Is DNA Testing Valuable?

What Is The True Value Of DNA Tests? 

Author: Dr. Stephen Chaney

Genetic TestingDNA 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 nutrigenomicsexciting 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?

SkepticAs 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

GeneticistIn 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.

  1. 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. microbiomeSimply 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? 

The TruthBy 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.

  1. 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.

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. They are of little value if they are only based on DNA testing.

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?

How Does DNA Testing Work Best?

Genetic TestingGenomics (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?

Clinical StudyThis 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?

Happy woman on scaleI 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?

DNA TestingThere 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.

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.”

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.

Does Vitamin D Prevent Type 1 Diabetes?

Does Genetics Influence Supplementation Benefits?

diabetesThe cause of type 1 diabetes is a mystery. If you go to an authoritarian source like the Mayo Clinic, you will discover that:

  • Type 1 diabetes is an autoimmune disease that selectively attacks the insulin-producing islet cells of the pancreas.
  • Certain genetic variants predispose individuals to type 1 diabetes.
  • The autoimmune response may be triggered by a viral infection or other unknown environmental factors in genetically susceptible individuals.
  • The incidence of type 1 diabetes increases as you travel away from the equator, which suggests that vitamin D may be involved.

The idea that vitamin D may be involved is an important concept because it suggests that vitamin D supplementation might reduce the risk of developing type 1 diabetes. This idea was reinforced by a Finnish study (E Hyponnen et al, Lancet, 358: 1500-1503, 2001) published in 2001 showing the vitamin D supplementation of newborn infants reduced the incidence of type 1 diabetes at age 1.

However, subsequent studies in other parts of the world have had mixed results. Some have confirmed the results of the Finnish study. Others have come up empty.

Similarly, some studies have shown a correlation between low 25-hydroxyvitamin D levels in the blood and the development of type 1 diabetes in children, while other studies have found no correlation.

Why the discrepancy between studies? Some of the differences can be explained by differences in the populations studied or differences in study design. But what if there were another variable that none of the previous studies has considered?

The study (JM Norris et al, Diabetes, 67: 146-154, 2018) I review this week describes just such a variable. The authors of the study hypothesized that the association between 25-hydroxyvitamin D levels and the risk of developing type 1 diabetes is influenced by mutations that affect the way vitamin D works in the body. Previous studies have not taken these mutations into account. If the author’s hypothesis is true, it might explain why these studies have produced conflicting results.

In this article, I will answer 3 questions:

  • Does vitamin D prevent type 1 diabetes?
  • If so, is supplementation with vitamin D important?
  • Who will benefit most from vitamin D supplementation?

But, before I answer those questions, I should begin by providing some background. I will start by reviewing the how diet, increased need, disease, and genetics influence the likelihood that we will benefit from supplementation. Then I will review vitamin D metabolism.

Does Genetics Influence Supplementation Benefits?

need for supplementsThe reason so many studies find no benefit from supplementation is that they are asking the wrong question. They are asking “Does supplementation benefit everyone?” That is an unrealistic expectation.

I have proposed a much more realistic model (shown on the left) for when we should expect supplementation to be beneficial. Simply put, we should ask:

  • Is the diet inadequate with respect to the nutrient that is being studied?
  • Is there an increased need for that nutrient because of age, gender, activity level, or environment?
  • Is there a genetic mutation that affects the metabolism or need for that nutrient?
  • Is there an underlying disease state that affects the need for that nutrient?

When clinical studies are designed without taking this paradigm into account, they are doomed to fail. Let me give you some specific examples.

  • The Heart Outcomes Prevention Evaluation study concluded supplementation with folate and other B vitamins did not reduce heart disease risk. The problem was that 70% of the people in the study were getting adequate amounts of folate from their diet at the beginning of the study. For those individuals not getting enough folate in their diet, B vitamin supplementation decreased their risk of heart disease by 15%. This is an example of poor diet influencing the need for supplementation.

The other three examples come from studies on the effect of vitamin E supplementation on heart disease that I summarized in an article in “Health Tips From The Professor” a few years ago. Here is a brief synopsis.

