Oral Cyanocobalamin Supplementation in Older People With Vitamin B12 Deficiency

Eussen, Simone J.P.M.; Groot, Lisette C. P. G. M. de; Clarke, Robert; Schneede, Jörn; Ueland, Per Magne; Hoefnagels, W.H.L.; Staveren, W.A. van

doi:10.1001/archinte.165.10.1167

Cited by 185 publications

(129 citation statements)

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“…Animal studies in mice and rats have already revealed that modulating Hcy levels by means of methionine-enriched diets caused an increase in bone resorption [34,35], indicating that nutrient intervention can modulate bone resorption via alteration of Hcy levels. In the elderly, Hcy levels can effectively be reduced by means of B 12 and folate supplementation [36][37][38]. The novel observation that MMA is also able to induce osteoclast formation indicates that not only Hcy but also MMA levels need to be attenuated in order to prevent osteoporosis via nutrient supplementation.…”

Section: Discussionmentioning

confidence: 99%

“…The novel observation that MMA is also able to induce osteoclast formation indicates that not only Hcy but also MMA levels need to be attenuated in order to prevent osteoporosis via nutrient supplementation. It has previously been shown that B 12 supplementation leads to a reduction in plasma MMA levels in elderly with B 12 deficiency [36,39]. To date, studies on the effect of B 12 and/or folate supplementation on bone health are limited.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B 12 deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B 12 , Hcy, and MMA on differentiation and activity of bone cells. B 12 deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B 12 deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B 12 , Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B 12 did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B 12 deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.Osteoporosis is a complex multifactorial disease with a strong genetic component, but lifestyle factors are also important for maintenance of bone mass. Nutrition is one of the factors that contributes to bone health. During the first decades of life, adequate intake of calcium and vitamin D is essential to establish peak bone mass (see [1,2] and references therein). It has also been observed that nutritional deficiencies can cause impaired growth and skeletal abnormalities during childhood [3], while in adults inadequate intake of nutrients such as proteins, vitamins, and minerals has been associated with loss of bone quality [2,4]. Nutritional deficiency is very common in the elderly, emphasizing that adequate nutrient intake may slow down the age-related loss of bone mass.A challenge in nutrition research is to identify food components that contribute to the maintenance of bone health. During the last years, vitamin B 12 has gained particular attention since a number of epidemiological studies have reported a correlation between B 12 status and bone quality and fracture risk [5][6][7][8][9]. The micronutrient B 12 is involved as a cofactor in two enzymatic reactions [10]. The enzyme methionine synthase requires B 12 for the remethylation of homocysteine (Hcy) into methionine. The other enzyme dependent on B 12 is methylmalonyl-CoA mutase, which catalyzes the conversion of methylmalonyl-CoA into succinyl-CoA. As a consequence of B 12 deficiency, these

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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“…Although a number of studies in healthy populations and in patients have investigated the effect of various doses of folic acid supplementation in lowering tHcy, few have examined the independent effects of vitamin B 12 . In those studies that have administered low-dose vitamin B 12 as a separate treatment, the response of vitamin B 12 biomarkers was the primary outcome and the tHcy response was measured as a secondary objective (21,22) . Furthermore, the study populations were selected for mild vitamin B 12 deficiency and were not pretreated with folic acid before vitamin B 12 supplementation.…”

