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Do Bad Genes Doom You To Bad Health?

October 1, 2024 by Dr. Steve Chaney

The Influence Of Genetics And Diet On Type 2 Diabetes

Author: Dr. Stephen Chaney

Does it ever feel like you have drawn the short straw?

Everyone in your family has succumbed to heart disease, diabetes, or cancer at a young age. Are you doomed to the same fate?

You ordered a DNA test. It sounded like fun. But when the gene report came back it said you had a “bad” genetic profile. You were told you are at high risk of diabetes, heart attack, stroke, cancer, or dementia. Are you doomed to a short and sickly life?

In both cases, you are probably wondering, “Is there anything I can do to improve my odds of a healthy life? What if I lost some of those extra pounds, exercised more, and ate a healthier diet? Would that make a difference?”

The study (J Merino et al, PLoS Medicine 19(4): e1003972, April 26, 2022) I will describe today was designed to answer these questions.

But before I describe the study, I should probably cover what I call Genetics 101: “How Genes Affect Your Health”.

Genetics 101: How Genes Affect Your Health

If you studied genetics in school, you probably learned about diseases like sickle cell anemia, which is caused by a single mutation in a single gene. If you get two copies of the “bad” gene, you will have sickle cell anemia. If you get one copy of the “bad” gene and one copy of the normal gene, you have sickle cell trait, which is much less severe.

Simply put, you either have the disease or you don’t. It’s dependent on your genetics, and you can’t do much about it.

If you know someone who has been treated for breast cancer, you are probably familiar with a more complex relationship between genetics and health. There are several “bad” genes that increase the risk of breast cancer. And knowing which gene is involved is important for selecting the best treatment regimen.

But most of the diseases that shorten our lives (like diabetes, heart disease, most cancers, and dementia) are what we call polygenetic diseases. Simply put, that means that there are dozens of genes that increase the risk of these diseases. Each gene makes a small contribution to the increased risk. So, we can only measure the genetic contribution to these diseases by measuring hundreds of mutations in dozens of genes, something called a polygenetic risk score.

The study I will be describing today looked at the relative effect of genetics (measured as the type 2 diabetes polygenic risk score) and diet quality (measured as the Alternative Healthy Eating Index (AHEI)) on the risk of developing type 2 diabetes.

How Was This Study Done?

The data for this study were obtained from 3 long-term clinical studies conducted in the United States – the Nurses’ Health Study (121,700 participants), the Nurses’ Health Study II (116,340 participants), and the Health Professionals Follow-Up Study (51,529 participants).

These studies measured lifestyle factors (including diet) every 4 years and correlated them with disease outcomes over 20+ years.

The study I will be discussing today was performed with 35,759 participants in these 3 studies for whom DNA sequencing data was available.

The DNA sequence data were used to generate a type 2 diabetes polygenic risk score for each participant in this study.

Food frequency questionnaires obtained every 4 years in these studies were used to calculate the Alternative Healthy Eating Index (AHEI) score for each participant.

- The AHEI is based on higher intake of fruits, whole grains, vegetables, nuts and legumes, polyunsaturated fatty acids, long-chain omega-3 fatty acids, moderate intake of alcohol, and lower intake of red and processed meats, sugar sweetened drinks and fruit juice, sodium, and trans-fat).

The investigators used these measurements to estimate the relative effect of genetics and diet quality on the risk of developing type 2 diabetes.

The Influence Of Genetics And Diet On Type 2 Diabetes

The participants were divided into low, intermediate, and high genetic risk based on their type 2 diabetes polygenic risk score.

Compared with low genetic risk:

Intermediate genetic risk increased the risk of developing type 2 diabetes by 26%.

High genetic risk increased the risk of developing type 2 diabetes by 75%.

Put another way, each 1 standard deviation increase in the polygenetic risk score:

Increased the risk of developing type 2 diabetes by 42%.

Simply put, bad genes can significantly increase your risk of developing type 2 diabetes. That’s the bad news. But that doesn’t mean you should think, “Diabetes is in my genes. There is nothing I can do.”

The investigators also divided the participants into those who had a high-quality diet, those who had an intermediate quality diet, and those who had a low-quality diet based on their AHEI (Alternative Healthy Eating Index) score.

Finally, they divided the participants into groups depending on their BMI, a measure of obesity.

Compared to an obese person consuming a low-quality diet, a lean person consuming a high-quality diet:

Reduced their risk of developing type 2 diabetes by around 43% for each category of genetic risk.

More specifically, a lean person consuming a high-quality diet reduced their risk of developing type 2 diabetes:

- By 41% if they were at low genetic risk.

- By 50% if they were at intermediate genetic risk.

- By 38% if they were at high genetic risk.

The investigators then made a statistical adjustment to remove BMI from their calculations, so they could focus on the effect of diet alone on the risk of developing type 2 diabetes.

Compared to a low-quality diet, a high-quality diet:

Reduced the risk of developing type 2 diabetes by around 33% for each category of genetic risk.

More specifically, a high-quality diet reduced the risk of developing type 2 diabetes:

- By 31% for those at low genetic risk.

- By 39% for those at intermediate genetic risk.

- By 29% for those at high genetic risk.

Looking at it another way:

When people at high genetic risk consumed a high-quality diet, their risk of developing type 2 diabetes was only 13% higher than people at intermediate genetic risk who consumed a low-quality diet (such as the typical American diet).

When people at intermediate genetic risk consumed a high-quality diet, their risk of developing type 2 diabetes was 5% less than people at low genetic risk who consumed a low-quality diet.

Simply put:

If you are at intermediate genetic risk, a high-quality diet may completely reverse your risk of developing type 2 diabetes.

If you are at high genetic risk, a high-quality diet can partially reverse your risk of developing type 2 diabetes.