  • The Women’s Health Study concluded that vitamin E did not decrease heart disease risk in the general population. However, the study also found that in women over 65 (who are at high risk of heart disease), vitamin E supplementation decreased major cardiovascular events and cardiovascular deaths by 25%. This is an example of increased need because of age and gender influencing the need for supplementation.
  • The Women’s Antioxidant Cardiovascular Study” concluded that vitamin E did not decrease heart disease risk in the general population. However, when they looked at women who already had cardiovascular disease at the beginning of the study, vitamin E supplementation decreased risk of heart attack, stroke, and cardiovascular death by 23%. This is an example of an underlying disease affecting the need for supplementation.
  • The HOPE study concluded that vitamin E did not decrease heart disease risk in the general population. However, when they looked at individuals with a mutation that increases the risk of heart disease, vitamin E supplementation significantly decreased their risk of developing heart disease. This is an example of genetics affecting the need for supplementation.

These are just a few of many examples. When you ask whether supplementation benefits everyone, the answer is often no. However, when you look at people with inadequate diet, increased need, underlying disease, and/or genetic predisposition, the answer is often yes.

This background sets the stage for the current study. Of course, to understand the author’s hypothesis that mutations in genes involved in vitamin D metabolism might influence the effect of vitamin D on the risk of developing type 1 diabetes, you need to know a little about vitamin D metabolism.

Biochemistry 101: Vitamin D Metabolism

Vitamin D MetabolismWhen sunlight strikes a metabolite of cholesterol in our skin, it is converted to a precursor that spontaneously isomerizes to form vitamin D3. Because this series of reactions is usually not sufficient to provide all the vitamin D3 our bodies require, we also need to get vitamin D3 from diet and supplementation.

However, vitamin D3 is not active by itself. It first needs to be converted to 25-hydroxyvitamin D by our liver and then to the active 1,25-dihydroxyvitamin D. 1,25-dihydroxyvitamin D is an important hormone that regulates many cells in our body.

Some of the 1,25-dihydroxyvitamin D is synthesized by our kidneys and released into the bloodstream. This 1,25-dihyroxyvitamin D binds to vitamin D receptors on the surface of many cells and initiates regulatory pathways that affect metabolism inside the cell.

Other cells take up 25-hydroxyvitamin D and convert it to 1,25-dihydroxyvitamin D themselves. In these cells both the synthesis and regulatory effects of 1,25-dihydroxyvitamin D occur entirely inside the cell.

In both cases, it is 1,25-dihydroxyvitamin D that regulates cellular metabolism. The only difference is the way this regulation is accomplished.

There are two additional points that are relevant to this study.

  • The efficiency of conversion of vitamin D to 25-hydroxyvitamin D varies from person to person.
    • Thus, blood levels of 25-hydroxyvitamin D are considered a more reliable measure of vitamin D status than dietary intake of vitamin D or sun exposure.
    • Blood levels of 25-hydroxyvitamin D levels ≥50 nmol/L are considered optimal, while levels of 30 to <50 nmol/L are considered suboptimal, and levels <30 nmol/L are considered deficient.
  • 1,25-dihydroxyvitamin D binds to the vitamin D receptor on immune cells. This initiates a series of reactions that decrease the risk of autoimmune responses by our immune system.

How Was This Study Done?

Clinical StudyThis study was called TEDDY (The Environmental Determinants Of Type 1 Diabetes in the Young). Between September 2004 and February 2010, 424,788 newborn infants from 6 medical centers in Colorado, Georgia, Washington, Finland, Germany, and Sweden were screened for genes that predispose to type 1 diabetes.

The investigators identified 21,589 high-risk infants, and 8,676 of them were enrolled in this study before age 4 months. Clinic visits for the children occurred every 3 months between 3 and 48 months of age and every 6 months thereafter.

