Nutritional Genomics in Clinical Practice

By: Dr. Michael Lam, MD, MPH; Dr. Justin Lam, ABAAHP, FMNM


nutritional genomics to improve your healthWith the mapping of the human genome, completed in 2003, we discovered there are about 22,300 protein-coding genes in human beings. We’re approximately 99.9 percent identical genetically. However, in that 0.1 percent, there is significant variability. It is within that very small percentage that the new science of nutritional genomics has grown to be very important.

It enables us to study and change how people and environment interact. The new technology that comes with this new science has allowed us to map out individual genetic blueprints for people and learn how to modify them to improve people’s lives.

Definitions of Importance in Nutritional Genomics

In general, nutritional genomics studies how foods can affect our genetic expression and how individual genetic differences affect our response to nutrients. This new science thus explores how genes and diet interact.

Nutrigenomics is the exploration of how the nutrients from the foods we eat affect our gene expression and gene regulation. It is possible through this study to develop “personalized diets” based on the genetic makeup of the person and his or her nutritional needs. It will also make it possible to understand dietary components that will have a benefit or detriment to that individual’s health. The identification of the relationship between diet and chronic diseases will also grow from this study.

Another facet of nutritional genomics is nutrigenetics. This branch of the new science explores how genetic factors in an individual affects his or her response to nutrients in the diet. It can explain why and how different people respond differently to the same nutrient.

Within the dramatically increasing field of genomics research, another fascinating tool has been developed. This is CRISPR, a genome editing tool. With CRISPR, we can literally reprogram our genetic code. CRISPR stands for clustered regularly interspaced short palindromic repeats. It is an old defense mechanism in bacteria that is naturally occurring and has the ability to protect the bacteria from viruses.

Essentially, CRISPR inserts bits of viruses into the genetic code for the bacteria in order to recognize the virus if it appears again. This enables the bacteria to defend itself against the virus. Another part of this process is the use of Cas (CRISPR-associated proteins) to literally cut apart any invading virus and prevent it from replicating. With CRISPR, practitioners now can take out parts of genes and substitute others.

CRISPR technology and epigenetic manipulation pave the way for the exploration of modifying genes in order to change risk factors for several chronic health conditions. Using these tools will allow individuals to express different aspects of their genetic code in order to avoid these illness conditions.

Single nucleotide polymorphisms (SNPs) are very common variants in human genes. Every SNP is a single difference in a nucleotide in human DNA. They are biological markers that help point out genes associated with disease. The variances in genes are proteins that can be changed.

Fundamental Role of Nutritional Genomics in Illness Conditions

The World Health Organization attributed 63 percent of the deaths that occurred in 2008 to illness conditions that were not communicable. Cancers, cardiovascular disease, Type 2 diabetes, and obesity were the major culprits. All of these have dietary factors as contributors.

All of these illness conditions can be significantly influenced by dietary factors and human genomics. The new science of nutritional genomics is very important in grasping the complex combination of diet and genes that can lead to chronic illness conditions.

Diet and nutrition are basic to making changes in the genome through epigenetic modifications. Making changes in SNPs in the genome can increase the effects of nutrition on susceptibility or resilience to illness factors due to diet.

Utilizing nutritional genomics in this way challenges the typical focus of modern medicine on illnesses and replaces it with maximizing the human potential for becoming more likely to resist chronic diseases.

A major step in using nutritional genomics as an intervention in preventing chronic illness conditions is in the area of dietary signaling. The nutrients in foods we eat act as dietary signals traveling to cells in the body where they’re interpreted by kinases. Healthy signaling comes with healthy food choices.

On the other hand, poor food choices lead to disorders of kinase signaling, bringing about poor genetic expression and, eventually, chronic illness conditions. Inadequate nutrition is one of the three factors that lead to up to 90 percent of deaths from chronic illness conditions in the U.S.

In the past, we had a relationship with foods commonly eaten. Dietary signals coming through these foods maintained health. With the introduction of the Standard American Diet (SAD), foreign substances and commercially prepared foods led to cellular stress and distorted messages that negatively impact physical functioning. With an emphasis on nutritional genomics, negative dietary signals, premature aging, and chronic illness no longer have to be part of our lives.

