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Do vitamin E supplements have a negative effect on bone formation?

Published on

23 March 2012

A new experiment using rodents and a study in postmenopausal women hypothesize that vitamin E supplements may be related to bone loss. Experts criticize that neither feeding rodents with extremely high doses of vitamin E nor measuring bone formation indirectly via a fault-prone marker in women would justify translating the findings into recommendations for supplement users.

To investigate the role of vitamin E in bone remodeling, bone mass and serum concentrations of alpha-tocopherol (the most predominant form of vitamin E in the body) were measured in mice with genetically induced vitamin E deficiency and non-modified animals (1). The study results showed that the modified rodents developed a higher bone mass as a result of a lower bone resorption activity compared to wild-type mice. In contrast, the bone formation activity was the same in both types of mice. Based on these findings, the researchers suggested that vitamin E seems to be an essential cofactor in the formation of bone resorbing cells (osteoclasts), which could possibly explain the beneficial effects of vitamin E in human studies related to bone health.

Furthermore, the scientists observed a reduction of bone mineral density when applying extremely high doses of alpha-tocopherol in the rodents’ diet. Experts noted that 600 mg of vitamin E per kg of body weight was applied to mice and rats, which would amount to 42 g of vitamin E per day for person weighing 70 kg. Considering that the tolerable upper intake level (UL) level of vitamin E is 1 g/day (US), this amount would be beyond any possible intake achievable by humans. Prudence should be used in trying to translate these experimental findings in rodents receiving extremely high and non-physiological doses of alpha-tocopherol into recommendations for humans.

In an experiment, blood samples of 497 postmenopausal women (mean age of 65.5 years) were analyzed to examine potential associations between dietary and total (dietary plus supplemental) alpha-tocopherol intake, gamma-tocopherol levels and blood concentrations of markers for bone formation and resorption, (2). The study results showed that high serum gamma-tocopherol levels and low serum alpha-tocopherol were associated with increased levels of a bone formation marker. The researchers hypothesized that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. On the other hand, people taking vitamin E (alpha-tocopherol) supplements had significantly lower serum gamma-tocopherol and higher serum alpha-tocopherol levels than those who did not use supplements. The scientists speculated that vitamin E supplements in the form of alpha-tocopherol may suppress serum gamma-tocopherol levels and therefore may have negative effects on bone formation.

Experts criticized the study for major shortcomings that place the main outcome in question. The measured bone formation marker was no longer the marker of choice, which they cited is because it potentially delivers unclear results. Furthermore, they pointed out that proof for the bone forming effect of gamma-tocopherol is currently lacking and any influence of alpha-tocopherol (from supplements) on gamma-tocopherol levels for bone health must be purely speculative.

Bone mass is maintained constant from puberty until menopause by a balance between bone formation by osteoblastic cells and bone resorption by osteoclastic cells, a process called bone remodeling. Among the fat-soluble vitamins AD and K are well known for their ability to maintain the skeleton (3,4), however, vitamin E has not been thoroughly examined in the process of bone remodeling. Vitamin E is an antioxidant that inhibits lipid peroxidation by scavenging reactive oxygen species and is believed protect against atherosclerotic change and the aging process (5).


  1. Fujita K. et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med. Published online March 2012.
  2. Hamidi M. S. et al. Effects of vitamin E on bone turnover markers among US post-menopausal women. J Bone Miner Res. Published online February 2012.
  3. Kato S. et al. The function of nuclear receptors in bone tissues. J. Bone Miner. Metab. 2003; 21:323–336.
  4. Cockayne S. et al. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch. Intern. Med. 2006; 166:1256–1261.
  5. Azzi A. et al. Specific cellular responses to ?-tocopherol. J. Nutr. 2000; 130:1649–1652.

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