genetic testing

Can Lifestyle Overcome Bad Genes?

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Lifestyle, Genetics, And Dementia Risk 

Author: Dr. Stephen Chaney 

Cognitive-DeclineAlzheimer’s disease and other forms of dementia are among the most feared diseases of aging. What use is it to have a healthy body, a loving family, and a successful career if you can’t remember any of it? You should be able to enjoy your Golden years, not see them slip through your fingers.

If you have a family history of dementia or have sent your DNA off for testing and learned you are genetically predisposed to dementia, you are probably worried.

Perhaps the scariest thing about Alzheimer’s is that the medical community has no answers. There are no drugs to prevent or cure Alzheimer’s and brain transplants are out of the question. Some medical professionals will tell you nothing can be done, but is that true?

Before I answer that question 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 genes do not have to determine our destiny. We have the power to overcome bad genetics. We also have the power to undermine good genetics.

With that in mind, let’s return to Alzheimer’s. Studies have suggested that a healthy lifestyle can help reduce your risk of developing Alzheimer’s and other forms of dementia. But what about genetics? Will a healthy lifestyle only reduce your risk of dementia if your genetic risk is low, or will it be equally effective when your genetic risk is high? Can lifestyle overcome genetics?

The current study (A Tin et al, Neurology, 99: e154-e163, 2022) was designed to answer these questions.

How Was This Study Done?

clinical studyThis study included 11,561 participants from the Atherosclerosis Risk In Communities (ARIC) study. The ARIC study recruited middle-aged adults (average age of 54) from both urban and rural areas of the United States and followed them for 26 years. The participants were 57% female and 53% white.

Simply put, the study was designed to look at the effect of a healthy lifestyle on the genetic risk of developing dementia.

A healthy lifestyle was defined based on something called “Life’s Simple 7” (LS7) score.

  • The LS7 score was developed by the American Heart Association to define the effect of lifestyle on the risk of developing heart disease. However, it works equally well for defining the effect of lifestyle on risk of developing dementia.
  • The LS7 score consists of 7 modifiable health factors.
    • The factors are diet, physical activity, BMI (a measure of obesity), smoking, total cholesterol, blood pressure, and fasting blood glucose.
  • The data for deriving the LS7 scores were derived from data gathered from each participant when they enrolled in the ARIC study.
    • Diet was assessed by a 66-item food frequency questionnaire.
    • Physical activity and smoking were assessed in separate questionnaires.
    • BMI, blood pressure, total cholesterol, and fasting blood glucose were measured during a visit to a designated clinic at the beginning of the study.
  • Each modifiable health factor was separated into 3 categories (ideal, intermediate, and poor) and the highest score was assigned to the ideal category. The LS7 score was the sum of the scores from all 7 modifiable health factors.

Genetic risk of developing dementia was defined based on something called “The Genetic Risk Score” (GRS).

  • We have known for years that individuals of European descent who have the APOE ɛ4 gene variant have a 2 to 5-fold increased lifetime risk of developing dementia.
  • In recent years scientists have discovered several additional gene variants that increase the risk of dementia.
  • These have been combined with APOE ɛ4 to create a Genetic Risk Score for dementia.
  • The Genetic Risk Score for each participant was determined by DNA sequencing at the beginning of the study, with the highest score indicating the greatest risk for developing dementia.

The onset and severity of dementia were determined based on 7 clinic visits during the study.

  • Questionnaires were administered at each visit to assess self-reported dementia symptoms.
  • Cognitive tests were administered at visits 2 and 4.
  • Detailed cognitive and functional assessments were conducted at visits 5, 6, and 7.
  • The data were reviewed by an expert committee of physicians and neuropsychologists to determine dementia status.

Lifestyle, Genetics, And Dementia Risk

DNA TestingAt the end of the 26-year study:

  • When participants with the highest Genetic Risk Scores were compared to those with the lowest Genetic Risk Scores:
    • European American participants were 2.7-fold more likely to develop dementia.
    • African American participants were 1.55-fold more likely to develop dementia.
  • When participants with the highest LS7 (healthy lifestyle) scores were compared to those with the lowest LS7 scores:
    • European American participants were 40% less likely to develop dementia.
    • African American participants were 17% less likely to develop dementia.
    • A healthy lifestyle decreased the risk of developing dementia to a comparable extent at all levels of genetic risk for dementia.

