Rescuing the Niacin Tradition the Medical Mainstream Ignored Part 2
In the spring of 1952, two physicians at a psychiatric hospital in Saskatchewan began the first double-blind placebo-controlled trial in the history of psychiatry
The disease they were trying to treat was schizophrenia and the treatment they were testing was niacin, at doses an order of magnitude higher than anyone then thought of as nutritional.
Within two years, the recovery rate in their treatment group was around 75 per cent. In the placebo group it was around 35 per cent.
The two men were Abram Hoffer and Humphry Osmond. Hoffer would go on to spend fifty-five years in clinical practice. He would treat more than five thousand schizophrenic patients and many thousands more with anxiety, depression, arthritis and addiction.
He would publish hundreds of papers, write or co-author over thirty books, and be nominated alongside Linus Pauling as a founder of orthomolecular medicine, the field that asks what happens when essential nutrients are given in amounts beyond the textbook minimum.
He took niacin himself, in gram doses, for the last fifty years of his life. He died in 2009 at the age of ninety-one, still in practice, still seeing patients, still answering letters from people whose lives his work had altered.
Part 1 of this series traced the early history of the B vitamins: the deficiency diseases the medical establishment refused to believe in, the diet-and-disease evidence that armies and academies ignored, the long road from a Chinese physician noting the connection between polished rice and beriberi to Robert Williams synthesising the molecule we now call thiamine in 1936.
The story of that early history is not what Medicine Girl tells. It is not an industry inventing deficiencies to sell the cure, it is an establishment refusing, sometimes lethally, to believe deficiency was real.
This article is about what happened next.
By the late 1940s the deficiency diseases were largely understood. Pellagra was niacin deficiency, beriberi was thiamine deficiency, pernicious anaemia was eventually identified as B12 deficiency, and the chemistry was being worked out one vitamin at a time.
The medical mainstream was, broadly speaking, happy with this picture. The B vitamins prevented diseases of severe nutritional inadequacy, and a small amount in the diet was sufficient to prevent those diseases. Case closed.
A small number of clinicians thought the case was not closed at all. They had noticed something the textbook picture did not predict. When they gave certain B vitamins at much higher doses, far above the minimum needed to prevent classical deficiency, patients with conditions that had nothing to do with classical deficiency began to recover.
Schizophrenics on niacin, arthritis patients on niacinamide and cardiac patients on thiamine. Decades later, when the molecular biology caught up, the receptor work and the metabolic studies would explain why. At the time, the clinicians had only their observations and their patients.
The medical mainstream did to them what it had done to Takagi and Goldberger. It ignored, ridiculed, and where it could, punished them. This is the chapter of the story Medicine Girl’s series cannot accommodate, because in her telling the modern supplement industry invented these uses to sell product.
The actual history is (once again) the opposite. The clinicians who pioneered high-dose B-vitamin therapy were inside the medical mainstream, were often working against the commercial grain of their own time, and were frequently destroyed professionally for what they reported.
The Saskatchewan Trials
When Hoffer and Osmond began their work in 1951, the standard treatment for schizophrenia was insulin coma therapy, electroconvulsive therapy, and the brand-new neuroleptic chlorpromazine, which had just arrived on the market.
The institutional answer for the patients who did not respond, which was most of them, was lifelong commitment to a state mental hospital. Saskatchewan in the early 1950s had a network of such hospitals running at capacity, and Hoffer, the new Director of Psychiatric Research, was looking at long wards full of people his profession had no idea how to help.
His starting point was a chemical observation. The molecule adrenaline, the body’s main stress hormone, can oxidise into a related compound called adrenochrome, and adrenochrome has hallucinogenic properties.
Hoffer and Osmond hypothesised that schizophrenic patients might be producing too much adrenochrome, or clearing it too slowly, and that the symptoms were the consequence: hallucinations, paranoia, thought disorder.
They needed a way to reduce the production of adrenochrome, and they reasoned that niacin, which acts as a methyl acceptor in the methylation cycle, might do it by diverting methyl groups away from adrenaline synthesis.
They were probably wrong about the precise mechanism. The adrenochrome hypothesis as Hoffer first set it out has not survived in the form he proposed. But their prediction, that high-dose niacin would help schizophrenic patients, was correct, and the trial they designed to test it was, for its time, extraordinary.
They randomised, they used placebo, they double-blinded the assessment, they followed their patients for two years, and they published. This was 1952. The standards for psychiatric trials at the time were almost non-existent. Hoffer and Osmond invented them, on the way to testing a vitamin.
The results held up. Their initial trials and their replications over the following years showed recovery rates roughly twice those of placebo. They published in mainstream psychiatric journals. They presented at conferences. They were taken seriously, initially, by their colleagues.
Then chlorpromazine and the pharmaceutical antipsychotics arrived in force, and the answer to schizophrenia became drugs rather than nutrients. The American Psychiatric Association in 1973 issued a report on Hoffer’s methods that has shaped psychiatric attitudes to orthomolecular treatment ever since.
The report concluded that the orthomolecular approach had no evidence base. Hoffer’s reply, which he kept reissuing for the rest of his career, was that the committee had not actually examined his evidence base, which by then ran to thousands of patients and decades of follow-up.
The mainstream answer to that reply was institutional silence.
What Niacin Actually Does
This is the point in the article where it would be easy to slip into the rhetoric Medicine Girl uses against any compound that has more than one effect. Niacin does behave pharmacologically at high doses.
It causes the famous flush, a histamine-mediated vasodilation that turns the skin red and warm. It alters lipid profiles. It changes glucose metabolism. It activates receptors. If you wanted to argue, as she does, that “vitamin acting like a drug” is proof that supplementation is a pharmaceutical con, niacin would be your strongest exhibit.
