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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.

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 we 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.

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.

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 and lifestyle and can change day-to-day.

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.

Do Low Fat Diets Reduce The Risk Of Diabetes?

May 4, 2021 by Dr. Steve Chaney

Why Is Nutrition So Confusing?

Author: Dr. Stephen Chaney

Sometimes the professor likes to introduce you to the frontiers of nutrition. Epigenetics is such a frontier. In recent years, the hype has centered on DNA sequencing. It seems like everyone is offering to sequence your genome and tell you what kind of diet is best for you, what foods to eat, and what supplements to take. But can DNA sequencing fulfill those promises?

The problem is that DNA sequencing only tells you what genes you have. It doesn’t tell you whether those genes are active. Simply put, it doesn’t tell you whether those genes are turned on or turned off.

This is where epigenetics comes in. Epigenetics is the science of modifications that alter gene expression. In simple terms, both DNA and the proteins that bind to DNA can be modified. This does not change the DNA sequence. But these modifications can determine whether a gene is active (turned on) or inactive (turned off).

This sounds simple enough, but here is where it really gets interesting. These modifications are affected by our diet, our lifestyle (BMI and exercise), our microbiome (gut bacteria), and our environment.

In today’s “Health Tips From The Professor” I am going to share a study (CQ Lai et al, American Journal of Clinical Nutrition, 112: 1200-1211, 2020) that looks at the effect of diet (low-fat versus low-carb diets) on a particular kind of DNA modification (methylation) that affects a gene (CPT) which influences our risk for metabolic diseases (obesity, high triglycerides, low HDL, insulin resistance, pre-diabetes, and type 2 diabetes).

[Note: For simplicity I will just refer to type 2 diabetes in the rest of this article. Just be aware that whatever I say about type 2 diabetes applies to other metabolic diseases as well.]

Previous studies have shown that:

Methylation of the CPT gene is the only epigenetic change in the entire genome that is associated with decreased risk of type 2 diabetes.

CPT gene activity regulates multiple metabolic pathways that influence the risk of type 2 diabetes.

High fructose and sucrose consumption increases CPT gene methylation in rats, and high fat diets suppress that methylation.

Based on those data, the authors hypothesized that carbohydrate and fat intake affect the methylation of CPT gene, which:

Alters the activity of the CPT gene and…

Affects the risk of developing type 2 diabetes.

Since we are talking about our diet making alterations to our DNA, we could consider this as an example of, “We are what we eat”.

Biochemistry 101: Why Is Nutrition So Confusing?

Now it is time for my favorite topic, Biochemistry 101. Along the way you will discover why nutrition is so complicated – and so confusing.

The CPT gene codes for a protein called carnitine palmitoyltransferase or CPT. CPT transports fats into the mitochondria where they can be oxidized to generate energy. Simply put, without CPT we would be unable to utilize most of the fats we eat. And, as you might expect, CPT is not required for carbohydrate metabolism.

In a simple world where our DNA sequence determines our destiny, we would either have an active CPT gene or an inactive mutant version of the gene. If we had the mutant version of the CPT gene, we would be unable to use fat as an energy source.

However, we don’t live in a simple world. Epigenetic modifications alter the activity of the CPT gene. When the CPT gene is unmethylated it is fully active. Methylation inactivates the gene.

In a simple world, a high fat diet would activate the CPT gene so our body would be able to utilize the fat in our diet. It would do that by decreasing methylation of the gene. Conversely, a high carbohydrate, low fat diet would decrease CPT gene activity by increasing methylation of the gene.

This is the one simple prediction that works exactly as expected.

In a simple world, CPT would be involved in transport of fat into our mitochondria and nothing else. In that world, the activity of the CPT gene would only affect fat metabolism.

However, we don’t live in a simple world. By mechanisms that are not completely understood, carnitine palmitoyltransferase (CPT) also influences both insulin resistance and release of insulin by our pancreas. That means the activity of the CPT gene also affects our risk of developing type 2 diabetes.

In the simplest terms, we can think of diabetes as an inability to properly regulate blood sugar levels. In a simple world, that would mean that carbohydrates are the problem, and we could reduce our risk of developing diabetes by restricting our intake of carbohydrates.

However, we don’t live in a simple world. There are short-term studies supporting the effectiveness of both low carb and low fat diets at helping to control blood sugar levels. However, longer term studies generally show that only whole food, low fat diets are associated with reduced risk of developing type 2 diabetes.

In other words, healthy carbohydrates aren’t the problem. They are the solution for reducing your risk of type 2 diabetes. This isn’t intuitive. It isn’t simple. But the weight of evidence points in this direction.

[I should add the emphasis is on “healthy” carbohydrates. I am talking about diets that emphasize whole food sources of carbohydrates (fruits, vegetables, whole grains, and legumes), not diets loaded with sugar, refined carbohydrates, and highly processed foods.]

Confused yet? Don’t worry. The authors of this study combined all this information into a single, unifying hypothesis.

They proposed that the fat and carbohydrate content of the diet influence methylation of the CPT gene, which influences the activity of the CPT gene, which influences both fat metabolism and the risk of developing type 2 diabetes. Specifically, they proposed that:

High fat diets reduce methylation of the CPT gene. This activates the CPT gene which results in more carnitine palmitoyltransferase (CPT) being produced. This improves fat metabolism, but also increases the risk of developing type 2 diabetes.

High carbohydrate, low fat diets increase methylation of the CPT gene. This inactivates the CPT gene which results in less CPT being produced. This is OK because there is little fat to be metabolized. However, it also has the advantage of reducing the risk of developing type 2 diabetes.

This can be visually represented as:

How Was This Study Done?

This study combined the results from 3,954 selected participants in three previous clinical trials:

The Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study.

The Framingham Heart Study.

