Niacin, more commonly known as vitamin B-3, plays a critical role in a variety of cellular and metabolic processes, helping to extract energy from carbohydrates while also protecting cells and tissues from damage. For about half a century a small cadre of clinicians and researchers has used high dosages of niacin to treat people with schizophrenia 2. Though the practice is controversial, proponents claim that supplementation with high levels of niacin decreases symptoms of schizophrenia and enhances emotional, social, cognitive and occupational functioning.

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How It Works

Advocates of niacin for the treatment of schizophrenia contend that brain and metabolic functioning of people with schizophrenia is compromised because of dysfunctions in the operation and metabolic processing that takes place in brain cells. Because of a genetic vulnerability to excessive oxidation, people who have schizophrenia have brains that don’t operate efficiently 2. Unstable oxygen molecules called free radicals circulate in the bloodstream, stealing electrons from cell walls, DNA and mitochondria, reducing the effectiveness of neural functioning. Niacin promotes several processes that reduce the number of free radicals or that protect mitochondria. For example, niacin increases the amount of a substance called glutathione, which strengthens mitochondria membranes. Also, nacin decreases inflammation, a process that is thought to contribute to several psychiatric conditions. Niacin helps to calm the brain as well, functioning like the anti-anxiety agent benzodiazepine by stimulating certain sites in the brain called gamma aminobutyric acid (GABA) receptors.


Abram Hoffer, one of the most widely known advocates of megadosing with niacin and other vitamins, published experimental and clinical research studies widely from the 1940s through the 1960s. Hoffer described various studies in which he administered 1.5 to 6 g of niacinamide, along with traditional psychiatric medications, to schizophrenic patients for periods varying from three months to five years. He reported that many patients had significant reduction in their symptoms. Using double-blind research designs, Hoffer found that his niacin-treated patients had decreases in hallucinations and delusions and had improvements in negative symptoms of schizophrenia, such as avolition. Niacin-treated patients had 50 percent fewer hospitalizations and had statistically significant reductions in suicide rates. They functioned better at home, and many were able to obtain and maintain jobs. Though he initially reported that niacin was effective only during early phases of the illness, he later concluded that administration of niacin for seven or more years can reduce symptoms in chronic patients.

Orthomolecular Psychiatry Controversy

Hoffer and other scientists, including Nobel Prize winner Linus Pauling, developed the field of orthomolecular psychiatry. This approach focuses on developing individualized treatment programs that combine megadoses of vitamins, dietary changes and traditional psychiatric medication. However, Hoffer’s theories and research fell into disrepute among the mainstream psychiatric community during the 1970s when several independent researchers failed to replicate his findings. Hoffer’s critics questioned his methods and the safety of administering megadoses of vitamins. Hoffer and his colleagues in turn criticized their methods. Hoffer and a few others continue to administer megadoses of niacin in the treatment of schizophrenia and continue to claim success, but most psychiatrists continue to disregard orthomolecular psychiatry 2.

Renewed Interest

In the December 2010 issue of “Medical Hypotheses,” author Sheila Seybolt asks if it might be time to reassess niacinamide therapy in schizophrenia. Seybolt suggests that niacinamide when taken in combination with alpha lipoic acid (ALA) may work synergistically to reduce oxidative stress and improve mitochondrial function to reduce the symptoms of schizophrenia.


Side effects for normal dosages of niacin can include increased blood sugar, an uncomfortable flushing sensation, nausea, increased liver enzymes and heartburn. Use of megadoses of niacin should be done only under medical supervision. While doses below 1,000 mg are considered safe, higher doses can increase your risk for gastritis, liver damage, blood uric acid levels and diabetes. A physician can monitor your status to ensure you don’t develop adverse side effects.