In short, the good news is that bad genes do not doom you to type 2 diabetes.

The investigators did not provide similar information for the effect of an ideal weight on the risk of developing type 2 diabetes, but it is likely that the combination of diet plus weight management would result in an even more significant reduction in risk of developing type 2 diabetes for individuals in the even the highest risk category.

The authors concluded, “These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.”

Do Bad Genes Doom You To Bad Health?

At the beginning of this article I posed the question, “Do bad genes doom you to bad health?”

Based on this study, the good news is that bad genes don’t doom you type 2 diabetes. And just because most of your relatives are diabetic doesn’t mean that must be your fate.

This study shows that a healthy diet significantly reduces your risk of developing type 2 diabetes at every genetic risk level.

And the study suggests that a healthy diet plus a healthy weight is even more beneficial at reducing your risk of type 2 diabetes.

While not included in this study, other studies have shown that exercise also plays a role in reducing type 2 diabetes risk.

None of this information is new. What is new is that a healthy diet is equally beneficial at reducing type 2 diabetes risk even in individuals with a high genetic risk of developing the disease. Simply put, you can reverse the effects of bad genes.

“And what is this magic diet?”, you might ask. In this study, it was based on AHEI score. Someone with a high AHEI score consumes:

Lots of fruits, whole grains, vegetables, nuts and legumes, polyunsaturated fatty acids, and long-chain omega-3 fatty acids.

Moderate or no amounts of alcohol.

Little or no red and processed meats, sugar sweetened drinks, fruit juices, sodium, and foods with trans-fat.

Any whole food, primarily plant-based diet from vegan to Mediterranean or DASH fits the bill.

Finally, while this study focused just on type 2 diabetes, other studies have come to similar conclusions for other diseases.

Should You Get Your DNA Tested?

If you are looking for guidance on how to reduce your risks, the answer is, “No”. In this study, the same diet and lifestyle changes lowered the risk of type diabetes at every genetic risk level. Despite what some charlatans may tell you, there is no special diet or magic potion for people with a high genetic risk for developing type 2 diabetes.

If you are looking for motivation, the answer may be, “Yes”. If knowing you are at high risk makes it more likely that you will make the diet and lifestyle changes needed to lower your risk of type 2 diabetes, a DNA test may be just what you need

The Bottom Line

If a serious disease runs in your family or if you have had your DNA tested and found out you are at high risk for some disease, you are probably wondering whether there is anything you can do or whether your bad genes have doomed you to a short and sickly life.

A recent study answered that question for type 2 diabetes. It showed a healthy diet significantly reduces the risk of type 2 diabetes even in people at high genetic risk of developing the disease.

Other studies have come to similar conclusions for other diseases. In short, bad genes don’t doom you to bad health.

For more details about the study and what it means for you, 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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My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

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About The Author

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years. Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 45 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

What Role Should DNA Testing Play In Nutritional Recommendations?

May 2, 2023 by Dr. Steve Chaney

The Promise And Problems Of Nutrigenomics

Author: Dr. Stephen Chaney

When the human genome was sequenced in 2003, many of us in the scientific community thought we were on the verge of a revolution in human health and longevity. We would soon be able to tell individuals their risk of developing various diseases.

Even better, we would be able to tell them the kind of diet and supplementation they needed to avoid those diseases. We would be able to personalize our nutritional recommendation for every individual based on their genome – something called nutrigenomics.

How naive we were! It has turned out to be much more complicated to design personalized nutrition recommendations based on someone’s genome than we ever imagined.

What Is Nutrigenomics?

As a Professor at the University of North Carolina I specialized in cancer drug development for over 30 years. Over the last decade of my career a ﬁeld called pharmacogenomics became widely accepted in the ﬁeld of cancer drug development. In simple terms, pharmacogenomics looks at how an individual’s genes influence the effectiveness and side effects of drugs.

Because of pharmacogenomics, drugs today are being approved to target cancers for people whose cancer cells have a particular genetic makeup. These drugs would not have been approved a decades ago because if you test them on cancer in the general population, they have little or no eﬀectiveness. They only work on a subset of people who have a form of cancer with a specific genetic makeup.

In principle, nutrigenomics is the same principle. You’ve heard for years that we all have unique nutritional needs. Now we are starting to learn why. It’s because we all have unique variations in our genetic makeup. These genetic mutations increase our risk of certain diseases, and they increase our needs for certain nutrients.

For example, mutations in the MTHFR gene increase the risk of certain birth defects, and supplementation with folic acid is particularly important for reducing birth defects in that population group.

Similarly, mutations in the vitamin D receptor, the VDR gene, interfere with vitamin D absorption from foods and are associated with a condition known as “vitamin D-resistant rickets”. Babies born with this genetic defect require mega doses of vitamin D for normal bone formation.

These are the best-established examples of gene mutations that affect nutritional needs. Many more gene-nutrient interactions have been proposed, but they have not been validated by follow-up experiments.

The situation is similar when we look at gene mutations associated with metabolic responses such as fat and carbohydrate metabolism, obesity, insulin resistance and type 2 diabetes. There are a few gene mutations that have strong associations with obesity and diabetes. Many more gene-metabolism interactions have been proposed, but the data are weak and inconsistent.

The Promise And Problems Of Nutrigenomics

The Promise Of Nutrigenomics.

Now that you understand what nutrigenomics is and have some background information about it, let’s look at the promise of nutrigenomics. One promise of nutrigenomics is personalized supplement programs.

We all have different nutritional needs. Wouldn’t it be wonderful if someone could analyze your genome and provide you with a personalized supplement program that precisely fits your genetically determined nutritional requirements?

There are companies that offer such personalized supplement programs. Are they providing you with something of value or is their testing bogus? Are their supplements worthless?

