Intervention studies

High-dose B-vitamin supplementation has been proven effective for treating hyperhomocysteinemia in https://www.datingranking.net/escort-directory/des-moines/ elderly individuals with or without cognitive impairment. However, homocysteine-lowering trials have produced equivocal results regarding the prevention of cognitive deterioration in this population. A systematic review and meta-analysis of 18 randomized, placebo-controlled trials examining the effect of B-vitamin supplementation did not find that the decrease in homocysteine level prevented or delayed cognitive ong older subjects (5six). A more recent randomized, double-blind, placebo-controlled clinical trial in 900 older individuals at high risk of cognitive impairment found that daily supplementation of 400 ?g of folic acid and 100 ?g of vitamin B_{a dozen} for two years significantly improved measures of immediate and delayed memory and slowed the rise in plasma homocysteine concentrations (57). However, supplemented subjects had no reduction in homocysteine concentrations compared to baseline, nor did they perform better in processing speed tests compared to placebo. Another two-year, randomized, placebo-controlled study in elderly adults reported that a daily regimen of 800 ?g of folic acid, 500 ?g of vitamin B₁₂, and 20 mg of vitamin B₆ significantly reduced the rate of brain atrophy compared to placebo treatment (0.5% vs. 3.7%). Interestingly, a greater benefit was seen in those with high compared to low homocysteine concentrations at baseline, suggesting the importance of lowering homocysteine levels in prevention of brain atrophy and cognitive decline (58, 59). The authors attributed the changes in homocysteine levels priin B₁₂ (59). Finally, the most recent randomized, double blind, placebo-controlled trial in over 2,500 individuals who suffered a stroke showed that the normalization of homocysteine concentrations by B-vitamin supplementation (2 mg of folic acid, 500 ?g of vitamin B₁₂, and 25 mg of vitamin B₆) did not improve cognitive performance or decrease incidence of cognitive decline compared to placebo (60). Currently, there is a need for larger trials to evaluate the effect of B-vitamin supplementation on long-term outcomes, such as the incidence of Alzheimer’s disease.

Anxiety

Observational studies have found as many as 30% of patients hospitalized for depression are deficient in vitamin B₁₂ (61). A cross-sectional study of 700 community-living, physically disabled women over the age of 65 found that vitamin B₁₂-deficient women were twice as likely to be severely depressed as non-deficient women (62). A population-based study in 3,884 elderly men and women with depressive disorders found that those with vitamin B₁₂ deficiency were almost 70% more likely to experience depression than those with normal vitamin B₁₂ status (63). ₁₂ deficiency and depression are not clear but ). SAM is a methyl group donor for numerous methylation reactions in the brain, including those involved in the metabolism of neurotransmitters whose deficiency has been related to depression (64). Severe vitamin B₁₂ deficiency in a mouse model showed dramatic alterations in the level of DNA methylation in the brain, which might lead to neurologic impairments (65). This hypothesis is supported by several studies that have shown supplementation with SAM improves depressive symptoms (66-69).

Increased homocysteine level is another nonspecific bioin B₁₂ deficiency that has been linked to depressive symptoms in the elderly (70). However, in a recent cross-sectional study conducted in 1,677 older individuals, higher vitamin B₁₂ plasma levels, but not changes in homocysteine concentrations, were correlated with a lower prevalence of depressive symptoms (71). Few studies have examined the relationship of vitamin B₁₂ status, homocysteine levels, and the development of depression over time. In a randomized, placebo-controlled, intervention study with over 900 older participants experiencing psychological distress, daily supplementation with folic acid (400 ?g) and vitamin B₁₂ (100 ?g) for two years did not reduce the occurrence of symptoms of depression despite significantly improving blood folate, vitamin B₁₂, and homocysteine levels compared to placebo (72). However, in a long-term randomized, double-blind, placebo-controlled study among sufferers of cerebrovascular accidents at high risk of depression, daily supplementation with 2 mg of folic acid, 25 mg of vitamin B₆, and 500 ?g vitamin B₁₂ significantly lowered the risk of major depressive episodes during a seven-year follow-up period compared to placebo (73). Although it cannot yet be determined whether vitamin B₁₂ deficiency plays a causal role in depression, it in B₁₂ deficiency in older individuals as part of a medical evaluation for depression.