The ultimate goal of nutritional genomics is using whole foods in our diet to prevent or at least delay the terrible health issues that are overwhelming our children. One of those catastrophic health issues plaguing our children, and adults, today is obesity.

Obesity vs Overweight

obesity and nutritional genomicsWhen addressing the issue of the epidemic of obesity in the U.S., we have to consider what we meant by that term and others. Obesity is an excess amount of body fat. Overweight is an excess amount of body weight that can be muscle, bone, fat, and water.

In the U.S. today, estimates are that more than two-thirds of adults are either obese or overweight. More than one-third are obese. More than one in twenty adults are thought to be extremely obese.

About 74 percent of men in the U.S. are thought to be overweight or obese. In both men and women, the prevalence of obesity is about 36 percent. Around 8 percent of women are considered extremely obese.

Children also suffer from this chronic condition. About a third of children age 6 to 19 are overweight or obese. One in six is considered to be obese.

Some of the illness conditions that may result from being overweight or obese include osteoarthritis, Type 2 diabetes, heart disease, high blood pressure, stroke, and some forms of cancer.

It is no surprise then, that the incidence of bariatric procedures to reduce conditions of being overweight or for obesity is increasing dramatically. From about 113,000 surgeries a year in 2009, the number of these weight loss surgeries increased to about 198,000 in 2015.

About half of the recipients of these surgeries gain back five percent or more of the weight lost over the two years post-operation. All of them must undergo significant changes in eating habits and dietary considerations. Sometimes, the emotional impact of these changes is significant.

Also no surprise is the vast number of popular diets that all promise to take off the pounds easily and keep them off. Every one of these diets has a cadre of proponents who swear by them. The truth is some diets work for some people and others work for other people.

There is no perfect diet.

weight controll and nutritional genomicsWeight loss programs based on the genetic makeup of the individual appear to be very effective. One study showed 33 percent more weight to be lost over two years when the diet was based on the individual’s genetic profile. One of the key elements in using a genetic profile in establishing a personalized diet is to be aware of which SNPs are relevant in the individual’s genetic makeup. Combinations of these SNPs can determine which diets work best for which individuals.

The one-size-fits-all viewpoint adopted by many in the diet industry and by many pharmaceutical companies no longer works. Multiple studies and clinical practice show sometimes contradictory results. In the diet industry, this is particularly true. When these studies show these kinds of results, there is something missing in the experiment. Some critical variable. And often that variable is genetics. More and more, research is showing this to be true in the case of obesity.

Obesity is probably the most common illness condition that is definitely nutrition related. It is closely associated with abnormalities of metabolism (metabolic syndrome) that includes insulin resistance, hyperinsulinemia, high blood pressure, impaired glucose tolerance, and non-insulin dependent diabetes mellitus. Often, obesity is the jumping-off point for other chronic illness conditions, such as cardiovascular disease and some kinds of cancer.

Whether an individual develops obesity is dependent on genetically determined energy balance regulation.

Obesity is also a strong cardiovascular risk factor. This highlights the fact that polymorphic genes play a part in making the individual at favorable or unfavorable risk for developing this illness condition. Nutritional genomics would suggest changes could be made in genetic expression to lower the risk factor for developing cardiovascular illness conditions and obesity.

We all know that through genetics we may be predisposed to certain health conditions. Obesity is one of them.

Working with a practitioner who is expert in genomic nutrition will enable the individual to understand how genes affect weight and how to modify genetic expression through nutrition to lose weight.

Specific Genes and Their Influence on Weight Loss

When using the principles of nutritional genomics to lose weight, the effects of numerous genes on the way we use nutrition and exercise have to be considered.

PPARG gene

This gene stimulates fat cell differentiation into smaller size cells. With this gene, a high-fat diet would stimulate fat cells to grow larger, possibly leading to insulin resistance factors. It has been associated with the development of health conditions like obesity, diabetes, and cancer. With the CG allele, individuals should avoid high-fat diets. With the CC allele, most people will respond well to just about any kind of diet. With the GG allele, results could go either way with diets.

