B Vitamins: The Evidence

How Bs Support Mental Health

Every cell of every body makes its energy by oxidizing ... essentially, "burning" ... its fuel in tiny structures called mitochondria. That's why we breathe oxygen in and carbon dioxide out, just like a fire. These gentle fires burn in a watery environment, at a controlled rate, without causing damage. B vitamins make this possible. They "catalyze", or lower, the amount of energy it takes to keep the cell fires burning. So no flame.

B vitamins are also instrumental in putting together and taking apart many of the things the body needs to run. The brain uses far more energy per gram than any other part of the body; it's far more metabolically active. Its neurons receive and transmit electrical signals, make and reabsorb neurotransmitters, immunotransmitters and more. B vitamins are crucial to all of this, so their role in supporting mental health is no surprise.

This article summarizes the peer-reviewed evidence base on the effects B vitamins have on mental health. For guidance in how to use B vitamins, click here.

Depression is a common symptom of multiple B vitamin deficiencies.1 Deficiencies of vitamin B1, thiamine, cause beri-beri. Early signs include symptoms like increased irritability, difficulty concentrating, depression and fatigue. B2, riboflavin, is an essential part of the process that builds neurotransmitters. It’s also involved in making thyroid hormones. In some inpatient populations B2 deficiency has been linked with a trend toward unipolar depression and riboflavin supplementation with improvement.2

Raising serotonin levels helps calm anxiety. Serotonin is made in the brain from tryptophan. B3 (nicotinic acid/niacinamide) and B6 (pyridoxine) are critical parts of the enzymatic pathways that make serotonin.3,3a

Estrogens can inhibit B6, leading to lower neurotransmitter levels including serotonin.Women on oral contraceptives should take extra B2,6,12 and folic acid4,5 to avoid being grumpy. Women displaying behaviors injurious to themselves and others just before the onset of their menstrual cycles non infrequently consume substantial amounts of dairy and sugar and show positive responses to B6 supplementation.6

But it’s not just a women’s issue. Reports have indicated B6 deficiencies may be a factor in a wide range of psychopathologies including autism, Alzheimer’s hyperactivity, learning disability, anxiety and depressive disorders.7,8

But it’s not a good idea to take large doses of individual B vitamins unless one has a very good reason. The B vitamins work as a team and they’re cheap. Why take just one when you can take them all and get multiple benefits? I usually recommend a B-50 product for all my patients and clients, but if one hasn’t taken any vitamins in years it’s important to not go straight from nothing to a powerful B like B-50 too quickly. Starting Bs too quickly can create an uncontrolled detox. Not fun.

(I find most of my clients who say they can’t take vitamins have issues with the Bs. There’s a detailed protocol for what to do in this case on the B Vitamins page.)

There’s more.

Cobalamin (B12) deficiency can also result in depression.9 High B12 levels are associated with a more favorable outcome in major depressive disorder,10,11 and a wide range of other morbidities associated with its deficiency.12 Folic acid is also a methylator. Methylation is an essential step in the creation of mood-elevating neurotransmitters like dopamine and norephinephrine. B12 levels were higher in bereaved men who reported less stress and anxiety.14

Folic acid, a closely related compound included in the B vitamin family, is also required for the synthesis of serotonin, noradrenaline and dopamine.15 A lack of folic acid has been linked to depression,16-23 irritability and hostility,24 and manic behavior.25 Supplementing folic acid has been shown to increase serotonin response to prescription antidepressants26 and all by itself to help a variety of psychopathologies in some individuals.27 A study of almost 3,000 Americans found those who’d had major depression or dysthymia in their lives (14.3%) had measurably lower folate levels than those who hadn’t.28

Depressed geriatric patients not infrequently respond well to B supplementation.29 One group of geriatric patients with depression showed an improved response to (and thus less need for) their anti-depressant medications, significantly improved mood and cognitive function on B1,B2 and B6 supplementation.30 In another study low vitamin B12 levels (particularly in conjunction with high folate levels) was associated with more rapid cognitive decline.29a

Abram Hoffer, Niacin .. and Medical Politics

In the middle of the twentieth century researchers noticed similarities between the mental symptoms associated with schizophrenia and pellagra, vitamin B3 (niacin) deficiency. Pellagra symptoms include irritability, sleeplessness, memory loss, confusion and emotional swings. In severe pellagra severe depression, hallucinations, paraonia and extreme withdrawal are seen. These symptoms overlap quite a bit with the classic symptoms of schizophrenia.

The researchers proposed that in some cases schizophrenia could be caused by abnormal metabolites of adrenaline, metabolites with hallucinogenic properties.31,32 Niacin was proposed as an agent that, if present in large enough quantities, could stop the production of these abnormal metabolites by soaking up the aberrant molecules (methyl groups) creating the hallucinogenic metabolites.