  • A DNA sample was taken at the time they entered the study and analyzed for mutations in genes involved in vitamin D metabolism.
  • 25-hydroxy vitamin D levels were obtained at each office visit. Because some studies have suggested the vitamin D status during the first year of life is important, the data were analyzed in two ways.
    1. An average of all 25-hydroxyvitamin D levels (referred to as “childhood 25-hydroxyvitamin D levels”).
    1. An average of 25-hydroxyvitamin D levels during the first 12 months (referred to as “early infancy 25-hydroxyvitamin D levels”).
  • Serum autoantibodies to pancreatic islet cells were measured at each office visit as a measure of an autoimmune attack on those cells. Persistent autoimmune response was defined as positive autoantibodies on two consecutive office visits.

While this study did not directly measure type 1 diabetes, children with an autoimmune response to their pancreatic islet cells are highly likely to develop type 1 diabetes. Thus, for purposes of simplicity I will refer to “risk of developing type 1 diabetes” rather than “persistent autoimmune response” in describing these results.

    1. 418 children developed persistent autoantibodies to their pancreatic islet cells during the study. The onset of this autoimmune response ranged from 2 months to 72 months with an average of 21 months.
    1. These children were compared to 3 matched controls from their medical center who did not develop an autoimmune response.

This study was remarkable for two reasons:

1) It was much larger than previous studies. This gave it greater power to detect an effect of vitamin D status on the risk of developing type 1 diabetes.

2) This was the first study to ask whether mutations in genes controlling the metabolism of vitamin D influenced the effect of vitamin D on the risk of developing type 1 diabetes.

Does Vitamin D Prevent Type 1 Diabetes?

Vitamin DThe study compared the risk of developing type 1 diabetes in children whose 25-hydroxyvitamin D levels were optimal (≥50 nmol/L) to children whose 25-hydroxyvitamin D levels were suboptimal (30 to <50 nmol/L). The results were:

  • Optimal vitamin D status during childhood was associated with a 31% decrease in the risk of developing type 1 diabetes.
  • Optimal vitamin D status during early infancy (first 12 months) was associated with a 40% decrease in the risk of developing type 1 diabetes.

In other words, having optimal vitamin D status significantly reduces the likelihood of developing of type 1 diabetes in childhood.

  • 25-hydroxyvitamin D levels >75 nmol/L provided no additional benefit.

In other words, you need sufficient vitamin D, but higher levels provide no additional benefit.

  • They tested 5 genes involved in vitamin D metabolism to see if they influenced the effect of vitamin D on the risk of developing type 1 diabetes. Only the VDR (vitamin D receptor) gene had any influence.
    • When the VDR gene was fully functional, optimal vitamin D status had no effect on the risk of developing type 1 diabetes. This means that even suboptimal (30 to <50 nmol/L) levels of 25-hydroxyvitamin D were sufficient to prevent type 1 diabetes when the vitamin D receptor was fully functional.
    • Only 9% of the children in this study were vitamin D deficient (<30 nmol/L 25-hydroxyvitamin D). Presumably, these children would be at high risk of developing type 1 diabetes even with a fully functional VDR gene. However, there were not enough children in that category to test this hypothesis.
  • When they looked at children with mutations in the VDR gene:
    • Optimal vitamin D status during childhood was associated with a 59% decrease in the risk of developing type 1 diabetes.
    • Optimal vitamin D status during early infancy (first 12 months) was associated with a 67% decrease in the risk of developing type 1 diabetes.

In short, the need for optimal vitamin D levels to reduce the risk of developing type 1 diabetes is only seen in children with a mutation in the VDR (vitamin D receptor) gene.

  • This is a clear example of genetics affecting the need for a nutrient.
    • For children with a fully functional VDR gene, even 30-50 nmol/L 25-hydroxyvitamin D was sufficient to reduce the risk of developing type 1 diabetes.
    • However, children with mutations in the VDR gene required ≥50 nmol/L 25-hydroxyvitamin D to reduce their risk of developing type 1 diabetes.
  • This is also an example of genetics affecting the need for supplementation with vitamin D.
    • 42% of the children in this study had suboptimal levels of 25-hydroxyvitamin D. Those who also have a mutation in the VDR gene would require supplementation to bring their 25-hydroxyvitamin D up to the optimal level to reduce their risk of developing type 1 diabetes.
    • Other studies have estimated that up to 61% of children in the US may have suboptimal 25-hydroxyvitamin D levels.