TNF gene

The tumor necrosis factor gene is one of the insulin resistance genes. It is proinflammatory as well. Inflammation plays a major role in many chronic health conditions, including obesity. If the A allele is present, inflammation will increase greatly. In order to lose weight, this inflammation must be controlled or reduced.

VDR-fok gene

nutritional genomics and vitamin DThis is another of the insulin resistance genes. Adding vitamin D to a person’s diet will overcome this insulin resistance. This gene aids in the production of a protein called vitamin D receptor that helps our bodies utilize vitamin D. Vitamin D helps keep the proper balance of several minerals in the body, particularly calcium and phosphate. It helps control the absorption of these two minerals from the small intestine into the bloodstream. VDR helps to regulate these minerals by turning on or off the vitamin D responsive genes.

FTO gene

This is a fat mass and obesity related protein that is also called the obesity gene. It has to do with food choices and not with either metabolism or activity levels. Research indicates a variant in this gene stimulates individuals to eat more high-calorie food but doesn’t affect metabolism. It seems to increase hunger, increase impulse eating, and decrease the feeling of satiety after meals.

GCKR gene

This gene inhibits glycolysis in the liver and pancreas. It possibly leads to maturity-onset diabetes of the young. It also typically increases triglycerides.

LEPR gene

the hypothalamus and nutritional genomicsThis metabolism gene is very strong and brings on a lower resting metabolic rate. This gene helps produce a protein called the leptin receptor. This protein is involved in body weight regulation. The leptin protein is found on the surface of many cells in the body, including the hypothalamus. The hypothalamus is a brain structure involved in the control of hunger and thirst, among other things. Leptin is normally released by fat cells in proportion to their size. Larger fat cells release more leptin. This signals that fat stores are higher. A feeling of satiety is brought on by the leptin receptor being stimulated in the hypothalamus.

ADRB2 gene

This metabolism gene and another, ADRB3, help determine the best exercise for weight loss for the individual. This gene has been associated with fat distribution in the body by research. It is associated also with obesity.

PPARGC1 gene

This metabolic gene provides the benefit of endurance exercise for fat loss. It also determines the response of an individual to thermogenesis for weight loss. It is important in oxidative stress, obesity, and insulin resistance. This gene stimulates a protein called PGC-1alpha that is a major regulator of the body’s ability to produce new mitochondria. Our mitochondria are the engines that produce our body’s energy. The alpha variant of this gene is expressed in body systems that utilize large amounts of energy. Systems such as heart, brain, liver, and brown adipose tissue. It helps determine how well we use fat or glucose as fuel for the body. PGC-1alpha is currently being studied intensely in its relationship to Type-2 diabetes and insulin sensitivity. This protein also influences the production of free radicals in mitochondria. A great number of free radicals are produced in the mitochondria. In a normally functioning system, the free radicals produced are neutralized as soon as they are generated. But these free radicals are released and not neutralized in mitochondria that are damaged due to aging or illness factors. That makes PGC-1alpha important in dealing with oxidative stress.

PLIN1 gene

This is a carbohydrate gene. Individuals who have this gene can eat starchy carbs to reduce abdominal fat. This abdominal fat burns up in the presence of these carbs. Also known as perilipin, this protein provides a protective coating on lipid droplets. This serves to protect them from the body’s lipases which break triglycerides into glycerol and free fatty acids to use in metabolism. The expression of this protein is elevated in obese animals and humans. Mice with low perilipin levels have increased leptin levels and are more likely to develop insulin resistance.

TAS1R3 gene

This dopamine-related gene deals with taste. It enables the individual to taste sweet. With a risk allele, the individual can’t taste sweet and requires more sweets to have the taste.

TAS2R38 gene

Another dopamine-related gene that deals with taste, especially bitter. With a particular variant of this gene, an individual can become a “super taster.” Mostly females have this variant. It has also been implicated in food preference and intake due to differences in taste perception.

