Reduced B vitamins help depressed patients with MTHFR C677T or A1298C polymorphisms

Scientific evidence keeps supporting the fact that nutrigenetics is ready for its primetime as a key piece of the jigsaw that is personalised nutrition, both for "simply" enhancing or optimising health in those patients who do not suffer from a diagnosed pathology, and for the fine-tuning and individualisation of care in those who are affected by a condition, sometimes with serious ramifications, such as major depressive disorder (MDD). 

Why is homocysteine relevant in the context of mental health? 

Homocysteine is an auto-oxidative molecule that results from the normal metabolism of the amino acid cysteine. Research shows that individuals with certain enzyme polymorphisms need higher amounts of B vitamins (particularly methyl donor B vitamins like B9/folate, B6 and B12) in order to clear homocysteine from their system and avoid homocysteinuria, the condition characterised by excessive accumulation homocysteine. 

Because homocysteine is oxidative in nature, it adds to the free radical load that contributes to neurodegeneration, which is why it is highly relevant in the context of mental health and cognitive function. High homocysteine is also an independent marker of cardiovascular disease risk, and of conditions like Alzheimer's Disease that have a vascular component to their pathogenesis.

And why is this trial and its results relevant?

A total of 330 patients were enrolled in this trial, and tested for both MTHFR C677T and A1298C polymorphisms in their methylenetetrahydrofolate reductase (MTHFR) gene. Patients' homocysteine levels were also measured at baseline and after 8 weeks. The treatment was based on 3 different forms of folate (vitamin B9), namely 1mg of citrated folic acid, 2.5 mg of folinic acid, and 7mg of l-methylfolate magnesium, 25μg of thiamine pyrophosphate, 25μg of flavin adenine dinucleotide, 25μg of pyridoxal 5’-phosphate, 50μg of adenosylcobalamin, 25μg of thiamine pyrophospahate, 25μg of nicotinamide adenine dinucleotide (NADH), 500μg of trimethyl glycine, 1.5mg of ferrous glycine cysteinate, 24mg of magnesium ascorbate, 1mg of zinc ascorbate, 1mg of l-threonic acid magnesium, and 20mg phosphatidylserine-omega-3 conjugated, administered for 8 weeks. 

 The results of the trial, published in the Journal of Clinical Psychiatry are significant for a number of reasons. The sample size (n=330) is modest but certainly not small, and the duration of the intervention, with a reassessment at 8 weeks, was long enough to ensure that the compliance of the treatment with reduced B vitamins was followed with excellent compliance. 

In those patients receiving supplementation (n=170) the combination of reduced B vitamins and micronutrients resulted in a clear separation from placebo by the second week of treatment. 42% of those patients achieved remission by week 8 without the need of further medication. Additionally, clinical improvement was strongly correlated with a significant reduction in homocysteine levels in a majority of responders. These results are significant because a) they support the homocysteine theory of depression and b) the safety and therapeutic benefit of reduced B vitamins as nutritional therapy for MDD, particularly in patients with MTHFR polymorphism.

References

Mech A., Farah A. (2016) Correlation of clinical response with homocysteine reduction during therapy with reduced B vitamins in patients with MDD who are positive for MTHFR C677T or A1298C polymorphism: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry, Mar 29. [Epub ahead of print]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27035272