The success of antidepressant drug therapy is not high, with studies suggesting 19%-60% of patients are unresponsive to the treatment.[1,2] It is essential that we continue the search for more effective mood disorder management. Integrative approaches may complement pharmaceuticals, or, offer an alternative in cases where negative side effects or contraindications are noted.
Antidepressant drugs function to prevent the re-uptake or degradation of our “feel good” neurotransmitters: serotonin, dopamine and noradrenalin. But what if an individual is depleted of these chemicals due to nutritional insufficiencies? Is this an underlying factor that must be addressed before optimal outcomes can be achieved? If so, how do we determine this, and how do we correct it?
Methylation support appears to be one very important piece of the mood puzzle. Methylation is required to manufacture neurotransmitters, and it’s no surprise then that hyperhomocysteinaemia, a complication of under-methylation, has been noted in both depression and bi-polar depression. Additionally, deficiencies in folate and vitamin B12, two key methylation nutrients, positively correlate with depression risk. Furthermore, it has been suggested that accumulation of homocysteine leads to excito-toxic reactions and may enhance depression, whilst high levels also interfere with GABA binding at its receptor contributing to anxiety.
Evidently, B vitamin supplementation to reduce homocysteine has demonstrated to reduce depression scores and improve cognitive function. This seems to support the hypothesis that such nutrients are key drivers in mood disorder management.
Supplying the methylation nutrients will assist not only in a reduction in the damaging chemical homocysteine, but will also improve beneficial neurotransmitter availability and therefore, offer a potential reduction in the symptoms of mood disorders.
When looking to provide the most suitable supplement for your patient, folinic acid (5-formyl THF) may be a superior choice in some instances where methylation support with folate is required. Synthetic folic acid requires numerous steps to be converted to 5-MTHF.
Folinic acid is a form of folate which naturally occurs within the food chain and is believed to be more biologically active. Folinic acid by-passes the deconjugation and reduction steps (involving dihydrofolate reductase (DHFR)) required for folic acid to be activated. Folinic acid may be the more desirable supplement for patients with malabsorption issues (e.g. inflammatory bowel disease), on specific medications or individuals with single nucleotide polymorphisms (SNPs) on the genes encoding for the DHFR enzyme.
Magnesium, zinc  and omega-3 fatty acids from fish oil  have demonstrated benefits for enhancing patient response to antidepressant therapy, thus repletion of these nutrients, as an adjunct to methylation support, are also valid considerations. Further integrative measures worthy for incorporation into a mood management protocol include physical activity, mindful meditation, anxiolytic herbs and, most importantly, appropriate counseling.
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