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Research on Folic Acid

Folic acid or homocysteine also have been associated with other diseases or chronic conditions.

Two studies indicate that elevated homocysteine concentrations were associated with an increased risk for bone fractures in elderly individuals (van Meurs et al. 2004, McLean et al. 2004). A longitudinal follow up study indicated that participants with high homocysteine concentrations had approximately 70% higher hip fracture risk, a relationship that was largely independent of B vitamin status (McLean et al. 2008).

Meta-analyses have reported significant positive associations between homocysteine and bone fracture risk (Yang et al. 2012b, van Wijngaarden et al. 2013). Homocysteine concentrations were significantly higher in postmenopausal women with osteoporosis compared to controls in a meta-analysis of case-control and cohort studies (Zhang et al. 2014a). A meta-analysis of randomized controlled trials failed to confirm a benefit of supplementation with folic acid, vitamin B6, or vitamin B12 toward bone turnover and fracture risk (Ruan et al. 2015).

The proposed mechanism may be the potential for homocysteine to interfere with collagen synthesis, thereby affecting bone structure independent of mineral content. A 2007 systematic review suggests that hyperhomocysteinemia adversely affects bone quality by a stimulation of bone resorption and disturbance of collagen crosslinking (Herrmann et al. 2007).

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