Vitamin B3 (niacin) is a water-soluble vitamin, absorbed in the small intestine and excreted in the urine. Because it is not stored, it is needed in frequent, small doses. Because it is easily excreted, it is also less likely to reach toxic levels; however, therapeutic dosing in the treatment of high blood cholesterol levels can cause dangerous side effects, especially liver problems, and must be monitored closely.

The human body uses niacin in more than 50 chemical reactions. Working together with various enzymes (coenzyme activity), niacin is instrumental in the release of energy from carbohydrates which fuels all body systems. It is necessary for proper central nervous system (brain) function. It is also involved in fat and cholesterol metabolism and the manufacture of many body compounds including sex and adrenal hormones. Other functions of vitamin B3 include the regulation of blood sugar, antioxidant mechanisms, and detoxification reactions.

Fifty percent of the niacin used by the body comes from the conversion of the amino acid tryptophan. Therefore, the richest sources of niacin are protein-rich foods such as extra-lean meats, chicken, fish, eggs, cooked dried beans and peas, brewer's yeast, liver and other organ meats, nonfat/lowfat milk and cheese, soybeans, and nuts. Other sources are enriched bread and cereals, and whole grains (except corn). The most abundant vegetable sources are mushrooms and greens. It is better to steam, bake, or stir-fry vegetables, as niacin may be lost in cooking water.

There are two main forms of vitamin B3: niacin (nicotinic acid, nicotinate) and niacinamide (nicotinamide). The amide form (niacinamide) has no vasodilator action nor any effect on serum lipids in the treatment of high cholesterol. Therefore, niacin is the form prescribed for lowering cholesterol levels, while niacinamide is preferred for arthritis and Type I diabetes. Preformed niacin is available from vegetable sources such as brewer's yeast, wheat germ, and nuts; however, most of the niacin our bodies use is that which is converted from the amino acid tryptophan provided by protein sources.

Niacin is available in the following forms.

• Tablets: 25 mg, 50 mg, 100 mg, 250 mg, 500 mg
• Elixir: 50 mg/5 ml
• Injection: 30 ml vials, 100 mg/ml

Timed-release capsules and tablets are widely available and were devised to help reduce "niacin flush" (a flushing of the face caused by capillary dilation). However, several studies have shown a significant increase in liver damage associated with the use of this type of preparation. Most literature suggests that sustained-release niacin should not be used because of its potential damage to the liver. Two recent eastern European studies indicate that wax-coated sustained-release niacin does not have undesirable side effects. But until further studies can be done, it would be prudent to avoid timed-release preparations of niacin.

Niacinamide is available in the following forms:

• Tablets: 50 mg, 100 mg, 500 mg
• Tablets (timed-release): 1,000 mg
• Injection: 100 mg/ml

Niacin is also available as inositol hexaniacinate, a preparation developed in Europe. Inositol hexaniacinate is a natural sustained-release delivery method that is not thought to lead to liver disorders.

Niacin:

• Effective in reduction of LDL and triglyceride levels
• Increases HDL levels
• Reduces the risk of developing cardiovascular disease
• Has a synergystic effect when combined with other cholesterol-reducing medications

Niacinamide:

• May help osteoarthritis and rheumatoid arthritis
• May be effective in treatment and control of early-onset insulin-dependent (Type I) diabetes
• In combination with vitamins A and E, niacin (nicotinic acid) helps prevent and treat heart disease
• Varying success in treatment of schizophrenia, anxiety, depression, and other mental illnesses
• Used in the treatment of alcoholism
• May be beneficial in the treatment of hypoglycemia
• Has been used as a treatment for insomnia due to its sedative effects

Because niacin can be obtained from tryptophan, it is measured in "niacin equivalents" and is based on estimates from overall calorie consumption. The niacin RDA is 6.6 mg equivalents/1,000 kcals, or a minimum of 13 mg daily, which should be consumed to maintain tissue store in healthy adults. The 1989 RDAs for niacin are:

• Infants up to 6 months: 5 mg
• Infants 6 months to 1 year: 6 mg
• Children 1 to 3 years: 9 mg
• Children 4 to 6 years: 12 mg
• Children 7 to 10 years: 13 mg
• Males 11 to 14 years: 17 mg
• Males 15 to 18 years: 20 mg
• Males 19 to 50 years: 19 mg
• Males 50+: 15 mg
• Females 11 to 18 years: 15 mg
• Females 19 to 50 years: 15 mg
• Females 50+: 13 mg
• Females pregnant: 17 mg
• Females lactating: 20 mg

Requirements may be higher for those who have cancer, those who are being treated with isoniazid (for tuberculosis), women taking oral contraceptives, and people with protein deficiencies.

Therapeutic dosing in the treatment of high blood cholesterol levels is within the range of 1,500 to 2,000 mg of pure crystalline niacin daily in divided doses. This level should be reached gradually over a period of four to six weeks. It should be taken with meals to minimize GI irritation.

Therapeutic doses of 150 mg/day have been reported to aid in migraine relief.

