KD Hall and J Guo, Gastroenterology, 152: 1718-1727, 2017 ) concluded that low-fat diets resulted in a higher metabolic rate and greater fat loss than isocaloric low-carbohydrate diets.

However, low-carb enthusiasts persisted. They argued that the studies included in the meta-analysis were too short to adequately measure the metabolic effects of a low-carb diet. Recently, a study has been published in the British Medical Journal (CB Ebbeling et al, BMJ 2018, 363:k4583 ) that appears to vindicate their position.

Are low carb diets best for long term weight loss?

Low-carb enthusiasts claim the study conclusively shows that low-carb diets are best for losing weight and for keeping it off once you have lost it. They are saying that it is time to shift away from counting calories and from promoting low-fat diets and focus on low-carb diets instead if we wish to solve the obesity epidemic. In this article I will focus on three issues:

  • How good was the study?
  • What were its limitations?
  • Are the claims justified?

 

How Was The Study Designed?

low carb diet studyThe investigators started with 234 overweight adults (30% male, 78% white, average age 40, BMI 32) recruited from the campus of Framingham State University in Massachusetts. All participants were put on a diet that restricted calories to 60% of estimated needs for 10 weeks. The diet consisted of 45% of calories from carbohydrate, 30% from fat, and 25% from protein. [So much for the claim that the study showed low-carb diets were more effective for weight loss. The diet used for the weight loss portion of the diet was not low-carb.]

During the initial phase of the study 161 of the participants achieved 10% weight loss. These participants were randomly divided into 3 groups for the weight maintenance phase of the study.

  • The diet composition of the high-carb group was 60% carbohydrate, 20% fat, and 20% protein.
  • The diet composition of the moderate-carb group was 40% carbohydrate, 40% fat, and 20% protein.
  • The diet composition of the low-carb group was 20% carbohydrate, 60% fat, and 20% protein.

Other important characteristics of the study were:

  • The weight maintenance portion of the study lasted 5 months – much longer than any previous study.
  • All meals were designed by dietitians and prepared by a commercial food service. The meals were either served in a cafeteria or packaged to be taken home by the participants.
  • The caloric content of the meals was individually adjusted on a weekly basis so that weight was kept within a ± 4-pound range during the 5-month maintenance phase.
  • Sugar, saturated fat, and sodium were limited and kept relatively constant among the 3 diets.

120 participants made it through the 5-month maintenance phase.

 

Do Low-Carb Diets Help Maintain Weight Loss?

low carb diet maintain weight lossThe results were striking:

  • The low-carb group burned an additional 278 calories/day compared to the high-carb group and 131 calories/day more than the moderate-carbohydrate group.
  • These differences were even higher for those individuals with higher insulin secretion at the beginning of the maintenance phase of the study.
  • These differences lead the authors to hypothesize that low-carb diets might be more effective for weight maintenance than other diets.

 

What Are The Pros And Cons Of This Study?

low carb diet pros and consThis was a very well-done study. In fact, it is the most ambitious and well-controlled study of its kind. However, like any other clinical study, it has its limitations. It also needs to be repeated.

The pros of the study are obvious. It was a long study and the dietary intake of the participants was tightly controlled.

As for cons, here are the three limitations of the study listed by the authors:

#1: Potential Measurement Error: This section of the paper was a highly technical consideration of the method used to measure energy expenditure. Suffice it to say that the method they used to measure calories burned per day may overestimate calories burned in the low-carb group. That, of course, would invalidate the major findings of the study. It is unlikely, but it is why the study needs to be repeated using a different measure of energy expenditure.

#2: Compliance: Although the participants were provided with all their meals, there was no way of being sure they ate them. There was also no way of knowing whether they may have eaten other foods in addition to the food they were provided. Again, this is unlikely, but cannot be eliminated from consideration.

#3: Generalizability: This is simply an acknowledgement that the greatest strength of this study is also its greatest weakness. The authors acknowledged that their study was conducted in such a tightly controlled manner it is difficult to translate their findings to the real world. For example:

  • Sugar and saturated fat were restricted and were at very similar levels in all 3 diets. In the real world, people consuming a high-carb diet are likely to consume more sugar than people in the other diet groups. Similarly, people consuming the low-carb diet are likely to consume more saturated fat than people in the other diet groups.
  • Weight was kept constant in the weight maintenance phase by constantly adjusting caloric intake. Unfortunately, this seldom happens in the real world. Most people gain weight once they go off their diet – and this is just as true with low-carb diets as with other diets.
  • The participants had access to dietitian-designed prepared meals 3 times a day for 5 months. This almost never happens in the real world. The authors said “…these results [their data] must be reconciled with the long-term weight loss trials relying on nutrition education and behavioral counseling that find only a small advantage for low carbohydrate compared with low fat diets according to several recent meta-analyses.” [I would add that in the real world, people do not even have access to nutritional education and behavioral modification.]