APOE3 gene

nutritional genomics and your cholesterol This gene stimulates the production of a protein called apolipoprotein E that combines with fats to produce lipoproteins. These lipoproteins carry cholesterol through the bloodstream. Normal levels of cholesterol are required for preventing disorders that affect the heart and blood vessels. High-fat diets increase lipoprotein levels thus influencing cholesterol levels that also can be synthesized by the liver. Individuals with the E4 expression will benefit from a low fat, high carb diet. Those with E2 expression will benefit more from a high fat, low carb diet. Those with the E4 variant are also at high risk for developing Alzheimer’s Disease. Variants of this gene have also been associated with cardiovascular disease, obesity, Type 2 diabetes, and metabolic syndrome.

ABCG8 gene

Assists in the production of half of a protein called sterolin, which is involved in getting rid of plant sterols. If this gene isn’t properly functioning, the plant sterols will continue working to prevent weight loss. Even vegetarians won’t be able to lose weight if this gene isn’t expressed properly.

The sterolin protein is a transporter protein. It carries plant sterols into the intestinal tract. In the liver, the sterolin adds sterols to bile, then carries it into the intestine to be expelled in feces. If this gene is mutated, it may allow a build-up of sterols, sometimes leading to atherosclerosis.

KLOTHO gene

This gene assists in the production of a protein related to beta-glucuronidase. Lower levels of this protein have been implicated in degenerative illness conditions. Mutations in this gene are also implicated in aging. It also provides a type of regulatory process concerning sensitivity to insulin.

Ways to Influence Genes with Nutrition

Everything you eat exerts some influence over your genes or vice versa. This is one of the fundamentals of nutritional genomics. The influence of nutrition on gene expression affects you physically and may affect any pathology that your genes may influence.

A nutritionally sound diet of fruits and vegetables is not only healthy for the body, it is much more than that. Instead of the classic metabolic conversion of food to energy, food also influences genetic activity. Through this influence, it also plays a part in adaptive responses to stress, metabolism, and immune responses.

Diet strongly assists in development and prevention of illness conditions related to aging. Epigenetic changes come about because of components in foods we eat. Cruciferous foods like broccoli contain a substance called isothiocyanates that can improve histone acetylation, influencing genetic expression. What this means is food not only can help us gain or lose weight, it also can bring about molecular changes in our bodies.

Diet planning for nutritional genomicsGenes associated with illness conditions such as Type 2 diabetes, cardiovascular disease, and some forms of cancer have been shown to respond to dietary factors. They can be activated by some foods we consume.

Diet also helps control our likelihood to develop some health conditions related to genes. Some genes related to health conditions also are calmed down by foods we eat.

Continued research in the new science of nutritional genomics will help us understand how our genes are influenced by diet as well as why individuals differ in their response to nutrients and diet.

Diet, Inflammation, and Genetics

Some researchers claim a diet with more than about 40 percent of the calories in carbohydrates will trigger our genes to begin the process that creates inflammation in the body. With inflammation being implicated in most, if not all, chronic health conditions, including obesity, this is something to consider.

Once our bodies respond to increased carbohydrates with inflammation, our immune systems respond as if the body has been attacked by bacteria or viruses. As soon as the immune system is triggered, insulin also is secreted and acts in one of its secondary roles in the body.

Our diets should be such that the need for insulin is not activated either by sugars or carbohydrates.

There are some specific foods that can be consumed in order to increase healthy gene expression. One of these foods is grains. Whole grains and not processed. Processed grains have the nutrient-packed outer part removed and the carbohydrate-packed endosperm left.

eaing grains and nutritional genomicsEating these grains will only increase the carbs consumed and the process of inflammation, immune response, and insulin activation is set in motion. Raw grains have large amounts of lignans, enzymes, and flavonoids. Wheat kernels and barley are good grains to eat. Barley especially is packed with B vitamins.

On the other hand, there are some possible drawbacks to eating a lot of grains. All, or nearly all, grains have some deficits in nutritional value. One of the drawbacks to eating a lot of grains is the lack of other foods that contain nutrient values.