Section: Vitamin B 12mentioning

confidence: 99%

Homocysteine, B-vitamins and CVD

et al. 2008

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There is considerable interest in plasma homocysteine (tHcy) as a CVD risk factor. Although the secondary prevention trials published to date have been inconclusive in confirming a benefit of tHcy-lowering treatment with B-vitamins on CVD events generally, such studies are widely recognised to have been insufficiently powered to detect a significant effect for the predicted magnitude of association between tHcy and heart disease risk, and therefore cannot be interpreted as evidence that no relationship exists. In fact, a recent meta-analysis of clinical trials has confirmed that folic acid supplementation reduces the risk of stroke, particularly in individuals without a history of stroke. Evidence supporting a causal relationship between elevated tHcy and heart disease also comes from genetic studies. The most important genetic determinant of tHcy in the general population is the common C677T variant in methylenetetrahydrofolate reductase (MTHFR) that results in higher tHcy. Individuals with the homozygous mutant (TT) genotype have a significantly higher (14-21 %) risk of heart disease. Plasma tHcy is very responsive to intervention with the B-vitamins required for its metabolism, in particular folic acid, and to a lesser extent vitamins B 12 and B 6 . Thus, although primarily aimed at reducing neural-tube defects, folic acid fortification may have an important role in the primary prevention of CVD via tHcy lowering. Besides folate, riboflavin is required as a cofactor for MTHFR and enhanced riboflavin status results in a marked lowering in tHcy specifically in individuals with the TT genotype, presumably by neutralising the variant form of the enzyme. About 10 % of the UK and Irish populations have the TT genotype. In the present paper the potential role of folate and related B-vitamins in the primary prevention of CVD and the implications for nutrition policy are explored. B-vitamins: Folate: Homocysteine: CVD Elevated homocysteine as a risk factor for CVDEvidence from numerous prospective and retrospective case-control studies has emerged in recent years to link elevated plasma homocysteine (tHcy) levels with an increased risk of CVD. Meta-analyses of prospective studies have predicted that lowering tHcy by 3 mmol/l (or a reduction of 25% based on an average tHcy of 12 mmol/l) would reduce the risk of heart disease by 11-16 % and stroke by 19-24 % (1,2) . Although none of the secondary prevention trials published in more recent years have been able to confirm the benefit of tHcy-lowering therapy on CVD events generally (3)(4)(5) , it should not be assumed that no relationship exists. It is now generally recognised that these trials lacked sufficient statistical power to detect an effect for the predicted magnitude of association between tHcy and heart disease (6) . In support of this viewpoint, a clear benefit in reducing stroke was shown in one of the previously mentioned 'negative' trials, although this result was not explicit in the conclusions (4) . Moreover, evidence just published from a meta-analysis o...

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“…Plasma homocysteine concentrations are influenced by a complex interaction of environmental and genetic factors, such as nutrition, lifestyle, renal function and hormonal factors. Elevated levels can be reduced by vitamin B6, B12 or folic acid supplementation, which are essential co-factors in the homocysteine metabolism (van Oort et al, 2003;Eussen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Homocysteine and the risk of nursing home admission and mortality in older persons

et al. 2011

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Background/Objectives: This study aimed to investigate whether higher homocysteine and lower vitamin B12 concentrations increase the risk of future nursing home (NH) admission and all-cause mortality in independently living older persons. Subjects/Methods: In total, 1117 independently living participants (mean age ¼ 75.1, s.d. ¼ 6.4) were included in this prospective sub-study of the Longitudinal Aging Study Amsterdam. EDTA plasma samples, collected in 1995-1996, were analysed for total homocysteine (mmol/l). Time to NH admission was assessed using a follow-up until [2002][2003]. In addition, we studied mortality until 1 June 2007. Cox proportional hazards models were used to examine the association between homocysteine in quartiles and risk of NH admission and mortality. Results: During follow-up, 126 persons (11.3%) were admitted to NHs, and 513 persons (45.9%) deceased. In men, no significant associations were observed. In women, after adjustment for confounding, the highest quartile of homocysteine was associated with a significantly higher risk of NH admission compared with the first quartile (hazard ratio (HR) ¼ 2.97, 95% confidence interval (CI) ¼ 1.36-6.49). Both women in the third and the fourth quartile of homocysteine had a significantly higher mortality risk (HR ¼ 1.70, 95% CI ¼ 1.08-2.65 and HR ¼ 1.91, 95% CI ¼ 1.22-3.00, respectively) compared with the first quartile. Vitamin B12 was not related to an increased risk of NH admission and mortality. Conclusions: Elevated plasma homocysteine is associated with an increased risk of NH admission and mortality in older women, but not in older men.

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Oral Cyanocobalamin Supplementation in Older People With Vitamin B12 Deficiency

Abstract: The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12) deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 mug daily.

Cited by 185 publications

References 22 publications

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Homocysteine, B-vitamins and CVD

Homocysteine and the risk of nursing home admission and mortality in older persons

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