Dr. Ron’s Research Review – March 6, 2013

© 2013

This week’s research review focuses on on how alpha-tocopherol reduces gamma-tocopherol.

Gamma-tocopherol has been identified as the cause of failure of vitamin E in clinical trials. (Jialal and Devaraj 2005)

Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. (Huang and Appel 2003) (Parker 2007)

Paradoxically, meta-analysis of human randomized controlled trials revealed that natural but not synthetic alpha-tocopherol supplementation significantly increases all-cause mortality at 95% confidence interval. The root cause was that natural alpha-tocopherol supplementation significantly depressed bioavailability of other forms of vitamin E that have better chemo-prevention capability. Alpha-Tocopherol depresses the bioavailability of alpha-tocotrienol and has antagonistic effect on tocotrienols in chemo-prevention against degenerative diseases. (Gee 2011)

Dr. Ron


Articles

Unleashing the untold and misunderstood observations on vitamin E

            (Gee 2011) Download

Paradoxically, meta-analysis of human randomized controlled trials revealed that natural but not synthetic alpha-tocopherol supplementation significantly increases all-cause mortality at 95% confidence interval. The root cause was that natural alpha-tocopherol supplementation significantly depressed bioavailability of other forms of vitamin E that have better chemo-prevention capability. Meta-analysis outcome demonstrated flaws in the understanding of vitamin E. Reinterpretation of reported data provides plausible explanations to several important observations. While alpha-tocopherol is almost exclusively secreted in chylomicrons, enterocytes secrete tocotrienols in both chylomicrons and small high-density lipoproteins. Vitamin E secreted in chylomicrons is discriminately repacked by alpha-tocopherol transfer protein into nascent very low-density lipoproteins in the liver. Circulating very low-density lipoproteins undergo delipidation to form intermediate-density lipoproteins and low-density lipoproteins. Uptake of vitamin E in intermediate-density lipoproteins and low-density lipoproteins takes place at various tissues via low-density lipoproteins receptor-mediated endocytosis. Small high-density lipoproteins can deliver tocotrienols upon maturation to peripheral tissues independent of alpha-tocopherol transfer protein action, and uptake of vitamin E takes place at selective tissues by scavenger receptor-mediated direct vitamin E uptake. Dual absorption pathways for tocotrienols are consistent with human and animal studies. alpha-Tocopherol depresses the bioavailability of alpha-tocotrienol and has antagonistic effect on tocotrienols in chemo-prevention against degenerative diseases. Therefore, it is an undesirable component for chemo-prevention. Future research directions should be focused on tocotrienols, preferably free from alpha-tocopherol, for optimum chemo-prevention and benefits to mankind.

Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans

            (Huang and Appel 2003) Download

Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients. We studied the effects of supplementing diets with RRR-alpha-tocopheryl acetate (400 IU/d) on serum concentrations of gamma- and delta-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of gamma- and delta-tocopherol from baseline to the end of the 2-mo experimental period. Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001). Consistent with trial results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum gamma-tocopherol than nonusers. In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted.

Failure of vitamin E in clinical trials: is gamma-tocopherol the answer?

         (Jialal and Devaraj 2005) Download

Oxidative stress and inflammation play a crucial role in atherosclerosis. However, prospective clinical trials of dietary antioxidants with anti-inflammatory properties, such as alpha-tocopherol (AT), have not yielded positive results. AT supplementation decreases gamma-tocopherol (GT) levels. GT is an antioxidant with potent anti-inflammatory activity, and plasma GT levels are inversely associated with cardiovascular diseases. Thus, studies using pure GT, alone or in conjunction with AT, will elucidate its utility in cardiovascular disease prevention.

A recent brief critical review on how an increased intake of alpha-tocopherol can suppress the bioavailability of gamma-tocopher

         (Parker 2007) Download


References

Gee, P. T. (2011). "Unleashing the untold and misunderstood observations on vitamin E." Genes Nutr 6(1): 5-16 PMID: 21437026

Huang, H. Y. and L. J. Appel (2003). "Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans." J Nutr 133(10): 3137-40 PMID: 14519797

Jialal, I. and S. Devaraj (2005). "High-dosage vitamin E supplementation and all-cause mortality." Ann Intern Med 143(2): 155; author reply 156-8 PMID: 16027470

Parker, R. S. (2007). "A recent brief critical review on how an increased intake of alpha-tocopherol can suppress the bioavailability of gamma-tocopher." Nutr Rev 65(3): 139 PMID: 17425066

Wolf, G. (2006). "How an increased intake of alpha-tocopherol can suppress the bioavailability of gamma-tocopherol." Nutr Rev 64(6): 295-9 PMID: 16808116