Nutritional Genomics in Clinical Practice – Part 2

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


Read Part 1 | Part 3

Specific Genes and Their Influence on Weight Loss

How nutritional genomics plays a role in your weightWhen 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

This 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

The nutritional genomics of 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

The nutritional genomics of 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 type of nutritional genomics 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

This gene’s nutritional genomics 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 nutritional genomics

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 Nutritional Genomics

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.

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


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