Vitamin B3 (therapeutic uses)

DEFINITION: Organic compound used to treat specific health conditions.

PRINCIPAL PROPOSED USES: Niacin: High cholesterol/triglycerides; niacinamide: diabetes treatment, osteoarthritis, photosensitivity; inositol hexaniacinate: intermittent claudication, Raynaud’s phenomenon

OTHER PROPOSED USES: Aging skin, cataracts, human immunodeficiency virus support, pregnancy support, rosacea, schizophrenia, tardive dyskinesia

PROBABLY NOT EFFECTIVE USES: Diabetes prevention in children at high risk, passing a urine drug screen

Overview

Vitamin B₃ is required for the proper function of more than fifty enzymes. Without it, the body would not be able to release energy or make fats from carbohydrates. Vitamin B₃ is also used to make sex hormones and other important chemical signal molecules.

Vitamin B₃ comes in two principal forms: niacin (nicotinic acid) and niacinamide (nicotinamide). When taken in low doses for nutritional purposes, these two forms of the vitamin are essentially identical. However, each has its own particular effects when taken in high doses. Additionally, a special form of niacin called inositol hexaniacinate has shown some promise as a treatment with special properties of its own.

Requirements and Sources

The official U.S. and Canadian recommendations for daily intake of niacin are as follows:

Infants aged 0 to 6 months (2 mg) and 7 to 12 months (4 mg); children aged 1 to 3 years (6 mg), 4 to 8 years (8 mg), and 9 to 13 years (12 mg); males aged 14 years and older (16 mg); females aged 14 and older (14 mg); pregnant women (18 mg); and nursing women (17 mg).

Because the body can make niacin from the common amino acid tryptophan, niacin deficiencies, called pellagra, are rare in developed countries. However, the antituberculosis drug isoniazid (INH) impairs the body’s ability to produce niacin from tryptophan and may create symptoms of niacin deficiency. Other risk factors include eating too little tryptophan, eating too much corn, Hartnup disease, or Carcinoid syndrome. Symptoms of vitamin B₃ deficiency include depression, anxiety, memory loss, dermatitis, diarrhea, and burning and twitching in the extremities.

Good food sources of niacin are seeds, yeast, bran, peanuts (especially with skins), wild rice, brown rice, whole wheat, barley, almonds, and peas. Tryptophan is found in protein foods, like chicken, turkey, sockeye salmon, pork tenderloin, ground beef, and roasted peanuts. Other sources include dairy products like milk, marinara sauce, brown rice, and fortified breakfast cereal.

Therapeutic Dosages

When used as therapy for a specific disease, niacin, niacinamide, and inositol hexaniacinate are taken in dosages much higher than nutritional needs, about 1 to 4 grams (g) daily. Because of the risk of liver inflammation at these doses, medical supervision is essential.

Many people experience an unpleasant flushing sensation and headache when they take niacin. These symptoms can usually be reduced by gradually increasing the dosage over several weeks or by using slow-release niacin. However, slow-release niacin appears to be more likely to cause liver inflammation than other forms of niacin. Inositol hexaniacinate may also cause less flushing than plain niacin, and if aspirin is taken along with niacin, the flushing reaction will usually decrease.

Therapeutic Uses

Niacin (but not niacinamide) is known to significantly improve cholesterol profile, reducing levels of total and low-density lipoprotein (LDL, or bad) cholesterol and raising high-density lipoprotein (HDL, or good) cholesterol. However, unpleasant flushing reactions, as well as a risk of liver inflammation and dangerous interactions with other cholesterol-lowering drugs, have kept niacin from being widely used.

Niacinamide may improve blood sugar control in both children and adults who already have diabetes. In addition, some evidence has suggested that regular use of niacinamide (but not niacin) might help prevent diabetes in children at special risk of developing it; however, subsequent studies indicate that it probably does not work.

Preliminary evidence suggests that niacinamide may be able to decrease symptoms of osteoarthritis and help control polymorphous light eruption, a type of photosensitivity. Somewhat surprisingly, topical niacinamide has shown some promise for skin conditions. In a double-blind study of fifty women with signs of aging skin, the use of a niacinamide cream significantly improved skin appearance and elasticity compared with placebo cream. Niacinamide cream has also shown promise for rosacea.

The inositol hexaniacinate form of niacin (taken orally) may be helpful for intermittent claudication14 and Raynaud’s phenomenon. In addition, weak and, in some cases, contradictory evidence suggests one of the several forms of niacin might be helpful for people with bursitis, cataracts, human immunodeficiency virus (HIV) infection, pregnancy, schizophrenia, Alzheimer's disease, and tardive dyskinesia.

In the early twenty-first century, some individuals began using very high doses (2.5 to 5 grams) of niacin in an attempt to mask drugs in their urine. However, not only does niacin fail to conceal the presence of drugs on a urine drug screen, but also, when taken suddenly at doses this high, niacin can cause life-threatening problems involving the liver and heart. In addition, it can dangerously disturb blood sugar regulation and blood coagulation. While this urban legend continued to circulate, no scientific evidence supported its assertions.

Scientific Evidence

Niacin is one of the best-researched vitamins, and the evidence for using it to treat at least one conditionhigh cholesterolis strong enough that it has become an accepted mainstream treatment.

