Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, recent research has clarified the importance of several additional nutrients and food constituents. Further, results of calcium and vitamin D supplementation trials have been inconsistent, suggesting that reliance on this intervention may be inadequate. In addition to dairy, fruit and vegetable intake has emerged as an important modifiable protective factor for bone health. Several nutrients, including magnesium, potassium, vitamin C, vitamin K, several B vitamins, and carotenoids, have been shown to be more important than previously realized. Rather than having a negative effect on bone, protein intake appears to benefit bone status, particularly in older adults. Regular intake of cola beverages shows negative effects and moderate alcohol intake shows positive effects on bone, particularly in older women. Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density.
Update on nutrients involved in maintaining healthy bone.
Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.
Rondanelli M, Opizzi A, Perna S, Faliva MA
Endocrinol Nutr Apr 2013 PMID: 23273614
[Diabetes mellitus and osteoporosis. Dietary therapy of diabetes related osteoporosis].
Diabetic patients are prone to fracture, even when their bone mineral density (BMD) is high, suggesting that BMD is not exclusive factor for bone health. Bone strength is determined by BMD and bone quality, the latter of which could influence fracture risk in diabetic patients. Calcium, vitamin D and vitamin K are essential for increasing and/or maintaining BMD. Vitamin B group and C, which contribute to maintain bone quality, are also important. Intake of these mineral and vitamins under controlling energy consumption plays a key role for bone health.
[Validation of questionnaires for the study of food habits and bone mass].
The loss of bone mass and density is influenced by nutritional factors that act on the bone mass peak, age-related bone loss and muscle strength. The objective of the present study was to validate a food frequency questionnaire applied to estimate the relationship between food habits and bone mineral density (BMD) in a healthy adult population.
The results of the food frequency questionnaire were compared with 24-hr recall findings. Calcaneus BMD was measured by densitometry.
The validity of the questionnaire was demonstrated, with Spearman correlation coefficients of 0.014 to 0.467. The Bland-Altman test also found no differences in study variables between the two methods. Correlation analysis showed that the BMD was significantly associated with the intake of vitamin D, vitamin A, vitamin B12, folate, thiamine and iron. Total fat consumption was not associated with BMD but the intake of monounsaturated fatty acids, EPA, DHA and cholesterol showed a significant correlation.
The questionnaire evaluates the consumption of energy and nutrients with adequate validity. Its application revealed the importance for bone health of a diet rich in B-group vitamins, vitamin D, calcium, iron, monounsaturated fatty acids and n-3.
The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people.
The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.
Eussen SJ, Ueland PM, Clarke R, Blom HJ…
Br. J. Nutr. Nov 2007 PMID: 17537289
Dietary intake of folate, but not vitamin B2 or B12, is associated with increased bone mineral density 5 years after the menopause: results from a 10-year follow-up study in early postmenopausal women.
Folate, vitamin B2 (riboflavin), and vitamin B12 may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on whether dietary intakes affect bone. Our aim was to investigate whether intake of folate, vitamin B2) and vitamin B12, as assessed by food records affects BMD and fracture risk. In a population-based cohort including 1,869 perimenopausal women from the Danish Osteoporosis Prevention Study, associations between intakes and BMD were assessed at baseline and after 5 years of follow-up. Moreover, associations between intakes and 5- and 10-year changes in BMD as well as risk of fracture were studied. Intakes of folate, vitamin B2, and vitamin B12 were 417 (range 290-494) microg/day, 2.70 (range 1.70-3.16) mg/day, and 4.98 (range 3.83-6.62) microg/day, respectively, i.e., slightly above the intakes recommended by the United Nations Food and Agriculture Organization. At year 5, but not at baseline, cross-sectional analyses showed positive correlations between daily intake from diet and from diet plus supplements of folate and BMD at the femoral neck (P < 0.01). However, no associations were found between intakes and changes in BMD. During 10 years of follow-up, 360 subjects sustained a fracture. Compared with 1,440 controls, logistic regression analyses revealed no difference in intakes between cases and controls. A high dietary intake of folate, but not vitamin B2 or B12, exerts positive effects on BMD; but further studies are needed to confirm this association.
Rejnmark L, Vestergaard P, Hermann AP, Brot C…
Calcif. Tissue Int. Jan 2008 PMID: 18175033
One year B and D vitamins supplementation improves metabolic bone markers.
Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people.
Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers.
At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover. One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.
Folic acid and vitamin B(12) supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized, double-blind, placebo-controlled trial.
An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B(12). The aim of this study was to determine whether there is an impact of folic acid and vitamin B(12) supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B(12) will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B(12) (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B(12) as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.
Keser I, Ilich JZ, Vrkić N, Giljević Z…
Nutr Res Mar 2013 PMID: 23507227
Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses.
Elevated homocysteine levels and low vitamin B12 and folate levels have been associated with deteriorated bone health. This systematic literature review with dose-response meta-analyses summarizes the available scientific evidence on associations of vitamin B12, folate, and homocysteine status with fractures and bone mineral density (BMD). Twenty-seven eligible cross-sectional (n = 14) and prospective (n = 13) observational studies and one RCT were identified. 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 (RR = 0.96, 95% CI = 0.92 to 1.00). Meta-analysis of eight studies including 11511 people showed an increased fracture risk of 4% per μ mol/L increase in homocysteine concentration (RR = 1.04, 95% CI = 1.02 to 1.07). We could not draw a conclusion regarding folate levels and fracture risk, as too few studies investigated this association. Meta-analyses regarding vitamin B12, folate and homocysteine levels, and BMD were possible in female populations only and showed no associations. Results from studies regarding BMD that could not be included in the meta-analyses were not univocal.
Protective effect of folic acid on cyclosporine-induced bone loss in rats.
Hyperhomocysteinemia is seen in patients with decreased bone mineral density. Cyclosporine can cause alveolar bone loss and osteopenia. It is also associated with elevated serum homocysteine levels. We aimed to investigate the effect of cyclosporine on serum homocysteine level, bone volume, and bone density, and determine whether folic acid had a protective effect against bone loss. In an experimental study, 40 male Sprague-Dawley rats were randomly assigned to five groups and received dietary supplementation for 6 weeks with olive oil (Group A), cyclosporine (Group B), folic acid (Group C), and cyclosporine plus folic acid (Group D), or no supplementation (Group F, control). Serum homocysteine, calcium, alkaline phosphatase, total bone volume, periodontal ligament volume, and volume density of bone were compared between groups. Mean serum homocysteine level (10.84 ± 0.93 μmol/l) was significantly higher in group B (cyclosporine supplementation) compared with the other groups (P = 0.001). Mean total mandibular volume was 46.3 ± 13.6 mm(3) in rats treated with cyclosporine, 80.4 ± 15.70 mm(3) in rats treated with folic acid (P = 0.004), and 73.9 ± 21.3 mm(3) in rats treated with cyclosporine plus folic acid (P = 0.028). In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine.
Mohammadi A, Omrani L, Omrani LR, Kiani F…
Transpl. Int. Jan 2012 PMID: 22039919