The Nutritional-Supplementational Advantage – Heart Health, Genes, Custom Nutrition
The aim of this article is to examine nutritional genomics as a potential tool for individualized nutritional therapy. The genes examined were all heart health susceptibility genes and their common genetic variants. The specific genes observed in this review were methylenetetrahydrofolate reductase (MTHFR), cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), apolipoprotein C-III (apo C-III), and interleukin 6 (IL-6). The function, genetic variants, and dietary interactions related to each gene are discussed. Specific dietary recommendations have been suggested, but not confirmed, based on the type of genes one possessed.
To fully understand the paper, it is important to define the difference between the two subcategories of nutritional genomics: nutrigenomics and nutrigenetics. Nutrigenomics speaks of the functional interactions that ceratin foods have with the human genome. For example, eicosapentaenoic acid and docosahexaenoic acid (found in fish oil) increase expression of genes involved in lipid metabolism and energy and decrease expression of genes involved in inflammation. Nutrigenetics can be defined as how certain individuals with unique genetic makeup respond to certain foods. For example, the genetic variant -13910C to T causes lactose tolerance. The T allele allows for better metabolism of lactose, while the C allele causes lactose intolerance.
The MTHFR gene is of paramount importance in the metabolism of homocysteine. Studies show that slightly elevated plasma homosyssteine is a risk factor for cardiovascular disease. The MTHFR gene catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The formation of this 5-product by MTHFR provides units for the conversion of homocysteine to methionine, therefore if a genetic mutation affects the efficiency of this conversion, elevated homocysteine levels will be present in the blood. Several polymorphisms of this gene can affect the enzyme efficiency of this gene. Increasing folic acid intake in people with these genetic defects has been found to reduce the likelihood of cardiovascular disease.
The CETP gene is involved in lipid metabolism. This hydrophobic glycoprotein, secreted by the liver, decreases the cardioprotective HDL fraction and increases the proatherogenic VLDL and LDL fractions in plasma. It is therefore detrimental to cardiovascular health to increase the activity of this gene above normal levels. Several genetic variants, such as the Taq1B variant, cause a decrease in CETP mass and activity. People without beneficial genetic variants of this gene would benefit from a diet that counteracts elevated levels of active CETP in the body. No special nutritional advice was given in this case.
The LPL gene is also involved in lipid metabolism. In particular, this glycoprotein is involved in the hydrolysis of the triglyceride core of circulating chylomicrons and VLDL. A more active LDL gene correlates with lower blood triglyceride levels, making it an atheroprotective enzyme. People with the 44Ser-Ter(X) SNP have a lower risk of cardiovascular disease. The identification of a genetic variant other than this in a subject is therefore a sign to nutrigenetic companies that that individual may need additional nutritional considerations. To increase LPL expression in individuals who do not carry favorable genetic variants, fish oil has been shown to be beneficial in increasing the efficiency of these genes. Mulberry, banaba and Korean ginseng have also been shown to increase expression of the LPL gene.
The Apo C-III gene is involved in the regulation of triglyceride metabolism by affecting lipolysis and receptor-mediated uptake of triglyceride-rich lipoproteins. Any genetic variant that increases the efficiency of this gene can cause an abnormal amount of triglycerides to remain in circulation. This is a definite risk factor for cardiovascular disease. The best-known variant of this gene is the SstI variant, which is associated with a 38% increase in blood triglyceride levels. A diet high in monounsaturated fats has been found to be a good way to lower plasma LDL-C, which is a product of overexpression of the apo C III gene. It was also found that omega-3 fatty acids (fish oil) decrease the efficiency of the apo C-III gene in SstI variants.
Interleukin-6 genes are important for immune and inflammatory responses in the body, as well as for upregulating the synthesis of C-reactive proteins. A functional polymorphism as position -174G to C has been associated with altered expression of the IL-6 gene. Elevated IL-6 levels have been linked to cardiovascular disease, namely atherosclerosis. Diets focused on weight loss have been shown to reverse the effects of unfavorable genetic variants of the IL-6 gene. Fish oil, alpha-linolenic acid, and vitamin E supplementation have also been shown to reduce inflammation. This is especially important for people with genetic variants that increase IL-6, as it increases inflammation in the body.
This is a great paper that highlights some of the fundamental genes that a nutritional genetics company is looking for in patients concerned about heart health. Specific genetic variants at each gene locus have been found to increase or decrease the risk of developing any number of cardiovascular diseases. Fish oil appears to be the most important supplement that people with elevated risk factors can add to their diet to prevent future cardiovascular problems. Its benefits range from reducing the expression of unfavorable genetic variants to reducing inflammation. As the study of the human genome continues, it will be interesting to see how genetic engineering will play into the mix. When scientists have already identified which genetic variants can improve or decrease health, genetic engineering of people with favorable genetic variants to form their genome will prove beneficial in improving the health of the human population as a whole. In addition, adapting the diet to the personal genotype will prove to be very beneficial.
-Vakili, B.S. “Personalized Nutrition: Nutritional Genomics as a Potential Tool for Targeted Medical Nutrition Therapy.” Nutrition Reviews v. 65 July 2007: pp. 301-315.
Thanks to Chris Bielke
