Folinic acid- The magic bullet for mental illness?

Supplementation with folic acid has a well established history for lowering homocysteine levels, preventing neural tube defects in newborns, correcting anaemia of pregnancy, vitiglio and even gingivitis. But a new activated form of the "reproduction vitamin" promises to combat neuropsychiatric illnesses like depression, schizophrenia-like syndromes and even dementia1.

The silent epidemic of folate deficiency

Folic acid occurs naturally as a complex of related substances called folates found in foods like sprouts, brewers yeast, liver and kidney. However their abundance in the diet is quickly reduced by cooking and processing and since many people do not consume high amounts of folate rich foods it is thought that folic acid deficiency is one of the most common nutritional deficiencies.1 Furthermore studies in healthy human subjects show that folic acid is poorly absorbed from the diet and results in very little metabolically active methylfolate being produced which means that correcting deficiencies with oral supplements is no mean feat.

This is because ordinarily dietary folic acid must undergo a series of complicated vitamin and energy-dependent changes in the body from the intestine to the liver before it becomes activated to its coenzyme form methylfolate. A break in any one of these steps resulting from dietary deficiency, malabsorption, liver disease or pregnancy can lead to a dearth of methylfolate in the brain and even neuropsychiatric symptoms like dementia, insomnia, irritability, forgetfulness, depression, peripheral neuropathy, schizophrenia and restless legs syndrome1 all of which can occur after normal blood readings for the vitamin. Once a folic acid deficiency has precipitated mental illness then it may remain unresponsive to regular oral folic acid supplements or even go unsuspected. Injections are often the only alternative but intravenous administration has its limitations because the body clears the vitamin in this form very quickly.

But a new form of dietary folate may be about to change all that. Folinic acid available supplementally as oral calcium folinate skips this inefficient transport and streamlining of dietary folates and supplies a ready-made precursor to the brain where it is lacking for a no-nonsense conversion to the coenzyme form methylfolate. Unlike regular folic acid supplements following an oral dose, up to 92% of folinic acid is absorbed from the gut, it remains in the body longer and the majority is converted to the active coenzyme In this form folinic acid can be directly up taken by the blood brain barrier that ordinarily remains impermeable to dietary folates and which probably accounts for its efficacy in treating mental disorders. 1

Beating depression with Folinic Acid

Studies show that the coenzyme resulting from folinic acid use when combined with conventional drugs significantly improves the clinical recovery of depressed patients with low folate levels. Indeed in one study when it was given to depressed and elderly subjects over an eight week period this resulted in a significant reduction in the Hamilton Depression Rating Scale which is an inventory of mental health symptoms and marked improvements in cognitive status like memory, attention and learning.2 Interestingly this effect was also conserved in patients experiencing depressive symptoms with normal folate status which indicates that despite normal blood readings, deficiencies in the folate coenzyme can secretly have a deleterious effect on mental function. In a second study of 123 subjects with acute psychiatric disorders such as depression and schizophrenia known to have a borderline deficiency of folate, six months of adjunctive treatment with folate coenzyme resulted in a significant clinical improvement than conventional drugs alone.3 Folinic acid's antidepressant effect is likely owing to is ability to regenerate the brains antidepressant and methylator Same from the toxic metabolite homocysteine which in turn directly bolsters the brain's "sunshine chemical" serotonin. This is a double barrel benefit because using up homocysteine with Folinic acid reduces our chances of being affected by Alzheimer's disease, depression, coronary heart disease, myocardial infarction, neural tube defects, diabetes, rheumatoid arthritis and alcoholism. What's more Folinic acid raises tetrahydrobiopterin (BH4) levels which is a crucial cofactor for the manufacture of all mood-regulating neurotransmitters like dopamine, noradrenalin and of course serotonin itself.

Epileptic patients too may benefit from folinic acid supplementation. German studies show that those patients with low folate levels are more likely to have an abnormal mental status but that folinic acid administration can improve mental wellbeing, cognitive ability and even reduce the duration of epileptic seizures.4 Indeed even anticonvulsant drugs themselves along with barbiturates, alcohol and contraceptives can be a hazard to folic acid by lowering serum and tissue concentrations of this important vitamin and leading in some cases to neuropsychiatric symptoms like depression and paranoia and more serious conditions like megaloblastic anaemia otherwise known as pernicious anaemia where there is an acute deficiency of vitamin B12 and peripheral neuropathy. Fortunately research is showing that low dose folinic acid supplementation can protect against such drug induced deficiencies and reverse mental deterioration where it exists.5

All this makes folinic acid a welcome addition to any psychiatrists tool box because its judicious use as an adjunct to drug therapies will directly increase levels of folate coenzyme where it is lacking and improve the outlook for those where it isn't. Therapeutic dosages vary between 400 and 800 mcg per day and should include vitamin B12 so as not to mask an underlying B12 deficiency. Side effects are rare but at high doses can cause flatulence, nausea and anorexia.

References
1. Folates: Supplemental Forms and Therapeutic Applications by Gregory S. Kelly N.D
2. Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res 1994;53:313-322.
3. Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990;336:392-395.
4. Froscher W, Maier V, Laage M, Wolfersdorf M, Straub R, Rothmeier J, Steinert T, Fiaux A, Frank U, Grupp D. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity.Clin Neuropharmacol 1995 Apr;18(2):165-82
5. Lambie DG, Johnson RH. Drugs and folate metabolism.Drugs 1985 Aug;30(2):145-55