Another promise of nutrigenomics is personalized diet advice. Some people seem to do better on low-fat diets. Other people do better on low-carb diets. Saturated fats and red meats may be more problematic for some individuals than for others. Wouldn’t it be wonderful if someone could analyze your genome and provide you with a personalized diet program – one that allows you to lose weight easily and gain vibrant health.

There are companies that will analyze your genome and tell you whether you are more likely to lose weight and be healthier on a low-fat or low-carbohydrate diet. Is their testing accurate or is it bogus? Are they providing you with useful information, or is their diet advice worthless?

The Problem With Nutrigenomics

The short answer to the questions I posed in the previous section is that personalized supplement and diet programs are on the horizon, but we are not there yet. Companies promising you personalized nutrition programs based only on DNA tests are misleading you. They quote a few studies supporting the tests they run and ignore the many studies showing their tests are worthless.

In case you think that is just my opinion, let me quote from some recent reviews on the current status of nutrigenomics.

For example, a review (C Murgia and MM Adamski, Nutrients, 366, 2017) published in 2017 concluded: “The potential applications to nutrition of this invaluable tool were apparent since the genome was mapped. The first articles discussing nutrigenomics and nutrigenetics were published less than a year after the first draft of the human DNA sequence was made available…However, fifteen years and hundreds of publications later, the gap between the experimental and epidemiologic evidence and health practice is not yet closed.”

“The [complexity] of the genotype information is not the only factor that complicates this translation into practice. The discovery of other levels of control, including epigenetics [modifications of DNA that affect gene expression] and the intestinal microbiome, are other complicating factors. While the science of nutritional genomics continues to demonstrate potential individual responses to nutrition, the complex nature of gene, nutrition and health interactions continues to provide a challenge for healthcare professionals to analyze, interpret and apply to patient recommendations.”

Another review (M Gaussch-Ferre et al, Advances in Nutrition, 9: 128-135, 2018) published in 2018 concluded: “Overall, the scientific evidence supporting the dissemination of genomic information for nutrigenomic purposes remains sparse. Therefore, additional knowledge needs to be generated…”

In short, the experts are saying we still don’t know enough to predict the best diets, or the best supplements based on genetic information alone. Why is that? Why is it so complicated? In part, it can be explained by a term called penetrance. Penetrance simply means that the same gene mutation can have different effects in different people. In some people, its effects may be barely noticeable. In other people its effects may be debilitating.

The Truth About DNA Testing And Personalized Nutrition

Penetrance is just a word. It’s a concept. The important question is, “What causes differences in genetic penetrance?” Here are the most likely explanations.

1) Human genetics is very complex. There are some gene mutations, such as those causing cystic fibrosis and sickle cell anemia, that can cause a disease by themselves. Most gene mutations, however, simply predispose to a disease or metabolic disturbance and are highly influenced by the activity of other genes. That’s because the products of gene expression form intricate regulatory and metabolic networks. When a single gene is mutated, it interacts with many other genes in the network. And, that network is different for each of us.

2) Many common diseases are polygenic. That includes diseases like heart disease, diabetes, and most cancers. Simply put, that means that they are not caused by a single gene mutation. They are caused by the cumulative effect of many mutations, each of which has a small effect on disease risk. The same appears to be true for mutations that influence carbohydrate and fat metabolism and affect nutrient requirements.

3) The outcome of gene mutations is strongly influenced by our diet, lifestyle, and environment. For example, a common mutation in a gene called FTO predisposes to obesity. However, the effect of this mutation on obesity is strongest when it is coupled with inactivity and foods of high caloric density (translation: junk foods and fast foods instead of fresh fruits and vegetables). Simply put, that means most of us are genetically predisposed to obesity if we follow the American lifestyle, but obesity is not inevitable.

4) Epigenetics has an important influence on gene expression. When I was a graduate student, we believed our genetic destiny was solely determined by our DNA sequence. That was still the prevailing viewpoint when the human genome project was initiated. We thought that once we had our complete DNA sequence, we would know everything we needed to know about our genetic destiny.

How short sighted we were! It turns out that our DNA can be modified in multiple ways. These modifications do not change the DNA sequence, but they can have major effects on gene expression. They can turn genes on or turn them off. More importantly, we have come to learn that these DNA modifications can be influenced by our diet, lifestyle, and exposure to environmental pollutants.

This is the science we call epigenetics. We have gone from believing we have a genome (DNA sequence) that is invariant and controls our genetic destiny to understanding that we also have an “epigenome” (modifications to our DNA) that is strongly influenced by our diet, lifestyle, and environment and can change day-to-day.

5) Our microbiome has an important influence on our health and nutritional status. Simply put, the term microbiome refers to our intestinal microbes. Our intestinal bacteria are incredibly diverse. Each of us has about 1,000 distinct species of bacteria in our intestines.

Current evidence suggests these intestinal bacteria influence our immune system, inflammation and auto-immune diseases, brain function and mood, and our predisposition to weight gain – and this may just be the tip of the iceberg.

More importantly, our microbiome is influenced by our diet. For example, vegetarians and meat eaters have entirely different microbiomes. Furthermore, the effect of diet on our microbiome is transitory. If you change your diet, the species of bacteria in your microbiome will completely change in a few weeks.

Finally, our microbiome also influences our nutritional requirements. For example, some species of intestinal bacteria are the major source of biotin and vitamin K2 for all of us and the major source of vitamin B12 for vegans. Intestinal bacteria may also contribute to our supply of folic acid and thiamine. Other intestinal bacteria inactivate and/or remove some vitamins from the intestine for their own use. Thus, the species of bacteria that populate our intestines can influence our nutritional requirements.