The authors concluded, “Higher LS7 scores [a measure of a healthy lifestyle] are largely associated with a lower risk of incident dementia across strata of genetic risk [at all levels of genetic risk], supporting the use of LS7 [a healthy lifestyle] for maintaining brain health and offsetting genetic risk. More studies with larger study populations are needed…”

I should briefly comment on why African Americans were less responsive to both genetic risk and a healthy lifestyle than European Americans. The reasons for these discrepancies are not known, but:

  • There are socioeconomic factors and health disparities that increase the risk of dementia that are not included in the LS7 score.
  • A recent study has identified genetic risk factors for dementia that are unique to African Americans that are not included in the genetic risk score used in this study.

Can Lifestyle Overcome Bad Genes?

Dr. James Watson, who was co-discoverer of the DNA double helix and was heavily involved in the sequencing of the human genome, asked that he not be told about his risk of developing Alzheimer’s when his own DNA was sequenced in the early 2000’s. His reasoning was, “Why know the risk if you can’t change it?”

If the study I discussed today is true, you can modify the risk. Your genes don’t have to be your destiny. But is it true?

There is good reason to believe it might be true. Multiple studies have shown that each of the health factors included in LS7 score reduce the risk of developing dementia. However, most of those studies have not looked at the interaction between a healthy lifestyle and genetic risk.

Fortunately, there is another recent study that looked at the interaction between a healthy lifestyle and genetic risk of developing dementia.

  • This study used a different database (The UK Biobank study which enrolled 500,000 participants) and different criteria for defining a healthy lifestyle (diet, physical activity, smoking, and alcohol use).

However, the conclusions of this study were very similar:

  • People at high genetic risk were almost twice as likely to develop dementia as those at low genetic risk.
  • A healthy lifestyle decreased the risk of developing dementia by about 40% for both people at high genetic risk and for people at low genetic risk.

But this study went one step further than the study I discussed in this article. The British study reported that:

  • People at low genetic risk and an unhealthy lifestyle (the typical American) were just as likely to develop dementia as people at high genetic risk and a healthy lifestyle.

In other words, bad genetics does not doom you to Alzheimer’s and dementia. A healthy lifestyle can cut your risk almost in half. Conversely, good genetics is not a “Get Out of Jail Free” card. You can squander the advantage of good genetics with an unhealthy lifestyle.

And, just like the hero of the movie I discuss at the beginning of this article, a healthy lifestyle may be able to overcome bad genes and make you just as healthy (with respect to the risk of developing dementia) as people with good genes and an unhealthy lifestyle – which includes most Americans.

The Bottom Line 

Alzheimer’s disease and other forms of dementia are among the most feared diseases of aging. What use is it to have a healthy body, a loving family, and a successful career if you can’t remember any of it?

If you have a family history of dementia or have sent your DNA off for testing and learned you are genetically predisposed to dementia, you are probably worried.

Perhaps the scariest thing about Alzheimer’s is that the medical community has no answers. There are no drugs to prevent or cure Alzheimer’s and brain transplants are out of the question. Some medical professionals will tell you nothing can be done, but is that true?

Studies have suggested that a healthy lifestyle can help reduce your risk of developing Alzheimer’s and other forms of dementia. But what about genetics? Will a healthy lifestyle only reduce your risk of dementia if your genetic risk is low, or will it be equally effective when your genetic risk is high? Can lifestyle overcome genetics?

A recent study was designed to answer these questions. It found:

  • When participants with the highest Genetic Risk Scores were compared to those with the lowest Genetic Risk Scores:
    • They were 1.5 to 2.7-fold more likely to develop dementia.
  • When participants with the highest LS7 (healthy lifestyle) scores were compared to those with the lowest LS7 scores:
    • They were 17% to 40% less likely to develop dementia.
  • A healthy lifestyle decreased the risk of developing dementia to a comparable extent at all levels of genetic risk for dementia.

The authors concluded, “Higher LS7 scores [a measure of a healthy lifestyle] are largely associated with a lower risk of incident dementia across strata of genetic risk [at all levels of genetic risk], supporting the use of LS7 [a healthy lifestyle] for maintaining brain health and offsetting genetic risk. More studies with larger study populations are needed…”

This, and other studies discussed in this issue of “Health Tips For The Professor” suggest that your genes don’t have to determine your destiny. You can overcome bad genes with a healthy lifestyle.

For more details on this study, 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?

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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.

Health Tips From The Professor