Vitamin B12 would be low if eating a diet that is high in grains. This vitamin is found only in animal products. You would have to supplement your diet with good quality vitamin B12. A deficiency in this vitamin could lead to cognitive dysfunction, arterial vascular problems, and thrombosis. There are also elements in some grains that interfere with the absorption of nutrients from other sources. The bioavailability of some minerals is inhibited in some grains as well.

All of this argues for a well-balanced diet with grains, fruits, vegetables, and meat in balance.

A Developing Relationship

Nearly everything about the emerging science of nutritional genomics points to a developing relationship with the science behind adrenal fatigue syndrome (AFS). AFS is the condition that arises from the body’s natural response to stress. Adrenal fatigue research shows the typical sequence of processes that lead to AFS.

Once the body is faced with stress from any source, the hypothalamic-pituitary-adrenal (HPA) axis is activated. Hormones released set in motion a cascade of processes as a response to stress. At one end of that cascade is the release of cortisol by the adrenal glands. Cortisol is the stress fighting hormone of the body. Normally, once the stress is gone, cortisol levels return to normal and the adrenals rest.

stress and nutritional genomicsHowever, in this stress-filled world in which we live, stress continues. This puts an additional burden on the adrenals to continue secreting cortisol to fight the stress. Eventually, adrenal fatigue sets in. No more cortisol is available to deal with the effects of stress, and the symptoms associated with adrenal fatigue set in.

Often, these symptoms are difficult to assess by traditional methods, so they are not always recognized as all related. Some of the symptoms are similar to those encountered by practitioners using research into nutritional genomics.

The Inflammation Circuit and Nutritional Genomics

One of the most frequently seen symptoms in both AFS and nutritional genomics is an increase in inflammation. This increase in AFS comes when the lining of the gut system becomes more permeable due to imbalances in the metabolic system, allowing toxins and bacteria to enter the bloodstream. This brings an inflammatory response, prompting the immune system to activate.

Inflammation is a major factor in nutritional genomics research.

Another major part of this developing relationship has to do with a more comprehensive approach to remediating health conditions called the NeuroEndoMetabolic (NEM) stress response model. Current medicine focuses on illness conditions and their symptoms. Remediation efforts typically are directed toward single organs or individual symptoms.

This is too narrow a model to follow if healthcare professionals desire to get to the root of health problems. The NEM model views organ systems as being interrelated. What affects one, affects others.

This model also recognizes the importance of imbalances in organ systems that are due to environmental factors that include diet, nutrition, exercise, and toxins. These imbalances and their causes are filtered through a set of unique genetic predispositions, beliefs, and attitudes of the individual, as well as lifestyle choices made by individuals.

Markers such as the TNF gene can affect inflammation levels in your body. Genes such as APOE4 and PPARGC1 that influence your weight and insulin resistance may affect inflammation levels in your body as well. All of these factors must be considered in order to find the underlying pathology that causes the health conditions of people.

Metabolism is an essential aspect of this approach. Not only does it convert food into energy for our bodies to use, it also directs the body’s inflammatory response and makes sure our bodies can detox themselves. Healthy metabolism keeps our bodies safe from oxidative stress by lowering the number of toxins in the body and preventing stress from damaging our bodies.

On the other hand, a weak metabolic system reduces the ability of our bodies to absorb nutrients from foods and slows down the detoxification efforts of our bodies. This is a direct link to the new research being carried out in nutritional genomics as seen with metabolic gene markers FTO, LEPR, and ADRB2 for example.

Other Health Conditions and Nutritional Genomics

This emerging science of nutritional genomics is concerned with other health conditions in addition to obesity. These other conditions are very significant in our culture today.

Cardiovascular Disease

nutritional genomics and cardiovascular diseasePossibly the number one diet-related chronic health condition today is cardiovascular disease (CVD). Inflammation at least partially due to diet is a major risk factor. CVD is said to be a group of conditions made up of many factors that include obesity, atherosclerosis, high blood pressure, and thrombosis. All of these are influenced by dietary considerations and genetics. A strong relationship between diet and CVD has been well established.