Now that you know the complexity of gene interactions you understand why we are not ready to rely on DNA tests yet. We don’t yet know enough to design a simple DNA test to predict our unique nutritional needs. That science is at least 10-20 years in the future. Companies that tell you otherwise are lying to you.

What Role Should DNA Testing Play In Nutritional Recommendations?

The algorithms that are most successful in creating personalized diet and/or supplement recommendations:

1) Start with an analysis of your diet and lifestyle. They powerfully affect both gene expression and your microbiome.

2) Add in health parameters such as blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and hemoglobin A1c (a measure of blood sugar control). For example, a DNA analysis may suggest you are at risk for having elevated cholesterol, but whether you do or not is influenced by many other factors. A simple blood test indicates whether that risk is real for you.

3) Consider your personal health goals. If nutritional recommendations are to be personalized to you, they should emphasize the health goals you value most.

4) Include any diseases you have and recommendations of your doctor. If your doctor has recommended you lower your blood pressure, your cholesterol, or blood sugar levels, that is valuable information to include in the mix.

5) Now you are ready to include DNA testing in the mix. It can provide some valuable insights, but those insights need to be filtered through the lens of all the critical information collected in the first four steps. Genetics gives you possibilities. The information collected in the first four steps represents your realities.

The Bottom Line

Nutrigenomics is defined as the interaction between our genetic makeup and our diet. How far have we advanced in the science of nutrigenomics? Can a simple DNA test provide us with useful information?

For example, we all have different nutritional needs. Wouldn’t it be wonderful if someone could analyze your genome and provide you with a personalized supplement program that precisely fits your genetically determined nutritional requirements?

There are companies that will analyze your genome and offer personalized supplement programs. Are they providing you with something of value or is their testing bogus? Are their supplements worthless?

Two recent reviews have surveyed the nutrigenomic literature (all published clinical studies) and have concluded that we still don’t know enough to predict the best diets, or the best supplements based on genetic information alone. Why is that? It is because:

1) Human genetics is very complex.

2) Many common diseases are polygenic (caused by the cumulative effect of many mutations).

3) The effect of gene mutations on our health and wellbeing is strongly influenced by our diet, lifestyle, and environment.

4) Epigenetics has an important influence on gene expression.

5) Our microbiome has an important influence on our health and nutritional status.

For more details on these studies and the kind of testing that best determines the right diet and/or supplement program for you, 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.

Is DNA Testing Valuable?

October 5, 2021 by Dr. Steve Chaney

What Is The True Value Of DNA Tests?

Author: Dr. Stephen Chaney

DNA testing is hot! DNA testing companies claim they can tell you your disease risk and personalize your diet and supplement program – all based on the sequence of your DNA.

On the other hand, most reputable medical sources say these DNA testing companies overpromise and underdeliver. They tell you that diet, lifestyle, and supplement recommendations based only on your DNA sequence are often inaccurate.

So, what should you believe? At this point you are probably wondering:

Is DNA testing valuable or is it a waste of money?

Is there a way to make DNA testing more accurate?

What is the true value of DNA testing to you, the consumer?

I will consider these 3 questions in my article below. But first let me share two stories about DNA testing, one true and the other fictional.

Perspectives on DNA Testing

When the human genome was first sequenced in 2003, it took 13 years and cost millions of dollars. That was an exciting time. Many of us in the scientific community thought we were on the verge of a revolution in human health and longevity. We would soon be able to tell individuals their risk of developing various diseases.

How naive we were! It has turned out to be much more complicated to design personalized nutrition recommendations based on someone’s genome than we ever imagined.

Today an analysis of your genome requires hours and costs less than $200. That represents a tremendous advance in technology. However, we are no closer to being able to make personal nutrition recommendations based on our DNA sequence today than we were 18 years ago.

Why is that? Let me share a fictional story because it provides a clue. In 1997, when I was still a relatively young scientist, I saw a film called GAATACA. [If you are looking for an entertaining film to watch, it is still available on some streaming services.]

This film envisioned a future society in which parents had their sperm and eggs sequenced so that their children would be genetically perfect. In that society the term “love child” had been redefined as a child who had been conceived without prior DNA sequencing.

The hero of this film was, of course, a love child. He was born with a genetic predisposition for heart disease. He was considered inferior, a second-class citizen of this future world.

Without giving away the plot of the film (I don’t want to spoil the enjoyment for you if you are thinking of watching it), he overcame his genetic inferiority. With a strict regimen of diet and physical fitness he became stronger and healthier than many of his genetically perfect peers.

This is when I first began to realize that our DNA does not have to be our destiny. We have the power to overcome bad genetics. We also have the power to undermine good genetics.

You might be wondering, “How can this be? Why doesn’t our DNA determine our destiny” I will answer that question in two parts.

First, I will share what experts say about the value of DNA testing.

Then I will put on my professor hat and discuss “Genetics 101 – What we didn’t know in 2003” (When the genome was first sequenced).

Is DNA Testing Valuable?

As I said above, most scientists are skeptical about the ability of DNA testing to predict our ideal diet and supplementation regimens. For example, here are two recent reviews on the current status of DNA testing. [Note: These scientists are using “science speak”. Don’t worry if you don’t understand all the terms. I will explain their message in simpler terms in the next section.]

One review (C Murgia and MM Adamski, Nutrients, 366, 2017) published in 2017 concluded: “The potential applications to nutrition of this invaluable tool [DNA sequencing] were apparent since the genome was mapped…However, fifteen years and hundreds of publications later, the gap between genome mapping and health practice is not yet closed.”

“The discovery of other levels of control, including epigenetics [modifications of DNA that affect gene expression] and the intestinal microbiome complicate the interpretation of genetic data. While the science of nutritional genomics remains promising, the complex nature of gene, nutrition and health interactions provides a challenge for healthcare professionals to analyze, interpret and apply to patient recommendations.”

