Nutrition, Disease & Polymorphisms

By Michael McBurney, PhD, Head of Scientific Affairs at DSM Nutritional Products LLC | August 15, 2012

My paternal grandmother lived to be 101. At the time of her death, she was not taking any prescription medicines. The longevity of my maternal family, however, has been augmented by medical interventions—prescriptions, angioplasty and bypass surgery. Both sides of my family lived in the same geographic region, ate similar foods, and worked on the land. So what could account for the familial differences in disease patterns? 
The answer probably lies in our genetics. A recent article in the Journal of the American College of Surgeons reports that a specific polymorphism in the vitamin D receptor (VDR Apal A2/A2) was more frequent in 164 Caucasian women with breast cancer. The authors suggest that the frequency of this polymorphism may partially explain higher rates of breast cancer observed among women living in Marin County, CA. Only time will tell. The polymorphism may or may not turn out to be a risk factor. Indeed, a 2007 study published in Breast Cancer Research did not find a significant overall relationship between VDR polymorphisms and breast cancer risk except for an interaction between Apa1 A2/A2 genotype in women consuming high levels of calcium.
Vitamin D may not, however, be the best candidate to elucidate nutrient-gene interactions because serum 25(OH)D status can be affected independently of diet—that is, by sun exposure.
Let’s consider another nutrient: Vitamin E.
Vitamin E is of interest because the average vitamin E intake from food (7-8 mg/d) is well below the Recommended Dietary Allowance (RDA) of 15 mg/d. The Institute of Medicine defines the RDA as the average daily dietary intake level that is sufficient to meet the nutrient requirement of nearly all healthy individuals in a particular life stage and gender group. Unlike most nutrients, the RDA for vitamin E is largely based on studies relating plasma α-tocopherol concentrations with measurements of hydrogen peroxide-induced erythrocyte lysis in men fed vitamin E depleted diets. In the words of the Linus Pauling Institute website, the vitamin E RDA is based on the prevention of deficiency symptoms rather than on health promotion and prevention of chronic disease.
People using vitamin E supplements would have better intakes. Unfortunately, the most recent iteration of “What We Eat in America” (2009-2010) does not report combined food and supplement intakes for vitamin E as done for other nutrients. We do know that vitamin E supplement sales have dropped since a 2005 report concluded that high-dose (≥ 400 IU daily) supplementation should be avoided. A 2011 meta-analysis of 57 vitamin E supplementation trials reported no effect of vitamin E supplementation on all-cause mortality at doses up to 5500 IU/d. Still, fewer people seem to be using vitamin E supplements.
Is this important and what does it have to do with polymorphisms? Well, some people may be more dependent upon dietary antioxidants than others. The reason lies in the fact that red blood cells have a 90-day lifespan. When these cells lyse, a protein, haptoglobin (HP), protects us from oxidative damage when hemoglobin and iron are released.
Polymorphisms in the antioxidant haptoglobin protein have been associated with increased oxidative stress and risk of cardiovascular events. Although vitamin E supplementation doesn’t benefit everyone, middle-aged diabetic individuals with the HP 2-2 genotype had a 50% reduction in incidence of cardiovascular events when using 400 IU vitamin E daily. When two vitamin E supplementation trials, HOPE and ICARE studies, were re-analyzed with consideration of the HP genotype, vitamin E supplementation protected individuals with the HP 2-2 genotype. In other words, vitamin E-HP genotype interactions may explain null or inconsistent effects observed in past vitamin E intervention trials.
This type of nutrient-gene interaction may be quite common and these discoveries have the potential to transform how we think about diet and disease risk. What if my maternal family carried the HP 2-2 genotype and a lack of dietary vitamin E increased their cardiovascular risk? Should my entire family be advised to eat vitamin E-rich foods because some might have a higher requirement due to their HP 2-2 genotype? Or is a simpler solution to genotype my family and give personal guidance regarding use of a vitamin E supplement? I don’t have the answer but it does make one ponder nutrition policies relative to nutrient requirements and disease prevention.

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