What Does This Study Mean For You?

Questioning WomanLet’s start with the three questions I proposed at the beginning of this article.

1) Does vitamin D prevent type 1 diabetes? Based on this study, the answer appears to be a clear yes. However, this is the first study of this kind. We need more studies that into account the effect of mutations in the VDR gene.

2) If so, is supplementation with vitamin D important? If we think in terms of supplementation with RDA levels of vitamin D or sufficient vitamin D to bring 25-hydroxyvitamin D into the optimal range, the answer is also a clear yes. However, there is no evidence from this study that higher doses of vitamin D provide additional benefits.

3) Who will benefit most from vitamin D supplementation? Based on this study, the children who will benefit the most from vitamin D supplementation are those who have a suboptimal vitamin D status and have a mutation in the VDR (vitamin D receptor) gene. To put this into perspective:

    • Up to 60% of children and adults in this country have suboptimal vitamin D levels.
    • The percentage of suboptimal vitamin D levels is highest for people who are obese, have pigmented skin, are institutionalized (eg, elderly in nursing homes), and/or live far from the equator.
    • Supplementation with a multivitamin containing the RDA for vitamin D reduces the risk of having suboptimal vitamin D status by 2.5 to 5-fold depending on the person’s ethnicity.
    • This study may be just the tip of the iceberg. The vitamin D receptor is also found on many other cells that control important biological functions.

Finally, if you are a parent or parent-to-be, you probably have several questions. Here are the ones I have New Parentsanticipated:

#1: Is my child at risk for developing type 1 diabetes? If you or a close family member has type 1 diabetes, you can assume your child is genetically predisposed to developing type 1 diabetes. Other factors that increase your child’s risk of developing type 1 diabetes are obesity, non-White ethnicity, and geographical location far from the equator.

#2: Should I have my baby tested for genetic predisposition to type 1 diabetes? That is not currently recommended. Just be aware of the risk factors listed above.

#3: Should I have my baby tested for VDR mutations? That is unnecessary. If your child has a VDR mutation, they just need sufficient vitamin D, not mega doses of vitamin D. And there are lots of other reasons for making sure your child gets sufficient vitamin D.

#4: How much vitamin D should my child be getting? The recommendation is 400 IU up to age 1 and 600 IU over age 1.

#5: Should I give my child vitamin D supplements? It is a good idea. For children over age 1, I recommend a multivitamin supplying 600 IU of vitamin D.

For infants, the American Association of Pediatrics recommends 400 IU vitamin D drops, regardless of whether the infants are breast or formula fed. That is because studies during the first year of life show that less than one-fifth of all infants get the recommended 400 IU/d from any source, and fewer than one out of 10 breast-fed infants meet the requirement – even if the mother is getting adequate vitamin D in their diet.

One Caution: I do not recommend exceeding 400 IU for infants or 600 IU for children unless directed by your health care provider. In terms of the risk of developing type 1 diabetes, your child needs sufficient vitamin D, and more is not better.

#6: Should I have my child tested for 25-hydroxyvitamin D levels? That is not done routinely at the present time. However, if your child has one or more of the risk factors listed above, it is a conversation you should have with your health care provider.

The Bottom Line

While it is widely accepted that vitamin D helps reduce the risk of developing type 1 diabetes in childhood, that has been difficult to prove. Clinical studies have provided conflicting results. The authors of a recent study postulated that the discrepancies between studies may have arisen because the studies neglected the effect of mutations in genes controlling vitamin D metabolism which may affect the ability of vitamin D to reduce the risk of developing type 1 diabetes.

This study found that:

1) Infants and children with optimal vitamin D status (25-hydroxyvitamin D levels ≥50 nmol/L) were 31-40% less likely to develop type 1 diabetes than children with suboptimal vitamin D status (25-hydroxyvitamin D = 30 to <50 nmol/L).