Another review (M Gaussch-Ferre et al, Advances in Nutrition, 9: 128-135, 2018) published in 2018 concluded: “Overall, the scientific evidence supporting the dissemination of genomic information for nutrigenomic purposes [predicting ideal diet and supplement regimens] remains sparse. Therefore, additional knowledge needs to be generated…”

In short, the experts are saying we still don’t know enough to predict the best diet or the best supplements based on genetic information alone.

Genetics 101 – What We Didn’t Know In 2003

In simple terms the experts who published those reviews are both saying that the linkage between our DNA sequence and either diet or supplementation is much more complex than we thought in 2003 when the genome was first sequenced.

That is because our understanding of genetics has been transformed by two new areas of research, epigenetics and our microbiome. Let me explain.

Epigenetics has an important influence on gene expression. When I was a graduate student, we believed our genetic destiny was solely determined by our DNA sequence. That was still the prevailing viewpoint when the human genome project was initiated. As I said above, we thought that once we had our complete DNA sequence, we would know everything we needed to know about our genetic destiny.

It turns out that our DNA can be modified in multiple ways. These modifications do not change the DNA sequence, but they can have major effects on gene expression. They can turn genes on or turn them off. More importantly, we have come to learn that these DNA modifications can be influenced by our diet and lifestyle.

2) Our microbiome also has an important influence on our health and nutritional status. Simply put, the term microbiome refers to our intestinal microbes. Our intestinal bacteria are incredibly diverse. Each of us has about 1,000 distinct species of bacteria in our intestines.

Current evidence suggests these intestinal bacteria influence our immune system, inflammation and auto-immune diseases, brain function and mood, and our predisposition to gain weight – and this may just be the tip of the iceberg.

More importantly, our microbiome is also influenced by our diet and lifestyle, and environment. For example, vegetarians and meat eaters have entirely different microbiomes.

Furthermore, the effect of diet and lifestyle on our microbiome also changes day to day. If you change your diet, the species of bacteria in your microbiome will completely change in a few days.

If you are wondering how that could be, let me [over]simplify it for you:

- What we call fiber, our gut bacteria call food.

- Different gut bacteria thrive on different kinds of fiber.

- Different plant foods provide different kinds of fiber.

- Whenever we change the amount or type of fiber in our diet, some gut bacteria will thrive, and others will starve.

- Bacteria grow and die very rapidly. Thus, the species of bacteria that thrive on a particular diet quickly become the predominant species in our gut.

- And when we change our diet, those gut bacteria will die off and other species will predominate.

Finally, our microbiome also influences our nutritional requirements. For example, some species of intestinal bacteria are the major source of biotin and vitamin K2 for all of us and the major source of vitamin B12 for vegans. Other intestinal bacteria inactivate and/or remove some vitamins from the intestine for their own use. Thus, the species of bacteria that populate our intestines can influence our nutritional requirements.

Now that you know the complexity of gene interactions you understand why we are not ready to rely on DNA tests alone. That science is at least 10-20 years in the future. Companies that tell you otherwise are lying to you.

What Is The True Value Of DNA Tests?

By now you are probably thinking that my message is that DNA tests are worthless. Actually, my message is a bit different. What I, and most experts, are saying is that DNA tests are of little value by themselves.

To understand the true value of DNA tests, let me start with defining a couple of terms you may vaguely remember from high school biology – genotype and phenotype.

Genotype is your genes.

Phenotype is you – your health, your weight, and your nutritional needs. Your phenotype is determined by your genes plus your diet and your lifestyle.

With that in mind, let’s review the take-home messages from earlier sections of this article.

The take-home message from the two stories in “Perspectives on DNA Testing” is that our DNA does not have to be our destiny. We have the power to overcome bad genetics. We also have the power to undermine good genetics.

The take-home message from “Genetics 101” is that while the genes we inherit do not change, the expression of those genes is controlled in part by:

- Epigenetic modifications to the DNA. And those epigenetic modifications are controlled by our diet and our lifestyle.

- Our microbiome (gut bacteria). And our microbiome is controlled by our diet and our lifestyle.

Now we are ready to answer the question, “What is the true value of DNA testing?” There are actually two answers to this question. You have probably guessed the first answer by now, but you will be surprised by the second.

DNA testing can only indicate the potential for obesity, the potential for nutritional deficiencies, and the potential for disease. But whether that potential is realized depends on our diet and lifestyle. Therefore, the true value of DNA testing comes from adding a comprehensive analysis of diet and lifestyle to the DNA test results. That includes:

- Questionnaires that assess diet, lifestyle, health goals, and health concerns.

For example, your genetics may indicate an increased need for vitamin D. This is a concern if your vitamin D intake is marginal but may not be a concern if you are getting plenty of vitamin D from your diet, supplementation, and sun exposure.

- Direct measurements of obesity such as height and weight (from which BMI can be calculated) and waist circumference (belly fat is more dangerous to our health than fat stored elsewhere in our body).

For example, most Americans have a genetic predisposition to obesity, but not everyone is obese. If you are overweight or obese, your nutrition and lifestyle recommendations should include approaches to reduce your weight. If not, these recommendations are not needed, even if you have a genetic predisposition to obesity.

- Blood pressure and blood markers of disease risk (cholesterol, triglycerides, and blood sugar).

For example, you may have genetic predisposition to high blood pressure or high cholesterol. If either of these are high, your recommendations should include nutrition and lifestyle approaches to lower them. However, if you are already keeping them under control through diet and lifestyle, no further changes may be necessary.

