High amounts (several grams per day) of niacin, a form of vitamin B3, lower cholesterol, an effect recognized in the approval of niacin as a prescription medication for high cholesterol.¹ The other common form of vitamin B3—niacinamide—does not affect cholesterol levels. Some niacin preparations have raised HDL cholesterol better than certain prescription drugs.² Some cardiologists prescribe 3 grams of niacin per day or even higher amounts for people with high cholesterol levels. At such intakes, acute symptoms (flushing, headache, stomachache) and chronic symptoms (liver damage, diabetes, gastritis, eye damage, possibly gout) of toxicity may be severe. Many people are not able to continue taking these levels of niacin due to discomfort or danger to their health. Therefore, high intakes of niacin must only be taken under the supervision of a doctor.

Symptoms caused by niacin supplements, such as flushing, have been reduced with sustained-release (also called “time-release”) niacin products. However, sustained-release forms of niacin have caused significant liver toxicity and, though rarely, liver failure.^{3 , 4 , 5 , 6 , 7} One partial time-release (intermediate-release) niacin product has lowered LDL cholesterol and raised HDL cholesterol without flushing, and it also has acted without the liver function abnormalities typically associated with sustained-release niacin formulations.⁸ However, this form of niacin is available by prescription only.

In the 1940s and 1950s, one doctor reported that supplemental niacinamide (a form of vitamin B3) increased joint mobility, improved muscle strength, and decreased fatigue in people with OA.^{9 , 10 , 11} In the 1990s, a double-blind trial confirmed a reduction in symptoms from niacinamide within 12 weeks of beginning supplementation.¹² Although amounts used have varied from trial to trial, many doctors recommend 250 to 500 mg of niacinamide four or more times per day (with the higher amounts reserved for people with more advanced arthritis). The mechanism by which niacinamide reduces symptoms is not known.

The niacin form of vitamin B3 has been reported to be effective in relieving menstrual cramps in 87% of a group of women taking 200 mg of niacin per day throughout the menstrual cycle. They then took 100 mg every two or three hours while experiencing menstrual cramps.¹³ In a follow-up study, this protocol was combined with 300 mg of vitamin C and 60 mg of the flavonoid rutin per day, which resulted in a 90% effectiveness for relieving menstrual cramps.¹⁴ Since these two preliminary studies were published many years ago, no further research has explored the relationship between niacin and dysmenorrhea. Niacin may not be effective unless taken for seven to ten days before the onset of menstrual flow.

One controlled study compared a type of niacin (vitamin B3) known as inositol hexaniacinate to the drug pyridinolcarbamate for the treatment of skin ulcers caused by PVD.¹⁵ A placebo was not included in this trial, and both 1.2 grams daily of inositol hexaniacinate and 1.5 grams daily of the drug produced beneficial results in about half of the patients.

The term “orthomolecular psychiatry” was coined by Linus Pauling in 1968 to refer to the treatment of psychiatric illnesses with substances (such as vitamins) that are normally present in the body. In orthomolecular psychiatry, high amounts of vitamins are sometimes used, not to correct a deficiency per se, but to create a more optimal biochemical environment. The mainstay of the orthomolecular approach to schizophrenia is niacin or niacinamide (vitamin B3) in high amounts. In early double-blind trials, 3 grams of niacin daily resulted in a doubling of the recovery rate, a 50% reduction in hospitalization rates, and a dramatic reduction in suicide rates.¹⁹ In a preliminary trial, some schizophrenic patients continued a course of vitamins (4 to 10 grams of niacin or niacinamide, 4 grams of vitamin C, and 50 mg or more of vitamin B6) after being discharged from the hospital, while another group of patients discontinued the vitamins upon discharge. Both groups continued to take their psychiatric medications. Those who continued to take the vitamins had a 50% lower re-admission rate compared with those who did not.²⁰ Several later double-blind trials, including trials undertaken by the Canadian Mental Health Association, have been unable to reproduce these positive results.^{21 , 22} Early supporters of niacin therapy contend that many of these trials were poorly designed.²³ One clinical trial reported no greater improvement in a group of schizophrenic patients given 6 grams of niacin than in others given 3 mg of niacin; all patients were also being treated with psychiatric medications.²⁴

There are potential side-effects of niacin therapy, including an uncomfortable flushing sensation, dermatitis (skin inflammation), heartburn, aggravation of peptic ulcers, increased blood sugar, increased panic and anxiety, and elevation of liver enzymes, which may indicate damage to liver cells. A positive side effect of niacin therapy is reduction of cholesterol levels. Some of these effects, such as flushing, gastric upset, and reduction of serum cholesterol, do not occur with the use of niacinamide.²⁵ Because of the seriousness of some of these side effects, high amounts of niacin should not be used without the supervision of a healthcare practitioner.

