27 May, 2013: 

Have you heard of a potential interaction between vitamin E and bone health? A recent study from Spain evaluated the relationship between vitamin E status and osteoporosis in early postmenopausal women [1]. Anthropometric data, osteoporosis risk factors, vitamin E serum levels, bone mineral density (BMD) and other serum parameters that may influence bone mineral density in postmenopausal women were analyzed in a cross-sectional study. The associations between osteoporosis and age, age of menopause, body mass index, osteocalcin, calcium, vitamin D, vitamin E (measured as 25-hydroxyvitamin D and as the α-tocopherol : lipid ratio, respectively), bone alkaline phosphatase, smoking status, leisure physical activity and alcohol intake were modeled by a multivariate logistic regression and multi-linear regression analysis in 232 early postmenopausal women. A lower vitamin E : lipid ratio was associated with osteoporosis in multivariate logistic regression. In a multivariate linear model with BMD of the lumbar spine as a dependent variable, the vitamin E : lipid ratio was clearly related with BMD of the lumbar spine (Fratio = 6.30,p= 0.002). BMD of the lumbar spine was significantly higher in the highest tertile of the vitamin E : lipid ratio than in the lowest tertile. The mean vitamin E : lipid ratio was significantly lower in osteoporotic postmenopausal women (Tscore ≤ -2.5) (3.0 ± 0.6 μmol/mmol) than normal postmenopausal women (Tscore > -1) (3.5 ± 0.7 μmol/mmol) using multivariable-adjusted BMD. These findings highlight that vitamin E may increase BMD in healthy postmenopausal women.

Comment

Vitamins are organic compounds required by an organism as a vital nutrient in limited amounts. An organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism and must be obtained from the diet. Each and every vitamin has its place in human physiology and severe deficiencies are well described; however, medical research probably has not yet reached the point of optimal knowledge on the effects of vitamins in the various bodily organs and systems. Clearly, the most relevant vitamin in the context of bone is vitamin D, which has a pivotal role in calcium–phosphorus metabolism and in maintaining bone health. But what are the effects of other vitamins, less recognized in this respect? Here is a short summary of the data on consumption of vitamins and risk of osteoporosis or fractures.

A prospective study from Singapore evaluated the association between any vitamin B (thiamin, riboflavin, niacin, pyridoxine, folate, and cobalamin) and risk of hip fracture in a population-based cohort that enrolled a total of 63,257 men and women aged 45–74 years [2]. After a mean follow-up period of 13.8 years, 1630 hip fracture incident cases were identified. A statistically significant inverse relationship between dietary pyridoxine intake and hip fracture risk was observed among women (pfor trend  =  0.002) but not among men. Dietary intakes of the other B vitamins of interest were not related to hip fracture risk. A recent overview reached somewhat similar conclusions [3]: 14 cross-sectional and 13 prospective observational studies and one randomized controlled trial were eligible. Meta-analysis on four prospective studies including 7475 people showed a modest decrease in fracture risk of 4% per 50  pmol/l increase in vitamin B12 levels, which was borderline significant (relative risk (RR) 0.96, 95% confidence interval (CI) 0.92–1.00). Meta-analysis of eight studies including 11,511 people showed an increased fracture risk of 4% per μmol/l increase in homocysteine concentration (RR 1.04, 95% CI 1.02–1.07). A conclusion regarding folate levels and fracture risk could not be drawn as too few studies investigated this association.

As for the other major vitamins, there are inconsistent results, as nicely reviewed by Ahmadieh and Arabi [4]. Their conclusion in regard to vitamin A, addressing the worry that high doses may be harmful to bone health, was that studies evaluating the association between serum retinol level or retinol intake and skeletal health in humans showed inconsistent results. Vitamin C (ascorbic acid) intake was investigated in regard to BMD in several large studies including the PEPI and WHI trials. PEPI found a positive association between vitamin C intake and BMD of the spine and hip, whereas, in the WHI study, although there was no significant association between vitamin C intake and BMD, the beneficial effect of hormone treatment on BMD at all skeletal sites was stronger with higher intakes of vitamin C [5]. Data on vitamin C were summarized by Ahmadieh and Arabi in the following way: ‘There is a positive but complex association between vitamin C intake and bone density, which may be related to the interaction of other factors like smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin E intake.’ The relationships between vitamin K (phylloquinone) and bone health are once again a little complicated. Although studies have shown that low circulating levels and/or low dietary intake are associated with low bone density and with increased fracture risk in humans, a protective effect of vitamin K supplementation was not confirmed in randomized controlled trials [4].

The fact that different vitamins, which act through seemingly different pathways (i.e. calcium–phosphorus homeostasis (vitamin D), or as anti-oxidants (vitamins E and C), or involved in the coagulation cascade (vitamin K), or being vital for vision (vitamin A), may still have bone effects as well is very intriguing. The relationships between vitamins other than vitamin D on bone are complex and are probably affected by many factors, including menopause and postmenopausal hormone therapy. Vitamins are essential to all cells and tissues, including bone, and therefore a healthy and well-balanced diet is always important.

Amos Pines
Department of Medicine ‘T’, Ichilov Hospital, Tel-Aviv, Israel

References

1. Mata-Granados JM, Cuenca-Acebedo R, Luque de Castro MD, Quesada Gómez JM. Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study. J Bone Miner Metab 2013 Mar 28. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/23536191
2. Dai Z, Wang R, Ang LW, Yuan JM, Koh WP. Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study. Osteoporos Int 2012 Dec 13. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/23238962
3. van Wijngaarden JP, Doets EL, Szczecińska A, et al. Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses. J Nutr Metab 2013;2013:486186.
http://www.ncbi.nlm.nih.gov/pubmed/23509616
4. Ahmadieh H, Arabi A. Vitamins and bone health: beyond calcium and vitamin D. Nutr Rev 2011;69:584-98.
http://www.ncbi.nlm.nih.gov/pubmed/21967159
5. Wolf RL, Cauley JA, Pettinger M, 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;82:581–8.
http://www.ncbi.nlm.nih.gov/pubmed/16155271