2) While the scientific community now knows the limitations of DNA testing, this information has not filtered down to the general public. This brings me to the second value of DNA testing. Several recent studies have shown that people are much more likely to follow recommendations based on DNA testing than recommendations based on dietary questionnaires, blood markers of disease, or even recommendations from their physician.

The Bottom Line

DNA testing is hot! DNA testing companies claim they can tell you your disease risk and personalize your diet and supplement program – all based on the sequence of your DNA.

So, what is the true value of DNA testing? To answer that question, we need to know two things:

1) Our DNA is not our destiny. We have the power to overcome bad genetics. We also have the power to undermine good genetics.

2) While the genes we inherit do not change, the expression of these genes is controlled in part by:

- Epigenetic modifications to the DNA. And those epigenetic modifications are controlled by our diet and our lifestyle.

- Our microbiome (gut bacteria). And our microbiome is controlled by our diet and our lifestyle.

With this information in mind, we are ready to answer the question, “What is the true value of DNA testing?” The true value of DNA testing is tw0-fold:

1) It comes from adding a comprehensive analysis of diet and lifestyle to the DNA test results. This includes:

- Questionnaires that assess diet, lifestyle, health goals, and health concerns.

- Direct measurements of obesity such as height and weight (from which BMI can be calculated) and waist circumference (belly fat is more dangerous to our health than fat stored elsewhere in our body).

- Blood pressure and blood markers of disease risk (cholesterol, triglycerides, and blood sugar).

2) In addition, several recent studies have shown that people are much more likely to follow recommendations based on DNA testing than recommendations based on dietary questionnaires, blood markers of disease, or even recommendations from their physician.

For more details and explanations of the statements in “The Bottom Line”, 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.

Can DNA Testing Help You Lose Weight?

June 30, 2020 by Dr. Steve Chaney

How Does DNA Testing Work Best?

Genomics (DNA testing) is hot. You are being told that if you just knew your genes, you could lose weight successfully, be healthier, be happier, leap tall buildings in a single bound (Actually, I haven’t heard the last claim, but it’s about the only claim that genomics marketers haven’t made). Which of these claims are true, and which are just hot air?

The experts agree that the benefits of DNA testing have been greatly oversold. As I said in a recent article on DNA testing, the idea that genes control our destiny is no longer considered valid. There are 3 reasons for this. I will start with the scientific term for each and then give you the non-scientific explanation.

Penetrance simply means that the severity of most gene mutations is influenced by our genetic background. Simply put, the same mutation can have a significant effect in one individual and a trivial effect in another individual.

Epigenetics refers to modifications of the DNA that influence gene expression. These DNA modifications are, in turn, influenced by diet and lifestyle.

Microbiome refers our gut bacteria. In many cases, our microbiome has just as much influence on our health as our genes. And our microbiome is influenced by diet and lifestyle.

Now you know the complexity of DNA testing, it is easy to see why experts feel that it is premature to use DNA testing to predict the best diet for either weight loss or health.

As an example, one recent study used DNA testing to predict whether study participants were more likely to lose weight on a low-carb or low-fat diet. The participants were then randomly assigned to low-carb and low-fat diets. At the end of 12 months:

There was no significant difference in weight loss for those on low-fat and low-carb diets. This has been reported in multiple previous studies but is an inconvenient truth that most low-carb enthusiasts tend to ignore.

DNA testing offered no predictive value as to whether a low-carb or low-fat diet was more effective for weight loss.

However, DNA testing may have one benefit that is overlooked by many experts. What if the DNA test results motivated people to do better? After all, most diet advice is generic. People feel it may or may not apply to them. Does personalized diet advice based on their genetic makeup motivate people to stick with the diet better?

Some studies have suggested that people may follow personalized diet plans based on their DNA more faithfully. However, most of those studies have been short-term.

That is why I have chosen today’s study (J Horne et al, BMJ Nutrition, Prevention & Health, 2020) to discuss. It is a very well-designed study and it lasted for a full year.

How Was The Study Done?

This was an extremely well-designed study. In fact, it was so well designed that it probably needs the “Results are not typical” designation the FDA requires when some diet companies make claims about weight loss success. Here are the details:

The study participants were highly motivated, college educated, middle-aged (average age = 55), obese (average weight = 216 pounds) Caucasian women who had a positive attitude about their ability to change what they ate. In case you weren’t counting, there were four characteristics of this group that might be considered atypical for the average American.

The participants volunteered for a highly structured weight loss program called the “Group Lifestyle Balance”, or GLB, program.

- Participants were given a detailed calorie-controlled nutrition plan at the beginning of the program.

- They were asked to track their daily food and beverage intake for the first 2-3 months of the program.

- In the second week of the program participants were educated on how to count and track calories and nutrients such as total fat or saturated fat.

- There were weekly meetings with dietitians the first 3 months and monthly meetings for the remainder of the 12-week program to provide the guidance and support needed to stick with their nutrition plan.

The plan also incorporated a behavior change program called Theory of Planned Behavior (TPB) that evaluates and influences attitudes, subjective norms, and behavioral control that are key to behavior change. During the regular meetings:

- The participants were informed about of the health benefits associated with a healthy lifestyle.

- They were educated on positive mindsets and mindfulness.

- They were taken through a stepwise, goal setting approach designed to positively impact behavioral change.

In short, this is a gold standard diet program that provided the nutritional support needed to stick with the diet program and the psychological support needed to change eating behavior. Unfortunately, this is also atypical. Very few diet programs provide this level of support.

Everyone in the study participated in this program. However, the participants were divided into two groups.

Both groups were advised to follow a standard calorie-controlled, moderately low-fat (25% of total calories) nutrition plan.

In addition, the second group was put on a plan that was either high protein or low saturated fat (<10% of total calories) based on their DNA test results.