Atherosclerosis

This condition is a combination of lipid transport and disorder of metabolism, along with high levels of inflammation. High levels of LDL cholesterol, overall cholesterol level, and triglycerides are the triggers for plaque formation that leads to atherosclerosis. High levels of HDL cholesterol are protective against this condition. People with apolipoprotein E4 and a high-fat content in their diets are at risk of developing this condition.

Arterial Hypertension

High blood pressure is affected by both genetic and dietary factors, also. Some genetic patterns have an effect on primary hypertension. The relationship between high blood pressure, obesity, and diet is well known. A decrease in blood pressure is seen when obese individuals lose weight.

Cancer

There appears to be a relationship between diet, genetics, and the emergence of cancers. Certain mutations in genes can be inherited, increasing the risk of developing cancer. This risk increases with the consideration of a diet-gene relationship. Twin studies have shown a ten percent chance of identical twins developing the same type of cancer. This suggests strongly that environmental factors (such as diet) play an important part in whether cancers develop or not.

Diet has been shown to be either a source of carcinogens or protectants for the development of cancers. It has also been shown that genetic mutations that affect metabolism can modify the chances of carcinogens coming in contact with target cells. This would occur at the initiation of the cancer process.

The influence of gene mutations on hormonal regulation is shown in those cancers that are related most closely to hormones. Breast, prostate, ovarian, and endometrial cancers are in this category. Dietary considerations also interact a great deal with hormone regulation. Obesity very much so.

Some food factors, like phytoestrogens, are metabolized by the same pathways as the sex hormones and may be affected by the mutations mentioned here.

Diet and Its Effect on Cancers

Research has shown all of the major signaling pathways detrimentally affected in different types of cancers to be influenced by nutrients. Some of these pathways include inflammation, DNA repair, oxidant/antioxidant balance, and more. To this point, over 1,000 phytochemicals have been shown to have anticancer properties.

Long-chain polyunsaturated fatty acids have been shown to have a benefit on physiological processes that are involved in nearly all chronic and degenerative illness conditions. Fish oil, with its Omega-3 fatty acids, has been shown to slow down the growth of colon tumors.

The biologically active factors in fruits and vegetables can prevent the onset of cancers through several mechanisms. They can increase detoxification efforts and thus block the metabolic activation of carcinogens. Plant foods can also increase the action of detoxification enzymes.

Diet can also increase the risk of developing some kinds of cancers. A diet high in consumption of red meat increases the risk of colorectal cancers. N-Acetyl Transferase (NAT) is implicated in acetylation of the heterocyclic aromatic amines present in muscle meat cooked at high temperatures. These amines can be activated through acetylation to ultimately bind DNA and lead to cancers. Through this process, there is an increased risk of developing colon cancer in those people who eat large quantities of red meat.

Excess body weight and lower activity levels combine to bring about one-fifth to one-third of the most common cancers. These cancers include breast, colon, endometrium, kidney, and esophagus.

Some salts and preservatives have been linked closely with the development of gastric cancer. Low levels of folate ingestion, vitamin B12, vitamin B6, or methionine have been implicated in the development of cancer in CC or TT phenotype of MTHFR gene.

Conclusion

The new science of nutritional genomics appears to hold great promise for limiting or even preventing the most common chronic illness conditions. Clearly, diet and genes are interrelated and affect each other for either good or ill.

We are what we eat, and we eat what we are. This is the relationship between diet and genes stated generally. We can choose to eat foods that improve the expression of our genes to boost our human potential. We also can eat foods that lead to better health and possibly longer life.

 
© Copyright 2017 Michael Lam, M.D. All Rights Reserved.


Dr. Lam’s Key Question

The emerging science of nutritional genomics shows how what we eat can affect the expression of our genes and how our genes influence what we eat. Diet is a major component of our health. Thus, this new science can lead to health benefits by influencing our genetic choices of foods.


nutritional genomics




Comment on the Article

Your email address will not be published.