Prostate Cancer and Vitamin E – The Forgotten “Nutrient of Concern”
For years, health professionals recommended vitamin E supplementation. The rationale can be found in a meta-analysis of 19 trials reporting significant increased risk of mortality associated with decreasing serum α-tocopherol concentrations below ~30 nmol/L (Fig 2). However, a 2005 meta-analysis of vitamin E intervention trials had a significant cooling effect on professional opinion, even though the pharmaceutical approach (intervention versus placebo) was used to evaluate the data did not consider serum α-tocopherol concentrations.
In a new study, Major and colleagues report that genetic variants in genes involved in vitamin E transport and metabolism may explain inconsistent conclusions from vitamin E supplementation trials, at least with respect to prostate cancer risk. Using data from 483 men with prostate cancer and 542 controls participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (mean serum α-tocopherol concentration of 44 µmol/L), they report lower prostate cancer risk among men whose genotypes reflected higher vitamin E status. In other words, men carrying single nuclear polymorphisms (SNPs) in regions affecting vitamin E transport and metabolism had lower prostate cancer risk and higher serum α-tocopherol concentrations were protective.
Other studies have found that genetics may influence vitamin E needs. Vitamin E supplementation reduced the risk of composite primary outcomes (myocardial infarction, stroke and cardiovascular death) by ~50% in individuals having a haptoglobin polymorphism (HP 2-2). Haptoglobin is an antioxidant protein where the HP 2-2 variant is less effective (vs HP1-1 and HP1-2 variants) and has a longer half-life. Carriers of the HP2-2 genotype are also at increased risk of vitamin C deficiency. All of these studies suggest that some people may be at greater health risk with suboptimal vitamin E status.
In 2010, the Dietary Guidelines Advisory Committee (DGAC) identified 10 nutrients where many people were not meeting dietary recommendations (Vitamins A, C, D, E, and K, choline, calcium, magnesium, potassium and dietary fiber). Four were named nutrients of concern (vitamin D, calcium, potassium, and dietary fiber). Vitamins A, C, K and E were not included because <5% of the population was deficient. Deficiency should not be the standard to define health. Dietary guidance should be based on maintain optimal nutrient status levels for good health.
Vitamin E (α-tocopherol) is an important antioxidant with a key role in the regulation of cell growth and differentiation. According to the CDC Second Nutrition Report Table 2.4.a.2, median serum α-tocopherol concentrations decline with age: 32 nmol/L for adults ≥ 60y, 28 nmol/L for those 40-59y, 23 nmol/L for those 30-49y, and ~18 nmol/L for those 6-19y. These levels are significantly lower than the median 44 µmol/L reported by Major et al (2014) or the ~30 nmol/L are optimal for health reported by Wright et al (2006).
Most Americans need to be consuming more vitamin E. The Institute of Medicine (IOM) set the vitamin E recommendation at 15mg RRR-α-tocopherol per day for adults. As Dr Mark Lino, USDA Economist, testified to the 2010 DGAC with regards to meeting this recommended intake within the Thrifty Food Plan basket, “We just couldn’t meet those – the cost was not the issue, it’s just the foods that are out there.” When nutrient recommendations and intake differ substantially, it justifies classifying vitamin E as a “nutrient of concern”.
With accumulating evidence that genetics may affect vitamin E requirements, vitamin E deserves more attention from researchers and policy makers. Just as was done by the IOM for vitamin D in 2011, deficiency [serum 25(OH)D levels ≤30 nmol/L] and insufficiency [ 30-50 nmol/L] concentrations need to be defined. Ultimately, optimal levels need to be identified [serum 25(OH)D concentrations].
Major JM, Yu K, Weinstein SJ, Berndt SI, Hyland PL, Yeager M, Chanock S, Albanes D. Genetic variants reflecting higher vitamin E status in men are associated with reduced risk of prostate cancer. 2014 J Nutr doi: 10.3945/jn.113.189928
Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. 2005 Ann Intern Med doi: 10.7326/0003-4819-142-1-200501040-00110
Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, Alshiek J, Bennett L, Kostenko M, Landau M, Keidar S, Levy Y, Khemlin A, Radan A, Levy AP. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: A prospective double-blinded clinical trial. 2008 Arter Thromb Vasc Biol doi:10.1161/ATVBAHA.107.153965
Cahill LE, El-Sohemy A. Haptoglobin genotype modifies the association between dietary vitamin C and serum ascorbic acid deficiency. 2010 Am J Clin Nutr doi:10.3945/ajcn.2010.29306
Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. 2008 Adv Exp Med Biol doi:10.1007/9878-0-387-77574-6_5
Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. 2006 Am J Clin Nutr 84:S1200-1207