Niacin

Description

Niacin (vitamin B-3) is a water-soluble vitamin required by all living cells. It functions in the release of energy from carbohydrates, fats, and proteins. Niacin is also involved in the synthesis of protein, fat, and pentoses needed for nucleic acid formation.

Niacin is a major constituent of the coenzyme NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). These compounds function to remove hydrogen atoms during biological reactions.

Method of Action

Niacin is absorbed in the intestine; little is stored in the body and any excess of the vitamin is excreted in the urine.

Niacin functions as a component of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). These enzymes are involved in respiration where they act as hydrogen acceptors. They are essential in the reactions involved in the release of energy from carbohydrates, fats, and proteins.

Niacin can be synthesized in the body from tryptophan. Only the L-isomer of tryptophan can be converted into niacin, and the conversion requires the presence of thiamine, pyridoxine, and riboflavin.

Niacin is stable to heat, light, acid and alkali; therefore little is lost during processing. Vitamin B-Complex, vitamin B-1, vitamin B-2, vitamin C, and phosphorus assist the absorption of niacin. Ethanol, coffee, sugar sweet corn, starches, and excess carbohydrates prevent absorption.

Properties & Uses

The major clinical application of niacin is in the treatment of pellagra.

There is also evidence which suggest that doses of one to two grams of niacin three times per day may result in lowered blood cholesterol levels. This may protect against recurrent nonfatal heart attacks.

Large doses of niacin have also been used to treat schizophrenia. Orthomolecular therapy, using extremely large amounts of vitamins, is a controversial treatment of psychiatric problems as very little scientific evidence exists in its support. Since the ingestion of large therapeutic amounts of nicotinic acid usually produces a flushing reaction, niacin prescribed for nutritional deficiency is taken as nicotinamide.

Niacin deficiency is also common in alcoholics. Low levels of niacin are also seen in patients with chronic hepatic failure.

Consequence of Deficiency

There are many symptoms of niacin deficiency. Initially, muscular weakness, anorexia, indigestion, and skin eruptions occur, with severe deficiencies of niacin commonly leading to pellagra. Symptoms of pellagra include dermatitis, senile dementia, and diarrhea. Tremors and a sore tongue are also symptomatic. With pellagra the skin becomes cracked and pigmented in the parts exposed to sunlight. Lesions can appear in the central nervous system, producing confusion, disorientation and neuritis.

Inflammation of the mucous membranes of the mouth and the gastrointestinal tract can result from digestive abnormalities developed in niacin deficiency. Symptoms of severe riboflavin deficiency appear; many of the niacin deficiencies are similar due to the close interrelationship of riboflavin and niacin in cell metabolism.

Often, people who suffer from pellagra are on very inadequate diets in which corn is a main foodstuff. Such a diet contains little niacin, while the tryptophan in the corn is unavailable and cannot be absorbed from the intestine. Thus, there is no trytophan available for conversion to niacin and niacin deficiency results.

Presoaking corn in lye makes tryptophan available for absorption, due to the presence of alkali.

Toxicity Factors

No real toxic effects of niacin are known. However, large doses cause side effects such as a tingling sensation, flushing of the skin, gastrointestinal distress, unusual nervousness, and glucose intolerance.

Recommended Dietary Allowance

age	RDA (mgEq*)	RNI (mgEq*)
infants/children
0-6 months	5	3
7-9 months	6	4
10-12 months	6	5
1-3 years	9	8
4-6 years	12	11
7-10 years	13	12
males
11-14 years	17	15
15-18 years	20	18
19-50 years	19	17
51+ years	15	16
females
11-14 years	15	12
15-18 years	15	14
19-50 years	15	13
51+ years	13	12
pregnancy	17	-
lactation	20	15

*niacin equivalent = available niacin + (tryptophan / 60)

Niacin requirements are affected by such factors as: aging, growth periods, body size, physical activity, illness, tissue trauma, pregnancy and lactation. The RDA standard, 6.6 milligrams per 1,000 kilocalories (but not less than 13 niacin equivalents at intakes of less than 2,000 kilocalories), is about 50% higher than the minimum requirement; this is in order to provide a safety margin to cover variances in individual need. These recommendations also allow for the contribution of tryptophan, in terms of niacin equivalents, from dietary protein sources.