The REGICORE study. This study is similar in design to the Framingham Heart Study except the participants were drawn from a region of Spain.

The participants were selected based on 4 criteria:

The study they were in measured metabolic disease outcome.

The study they were in included a detailed diet analysis.

A DNA methylation analysis was performed on blood taken from these participants so that the methylation status of the CPT gene could be determined.

mRNA levels were measured for the CPT gene (This is a measure of how active the gene is. Active genes will produce lots of mRNA. Inactive genes will produce very little mRNA).

The study then analyzed the data and looked at the associations between carbohydrate and fat intake with:

Methylation of the CPT gene.

Activity of the CPT gene (measured as the amount of CPT mRNA produced by the gene).

Type 2 diabetes and other metabolic diseases.

Do Low Fat Diets Reduce The Risk Of Diabetes?

The authors systematically tested the predictions of their unifying hypothesis (To help you understand the significance of their findings, I am repeating the visual representation of their unifying hypothesis below):

Methylation of the CPT gene was negatively associated with type 2 diabetes. Simply put, when the methylation of the of the CPT gene was high, the risk of type 2 diabetes was low. This confirmed the results of previous studies.

2) Carbohydrate and fat intake influenced methylation of the CPT gene. Specifically:

- Carbohydrate intake and the ratio of carbohydrate to fat intake were positively associated with CPT methylation. Simply put, a high carbohydrate, low fat diet resulted in increased methylation of the CPT gene.

- Fat intake was negatively associated with CPT methylation. Simply put, a high fat, low carbohydrate diet resulted in decreased methylation of the CPT gene.

3) Carbohydrate and fat intake influenced the activity of the CPT gene. Specifically:

- Carbohydrate intake and the ratio of carbohydrate to fat intake was negatively associated with CPT mRNA levels (a measure of CPT gene activity). Simply put, a high carbohydrate, low fat diet resulted in lower CPT gene activity. This means the CPT gene produced less CPT. And, combined with the previous data, it also means that methylation of the CPT gene decreases its activity.

- Fat intake was positively associated with CPT mRNA levels. Simply put, a high fat, low carbohydrate diet resulted in greater CPT gene activity. This means the CPT gene produces more CPT. And, combined with the previous data, it also means that reducing methylation of the CPT gene increases its activity.

4) CPT gene activity influenced the prevalence of type 2 diabetes. Specifically:

- High CPT gene activity was positively associated with the risk of type 2 diabetes.

- Low CPT gene activity was negatively associated with the risk of type 2 diabetes.

Putting this all together, as the authors had predicted,

High fat, low carbohydrate diets reduce methylation of the CPT gene. This activates the CPT gene which results in more CPT being produced. This improves fat metabolism, but also increases the risk of developing type 2 diabetes.

2) High carbohydrate, low fat diets increase methylation of the CPT gene. This results in less CPT being produced. This is OK because there is little fat to be metabolized. However, it also has the advantage of reducing the risk of developing type 2 diabetes.

In short, the results of the study confirmed all the predictions of the author’s unifying hypothesis.

Putting it all together, the authors concluded, “Our results suggest that the proportion of total energy supplied by carbohydrate and fat can have a causal effect on metabolic diseases [like type 2 diabetes] via the epigenetic status (DNA methylation) of the CPT gene.” Simply put, their data suggested that high carbohydrate, low fat diets reduced the risk developing type 2 diabetes.

What Does This Study Mean For You?

Let me start by saying that occasionally I like to give you a peak behind the curtain and talk about emerging areas of research. We should think of this article as the beginning of an exciting new area of research rather than as a definitive study.

I should start with the disclaimer that this study looks at associations between diet, methylation of the CPT gene, and risk of developing type 2 diabetes.

Associations do not prove cause and effect. This study does not prove that epigenetic changes to the CPT gene caused the reduction in type 2 diabetes risk.

High carbohydrate and high fat diets likely influence the risk of developing type 2 diabetes in other ways as well. For example, the fiber in healthy high carbohydrate diets may support friendly gut bacteria that reduce the risk of developing type 2 diabetes.

I also don’t view this study as one that settles the debate as to whether low carb or low fat diets are better for reducing the risk of type 2 diabetes. It does not clinch the argument for low fat diets. Rather, this study suggests a mechanism by which low fat diets may reduce the risk of metabolic diseases.

In summary, this study does not end the debate as to whether low carb or low fat diets are best. However, it does remind us just how complex the human body is. It reminds us that simple assumptions about how foods affect our bodies may not be the correct assumptions. It also helps us understand why nutrition can be so confusing.

The Bottom Line

In recent years, DNA sequencing has become all the rage. It seems like everyone is offering to sequence your genome and tell you what kind of diet is best for you.

That is where epigenetics comes in. Epigenetics is the science of modifications that alter gene expression. In simple terms, both DNA and the proteins that bind to DNA can be modified. This does not change the DNA sequence. But these modifications can determine whether a gene is active (turned on) or inactive (turned off).

Epigenetics makes nutrition more complicated, and more confusing. For example, diabetes is characterized an inability to control blood sugar levels properly. Accordingly, it seems only logical that carbohydrates, especially sugars and simple carbohydrates, are the problem.

This study showed that high carbohydrate, low fat diets cause epigenetic modifications to a gene that reduces the risk of developing type 2 diabetes and other metabolic diseases. Conversely, high fat, low carb diets have the opposite effect.

This mechanism is consistent with multiple long-term studies showing that whole food, low fat diets reduce the risk of developing type 2 diabetes.

This study does not end the debate as to whether low carb or low fat diets are best. However, it does remind us just how complex the human body is. It reminds us that simple assumptions about how foods affect our bodies may not be the correct assumptions. It also helps us understand why nutrition can be so confusing.

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.