Vitamin B6 has been used in combination with niacin in the orthomolecular approach to schizophrenia. Pioneers of orthomolecular medicine reported benefits from this combination. However, although two placebo-controlled trials found significant improvement when schizophrenic patients were given either 3 grams of niacin or 75 mg of pyridoxine along with their psychiatric medications, this improvement was lost when the two vitamins were combined.^{26 , 27} In a double-blind trial, schizophrenic patients were given either a vitamin program based on their individual laboratory tests or a placebo (25 mg of vitamin C) in addition to their psychiatric medications. The vitamin program included large amounts of various B vitamins, as well as vitamin C and vitamin E. After five months, the number of patients who improved was not different in the vitamin group compared with the placebo group.²⁸

Clinical trials of the effects of vitamin B6 have yielded differing results. The results of supplementation with 100 mg daily in one schizophrenic patient included dramatic reduction in side effects from medication, as well as reduction in schizophrenic symptoms.²⁹ In a preliminary trial, 60 mg per day of vitamin B6 resulted in symptomatic improvement in only 5% of schizophrenic patients after four weeks.³⁰ Another preliminary trial, however, found that a higher amount of vitamin B6—50 mg three times daily given for eight to twelve weeks—in addition to psychiatric medications, did bring about significant improvements in schizophrenic patients. These patients experienced a better sense of well-being, increased motivation, and greater interest in their “personal habits and their environment.”³¹

Taking large amounts of niacin (a form of vitamin B3), such as 2 to 3 grams per day, may impair glucose tolerance and should be used by people with diabetes only with medical supervision.^{32 , 33}

Some clinical trials have shown that niacinamide (another form of vitamin B3) supplementation might be useful in the very early stages of type 1 diabetes,³⁴ though not all trials support this claim.^{35 , 36 , 37} Although an analysis of research shows that niacinamide does help preserve some function of insulin-secreting cells in people recently diagnosed with type 1 diabetes, the amount of insulin required for those given niacinamide has remained essentially as high as for those given placebo.³⁸ A controlled trial found no beneficial effect of niacinamide supplementation (700 mg three times per day in addition to intensive insulin therapy) on pancreatic function and glucose tolerance in people newly diagnosed with type 1 diabetes.³⁹

Some,⁴⁰ but not all,⁴¹ reports suggest that healthy children at high risk for type 1 diabetes (such as the healthy siblings of children with type 1 diabetes) may be protected from the disease by supplementing with niacinamide. Parents of children with type 1 diabetes should consult their doctor regarding niacinamide supplementation as a way to prevent diabetes in their other children. Although the optimal amount of niacinamide is not known, recent evidence suggests that 25 mg per 2.2 pounds of body weight per day may be as effective as higher amounts.⁴²

Many alcoholics are deficient in B vitamins, including vitamin B3. John Cleary, M.D., observed that some alcoholics spontaneously stopped drinking in association with taking niacin supplements (niacin is a form of vitamin B3). Cleary concluded that alcoholism might be a manifestation of niacin deficiency in some people and recommended that alcoholics consider supplementation with 500 mg of niacin per day.⁴³ Without specifying the amount of niacin used, Cleary’s preliminary research findings suggested that niacin supplementation helped wean some alcoholics away from alcohol.⁴⁴ Activated vitamin B3 used intravenously has also helped alcoholics quit drinking.⁴⁵ Niacinamide—a safer form of the same vitamin—might have similar actions and has been reported to improve alcohol metabolism in animals.⁴⁶

The daily combination of 3 grams of vitamin C, 3 grams of niacin, 600 mg of vitamin B6, and 600 IU of vitamin E has been used by researchers from the University of Mississippi Medical Center in an attempt to reduce anxiety and depression in alcoholics.⁴⁷ Although the effect of vitamin supplementation was no better than placebo in treating alcohol-associated depression, the vitamins did result in a significant drop in anxiety within three weeks of use. Because of possible side effects, anyone taking such high amounts of niacin and vitamin B6 must do so only under the care of a doctor.