For over thirty years, Recommended Daily Amounts has existed in the United Kingdom. It has been used to measure the adequacy of an individual's diet. However, in 1991 the Committee on Medical Aspects of Food Policy (COMA) gave forth a whole new set of figures upon the request of the Department of Health's Chief Medical Officer. Reference Nutrient Intake (RNI) is one of these sets collectively known as "Dietary Reference Values." RNI is an amount of a nutrient that is enough for almost every individuals, even someone who has high needs for the nutrient. This level of intake is, therefore, considerably higher than what most people would need. If individuals are consuming the RNI of a nutrient they are most unlikely to be deficient in that nutrient.

The daily allowance of vitamin B-3 should be based on caloric intake.

Note: it is recognized that one milligram of niacin is derived from each 60 milligrams of dietary tryptophan.

Food Sources

High: (10 - 100 mg/100 g)

Beef kidney	Beef liver
Brewer's yeast	Chicken light meat
Chicken liver	Halibut
Meat extracts	Peanuts (roasted)
Pork kidney	Pork liver
Rabbit light meat	Rice bran
Swordfish	Tuna
Turkey light meat	Veal heart
Veal liver

Medium: (1 - 10 mg/100 g)

Almonds (dry)	Asparagus
Avocados	Barley
Beef	Broccoli
Brown rice	Camembert
Cashews	Chestnuts
Chicken dark meat	Clams
Corn	Dates
Duck	Fig (dried)
Fish, except tuna, halibut, swordfish	Green peas
Kale	Kidney beans
Lamb	Lentil
Lima beans	Molasses
Mushrooms	Oat flakes
Oysters	Parsley
Potatoes	Prunes (dry)
Roquefort	Rye bread
Shrimp	Soybeans (dry)
Swiss cheese	Veal
Walnuts	Wheat
Wheat germ

Low: (0.1 -1.0 mg/100 g)

Apples	Apricots
Bananas	Beet greens
Beets	Black currants
Blackberries	Blueberries
Brussels sprouts	Cabbage
Carrots	Cauliflower
Celery	Cherries
Chicory greens	Coconuts	Spinach
Cranberries	Cucumbers
Dandelion greens	Eggplant
Eggs	Endive
Figs	Grapefruit
Grapes	Hot chili peppers
Kohlrabi	Lemons
Lettuce	Melons
Milk	Onions
Oranges	Parsnips
Peaches	Pears
Pecans	Pineapples
Plums	Pumpkins
Radishes	Raisins
Raspberries	Rhubarb
Strawberries	Sweet potato
Tangerines	Tomato
Turnips	Watercress

Abstracts

Research - Nicotinamide

Acne vulgaris

Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance.

Data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.

Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Shalita-AR; Smith-JG; Parish-LC; Sofman-MS; Chalker-DK. Int-J-Dermatol. 1995 Jun; 34(6): 434-7.


Exercise in coronary patients

The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known.

Nicorandil was found to increase the rate of VO2, increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.

Effects of nicorandil on kinetics of oxygen uptake at the onset of. Koike-A; Hiroe-M; Yajima-T; Adachi-H; Shimizu-N; Kano-H; Sugimoto-K; Miyahara-Y; Korenaga-M; Marumo-F. Am-J-Cardiol. 1995 Sep 1; 76(7): 449-52.


IDDM

Nicotinamide has been recently introduced, in addition to intensive insulin therapy for patients with recent-onset insulin-dependent diabetes mellitus (IDDM) to protect beta cells from end-stage destruction. However, available data are conflicting.

IDDM patients received nicotinamide for 12 months at a dose of 25 mg/kg body weight or placebo

Whether this treatment improved the integrated parameters of metabolic control (insulin dose, glycated haemoglobin and C-peptide secretion) in the year after diagnosis

When age at diagnosis was taken into account, nicotinamide treated older patients ( > 15 years of age) showed significantly higher stimulated C-peptide secretion than placebo treated patients. These results suggest that nicotinamide can preserve and improve stimulated beta-cell function only in patients diagnosed after puberty.

Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study). Pozzilli-P; Visalli-N; Signore-A; Baroni-MG; Buzzetti-R; Cavallo-MG; Boccuni-ML; Fava-D; Gragnoli-C; Andreani-D; et-al. Diabetologia. 1995 Jul; 38(7): 848-52.


Diabetes prevention

Nicotinamide and diabetes prevention. Behme-MT. Nutr-Rev. 1995 May; 53(5): 137-9.

Individuals at high risk of developing insulin-dependent diabetes mellitus can now be identified by immunologic testing. This ability to predict future cases of IDDM raises the possibility of intervention to prevent the disease. An intervention study in New Zealand using nicotinamide treatment showed a 50% reduction in the development of IDDM in a 5-year period.


Skin lesions

In 1986, Berk and Lorincz reported the efficacy of tetracycline and nicotinamide in the treatment of bullous pemphigoid (BP).

A regimen of 2 g tetracycline combined with 2 g nicotinamide daily was effective in clearing the skin lesions.

Bullous pemphigoid successfully controlled by tetracycline and nicotinamide. Kolbach-DN; Remme-JJ; Bos-WH; Jonkman-MF; De-Jong-MC; Pas-HH; van-der-Meer-JB. Br-J-Dermatol. 1995 Jul; 133(1): 88-90.


Tumours

Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Although clinical attempts to overcome hypoxia have met with some success, the results have been far from satisfactory.

Studies have shown that nicotinamide and structurally related analogs can effectively sensitise murine tumours to both single and fractionated radiation treatments

Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically for the treatment of a variety of disorders, with daily doses of up to 6 g being considered reasonably safe and associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to radiation. These findings have now resulted in phase I/II clinical trials of nicotinamide, in combination with carbogen breathing, as a potential radiosensitizing treatment.

Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours. A review. Horsman-MR. Acta-Oncol. 1995; 34(5): 571-87.

References

Alhadeff, L., Gualtieri, G.T., Lipton, M. Nutr Rev., 1984; 42; 33-40.

Behme-MT: Nicotinamide and diabetes prevention. Nutr-Rev. 1995 May; 53(5): 137-9.

Bendich, A., Cohen, M. In: Nutrition and Immunology. Alan R. Liss: New York, 1988, pp. 114-115.

Brown-BG et al: Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease. Observations from the FATS Trial. Familial Atherosclerosis Treatment Study. Ann-N-Y-Acad-Sci. 1995 Jan 17; 748: 407-17; discussion 417-8.

Brown-WV: Niacin for lipid disorders. Indications, effectiveness, and safety. Postgrad-Med. 1995 Aug; 98(2): 185-9, 192-3.

Cheraskin, E., Ringsdorf, W.M., Jr. Medford, F.H. Int J Vit Nutr Res., 1976; 46: 58-60.

Czajkanarin, D.M. 1984. Minerals - Food, Nutrition and Diet Therapy M.V. Krause and L.K. Mahan. W.B. Saunders Company, Philadelphia.

Einstein, N., et al. Am J Digest Dis., 1975; 20: 282-286.Borrman, W.R. 1979. Comprehensive Guide to Nutrition. New Horizons Pub Corp. Chicago, Illinois.

Figge, H.L., et al. Pharmacotherapy, 1988; 8: 287-294.

Gaby, S.K. In: Vitamin Intake and Health: A Scientific Review. Marcel Dekker: New York, 1191, pp. 189-192.

Goldsmith, G.A., Miller, O.N., Unglaub, W.G. J Nutr., 1961; 73: 172-176.

Goodhart, Robert S. and Maurice E. Shills. Modern Nutrition In Health And Disease. 6th edition. Philadelphia: Lea and Febiger, 1973.

Grundy, S.M. Scand J Clin Lab Invest., 1990; (Suppl 199) 50; 63-72.

Guthrie, Helen A. Introductory Nutrition. 5th edition. St. Louis: C.V. Mosby Co., 1971.

