Correlation of Clinical Response With Homocysteine Reduction During Therapy With Reduced B Vitamins in Patients With MDD Who Are Positive for <em>MTHFR</em> C677T or A1298C Polymorphism

Abstract

Objective: This study was designed to evaluate the efficacy and safety of reduced B vitamins as monotherapy in adults with major depressive disorder (MDD) who were also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with depression and further test the hypothesis that reduced (metabolized) B vitamins will lower homocysteine in a majority of clinically responding patients. Methods: 330 adult patients with MDD (DSM-5) and positive for either MTHFR C677T or A1298C polymorphism were enrolled in a trial conducted between August 1, 2014, and April 3, 2015. 160 patients received placebo, while 170 received a capsule containing a combination of reduced B vitamins. Plasma homocysteine levels were measured at baseline and week 8. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate efficacy for MDD. Results: 159 of 170 vitamin-treated patients and 123 of 160 placebo-treated patients were completers. Of the active treatment group, 131 (82.4%) showed a reduction in homocysteine (for a mean in this subgroup of 25%, P < .001), while 28 (17.6%) showed no significant change.Placebo patients demonstrated a small elevation in homocysteine. Active-treatment patients demonstrated, on average, a 12-point reduction on the MADRS by week 8, and 42% achieved full remission (P < .001). No side effect was significantly different between groups. No patients experienced mania. Conclusions: A combination of reduced B vitamins and micronutrients, when used in the treatment of MDD in patients with MTHFR polymorphism, resulted in a separation from placebo by week 2, and 42% of the treatment arm achieved remission by week 8. Further, clinical improvement correlated with a significant reduction in homocysteine levels in a majority of responders. These results support the homocysteine theory of depression and the safety and therapeutic benefit of reduced B vitamins as monotherapy for MDD, particularly in patients with MTHFR polymorphism. Trial registration: ClinicalTrials.gov identifier: NCT02709668 Clin Psychiatry 2016;77(5):668-671 dx.doi.org/10.4088/JCP.15m10166 J

Vitamin‐mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo‐controlled trial

“…High levels of homocysteine have been implicated in increasing oxidative stress, inhibiting methylation reactions, and increasing DNA damage (Kennedy, ). Reduction of homocysteine levels has been associated with improvements in mood (Mech & Farah, ) and cognitive function (Smith et al., ). Micronutrients also assist with the citric acid cycle and electron transport chain, acting as co‐enzymes in mitochondrial aerobic respiration and energy production (Kennedy, ).…”

“…Subsequently, the considerable human research has suggested that broad-spectrum micronutrient treatment approaches have been more beneficial for the improvement of mood and behaviour than single nutrient studies (for reviews see: (Kaplan, Crawford, Field, & Simpson, 2007;Popper, Kaplan, & Rucklidge, 2017;Rucklidge, Johnstone, & Kaplan, 2009;Rucklidge & Kaplan, 2013). There are now a number of double-blind randomized controlled trials (RCT) supporting the positive effect of broad-spectrum micronutrients for the treatment of symptoms associated with clinical conditions, including autism (Adams et al, 2011), ADHD (Rucklidge, Frampton, Gorman, & Boggis, 2014), conduct disorder (Schoenthaler & Bier, 2000) and depression (Mech & Farah, 2016).…”

An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms

“…V itamins and minerals (micronutrients) given in combination may provide an alternative to medication for the treatment of mental health issues with a growing body of literature supporting their efficacy. 1,2 Indeed, providing nutrients in combination appears to show some clinical benefit based on randomized placebo controlled trials (RCTs) [3][4][5][6][7] ; however, there are little long-term data systematically investigating their safety. A study that has investigated safety within a mostly North American community setting showed a reassuring safety profile.…”

Pathogenetic effects of folate-containing combined oral contraceptive in patients with PCOS

“…A. Mech и соавт. [29] продемонстрировали преимущества метилфолата и других биоактивных витаминов группы В в качестве монотерапии у пациентов с мутациями гена MTHFR и тяжелым депрессивным расстройством.…”