Genetic Testing in Integrative and Functional Medicine – Part 2

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

Read Part 1 | Part 3

Eating Behavior

How does eating behavior relate to integrative and functional medicine?Integrative and functional medicine practitioners view eating behavior as important for overall health. These behaviors include snacking, feelings of satiety, craving for sweets, desire for food or certain foods, and the disinhibition of eating.

Nutrigenetics and nutrigenomics are two new fields of study related to how genes affect our diet and how our diet affects genes, respectively. Obesity, cancer, and heart disease are three of the health conditions most investigated in these two new fields.

One study involving these new fields showed the bitter taste gene receptor hTAS2R38 to be involved in tasting glucosinolates, found in some fruits and vegetables. Three genotypes in this gene receptor have been identified: PAV/PAV, PAV/AVI, and AVI/AVI.

Those individuals with PAV/PAV are said to be supertasters. They are very sensitive to bitter tastes in some foods and in some man-made compounds used in research. People with PAV/AVI are considered medium tasters. They can taste bitter in the research compounds, but not as much as the supertasters. Individuals with AVI/AVI are labeled non-tasters. They don’t taste bitter in the research compounds.

While it’s difficult to completely understand why these differences occur, it does appear they can make a difference in people’s diets. It could be that people who taste bitter greatly or somewhat will avoid certain vegetables that contain this bitter taste. Vegetables like kale and broccoli have this taste.

In this way, genetics have a significant influence on eating behavior.

Research indicates taste is only one of the ways genetics affects eating behavior. Caloric intake, meal size, and frequency of eating also appear to be affected. People’s desire for fats, carbohydrates, or proteins also may be influenced by genetics.

Integrative and functional medicine research has found apolipoprotein A-II (APOA2) to be implicated in this kind of desire. Three variants in this gene, TT, TC, and CC, have been isolated as factors affecting the choice of fats, carbs, and proteins. One study showed both men and women who had the recessive CC chose more fat and protein and fewer carbs than either of the T alleles. The CC group ate about 200 more calories than the other group and tended to develop obesity more frequently.

Having a healthy breakfast is an important factor in integrative and functional medicineIt appears that APOA2 may affect not only food choices but also feelings of satiety.

Nontasters seem to prefer and seek out fats and flavors, so dieting may be more difficult for them to stick with and lose weight. Supertasters, on the other hand, enjoy a variety of foods, especially those that are spicy and robust. This may help them with diets.

Understanding the factors that appear to influence eating behaviors has gained importance with the tremendous increase in obesity in the U.S. and around the world, along with diabetes and cardiovascular disease. Eating behavior must be seen as a complex inter-relationship among psychological, cultural, physical, and genetic factors that influence the choice of foods, the amount of food intake, caloric intake, and timing of meals.

Regulating Eating Behavior

Clearly, taste affects food choices as seen in the discussion above. Another of the bitter receptors, TAS2R5, may also assist in regulating eating behavior. Alcohol dependence has been associated with an SNP in this receptor, along with another receptor, TAS2R16. These research findings seem to indicate variants in the TAS2R gene to be associated with ingestive behavior.

Genetic influence over meal amounts, how often people eat, and the timing of meals is a new area of study and may involve digestive neuroendocrine hormones such as CCK, leptin, and ghrelin. Studies are underway investigating the effects of these hormones on pathways that influence eating behavior.

A gene with a strong association with the risk of obesity, FTO, appears to contribute to obesity by downregulating leptin production in adipocytes. Adiposity and satiety appear to be associated with a fairly common variant, rs9939609. One study showed the A allele of rs9939609 to influence post-meal feelings of satiety and possibly to influence the excess caloric intake seen in men and women with high BMIs.

A gene involved in the detoxification of nutrients during digestion, AKR1B10, also appears to play a role in influencing human eating behavior.

Nutritional Needs and Genetic Testing

Another area in which integrative and functional medicine practitioners use genetic testing is in determining nutritional needs of their patients. As we have seen previously, genetic variants have an effect on taste and thus on nutrition. When people choose foods that “fit” their tastes but are short on nutrients, their health suffers. People also appear to have genetic responses to some supplements, such as some of the B vitamins and vitamin C.

The impact of nutrition is a lifetime factor, and practitioners of integrative and functional medicine evaluate nutritional needs closely. Any genetic variant that leads to abnormal nutritional requirements would likely be incompatible with survival. For example, miscarriage is more likely in a woman whose fetus has two alleles that negatively affect the use of any given nutrient than a woman whose fetus just has the common functional variants.

Several studies have isolated genes and alleles that affect nutrients and their utilization. For example, an SNP (Ala222Val) in the methylenetetrahydrofolate reductase (MTHFR) gene leads to a significant alteration in folate metabolism, increasing the risk of neural tube defects (NTDs) and cardiovascular disease, but lowering the risk of colon cancer. Increasing folate intake lowers the risks of developing serious health conditions.

Research has found other SNPs that alter homocysteine metabolism and folate uptake and transport. SNPs in enzymes that affect utilization and metabolism of vitamin B12 seem to be associated with NTDs and the possible development of Down syndrome and colon cancer.