The nutritional support was identical except that the second group was told that their nutrition plan was specific for them, based on their DNA analysis.

The dietary intake of both groups was assessed with a 3-day dietary recall (2 week days and 1 weekend day) at baseline (before the program began) and at 3, 6, and 12 months to assess the participants adherence to their diet plan.

Can DNA Testing Help You Lose Weight?

I hate to disappoint you, but the short answer to this question, is no. Both groups lost the same amount of weight, which is not surprising considering the comprehensive nature of the diet program that both groups were enrolled in.

However, the group given advice based on their DNA test were more motivated to stick with their personalized nutrition goals. Specifically:

Long-term adherence to reductions in saturated fat intake was significantly greater in the group that was told their diet plan was personalized based on their DNA analysis.

- The control group reduced their saturated fat intake by 12% at 3 months, but only by 4% at 6 months, and 2.5% at 12 months.

- The group with the personalized diet plan reduced their saturated fat intake by 14% at 3 months, 18% at 6 months, and 22% at 12 months.

Long-term adherence to reductions in total fat intake was also significantly greater in the group that was told their diet plan was personalized based on their DNA analysis.

- The control group reduced their total fat intake by 18% at 3 months, but only by 4% at 6 and 12 months.

- The group with the personalized diet plan reduced their total fat intake by 11% at 3 months, 13% at 6 months, and 16% at 12 months.

- It is important to remember that both groups had been advised to reduce their total fat intake to 25% of calories and had received nutritional and psychological support to achieve that goal. The only difference was that the second group had been told that advice was based on their DNA test.

The authors of the study concluded: “Weight management interventions guided by nutrigenomics can motivate long-term improvements in dietary fat intake above and beyond gold-standard population-based interventions.”

How Does DNA Testing Work Best?

There remain significant concerns about the validity of personalized weight loss advice based on DNA testing. However, this and other studies suggest that DNA testing may provide one valuable asset for weight loss programs. It appears that people are more likely to stick with a program they believe has been personalized for them.

There are, however, several caveats to this conclusion.

Participants in this study received nutritional and psychological support throughout the 12-month program. We don’t know how well participants would have stuck with the program if they had not been continually reminded that the program had been personalized for them.

Participants in this study were well-educated, highly motivated, Caucasian women. We don’t know whether these results apply to men and to other ethnic and socioeconomic groups.

This study only looked at personalized diet advice based on DNA testing. Some studies suggest that other methods of diet personalization may also improve adherence.

Personalization can be misused to recommend unhealthy dietary changes. It is not enough to follow personalized diet advice. You also need to ask whether it is healthy dietary advice.

For example, DNA test results consistent with reduced carbohydrate intake are sometimes used to recommend unhealthy diets that eliminate one or more food groups rather than low-carb versions of healthy diets like the Mediterranean diet.

The Bottom Line

There remain significant concerns about the validity of personalized weight loss advice based on DNA testing. However, DNA testing may provide one valuable asset for weight loss programs. Some studies have suggested that people are more likely to stick with a program they believe has been personalized for them.

However, most of these studies have been short term. A recent study asked whether the improvement in motivation lasted for 12 months.

Two matched groups of well-educated, highly motivated women were enrolled in a “gold-standard” weight loss program that provided both nutritional and psychological support for 12 months.

Both groups were given a diet plan that restricted total calorie intake and advised reducing fat intake to 25% of total calories. However, based on their DNA test results one group was given a personalized diet plan that also advised them to reduce their saturated fat intake to less than 10% of total calories.

The group receiving personalized diet advice did a better job of reducing both saturated and total fat intake and maintaining that change for 12 months compared to the group that just received a set diet plan.

These results suggest that personalization of diet advice may improve long-term adherence to healthy dietary changes.

There are, however, several caveats to this conclusion.

Participants in this study received both nutritional and psychological support throughout the 12-month program. We don’t know how well participants would have stuck with the program if they had not been continually reminded that the program had been personalized for them.

Participants in this study were well-educated, highly motivated, Caucasian women. We don’t know whether these results apply to men and to other ethnic and socioeconomic groups.

This study only looked at personalized diet advice based on DNA testing. Some studies suggest that other methods of diet personalization may also improve adherence.

Personalization can be misused to recommend unhealthy dietary changes. It is not enough to follow personalized diet advice. You also need to ask whether it is healthy dietary advice.

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.

Can Genetics Predict Which Diet is Best For You?

March 13, 2018 by Dr. Steve Chaney

Author: Dr. Stephen Chaney

It is so confusing. The weight loss claims for popular diets sound so convincing, but they can’t all be true.

The low carb proponents give impressive metabolic arguments for why their diet works best. (Of course, you aren’t a biochemist. You have no idea whether they are speaking the truth or just trying to pull the wool over your eyes.) They quote clinical studies and offer testimonials that “prove” their diet works.

Other “experts” tell you that is nonsense. Your diet needs to be individualized to fit your genetic and metabolic profile. Who do you believe? Do low-carb or low-fat diets work better? Are individualized diet plans the solution?

Fortunately for you a recent study (CD Gardner et al, JAMA, 319: 667-679, 2018 ) has answered your questions. Let me start with some background to put this study in perspective. Then I will describe how the study was done, the study results, and what this study means for you.

What Did We Already Know About Diets?

The studies that low-carb proponents quote to “prove” the success of their diet approach are misleading because:

Most of the studies are short-term. This is misleading because low-carb diets lead to an initial loss of water weight that is not seen with low-fat diets.
Most of the comparisons are done with the typical American diet (which is high in sugar, refined carbohydrates, and junk food) rather than a healthy low-fat diet.
Note: This is the short version. I cover this in more detail in my new “Slaying The Food Myths” book.