Niacinamide (a form of vitamin B3) has been shown in animals to work in the brain in ways similar to drugs such as benzodiazepines (Valium-type drugs), which are used to treat anxiety.⁴⁸ One study found that niacinamide (not niacin) helped people get through withdrawal from benzodiazepines—a common problem.⁴⁹ A reasonable amount of niacinamide to take for anxiety, according to some doctors, is up to 500 mg four times per day.

People with low blood levels of antioxidants and those who eat few antioxidant-rich fruits and vegetables have been reported to be at high risk for cataracts.^{50 , 51}

Vitamin B2 and vitamin B3 are needed to protect glutathione, an important antioxidant in the eye. Vitamin B2 deficiency has been linked to cataracts.^{52 , 53} Older people taking 3 mg of vitamin B2 and 40 mg of vitamin B3 per day were partly protected against cataracts in one trial.⁵⁴ However, the intake of vitamin B2 in China is relatively low, and it is not clear whether supplementation would help prevent cataracts in populations where vitamin B2 intake is higher.

Preliminary observations suggest a possible role for vitamin B3 in HIV prevention and treatment.⁵⁵ A form of vitamin B3 (niacinamide) has been shown to inhibit HIV in test tube studies.⁵⁶ However, no published data have shown vitamin B3 to inhibit HIV in animals or in people. One study did show that HIV-positive people who consume more than 64 mg of vitamin B3 per day have a decreased risk of progression to AIDS or AIDS-related death.^{57 , 58} Clinical trials in humans are required to validate these preliminary observations.

Research has shown that supplementing with chromium (200 mcg per day)⁵⁹ or magnesium (340 mg per day)⁶⁰ can prevent blood sugar levels from falling excessively in people with hypoglycemia. Niacinamide (vitamin B3) has also been found to be helpful for hypoglycemic people.⁶¹ Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.⁶² Since there are similarities in the way the body regulates high and low blood sugar levels, these nutrients might be helpful for hypoglycemia as well, although the amounts needed for that purpose are not known.

Preliminary data indicate that vitamin B3 (niacin) supplementation may decrease thyroid hormone levels. In one small study, 2.6 grams of niacin per day helped lower blood fat levels.⁶³ After a year or more, thyroid hormone levels had fallen significantly in each person, although none experienced symptoms of hypothyroidism. In another case report, thyroid hormone levels decreased in two people who were taking niacin for high cholesterol and triglycerides; one of these two was diagnosed with hypothyroidism.⁶⁴ When the niacin was discontinued for one month, thyroid hormone levels returned to normal.

Niacinamide , a form of vitamin B3, can reduce the formation of a kynurenic acid—a substance that has been linked to photosensitivity. One trial studied the effects of niacinamide in people who had polymorphous light eruption.⁶⁵ While taking one gram three times per day, most people remained free of problems, despite exposure to the sun. Because of the potential for adverse effects, people taking this much niacinamide should do so only under medical supervision.

During a ten-year period, doctors at the North Nassau Mental Health Center in New York treated approximately 11,000 people with schizophrenia with a megavitamin regimen that included vitamin C (up to 4 grams per day), vitamin B3—either as niacin or niacinamide—(up to 4 grams per day), vitamin B6 (up to 800 mg per day), and vitamin E (up to 1,200 IU per day). During that time, not a single new case of TD was seen, even though many of the people were taking neuroleptic drugs.⁶⁶ Another psychiatrist who routinely used niacinamide, vitamin C, and vitamin B-complex over a 28-year period rarely saw TD develop in her patients.⁶⁷ Further research is needed to determine which nutrients or combinations of nutrients were most important for preventing TD. The amounts of niacinamide and vitamin B6 used in this research may cause significant side effects and may require monitoring by a doctor.