The first two researchers to gain prominence with this approach were Canadians, Abram Hoffer and Humphrey Osmond. They began using large amounts of niacin in trials with acute-onset schizophrenics in 1952, reporting excellent results.33-35

A number of researchers set out to replicate Hoffer and Osmond’s results in chronic schizophrenia. Unfortunately they appear to have missed a critical point: Hoffer never claimed that niacin or niacinamide all by themselves would help chronic schizophrenics; he did report that it appeared to help acute cases with a rapid onset.36

Nevertheless a number of studies were done examining the effect of niacin or nicotinamide on chronic schizophrenics.37-43 Not surprisingly these studies produced negative or inconclusive results; these results were widely disseminated in the professional literature without noting the crucial difference in syndrome chronicity. One investigator got negative results when he tried niacin on chronic schizophrenics44 but then noticed that a subgroup of patients with a recent onset and a history of positive social interactions before their diagnoses did in fact seem to respond substantially better to it.45 No one took notice.

For many years this problem of testing a therapy which was originally proposed as useful in acute cases in chronic cases and then finding it wanting was not addressed in the mainstream literature and nutritional approaches to mental disease fell into disrepute, along with Dr. Hoffer and his colleagues. Reviews published in mainstream scientific journals throughout the 1980s and early 1990s concluded that the efficacy of niacin in schizophrenia was not supported by the evidence, without however mentioning the chronicity issue.46-48

Eventually other investigators began to notice that when large amounts of niacin were administered to schizophrenics their bodies seemed to respond differently to it than the bodies of non-schizophrenics. At first, when large amounts of niacin are given to normal people who haven’t been taking it in those doses, a characteristic reddening of the skin and a sensation of prickly heat appears, commonly known as the “niacin flush.” Many researchers began noticing that this characteristic reaction did not appear in schizophrenic patients49-54 although this finding was not universal.55

Today it’s recognized that this lack of a flushing reaction to niacin characterizes only some sub-types and groups of schizophrenics,56-58 and that the absence of this reaction implies disorders in the construction of cell membranes throughout the body, including the brain.59,60 Cell walls throughout the body, including the central nervous system, are made from phospholipids. Phospholipids are useful for this purpose because one end of the molecule attracts water while the other end repels it. The result of this is that it’s easy for these molecules to line up in a double-row with the water-attracting end facing outward and the water-repelling end facing inward. The arranging of phosopholipids in rows sharing the same orientation is how cell walls are constructed.

Substantial evidence has accumulated suggesting that phospholipid abnormalities characterize schizophrenia:

  • Enzymes that help form phospolipids are abnormally low in the frontal and temporal lobes of schizophrenics, and enzymes that break phospholipids down are abnormally high,61-63
  • Abnormally high levels of another enzyme that breaks down phospholipids have been found in the blood and brains of schizophrenics,64-66
  • Studies show reduced levels of w3 and w6 EFAs in the blood and brains of schizophrenics,67-71
  • In nations that consume large amounts of EFA-rich fish there is a substantially lower rate of schizophrenia,72
  • At least one major review has reported that while randomized controlled trials of EFAs in schizophrenia have produced inconsistent results there has been enough evidence of efficacy to recommend incorporating them into treatment programs.73

In the meantime Hoffer continued his work with schizophrenics in Canada. He reported excellent results in acute and chronic cases, but only when utilizing a matrix of nutrients including niacin (B3), pyridoxine (B6), vitamin C, manganese and zinc, and then only when this combination is administered over substantial periods of time.74 And in support of Drs. Hoffer, Osmond and Pauling’s original approach of forty years ago, it turns out that niacin (in the form of NADPH) is a key substance required for the formation of phospholipids, and that schizophrenics show high levels of oxidative damage in their brains.75-78 Vitamin C, of course, protects against oxidative stress.

In the early skirmishes between orthomolecular researchers and their detractors, the detractors won. Their erroneous findings are still the accepted wisdom among all too many otherwise well-informed authorities today.

In an age when one in four american women are on anti-depressant medication,79 today’s heavy emphasis on pharmaceutical treatment for these issues, informed by the early false negative findings about nutrition and accompanied by the inevitable dependencies, expense and side effects, could use some re-examination.


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 2. Smidt, L.J., et al. 1991. Influence of thiamin supplementation on the health and general well-being of an elderly Irish population with marginal thiamin deficiency. Journal of Getontology. 46(1):M16-22.

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 5. Bermond, P. 1982. Therapy of side effects of oral contraceptive agents with vitamin B6. Acta Vitaminologica et Enzymologica. 4(1-2):45-54.

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11. Baldewicz, T.T., et al. 2000. Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men. Journal of Psychosomatic Research. 48(2):117-185.

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15. Coppen, A. et al. 1989. Depression and tetrahydrobiopterin: the folate connection. Journal of Affective Disorders. 16(2-3):103-107.

16. Coppen, A. et al. 1989. Ibid.

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79. http://medco.mediaroom.com/index.php?s=17872&item=85081