Niacin

Niacin, which is also known as vitamin B3, is the common name for both nicotinic acid and nicotinamide (or niacinamide). The niacin deficiency disease, pellagra, was first recognized in the early 18th century but it was not until the 1930s that niacin was found to cure the disease. Niacin is a water soluble white powder and is more resistant to destruction than other B complex vitamins. The body can convert the amino acid tryptophan into niacin.

What it does in the body

Metabolism

Like other B vitamins, niacin is essential for the manufacture of enzymes that provide cells with energy through tissue respiration and carbohydrate, protein and fat metabolism. These enzymes are nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin is involved in over 200 enzyme reactions and is essential for healthy skin, tongue and digestive tract tissues and the formation of red blood cells.

Hormones

Niacin is essential for the synthesis of various hormones including sex hormones, cortisone, thyroxin and insulin. Nicotinic acid is part of the glucose tolerance factor, a compound which enhances the body’s response to insulin (the hormone responsible for transporting glucose into cells and storing it in the liver and muscles).

Protection of genetic material

The repair of the genetic damage that occurs when cells are exposed to viruses, drugs or other toxic substances requires niacin-dependent coenzymes.

Nervous system

Niacin is essential for the normal functioning of the brain and nervous system.

Absorption and metabolism

Niacin is absorbed in the small intestine, mostly in the form of NAD or NADP. These compounds are then broken down to form nicotinamide which can be converted by bacteria to nicotinic acid. As niacin is water soluble, excess is excreted in the urine, although small amounts may be stored in the liver.

The amino acid, tryptophan, is converted to niacin in the body if sufficient iron, riboflavin and vitamin B6 are present. More than half the RDA for niacin can be obtained through the conversion of tryptophan.

Deficiency

Severe niacin deficiency causes the disease known as pellagra. Symptoms include the ‘three Ds’: diarrhea, dementia and dermatitis. The most characteristic sign is a reddish skin rash on the face, hands and feet which becomes rough and dark when exposed to sunlight. Other symptoms include weakness, loss of appetite, lethargy, a sore mouth and tongue, inflamed membranes in the intestinal tract and diarrhea. Nervous system effects include dementia, tremors, irritability, anxiety, confusion and depression. Pellagra may actually be a complex disorder involving thiamin, riboflavin and other nutrients. Niacin deficiency was originally observed in cultures whose diets relied heavily on corn prepared in a way which left the niacin unavailable for absorption.

Large amounts of tryptophan can overcome a niacin-poor diet and deficiency is usually seen in those whose diets are low in both niacin and protein. People at risk of deficiency include those with absorption difficulties, alcoholics, the elderly who neglect their diet, some infants and pregnant women.

Sources

Most niacin in food is in the form of NAD or NADP. The richest sources of niacin and tryptophan are chicken, fish, cooked dried beans and peas, brewer’s yeast, wheat bran, peanuts, beef, and whole grain wheat products. Niacin in grain foods is bound to other compounds and only around 30 per cent is available for absorption. Fruits, vegetables and dairy products all contain some niacin as do dates, figs and prunes. Milk and eggs are good sources of tryptophan. Processing of grains removes most of their niacin content so flour is enriched with the vitamin. Niacin is relatively stable to heat and light, and little is lost during cooking. Treating corn with lime water, a procedure which is common in Central America and Mexico, increases the availability of niacin.

Under normal conditions, tryptophan obtained in the diet is first used for the maintenance of protein levels and then for the manufacture of niacin. Although it appears to vary widely, an average conversion rate is 60 mg tryptophan to 1 mg niacin.

Tuna, canned 1 can 41.8

Salmon, canned ½ cup 29.7

Special K 1 cup 22.6

All Bran ½ cup 16.7

Lamb liver, fried 100g 12.2

Swordfish 100g 11.8

Veal, cooked 100g 10.5

Peanuts, salted ½ cup 8.8

Trout 1 fillet 8.3

Chicken, roast 100g 7.9

Lamb, cooked 100g 6.6

Lamb kidney, simmered 100g 6.0

Mackerel 1 fillet 6.0

Beef, cooked, lean and fat 100g 3.9

Wheat germ ½ cup 3.9

Plain hamburger 1 serve 3.7

Pork, cooked, lean and fat 100g 2.5

Pork sausage 100g 4.5

Kidney beans 1 cup 3.0

Corn 1 cup 2.6

Spaghetti, cooked 1 cup 2.3

Recommended dietary allowances

The RDAs for niacin in the USA were revised in 1998.