2) However, the effect of vitamin D on the risk of developing type 1 diabetes was only seen in children with one or more mutations in the VDR (vitamin D receptor) gene. To interpret this observation, you need to know that:

    • Type 1 diabetes is caused by an autoimmune attack on the pancreatic islet cells that release insulin.
    • 1,25-dihydroxyvitamin D promotes immune tolerance and decreases the risk of autoimmune responses.
    • 1,25-dihydroxyvitamin D exerts this effect by binding to the vitamin D receptor on the surface of immune cells.

3) Thus, mutations in the VDR gene modify the effect of vitamin D on the risk of developing type 1 diabetes. Specifically:

    • When the VDR gene is fully active, even suboptimal levels of vitamin D appear to be sufficient to prevent the development of type 1 diabetes in childhood.
    • However, when the VDR gene has mutations that reduce its activity, suboptimal levels of vitamin D no longer prevent type 1 diabetes. Optimal levels of vitamin D are required to reduce the risk of developing type 1 diabetes.

This is an example of genetics increasing the need for a nutrient (vitamin D) and increasing the need for supplementation to make sure that optimal levels of that nutrient are achieved.

While this study focused on the effect of vitamin D on the development of type 1 diabetes, this may just be the tip of the iceberg. The vitamin D receptor is also found on many other cells that control important biological functions.

For more details, read the article above. You will probably want to read the section “What Does This Mean For You?”, including my recommendations for parents of young children

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 a Genetic DNA Test Provide Real Insight on Your Health?

None Of Us Are Perfect

Author: Dr. Stephen Chaney

 

genetic dna testMost of us think of genetic diseases as something that is very rare. We have learned about diseases like cystic fibrosis or sickle cell disease in school. Those are examples of diseases caused by a rare mutation. If both chromosomes carry the mutation, you have the disease. If not, you don’t.

Can a genetic dna test give you real insight on your health?

We also know that family history is a strong predictor of genetic predisposition. If you are a guy, and most of the males in your family tree have dropped dead of a heart attack at an early age, you can assume you are genetically predisposed to heart disease. If you are a gal and most of the women in your family tree have developed breast cancer at an early age, you can assume you are genetically predisposed to breast cancer.

However, if none of these apply, we assume we are “normal”. We think we’ll probably live to 120. All this healthy lifestyle “stuff” is nice, but it isn’t a priority. It makes me think of Garrison Keillor’s tales of “Lake Wobegon” where all the children were above normal.

What if that weren’t true? What if none of us were normal? What if all of us are predisposed to some disease, perhaps even multiple diseases, and didn’t know it? Would that change how we thought about making the effort to follow a healthy lifestyle?

None Of Us Are Perfect

humans are not perfectOn one hand, this study (MacArthur et al, Science, 335: 823 – 828, 2012 ) may seem of interest only to geneticists, but its implications are huge. The authors looked at genetic variation among the human genomes sequenced as part of the human genome project. Specifically, they looked for loss of function (LOF) variants – mutations that would either partially or completely prevent the synthesis of a functional protein.

After a very complex genetic analysis they concluded that each of us harbors about ~100 LOF variants (mutations) in our genome.

Some of those mutations were in genes coding for proteins that have no known function. Other mutations coded for proteins whose loss might affect minor things like taste sensation.

Still other mutations were in genes coding for proteins that were redundant because there are other proteins in the cell that can perform the same function (Just as NASA designed the space shuttle with backup systems that could take over if a primary system failed, our bodies are frequently designed with more than one enzyme that can carry out the same function).

And, as you might expect, some of those mutations were in genes associated with known diseases like sickle cell disease or cystic fibrosis – but those mutations were very rare.

However, the authors concluded that each of us harbors about 20 LOF mutations that completely inactivate essential genes and might increase the probability that we will develop certain diseases.

That got me thinking. It validated scientifically something that we have all known instinctively for a long time – none of us are perfect. Or, as my childhood friends might have more cruelly put it: “We’re all defective in one way or another.”

What Does This Mean For You?

Now some of you may be saying: “What does this mean for me?” When you carry this idea through to its ultimate conclusion, the bottom line message is:

1) Nutritional recommendations are based on averages – none of us are average.