Integrative and functional medicine view on asthmaSNPs in the vitamin D receptor may be associated with asthma in both children and adults. Lipid pathways, alcohol metabolism, and lactose metabolism appear to be affected by SNPs in other genes, also. A beneficial effect of these SNPs in the ancestors of certain ethnic groups or ancestral subpopulations may have been present, even though they tend to carry the risk of an adverse outcome today.

Environmental changes have been shown to bring a previously silent allele into a role as a disease allele. The aldolase B enzyme metabolizes fructose and was silent even with a high number of polymorphisms. In recent times, when fructose was added to foods as a sweetener, the polymorphisms began presenting as disease alleles.

Integrative and functional medicine professionals can use this information to guide their patients into more healthy lives.

Genetic Testing and Exercise

Integrative and functional medicine also uses genetic testing to determine the best types of exercise for different people and to explore the likelihood of injuries of several kinds in athletes. This latter area of research and clinical practice can help reduce the number and severity of athletic injuries for adult and child athletes.

While there have been some gene variants associated with athletic ability, none have been shown to be predictive to any degree. Research in this area is promising for decreasing serious injury in young athletes. But to date, little scientific information regarding a genetic variation in young athletes is available.

Genetic testing as a way of choosing which athlete to select for a particular sport is increasing. However, little evidence has been found to show it is more accurate than traditional ways of selecting candidates. The ethics of this kind of testing for young athletes has been brought into question.

ACE Genes

Two genes and the SNPs associated with them have been examined in several population samples and thus have robust findings. The ACE I/D polymorphism was first found to be associated with human performance several years ago. This gene is part of the renin-angiotensin system that controls blood pressure through its effect on the regulation of body fluid levels.

The ACE I allele lowers ACE activity in serum and tissue. The D allele increases ACE activity in serum and tissue. The ACE I/I genotype has been shown over and over again to indicate performance endurance and greater efficiency in exercise. The ACE DD genotype has been shown to indicate strength and power performance levels.

This ACE I/D genotype does not appear to have predictive ability in Kenyan athletes, suggesting the confounding influence of ethnicity or geography.

ACTN3 Gene

Integrative and functional medicine and ACTN3 geneThe ACTN3 is strongly associated with the protein alpha-actinin-3. This protein is involved exclusively in fast type II muscle fibers that are used in explosive activities. SNP R577X indicates a stop codon at position 577 rather than an arginine (R). An R allele puts athletes at an advantage in power sports. A study of the ACTN3 R577X variant in elite European athletes showed those in power event to be 50 percent less likely to have the XX variant and those involved in endurance events to be 1.88 times more likely to have the XX variant. For world-class endurance athletes, the odds of having the XX variant were 3.7 times larger when compared with lower-level athletes. It appears the ACTN3 gene is more important at the upper levels of sports.

While research shows the effects of the ACTN3 gene on athletic performance, especially in higher class athletes, the effects in the general population were negligible. It is unclear just what the association of this gene in the general population and choice of athletic activities in this population might be.

Resistance to injury and the ability to recover from injuries are also very important factors not only in professional sports but also for the general population. The emphasis on physical activity currently seen in the culture increases the risk of injury and the need for information regarding recovery.

Concussions and tendinopathies have been studied fairly extensively. Information on these two growing areas of injury among young athletes has been valuable for integrative and functional medicine specialists.

These two areas are important due to the long-lasting effects of both on young athletes. Research and clinical practice have shown the effects of concussion to linger into old age where they can increase the cognitive decline normally seen at that time of life.

APOE4 Gene

A better understanding of the genetic aspects of injury and recovery can help practitioners of integrative and functional medicine to both protect those young athletes at risk for injury and to better treat those who suffer injuries.

Regarding concussion, the gene most studied is APOE and its three alleles. The APOE e4 allele has been implicated in the development of Alzheimer’s Disease. This allele has been studied recently to determine its association, if any, with concussion risk and outcomes of traumatic brain injury. To date, the results are not clear.

Some findings have shown people with the e4 allele to have less favorable outcomes from traumatic brain injuries and boxers with this allele had higher chronic brain injury scores. These findings are consistent with e4 being a risk allele. However, one study of college athletes with the e4 allele did not find them to be more likely to suffer a concussion. Another study showed the e4 allele was not associated with poorer head trauma outcomes in children.

Another APOE variant, G-219T, has been linked with increased risk of concussion in athletes. Those athletes with the TT genotype compared to those with the GG genotype had a risk of concussion three times larger. A weak association was found in that same study between the tSer53Pro polymorphism in MAPT, the tau-protein encoding gene, and risk of concussion.

Collagen Genes and Integrative and Functional Medicine

Integrative and functional medicine and collagen genesCollagen is the primary component of tendons and ligaments, thus it is connected very closely with research into tendinopathies. It is no surprise that two variants in genes coding for collagen (COL1A1 and COL5A1) have been shown to suggest increased risk of injury to tendons. MMP3, a gene associated with connective tissue wound repair and the gene encoding TNC, an extracellular matrix protein, have also been implicated in increased risk of tendinopathies.

These are preliminary studies that need replication and further study to validate the findings of integrative and functional medicine.

Read Part 1 | Part 3

© Copyright 2018 Michael Lam, M.D. All Rights Reserved.

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