Hegsted, M.D. 1976. Present Knowledge In Nutrition. 4th ed. The Nutrition Foundation Pub., Washington D.C. 605.

Holvoet-P & Collen-D: Lipid lowering and enhancement of fibrinolysis with niacin [editorial; comment] Circulation. 1995 Aug 15; 92(4): 698-9.

Horsman-MR: Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours. A review. Acta-Oncol. 1995; 34(5): 571-87.

Kirschmann, J.D. Nutrition Almanac: Nutrition Search. McGrew-Hill: New York. 1990.

Koike-A et al: Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease. Am-J-Cardiol. 1995 Sep 1; 76(7): 449-52.

Kolbach-DN et al: Bullous pemphigoid successfully controlled by tetracycline and nicotinamide. Br-J-Dermatol. 1995 Jul; 133(1): 88-90.

Krause, M.V. & L.K. Mahan. 1979. Food, Nutrition and Diet Therapy. 6th ed. W.B. Saunders Company, Philadelphia. 963.

Kutsky, R.J. 1973. Handbook of Vitamins and Hormones. Van Nostrand Reinhold, Co. New York, New York. 278.

Lal-SM et al: Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-labeled crossover trial.. Am-J-Kidney-Dis. 1995 Apr; 25(4): 616-22.

Lloyd, L.E. 1978. Fundamentals of Nutrition. W.H. Freeman and Company, San Francisco, Ca.

Murray, M.T. & Pizzorno, J.E. Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing,1991.

O'Hara, J., Jolly, P.N., Nicol, C.G. Br J Clin Practice, 1988; 42: 377- 383.

O'Keefe-JH Jr et al: Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemiaAm-J-Cardiol. 1995 Sep 1; 76(7): 480-4.

Oster-G et al: A randomized trial to assess effectiveness and cost in clinical practice: rationale and design of the Cholesterol Reduction Intervention Study (CRIS). Control-Clin-Trials. 1995 Feb; 16(1): 3-16.

Patterson, J.I. Am J Clin Nutr., 1980; 33: 2157-2167.

Pigott-K et al: Short communication: the addition of carbogen and nicotinamide to a palliative fractionation schedule for locally advanced breast cancer. Br-J-Radiol. 1995 Feb; 68(806): 215-8

Poskitt-L & Wojnarowska-F: Treatment of cicatricial pemphigoid with tetracycline and nicotinamide. Clin-Exp-Dermatol. 1995 May; 20(3): 258-9.

Pozzilli-P et-al: Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study). Diabetologia. 1995 Jul; 38(7): 848-52.

Recommended Dietary Allowances. 1989. National Academy of Science, National Academy Press, Washington, D.C.

Robitaille, G. Heavy-Metal Accumulation in the Annual Rings of Balsam Fir Abies Balsamea (L.) Mill. Environmental Pollution, Series B, 2 1981.

Shakir-KM et al: Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo-Clin-Proc. 1995 Jun; 70(6): 556-8.

Shalita-AR et al: Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Int-J-Dermatol. 1995 Jun; 34(6): 434-7.

Shansky, A. Drug Cosmet Indust., 1981; 129; 68-69.

Ueki-M et al: Protection of intrahepatic islet grafts from hyperglycemic toxicity by nicotinamide treatment. Transplant-Proc. 1995 Feb; 27(1): 618

Utoh-J et al: Hemodynamic effects of bolus nicorandil compared with nitroglycerin [letter]. Am-J-Emerg-Med. 1995 Sep; 13(5): 610-2.

Walji, H., Vitamin Guide: Essential nutrients for healthy living., Element: Dorset, U.K. 1992.

Walji, H., Vitamin Minerals & Dietary Supplements., Hodder Headline Plc.: London, U.K. 1994.

Williams, Sue Rodwell. Nutrition And Diet Therapy. 5th edition. St Louis: Times Mirror Mosby, 1985.

Yeshurun-D & Gotto-AM Jr: Hyperlipidemia: perspectives in diagnosis and treatment. South-Med-J. 1995 Apr; 88(4): 379-91.

Zemel, M.B. Phosphates and Calcium. Journal Of The American Dietetic Association, 81. 1982.