Vitamin E and Bone Health — The Alpha and the Gamma
Bone Health
Vitamin E and Bone Health The Alpha and the Gamma
Abstract & Commentary
By Donald J. Brown, ND. Managing Director, Natural Product Research Consultants, Seattle, WA. Dr. Brown reports no financial relationships relevant to this field of study.
Synopsis: Alpha-tocopherol is the primary form of vitamin E used in dietary supplements. The results from this study suggest that supplementation with alpha-tocopherol by postmenopausal women may reduce serum gamma-tocopherol levels and negatively impact bone formation.
Source: Hamidi MS, et al. Effects of vitamin E on bone turnover markers among U.S. postmenopausal women. J Bone Mineral Res 2012;27:1368-1380.
Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, the researchers examined the association between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged ≥ 45 years. Adjusting for relevant confounders (e.g., ethnicity, nicotine exposure, central adiposity, dietary supplement use in the past month, and total cholesterol and triglycerides), the association between intake and serum levels of tocopherols and serum bone-specific alkaline phosphatase (BAP) and urinary N-teleopeptides/creatinine (uNTx/CR) were measured. BAP is a biomarker of bone formation and uNTx/Cr is a biomarker of bone resorption. The study sample included 497 postmenopausal women (mean age 65.5 ± 0.6 years) who were not taking estrogen, steroids, or osteoporosis medications, and were free from kidney and liver disease, cancer, and rheumatoid arthritis. All subjects were fasting for > 9 hours prior to a visit where they completed a 24-hour dietary recall and a questionnaire regarding daily intake of alpha-tocopherol from dietary supplements. Respondents were classified as vitamin E supplement users if they reported using supplements at least 15 times in the previous 30 days. Data for gamma-tocopherol were not available. Fasting serum samples were collected on the examination day and used to measure alpha-tocopherol and gamma-tocopherol. BTMs also were measured during the examination.
More than 45% of the subjects had used vitamin E (alpha-tocopherol) supplements in the past month. Among those who used dietary supplements, 81.4% consumed a supplement that contained alpha-tocopherol; other forms of vitamin E were not documented. Of those women, 39.4% had intakes > 400 IU. The average daily intake of alpha-tocopherol from supplements ranged from 6.7-1188 IU, with a median intake of 90.64 IU. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol, and a higher ratio of serum alpha-tocopherol to gamma-tocopherol than non-users. High total alpha-tocopherol and serum alpha-tocopherol were associated with decreased BAP levels in the unadjusted analysis, but not in the analysis adjusted for potential confounders. Conversely, high serum gamma-tocopherol levels and a low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (P < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr.
Commentary
Alpha-tocopherol and gamma-tocopherol are the two predominant isomers of vitamin E in the human body and diet, respectively. The other two isomers are beta-tocopherol and delta-tocopherol. Gamma-tocopherol comprises about 70% of the vitamin E in the typical American diet and is found in high levels in the commonly ingested soybean oil. Although alpha-tocopherol has higher antioxidant activity, gamma-tocopherol has superior anti-inflammatory properties.1,2 The predominant form of vitamin E used in dietary supplements, alpha-tocopherol in doses 400-1,200 IU/day, has been shown to decrease serum levels of gamma-tocopherol by accelerating its metabolism.3,4 Some experts have suggested that some of the adverse effects attributed to long-term vitamin E supplementation may be due alpha-tocopherol's depletion of gamma-tocopherol.5
The findings of this study may add further fuel to concerns about alpha-tocopherol supplementation and the depletion of gamma-tocopherol. As noted by the researchers, the results of this study, as well as in vitro and animal studies, lead to the hypothesis that gamma-tocopherol may uncouple bone turnover, resulting in increased bone formation without affecting bone resorption. In short, postmenopausal women taking vitamin E supplements in the form of alpha-tocopherol may be negatively impacting bone formation.
The Women's Health Initiative also examined the relationship between vitamin E intake, serum alpha-tocopherol and gamma-tocopherol, and bone health in postmenopausal women.6 The study found no association between tocopherols and bone mineral density (BMD). It is interesting to note that serum tocopherols reflect short-term dietary intake, while BMD is affected by long-term dietary intake. The decision to use BTMs better matches changes in bone formation and resorption with changes in serum tocopherol levels.
The researchers point out several limitations to their study. Due to the cross-sectional design, a causal relationship between vitamin E and BTM levels could not be determined. Also, they correctly point out that people consume foods and often multiple dietary supplements, not single nutrients. This may make the association between any single nutrient or select number of nutrients with disease outcomes incorrect because of residual confounding. Finally, intake of gamma-tocopherol was not available for NHANES 1999-2002.
A small handful of nutritional experts have advocated for the use of vitamin E supplements that offer mixed tocopherols with at least 50-100 IU of gamma-tocopherol per 400 IU of D-alpha-tocopherol.7 Although further research is needed to more clearly identify the role that gamma-tocopherol may play in bone formation, it may be time to heed this advice when recommending vitamin E supplements.
References
1. Jiang Q, et al. Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 2001;74:714-722.
2. Wagner KH, et al. Gamma-tocopherol an underestimated vitamin? Ann Nutr Med 2004;48:168-188.
3. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr 2003;133:3137-3140.
4. Sundl I, et al. The decrease in gamma-tocopherol in plasma and lipoprotein fractions levels off within two days of vitamin E supplementation. Ann NY Acad Sci 2004;1031:378-380.
5. Klein EA, et al. Vitamin E and the risk of prostate cancer: The selenium and vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-1556.
6. Wolf RL, et al. Lack of a relation between vitamin and mineral antioxidants and bone mineral density: Results from the Women's Health Initiative. Am J Clin Nutr 2005;82:581-588.
7. Gaby AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing; 2011: 117-129.
Alpha-tocopherol is the primary form of vitamin E used in dietary supplements. The results from this study suggest that supplementation with alpha-tocopherol by postmenopausal women may reduce serum gamma-tocopherol levels and negatively impact bone formation.Subscribe Now for Access
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