High cholesterol/triglycerides. Niacin has been used since the 1950s to improve cholesterol profile. Several well-designed double-blind, placebo-controlled studies have found that niacin can reduce LDL (bad) cholesterol by approximately 10 percent and triglycerides by 25 percent while raising HDL (good) cholesterol by 20 to 30 percent. Niacin also lowers levels of lipoprotein(a), another risk factor for atherosclerosis, by about 15 to 35 percent. Long-term studies have shown that the use of niacin can significantly reduce death rates from cardiovascular disease. Niacin also appears to be a safe and effective treatment for high cholesterol in people with diabetes and, contrary to previous reports, does not seem to raise blood sugar levels. Used in combination with statin therapy to ensure the best patient outcomes.

Treating diabetes. When a child develops diabetes, there is an interval called the honeymoon period in which the pancreas can still make some insulin, and there is little to no need for injected insulin. Weak evidence suggests that niacinamide might slightly delay the onset of more severe symptoms. A cocktail of niacinamide plus antioxidant vitamins and minerals has also been tried, but the results were disappointing in one study. However, in another study, the use of intensive insulin therapy along with niacinamide and vitamin E was more effective than insulin plus niacinamide alone in prolonging the honeymoon period. Another study suggests that niacinamide may also improve blood sugar control in type 2 diabetes, but it did not use a double-blind design. Overall, niacin impacts individuals with diabetes in positive and negative ways, so it should only be taken at the direction of a doctor.

Intermittent claudication. Double-blind studies involving about four hundred individuals have found that inositol hexaniacinate can improve walking distance for people with intermittent claudication. For example, in one study, one hundred individuals were given either a placebo or 4 g of inositol hexaniacinate daily. Over three months, participants improved significantly in the number of steps they could take on a special device before experiencing excessive pain.

Osteoarthritis. There is some evidence that niacinamide may provide some benefits for those with osteoarthritis. In a double-blind study, seventy-two people with arthritis were given either 3,000 milligrams (mg) daily of niacinamide in six equal doses or placebo for twelve weeks. The results showed that treated participants experienced a 29 percent improvement in symptoms, whereas those given a placebo worsened by 10 percent. However, at this dose, liver inflammation is a concern that must be taken seriously. In other studies, niacin improved joint mobility and allowed patients to take fewer over-the-counter pain medicines, which can also cause damage to the liver in large amounts.

Raynaud’s phenomenon. According to one small double-blind study, the inositol hexaniacinate form of niacin may be helpful for Raynaud’s phenomenon. The dosage used was 4 g daily—once again, a dosage high enough for liver inflammation to be a real possibility. Though some benefits have been observed, the risk of side effects outweighs the potential therapeutic impact of niacin for Raynaud’s phenomenon.

Safety Issues

When taken at a dosage of more than 100 mg daily, niacin frequently causes annoying skin flushing, especially in the face, as well as stomach distress, itching, and headache. In studies, as many as 43 percent of individuals taking niacin quit because of unpleasant side effects.

A more dangerous effect of niacin is liver inflammation. Although some reports suggest that it occurs most commonly with slow-release niacin, it can occur with any type of niacin when taken at a daily dose of more than 500 mg (usually 3 g or more). Regular blood tests to evaluate liver function are therefore mandatory when using high-dose niacin (or niacinamide or inositol hexaniacinate). This reaction almost always goes away when niacin is stopped. Contrary to claims on some manufacturers’ websites, there is no reliable evidence that inositol hexaniacinate is safer than ordinary niacin.

As noted above, a single dose of 2.5 to 5 g of niacin, used in the vain hope of passing a urine drug test despite the presence of drugs in the system, can cause life-threatening disturbances in body function. Since this range includes the high-end of the dosage used for treating cholesterol, presumably, people who gradually work up to taking several grams of niacin daily can accommodate it in a way that those who take it suddenly cannot.

People who have liver disease, ulcers (presently or in the past), gout, or drink too much alcohol should not take high-dose niacin except on medical advice. While there has been some concern that niacin may raise blood sugar levels in diabetics, the effect appears to be slight, and it carries little, if any, clinical significance.

Combining high-dose niacin with statin drugs, the most effective medications for high cholesterol further improves cholesterol profile by raising HDL (good) cholesterol. However, there are real concerns that this combination therapy could cause a potentially fatal condition called rhabdomyolysis.

A growing body of evidence, however, suggests that the risk is relatively slight in individuals with healthy kidneys. Furthermore, even much lower doses of niacin than the usual dose given to improve cholesterol levels (100 mg versus 1,000 mg or more) may provide a similar benefit. At this dose, the risk of rhabdomyolysis should be decreased. Nonetheless, it is not safe to try this combination except under close physician supervision. Rhabdomyolysis can be fatal.

Another potential drug interaction involves the anticonvulsant drugs carbamazepine and primidone. Niacinamide might increase blood levels of these drugs, possibly requiring a reduction in drug dosage. People should not use this combination except under physician supervision. The maximum safe dosage of niacin for pregnant or nursing women has been set at 35 mg daily (30 mg if eighteen years old or younger).

Important Interactions

For people who are taking cholesterol-lowering drugs in the statin family, niacin might offer potential benefits; however, there are real dangers to this combination. People should not try it except under physician supervision.

People taking the antituberculosis drug isoniazid (INH) may need extra niacin. People who take anticonvulsant drugs, such as carbamazepine or primidone, should not take niacinamide except under physician supervision. Similarly, people who drink alcohol excessively should not take niacin except under physician supervision.

Toxicity may occur when using niacin supplements, leading to liver damage, flushing of the face, blurred vision, hyperglycemia, headaches, rashes, dizziness, nausea, vomiting, and light-headedness.

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