USA

Men 16 mg

Women 14 mg

Pregnancy 18 mg

Lactation 17 mg

UK

Men 17 mg

Women 13 mg

Pregnancy 13 mg

Lactation 15 mg

Australia

Men 19 mg

Women 13 mg

Pregnancy 15 mg

Lactation 18 mg

As for the other B vitamins, niacin requirements are greater in women pregnant with or breastfeeding more than one child.

Supplements

Niacin supplements are available in nicotinic acid and niacinamide forms, both separately and combined. These have different applications. Sustained release niacin supplements are available and although these may reduce the skin flushing reaction caused by large doses of niacin, they may be more toxic to the liver.

A newer form of niacin known as inositol bound niacin or inositol hexanicotinate is now available, and may be safer than other forms as it does not cause liver damage or flushing.

Toxic effects of excess intake

Doses in excess of 1000 mg of nicotinic acid can produce flushing of the skin, intense itching, headaches, tingling and burning, severe heartburn, nausea, vomiting, abnormalities of glucose metabolism, and eye problems such as blurred vision. The flushing is caused by the action of hormone-like compounds called prostaglandins which dilate blood vessels. Doses in the thousands of milligrams can cause liver damage and jaundice (a yellowing of the skin and eyes). The flushing can be minimized by taking nicotinic acid with meals or by taking an aspirin 30 minutes before each dose. The nicotinamide form of niacin does not cause flushing.

Therapeutic uses of supplements

Cardiovascular disease

Niacin has been used for many years to treat high blood lipid levels. It reduces total cholesterol, harmful LDL cholesterol and triglycerides, and increases beneficial HDL cholesterol levels. It has been shown to reduce the incidence of heart attacks and deaths from heart disease. Niacin also favorably influences other lipid levels including lipoprotein (a). Doses used range from 1500 to 2500 mg. Sustained-release niacin may be associated with more dramatic changes in LDL cholesterol and triglyceride, whereas the short-acting preparation may cause greater increases in HDL cholesterol. The increase of HDL cholesterol seems to occur at a lower dose (1500 mg per day) than the reduction of LDL cholesterol. In general it is usual to start taking lower doses (around 50 to 100 mg) and then gradually increase to the higher doses over a period of two to three weeks.

Researchers involved in a 1997 study done in Minneapolis compared blood lipid levels in 244 patients treated with niacin and 160 treated with lovastatin, a widely used cholesterol-lowering drug. The results showed that both lovastatin and niacin effectively reduced LDL cholesterol levels with a greater drop seen in those taking lovastatin. Niacin use was associated with a 16.3 per cent improvement in HDL cholesterol, while HDL cholesterol levels in the lovastatin group improved 1.5 per cent. The improvement in triglyceride levels was also much greater in the niacin group.1

Nicotinic acid can also enhance the effects of other cholesterol-lowering medications. This may mean that the doses of these drugs can be reduced, thus lessening the possibility of undesirable side effects. In a recent US study, researchers found that combination therapy with niacin and low dose lovastatin was as effective as high dose lovastatin.2

In a 1997 US study, researchers assessed the effect of 1.5 mg of niacin per day in 23 diabetic patients who were unable to achieve desirable blood lipid levels with low-dose pravastatin treatment. The results showed significant reductions in LDL cholesterol with niacin treatment.3 Taking vitamins A and E with nicotinic acid may reduce the dose of niacin necessary to produce beneficial effects.

Nicotinic acid has also been shown to have favorable effects on the blood clotting system which can reduce the build-up of atherosclerotic plaque.4 It has also been used to treat peripheral vascular disease and circulatory disorders such as Raynaud’s disease as it dilates blood vessels, thereby increasing blood flow to certain areas of the body.

Type I diabetes

Nicotinamide has been shown to prevent the development of Type I (insulin dependent) diabetes in animals, possibly by helping insulin to act more efficiently and by preventing the immune system from attacking the pancreatic beta cells which produce insulin. Because it has a protective effect on beta cells it needs to be given early in the course of the disease while there are beta cells still remaining. Several small scale studies in humans suggest that nicotinamide may have a role to play in preventing the onset of Type I diabetes.