The most common side effect of niacin at doses of 75 mg or more is "niacin flush," a sometimes painful tingling sensation and flushing of the face and upper torso caused by dilation of capillaries. Onset of niacin flush is seen 15 to 30 minutes after ingestion. While generally not harmful, it can be uncomfortable or frightening for some people. Niacin flush can be reduced or sometimes eliminated by the ingestion of 80 to 325 mg of aspirin 30 minutes prior to taking the niacin.

The most serious problem associated with high-dose niacin therapy is the risk of liver toxicity. Doses over 2,000 mg increase the risk of abnormal liver function and necessitate frequent monitoring. Side effects can be reduced by developing tolerance to niacin supplementation over several weeks. Starting at low doses and increasing every four to seven days up to a therapeutic dose (500 mg to 2 g/day) may help reduce the amount of flushing and also reduce the risk of liver toxicity. Niacin flush is caused by a release of histamines; therefore, asthma sufferers should avoid high doses.

Other side effects of high doses of niacin include heartburn, nausea, vomiting, diarrhea, ulcers, liver malfunction, low blood pressure, and fainting. High doses of niacin (nicotinic acid) can also increase the blood levels of uric acid and glucose, leading to possible misdiagnosis of diabetes or gout.

Niacinamide does not cause niacin flush even at high doses, but also does not provide the beneficial cholesterol-lowering effects of niacin. Niacinamide can also have a sedative effect. Inositol hexaniacinate is an effective delivery method not thought to cause liver problems.

Niacin supplementation at therapeutic doses can cause liver damage and peptic ulcers; therefore, persons with a history of these ailments should not take large doses. Asthma sufferers should not take more than 75 mg of niacin due to histamine release, but can safely take niacinamide for dietary supplementation or other purposes. Diabetics, gallbladder patients, and gout patients should be supervised closely by a health care practitioner if taking therapeutic doses of niacinamide. Due to side effects, therapeutic dosing needs to be monitored closely by a health care practitioner to avoid toxic effects. Liver function and blood glucose should be closely monitored in all patients early in therapy.

In a randomized, double-blind, placebo-controlled study with 31 healthy subjects, administration of aspirin (325 mg) prior to treatment with niacin (500 mg) significantly reduced the incidence of flushing associated with niacin (Whelan et al. 1992). However, concomitant administration of higher doses of aspirin (1 g) with niacin (0.075 to 0.100 mg/kg/min IV) reduced the clearance of niacin in six healthy volunteers (Ding et al. 1989). Administration of aspirin (325 mg) at least 30 minutes before niacin treatment may alleviate intolerance to cutaneous reactions associated with niacin therapy.

Lipid-lowering doses of nicotinic acid may cause hyperglycemia and lead to loss of glycemic control (PDR 2000). Patients taking niacin while on metformin should be monitored closely for glycemic control.

Niacin binds to these bile acid sequestrants and should be taken at different times of the day (Bays and Dujovne 1998).

Niacin combined with fluvastatin is more effective at lowering serum lipids than either substance administered alone (Jokubaitis 1996). A more recent study evaluating the combination of an extended-release form of niacin (1 to 2 g/day) with a statin drug in 269 hypercholesterolemic adult patients supported these findings (Guyton et al. 1998).

In a prospective, open-label trial, the combination of niacin with pravastatin produced favorable results on lipid profiles in 16 diabetic patients over 14 weeks (Gardner et al. 1997). The addition of niacin (up to 500 mg tid) to pravastatin (20 mg/day) significantly lowered LDL cholesterol levels. Only five patients required minor modifications to their hypoglycemic therapy to maintain glycemic control.

However, the risk of myopathy and/or rhabdomyolysis is increased when HMG- CoA reductase inhibitors are coadministered with niacin (Yee et al. 1998). The degree of risk may depend upon the type of drug administered because myotoxicity has been observed with lovastatin but not with fluvastatin (Hill and Bilbao 1999; Jokubaitis 1996). In addition, hepatic dysfunction may be associated with high dose niacin therapy; liver function tests should be performed periodically (PDR 2000).

Lipid-lowering doses of nicotinic acid may cause hyperglycemia and lead to loss of glycemic control (PDR 2000). However, nicotinamide has been used in conjunction with intensive insulin therapy to reduce beta-cell dysfunction in patients with recent-onset Type I diabetes (Visalli et al. 1999). In a randomized, blinded, multicenter trial with 74 patients on insulin therapy for the treatment of Type I diabetes, nicotinamide (25 mg/kg and 50 mg/kg) affected clinical remission and markers of metabolic control such as insulin dose, HbA(1c), and C-peptide. Lower doses of nicotinamide are preferable to avoid the development of insulin resistance. Patients taking both insulin and niacin should be monitored closely to maintain glycemic control.

Administration of neomycin sulfate (1 g bid) with niacin (maximum dose of 1 g tid) decreased levels of total cholesterol by 26%, LDL cholesterol by 32%, and lipoprotein by 45% (Gurakar, et al. 1985). Neomycin monotherapy only decreased levels by 18%, 23%, and 24%, respectively.

Repeated exposure to niacin (250 mg tid) and transdermal nicotine patches (21 mg/day) in a 60-year-old female patient resulted in flushing reactions within 30 minutes after taking niacin (Rockwell 1993).

Nicotinic acid may decrease the hypoglycemic effect of sulfonylureas (PDR 2000) and cause significant deterioration in glycemic control (Garg 1992).

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