Vitamin C, Vitamin B12, Folate and the Risk of Osteoporotic Fractures. A Case-Control Study

Vitamin C is an important antioxidant and cofactor which is involved in the regulation of development, function and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures.

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“…Three of these defined a case based on fracture (hip (26,34) or any fragility fracture (35) and measured blood levels of AA. Falch, et.…”

Section: Epidemiology and Human Studies In Vitamin Cmentioning

confidence: 99%

The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments

Aghajanian

Hall

Wongworawat

et al. 2015

Journal of Bone and Mineral Research

179

141

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“…Blood vitamin C was inversely correlated with fracture risk in elderly adults 69,70 and was significantly lower in elderly osteoporotic females 29 . some studies found that low vitamin C status in smokers significantly increased the risk of hip fracture, particularly where vitamin e intake was low 66,71 , although others have found no association 72 .…”

Section: Calcificationmentioning

confidence: 98%

Cardiovascular calcification and bone: a comparison of the effects of dietary and serum antioxidants

Nicoll¹,

Howard²,

Henein³

2015

ICFJ

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Severe cardiovascular (CV) calcification can manifest as fully formed bone and is regularly found with osteoporosis; both have been shown to be associated with oxidative stress. Studies of the effect of antioxidants on CV calcification are few, but show that deficiency can induce both CV calcification and bone loss, while in conditions of oxidative stress such as renal failure, diabetes and smoking or in osteoporosis and fracture, antioxidants can reduce CV calcification and improve bone. The benefit of antioxidants in healthy adults is less clear and some may be detrimental. Higher intake of α-tocopherol (105.5mg/d vs 76.4mg/d) and β-cryptoxanthin may increase risk of CV calcification while high intake of retinol (≥3000mcg/d) may increase hip fracture risk, although possibly only with vitamin D intake ≤440IU/d; the carotenoids lycopene and β-carotene, however, appear beneficial in bone. Vitamin C shows little effect on CV calcification, although longer term supplementation may improve bone mineral density where calcium intake is >500mg/d. Potential reasons for this include a U-shaped dose/response curve for the fat-soluble antioxidants vitamins A and E (with peak bone mass achieved with retinol intake of 600–840 mcg/d), a failure to measure baseline concentrations so that the response cannot be stratified by requirement, the need to be replete in calcium and vitamin D and supplementation of the wrong isomer of vitamin E. Finally, although little studied, tocotrienols, tocopherols (with the exception of α-tocopherol), resveratrol, epigallocatechin gallate, quercetin, α-lipoic acid and N-acetylcysteine may be effective in both the CV system and bone.

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“…Results from three observational studies have indicated that significant associations with bone health 361 were surprisingly stronger for moderate rather than higher vitamin C intakes (6,79,81) . For example,…”

mentioning

confidence: 99%

“…for the second quartile (79) or for the third quartile (6,81) of vitamin C intake rather than the highest intake 364 levels. Similar cross-sectional observations have been reported for associations with serum vitamin…”

mentioning

confidence: 99%

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Is there a role for vitamin C in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence

2014

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Osteoporosis and related fractures are a major global health issue, but there are few preventative strategies. Previously reported associations between higher intakes of fruits and vegetables and skeletal health have been suggested to be partly attributable to vitamin C. To date, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention but an overall consensus of published studies has not yet been drawn. The present review aims to provide a summary of the proposed underlying mechanisms of vitamin C on bone and reviews the current evidence in the literature, examining a potential link between vitamin C intake and status with osteoporosis and fractures. The Bradford Hill criteria were used to assess reported associations. Recent animal studies have provided insights into the involvement of vitamin C in osteoclastogenesis and osteoblastogenesis, and its role as a mediator of bone matrix deposition, affecting both the quantity and quality of bone collagen. Observational studies have provided some evidence for this in the general population, showing positive associations between dietary vitamin C intake and supplements and higher bone mineral density or reduced fracture risk. However, previous intervention studies were not sufficiently well designed to evaluate these associations. Epidemiological data are particularly limited for vitamin C status and for fracture risk and good-quality randomised controlled trials are needed to confirm previous epidemiological findings. The present review also highlights that associations between vitamin C and bone health may be non-linear and further research is needed to ascertain optimal intakes for osteoporosis and fracture prevention.

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Vitamin C, Vitamin B₁₂, Folate and the Risk of Osteoporotic Fractures. A Case-Control Study

Cited by 17 publications

References 50 publications

The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments

The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments

Cardiovascular calcification and bone: a comparison of the effects of dietary and serum antioxidants

Is there a role for vitamin C in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence

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