Researchers in New Zealand carried out a controlled trial of oral nicotinamide in the prevention of the onset of diabetes mellitus in a group of high risk children. All eight of the untreated children developed diabetes during the follow-up period of the study whereas only one of 14 treated children did.5 In 1996, the same researchers published the findings of a population-based diabetes prevention trial involving nicotinamide treatment of 173 children aged 5 to 8 at risk for Type I diabetes. The results showed a 50 per cent reduction in the development of diabetes in a five-year period and suggest a protective effect of nicotinamide.6

Mental disorders

Both tryptophan and niacin have been used to treat depression, anxiety and insomnia. The psychiatric symptoms of niacin deficiency disease resemble the symptoms of schizophrenia and large doses of niacin have been used to treat this disorder. In some cases, the results of such studies have been promising, while in others niacin has failed to show any beneficial effect.

Other uses

Niacin has been used to stimulate tooth eruption, to treat fatigue, irritability, digestive disorders, headaches, migraines, arthritis, cramps and nerve problems such as Bell’s Palsy and trigeminal neuralgia.

Interactions with other nutrients

Vitamin B6, riboflavin and iron are necessary for the conversion of tryptophan to niacin. Niacin works with other B vitamins to perform its functions in the body. The amino acid, leucine, competes with tryptophan for absorption and diets low in niacin and high in leucine may lead to niacin deficiency disease. Niacin may also enhance the utilization of zinc and iron.7

Interactions with drugs

Niacin may reduce the toxic side effects on heart tissue of the anticancer drug adriamycin without reducing its effectiveness in the treatment of cancer. It may also enhance the effectiveness of anticonvulsant drugs such as phenobarbital. Antibiotics may cause niacin flushes to become more severe. The drug, isoniazid, may cause niacin deficiency disease as it reduces the conversion of tryptophan to niacin. Oral contraceptives appear to increase the conversion efficiency of tryptophan to niacin.

Alcohol may increase niacin needs and nicotinamide has been shown to protect against the damage to liver cells caused by drinking a large quantity of alcohol.8

Cautions

High doses of nicotinic acid should be avoided in those with impaired liver function, gall bladder disease, gout, asthma, cardiac arrhythmias, inflammatory bowel disease, migraine, or an active peptic ulcer. Nicotinic acid in high doses can reduce blood pressure and should be avoided by those taking drugs to control high blood pressure. Niacin in high doses can affect glucose metabolism and should be used cautiously by diabetics.

1 O’Connor PJ; Rush WA; Trence DL. Relative effectiveness of niacin and lovastatin for treatment of dyslipidemias in a health maintenance organization. J Fam Pract, 1997 May, 44:5, 462-7

2 Gardner SF; Schneider EF; Granberry MC; Carter IR. Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy, 1996 May, 16:3, 419-23

3 Gardner SF; Marx MA; White LM; Granberry MC; Skelton DR; Fonseca VA. Combination of low-dose niacin and pravastatin improves the lipid profile in diabetic patients without compromising glycemic control. Ann Pharmacother, 1997 Jun, 31:6, 677-82

4 Johansson JO; Egberg N; Asplund Carlson A; Carlson LA. Nicotinic acid treatment shifts the fibrinolytic balance favourably and decreases plasma fibrinogen in hypertriglyceridaemic men. J Cardiovasc Risk, 1997 Jun, 4:3, 165-71

5 Elliott RB; Chase HP. Prevention or delay of type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. Diabetologia, 1991 May, 34:5, 362-5

6 Elliott RB; Pilcher CC; Fergusson DM; Stewart AW A population based strategy to prevent insulin-dependent diabetes using nicotinamide. Pediatr Endocrinol Metab, 1996 Sep, 9:5, 501-9

7 Agte VV; Paknikar KM; Chiplonkar SA. Effect of nicotinic acid on zinc and iron metabolism. Biometals, 1997 Oct, 10:4, 271-6

8 Volpi E; Lucidi P; Cruciani G; Monacchia F; Reboldi G; Brunetti P; Bolli GB; De Feo P Nicotinamide counteracts alcohol-induced impairment of hepatic protein metabolism in humans. J Nutr, 1997 Nov, 127:11, 2199-204