Depression

The relationship between folate and depression has been linked to hyperhomocysteinaemia, as well as its role in neurotransmitter synthesis and methylation, independent of homocysteine (Bottiglieri et al 2005, Lerner et al 2006). Overall, it has been estimated that between 1 5% and 38% of depressed people also have a folate deficiency (AIpert & Fava 1997). Studies have demonstrated that dietary folate consumption below the median (256 fjg/day) (Tolmunen et al 2004), serum folate <3.5 ng/mL (Lerner et al 2006) and a MTHFR C677T genotype are all independently associated with an increased risk of depression (Kelly et al 2004). Preliminary evidence from a study of geropsychiatric patients has found evidence of neuropathology in the absence of frank folate deficiency prompting a reassessment of the currently accepted 'healthy range' for this subpopulation (Scott et al 2004).

A Cochrane systematic review of three controlled trials involving 247 depressed people suggested that, on the evidence available, folate shows potential, but whether its effectiveness is restricted to only those patients with an existing deficiency remains unclear (Taylor 2003). The studies assessed used 500 fjg folic acid, 15 mg methyltetrahydrofolate and 50 mg methyltetrahydrofolate once daily and lasted from 8 weeks to 6 months. Two studies used folate as an adjunct to standard therapy.

Given the volume of evidence linking folate with depression it is surprising that so few clinical trials have been conducted using folic acid.

Affects response to standard antidepressants Research investigating folate's effects on the success of antidepressant treatment has escalated in recent years and there is now evidence of a reduced response to fluoxetine with declining folate levels, from 44.7% in subjects with normal serum folate to 7.1% of patients with folate deficiency (<2.5 ng/mL) (Papakostas et al 2004a,b). Reduced folate levels have also been associated with reduced response to sertraline (Alpert et al 2003). In addition to this, poor folate status appears to negatively impact response time (+1.5 weeks) (Papakostas et al 2005) and relapse rates during continuation of fluoxetine (42.9% relapse in patients with low folate levels vs 3.2%) (Papakostas et al 2004a,b), independent of B12 and homocysteine levels.

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