Yes, niacin at high doses acts pharmacologically, and this is not a scandal, it is the point. The orthomolecular tradition is built on the observation that some essential nutrients, when given in amounts beyond the textbook minimum, produce therapeutic effects that have nothing to do with correcting classical deficiency.
This is not “a vitamin pretending to be a drug.” It is a vitamin being asked to do a different job from preventing deficiency disease. The question is whether the job gets done safely and well.
The safety record of high-dose niacin is one of the most extensive in clinical nutrition. Hoffer worked with patients at doses up to forty grams per day for decades without observing the kind of toxicity that pharmaceuticals routinely produce.
The American Association of Poison Control Centers has reported zero deaths attributable to niacin in adults for the entire history of their reporting. Liver enzyme elevations occur at sustained high doses, particularly with sustained-release formulations, and require monitoring; this is a caveat that the orthomolecular tradition takes seriously and that Hoffer himself wrote about.
But the safety profile sits in a completely different universe from that of the pharmaceuticals niacin has competed against in cardiovascular medicine.
The flush is not toxicity. It is a transient prostaglandin-D2-mediated vasodilation, well understood physiologically, dampened by aspirin or by tolerance over a few weeks of regular dosing. Hoffer’s arthritic patients sometimes stopped niacin briefly so they could feel the flush return, because the warming sensation in their joints felt good.
Medicine Girl reads the flush as the body’s warning signal of toxicity. The clinical literature reads it as a physiological response to acute vasodilation, no more dangerous than the flush of embarrassment.
Niacin and the Founder of AA
The most famous patient Hoffer ever treated was not psychiatric at all. He was the co-founder of Alcoholics Anonymous.
Bill Wilson, known to the millions of recovering alcoholics who follow the programme he built simply as Bill W., had been sober for decades by the time he met Abram Hoffer in New York in the late 1950s.
He was a global figure, the author of the Big Book, the man whose introduction “My name is Bill W., and I’m an alcoholic” had given shape to the modern recovery movement. He was also, privately, profoundly depressed.
The fatigue and low mood that had followed him into sobriety had never lifted, and the pharmaceutical antidepressants of the period had done nothing for him.
Hoffer and Osmond introduced him to the concept of megavitamin therapy. Wilson, characteristically, decided to test it on himself. He began taking three grams of niacin a day, divided across his meals. Within a few weeks the fatigue and depression that had plagued him for years had gone.
He then did what he had always done with anything he believed in, he told other alcoholics. He gave niacin to thirty of his closest friends in AA, all of them sober but most still struggling with the residual depression, anxiety and exhaustion that recovery had not resolved.
Within a month, ten of them were free of those symptoms. Within two months, twenty were. Wilson wrote up the case series in a pamphlet called The Vitamin B-3 Therapy, addressed to AA’s physicians, and published it in December 1965 at his own expense from an office he set up outside AA’s official premises.
A second communication followed in February 1968. He travelled with Hoffer to medical conferences. He spent the last five years of his life advocating for niacin therapy in alcoholism.
The opposition came from inside his own house. The International Board of Alcoholics Anonymous, whose medical members Wilson himself had appointed, refused to endorse the work. Their stated objection was that Wilson was not a doctor and should not be making therapeutic recommendations.
The deeper objection was almost certainly that vitamin therapy did not fit the spiritual-recovery model AA had built its identity around. The pamphlets circulated unofficially, hand to hand, through the AA community for years after Wilson’s death in January 1971, but they were never adopted as official material.
The founder of the most successful recovery movement in modern history was sidelined within his own organisation for the last work of his life.
What this story illustrates is not a new clinical claim. The case series of thirty was small and uncontrolled. What it illustrates is the same pattern that runs through this whole history. An observer in an unusually good position to see the effect of a high-dose nutrient on the conditions he cared about reported what he saw.
The institutional response, even in an organisation he had founded, was to refuse to look. The pamphlets are still findable, the doses Wilson used are well documented, and the niacin he believed had saved him is still on the shelves of every supplement shop in the world, but sadly, the organisation he built does not officially recommend it.
Kaufman and the Arthritis Story
Hoffer was not the only mid-century clinician working with the niacin family. In 1949, William Kaufman, a physician practising in Bridgeport, Connecticut, published a book called The Common Form of Joint Dysfunction.
The book set out, in clinical detail, what Kaufman had observed in his practice: that niacinamide, the amide form of niacin which does not cause the flush, at gram doses produced measurable improvements in joint mobility, often dramatic ones, in patients with arthritis.
Kaufman did not run randomised trials. He did something almost as valuable. He developed an objective measurement, the Joint Range Index, and tracked it across hundreds of patients over years.
The improvements were not subjective patient reports; they were measured changes in the actual range of motion of arthritic joints, recorded by Kaufman with the kind of methodical precision the mainstream rheumatology of his day rarely matched.
His patients regained the ability to lift their arms, climb stairs, hold cutlery, and, in the case of one elderly woman, play the piano again. However, the arthritis establishment of the 1950s did not engage with Kaufman’s findings. They were ignored.
The arrival of corticosteroids in the early 1950s and later of non-steroidal anti-inflammatories, both of which produced rapid symptomatic relief and offered the pharmaceutical industry vastly more profitable franchises, swept Kaufman’s slower, cheaper intervention out of the conversation.
Kaufman continued practising in Bridgeport, continued treating arthritic patients with niacinamide, and continued documenting their joint ranges, for the rest of his career.
He was inducted into the Orthomolecular Medicine Hall of Fame in 2002.
By then his work had been ignored by mainstream rheumatology for half a century.
This is taken from a long document. Read the rest here substack.com
Header image: News-Medical.net