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Additionally, a randomized, double-blind, placebo-controlled trial in 2,588 healthy older adults with mild hyperhomocysteinemia found that daily supplementation with 500 g of vitamin B 12 and 400 g of folic acid for two years reduced blood homocysteine concentrations but had no benefit on depressive symptoms in those with or without depressive symptoms at baseline (110)

They can also occur as a result of a sudden injury, such as a direct blow to the knee

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