2) The identified risk factors for developing diseases are based on averages – none of us are average.

3) Clinical trial results are based on averages – none of us are average.

4) Clinical trials on the benefits and dangers of supplementation are based on averages – none of us are average.

5) Even clinical trials of drug efficacy for treating disease or drug safety are based on averages – none of us are average.

That means lots of the advice you may be getting about your risk of developing disease X, the best way to treat disease X, or the role of supplementation in preventing disease X may be generally true – but it might not be true for you.

So, my advice is not to blindly accept the advice of others about what is right for your body. Learn to listen to your body. Learn what foods work best for you. Learn what exercises just feel right for you. Learn what supplementation does for you.

Don’t ignore your doctor’s recommendations, but don’t be afraid to take on some of the responsibility for your own health. You are a unique individual, and nobody else knows what it is like to be you.

 

What Can a Genetic DNA Test Tell You About Your Health?

no-one is averageYou may be thinking: “If we know all the loss of function (LOF) mutations that cause disease, I should just send my saliva off to one of those companies that promises to give you a genetic DNA test and advise you of all your disease risks.”

Not so fast. It isn’t that simple. Here’s what those genetic testing companies aren’t telling you.

  • Genetic predisposition to most diseases is caused by multiple mutations that each make small contributions to your disease risk. There are only a few LOF mutations that dramatically increase your risk of major diseases like cancer, heart disease, and diabetes. Unless you have one of those rare mutations, you are in the dark about your disease risk.
  • LOF mutations are just the tip of the iceberg. There are many more mutations that affect regulation of metabolic pathways which impact your health. Many of these mutations are poorly defined at present. You might get a perfect score on your genetic testing and still be at risk for some major diseases.
  • The effect of LOF mutations on health outcomes varies from person to person. This is a phenomenon that my geneticist colleagues call “penetrance”. Simply put, the effect of any single mutation is modified by the expression of multiple other genes, which also vary from person to person. Your “score” on a genetic testing analysis may not predict your actual risk of disease.
  • Gene expression is modified by diet, lifestyle, and your environment. I have discussed this in previous articles like “Can Diet Alter Your Genetic Destiny?” and “What Is Epigenetics?”.  In short, genes do not determine your destiny. Your healthy lifestyle may protect you from a genetic predisposition to disease. Your unhealthy lifestyle may doom you to poor health in spite of a perfect score on your genetic testing analysis.

I only recommend genetic testing if you have a strong family history of a major disease and plan on working with a certified genetic counselor who can put the results of the analysis into the proper context.

 

The Bottom Line

 

  • A recent study looked at genetic variation among the human genomes sequenced as part of the human genome project. Specifically, the authors looked for loss of function (LOF) variants – mutations that would either partially or completely prevent the synthesis of a functional protein.
  • After a very sophisticated statistical analysis, the authors concluded that each of us harbors about 20 LOF mutations that completely inactivate essential genes and might increase the probability that we will develop certain diseases.
  • That means none of us are perfect. None of us are “average”. We all have genetic defects that predispose us to certain diseases. The implications are staggering.
  • Nutritional recommendations are based on averages – none of us are average.
  • The identified risk factors for developing diseases are based on averages – none of us are average
  • Clinical trial results are based on averages – none of us are average.
  • Clinical trials on the benefits and dangers of supplementation are based on averages – none of us are average.
  • Even clinical trials of drug efficacy for treating disease or drug safety are based on averages – none of us are average.
  • That means lots of the advice you may be getting about your risk of developing disease X, the best way to treat disease X, or the role of supplementation in preventing disease X may be generally true – but it might not be true for you.
  • So, my advice is not to blindly accept the advice of others about what is right for your body. Learn to listen to your body. Learn what foods work best for you. Learn what exercises just feel right for you. Learn what supplementation does for you.

I am not saying we know everything we need to know about genetic predisposition to disease. I’m not saying that genes determine our destiny. I’m not recommending you send off your saliva for a genetic analysis to determine your risk of developing a major disease. To understand why, 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.

Health Tips From The Professor