 

low carb diet and youWhat Does This Study Mean For You?

  • This study shows that under very tightly controlled conditions (dietitian-prepared meals, sugar and saturated fat limited to healthy levels, calories continually adjusted so that weight remains constant) a low-carb diet burns more calories per day than a moderate-carb or high-carb diet. These findings show that it is theoretically possible to increase your metabolic weight and successfully maintain a healthy weight on a low-carb diet. These are the headlines you probably saw. However, a careful reading of the study provides a much more nuanced viewpoint. For example, the fact that the study conditions were so tightly controlled makes it difficult to translate these findings to the real world.
  • In fact, the authors of the study acknowledged that multiple clinical studies show this almost never happens in the real world. These studies show that most people regain the weight they have lost on low-carb diets. More importantly, the rate of weight regain is virtually identical on low-carb and low-fat diets. Consequently, the authors of the current study concluded “…translation [of their results to the real world] requires exploration in future mechanistic oriented research.” Simply put, the authors are saying that more research is needed to provide a mechanistic explanation for this discrepancy before one can make recommendations that are relevant to weight loss and weight maintenance in the real world.
  • The authors also discussed the results of their study in light of a recent, well-designed 12-month study (CD Gardener et al, JAMA, 319: 667-669, 2018 ) that showed no difference in weight change between a healthy low-fat versus a healthy low-carbohydrate diet. That study also reported that the results were unaffected by insulin secretion at baseline. The authors of the current study noted that “…[in the previous study] participants were instructed to minimize or eliminate refined grains and added sugars and maximize intake of vegetables. Probably for this reason, the reported glycemic load [effect of the diet on blood sugar levels] of the low-fat diet was very low…and similar to [the low-carb diet].” In short, the authors of the current study were acknowledging that diets which focus on healthy, plant-based carbohydrates and eliminate sugar, refined grains, and processed foods may be as effective as low-carb diets for helping maintain a healthy weight.
  • This would also be consistent with previous studies showing that primarily plant-based, low-carb diets are more effective at maintaining a healthy weight and better health outcomes long-term than the typical American version of the low-fat diet, which is high in sugar and refined grains. In contrast, meat-based, low-carb diets are no more effective than the American version of the low-fat diet at preventing weight gain and poor health outcomes. I have covered these studies in detail in my book “Slaying The Food Myths.”

Consequently, the lead author of the most recent study has said: “The findings [of this study] do not impugn whole fruits, beans and other unprocessed carbohydrates. Rather, the study suggests that reducing foods with added sugar, flour, and other refined carbohydrates could help people maintain weight loss….” This is something we all can agree on, but strangely this is not reflected in the headlines you may have seen in the media.

The Bottom Line

 

  • A recent study compared the calories burned per day on a low-carb, moderate-carb, and high-carb diet. The study concluded that the low-carb diet burned significantly more calories per day than the other two diets and might be suitable for long-term weight control. If confirmed by subsequent studies, this would be the first real evidence that low-carb diets are superior for maintaining a healthy weight.
  • However, the study has some major limitations. For example, it used a methodology that may overestimate the benefits of a low-carb diet, and it was performed under tightly controlled conditions that can never be duplicated in the real world. As acknowledged by the authors, this study is also contradicted by multiple previous studies. Further studies will be required to confirm the results of this study and show how it can be applied in the real world.
  • In addition, the kind of carbohydrate in the diet is every bit as important as the amount of carbohydrate. The authors acknowledge that the differences seen in their study apply mainly to carbohydrates from sugar, refined grains, and processed foods. They advocate diets with low glycemic load (small effects on blood sugar and insulin levels) and acknowledge this can also be achieved by incorporating low-glycemic load, plant-based carbohydrates into your diet. This is something we all can agree on, but strangely this is not reflected in the headlines you may have seen in the media.
  • Finally, clinical studies report averages, but none of us are average. When you examine the data from the current study, it is evident that some participants burned more calories per hour on the high-carb diet than other participants did on the low carb diet. That reinforces the observation that some people lose weight more effectively on low-carb diets while others lose weight more effectively on low-fat diets. If you are someone who does better on a low-carb diet, the best available evidence suggests you will have better long-term health outcomes on a primarily plant-based, low-carb diet such as the low-carb version of the Mediterranean diet.

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.

UA-43257393-1