In contrast, there have been numerous studies comparing the effectiveness of low-carb versus low-fat diets long term (12 months or more). These studies have not found a dimes worth of difference between the two diets. Weight loss was virtually identical.

That has led some weight loss experts to point out that any “one size fits all” diet fails to account for individual variability. They point out that while average weight loss on a particular diet might be 12-15 pounds, some people will have lost 45 pounds and others gained 5 pounds. That has led to research efforts to discover biomarkers that could predict which diet will work best for you. Let me share the two most promising approaches.

A DNA testing approach measures genetic variation in the PPARG, ADRB2, AND FABP2 genes [Don’t worry. There won’t be a quiz.] These are genes involved in fat and energy metabolism. Animal studies have suggested that genetic variation in these genes might be useful in predicting whether individuals respond better to a low-fat or low-carb diet. One preliminary clinical study has suggested it may work for humans as well.

An insulin sensitivity approach measures insulin levels 30 minutes after a glucose challenge (a measurement called INS-30). Some small clinical studies have suggested this approach might also have value in predicting the success of low-carb versus low-fat diets for weight loss.

Unfortunately, some companies are already promoting individualized diet plans based on DNA testing and insulin sensitivity measurement – even though the clinical support for the predictive power of those tests is very preliminary at present.

The current study was designed to compare the effectiveness of healthy low-carb and low-fat diets on weight loss. In addition, it evaluated whether either DNA testing or insulin sensitivity measurements could effectively predict whether individuals lost weight better on low-fat or low-carb diets.

How Was This Study Done?

This was an excellent study. In fact, it is one of the best studies comparing weight loss diets I have seen in recent years. It enrolled 609 middle-aged (average age = 40), overweight (average BMI = 33) adults from the San Francisco Bay area in a 12-month weight loss study. Here was the breakdown of participants:

57% were women, 43% were men.
40% had a DNA pattern considered favorable for a low-fat diet, 30% had a DNA pattern considered favorable for a low-carb diet (30% had an intermediate DNA pattern that did not predict either low-carb or low-fat).
67% had insulin sensitivity values considered favorable for low-carb diets, 33% had insulin sensitivity considered favorable for a low-fat diet.

The study participants were randomly assigned to either the low-carb diet group or low-fat diet group by a computerized protocol that assured DNA patterns and insulin sensitivity were equally distributed across the two groups.

In contrast to many earlier studies, both groups followed a relatively healthy diet. They were instructed to:

Maximize vegetable intake.
Minimize intake of added sugars, refined flours, and trans-fats.
Focus on whole foods that were minimally processed, nutrient dense, and prepared at home whenever possible.

The participants were not advised to restrict their calories. However, they were given an extraordinary degree of support. They were further divided into groups of 17 that met a total of 22 times over the 12 months with a registered dietitian who provided instruction, support and encouragement. That level of support assured that the participants stuck with their diet for the full 12-month period.

Can Genetics Predict Which Diet Works Best?

Participants in the study lost an average of 12 pounds. That is not a huge amount of weight, but it is enough weight loss to make a difference, and it is consistent with the results of most long-term studies. When the results were broken down further:

There was no significant difference in weight loss between the low-carb group and low-fat group at 12 months. This is consistent with multiple previous studies.
Both diets were equally effective at improving lipid profiles and lowering blood pressure, insulin, and blood sugar levels. This is the dirty little secret that many low-carb enthusiasts don’t tell you. The improvements seen in health parameters such as lipids, blood pressure, insulin, and blood glucose are due to the weight loss, not whether the diet is low-carb or low-fat.
Neither the DNA pattern or insulin sensitivity offered any predictive value as to whether a low-carb or low-fat diet was more effective for weight loss.

That does not mean that DNA testing is of no value. It simply means that the human genome is far more complex than the companies offering DNA tests have assumed. There will be a day when we know enough to individualize diets based on DNA testing. That day is not now.

What Does This Mean For You?

Forget the weight loss claims of the low-carb enthusiasts. Ignore companies that promise they can select the best diet approach for you based on some simple DNA tests and/or measurements of insulin sensitivity.

This study does not provide definitive answers, but it hints at the weight loss tips that really matter:

Ditch the sodas, sweets, fast and processed foods. Instead focus on whole foods, primarily fruits and vegetables, whole grains, and legumes.
If you wish to follow a low-carb diet, choose one that is primarily plant-based rather than meat-based.
Focus on what you are eating rather than on calories.
Find a group to provide support and encouragement. It doesn’t need to be some expensive diet program. It could just be a group of friends who agree to provide each other with support, encouragement, and accountability.

I cover this topic in much more detail in my new book “Slaying The Food Myths”.

The Bottom Line:

A recent study compared the effectiveness of healthy low-carb and low-fat diets on weight loss over a 12-month period. In addition, it evaluated whether DNA testing or insulin sensitivity measurements could effectively predict whether individuals lost weight better on low-fat or low-carb diets.

There was no significant difference in weight loss between the low-carb and low-fat groups at 12 months. This is consistent with multiple previous studies.
Both diets were equally effective at improving lipid profiles and lowering blood pressure, insulin, and blood sugar levels. This is the dirty little secret that many low-carb enthusiasts don’t tell you. The improvements seen in health parameters such as lipids, blood pressure, insulin, and blood glucose are due to the weight loss, not whether the diet is low-carb or low-fat.
Neither the DNA pattern or insulin sensitivity offered any predictive value as to whether a low-carb or low-fat diet was more effective for weight loss.

That means you can forget the weight loss claims of the low-carb enthusiasts. You should also ignore companies that promise they can select the best diet approach for you based on some simple DNA tests and/or measurements of insulin sensitivity.

As for what works and why, I cover that in detail in my new book “Slaying The Food Myths”

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.