NIACIN AND TRYPTOPHAN

Function and essentiality The generic descriptor "niacin" includes nicotinic acid and nicotinamide, which functions as the reactive part of the nicotinamide nucleotide coenzymes, NAD and NADP. Nicotinamide can be synthesised from the amino acid tryptophan. The major metabolic role of NAD(P) is a coenzyme in oxidation and reduction reactions. Niacin is thus of central importance in intermediary metabolism, and the requirement is related to energy expenditure. Niacin deficiency results in pellagra, which is characterised by a severe sunburn-like skin lesion in areas of the body exposed to sunlight, and in areas such as the knees, ankles, wrists and elbows which are subjected to pressure. Diarrhoea is a characteristic, but not inevitable, symptom of pellagra. In advanced cases there may be dementia with intermittent periods of lucidity. Untreated pellagra is fatal.


Tryptophan-niacin equivalence The equivalence of dietary tryptophan and preformed niacin has been determined in volunteers maintained on controlled diets. There is a wide variation between individuals and from day to day in any one person. High dietary intake of tryptophan results in a greater apparent efficiency of conversion to niacin. Oestrogens reduce the rate of tryptophan metabolism, so that in areas where pellagra is or has been common, approximately twice as many women as men are affected although before puberty and after the menopause there is no sex difference. Kynureninase and kynurenine hydroxylase, two enzymes involved in tryptophan metabolism, are vitamin B6 and riboflavin dependent; deficiency of either of these vitamins may result in secondary pellagra, despite an apparently adequate intake of tryptophan and niacin (1,2). The Panel accepted the widely adopted convention that 60 mg tryptophan can be taken as equivalent to 1 mg dietary niacin (3). This ratio includes an allowance for individual variation. The niacin equivalence of diets is then the amount of preformed niacin + (1 /60 x tryptophan).


Requirements There is no wholly satisfactory laboratory assessment of niacin status. In experimental animals, measurement of whole blood NAD(P) can provide a sensitive index of niacin depletion (4), while the determination of the urinary excretion of N-methyl nicotinamide (NMN) and its onward metabolite methyl pyridone carboxamide (MPCX) offers the only other method available.

Adults The mean observed requirement for niacin to prevent or cure pellagra, or to normalise urinary excretion of NMN and MPCX, in experimental subjects maintained on niacin deficient diets and in energy balance, is 5.5 mg/1,000 kcal (3). A coefficient of variation of 10 per cent gives an RNI of 6.6 mg/ 1,000 kcal and an LRNI of 4.4 mg/ 1,000 kcal.

Infants The Panel accepted the DHSS Guidelines for Artificial Feeds for the Young Infant that infant milks should provide not less than 3.3-3.85 mg preformed niacin/1,000 kcal (5). With the tryptophan present in cows' milk protein, infants would have similar intakes of niacin equivalent/1,000 kcal to those of adults, and the Panel saw no reason to set DRVs for infants or children at a different level than those for adults.

Pregnancy There are considerable changes in tryptophan metabolism in late pregnancy as a result of hormonal changes, such that 30mg of tryptophan is equivalent to I mg dietary niacin (6). The Panel agreed that any additional requirement for niacin would be met by changes in the metabolism of tryptophan, and that an increased dietary intake was unnecessary.

Lactation Mature human milk provides about 2.3 mg preformed niacin/d at a concentration of 2.7 mg/L. In the absence of information about the equivalence of dietary tryptophan and niacin in lactation, the Panel agreed that such an increase in dietary niacin plus tryptophan would be prudent to meet this extra need, above that appropriate for the increased energy intake

Intakes Under normal conditions for an adult in nitrogen balance, the amount of tryptophan present in dietary protein provides adequate niacin without the need for any preformed vitamin at all. Median protein intakes in Britain are 84.0 g/d by men and 61.8 g/d by women (7) containing 12.6 mg tryptophan/g (8). At an equivalence of 60 mg tryptophan: I mg niacin this alone is equivalent to 17.6 mg/d niacin for men and 13.0 mg/d for women.

Guidance on high intakes Very high doses of nicotinic acid (3-6 g/d) cause changes in liver ultra-structure and function, in carbohydrate tolerance and in uric acid metabolism, which may result in clinical signs of hepatotoxicity but which appear to be reversible on withdrawal of the vitamin. Doses of nicotinic acid but not of nicotinamide in excess of about 200 mg cause vasodilatation of cutaneous blood vessels, and hence flushing. Higher doses may also cause dilatation of other blood vessels, and a transient fall in blood pressure. The effect wears off after some days' repeated administration. There is no evidence that intakes of niacin above those required to prevent pellagra confer any benefit. Indeed, the main response to higher intakes of nicotinic acid, nicotinamide or tryptophan is an increase in the urinary excretion of their metabolites (9).

References

1 Bender D A. Biochemistry of tryptophan in health and diseftse. Molec Aspects Med 1983; 6: 101-197.

2 Bender D A, Bender A E. Niacin and tryptophan metabolism: the biochemical basis of niacin requirements and recommendations. Nutr Abs Rev 1986; 56: 695-719.

3 Horwitt M K, Harvey C C, Rothwell W S, Cutler J L, Haffron D. Tryptophan-niacin relationships in man. Studies with diets deficient in riboflavin and niacin together with observations on the excretion of nitrogen and niacin metabolites. J Nutr 1956; 60 (suppi 1): 1-43.

4 Magboul B 1, Bender D A. Effects of a dietary excess of leucine on the synthesis of nicotinamide nucleotides in the rat. Br JNutr 1983; 49: 321-329.

5 Department of Health and Social Security. Artificial Feeds for the Young Infant. London: HMSO, 1980. (Reports on health and social subjects; 18).

6 Wertz, A W, Lojkin M I, Bouchard B S, Derby M B. Tryptophan-niacin relationships in pregnancy. J Nutr 1958; 64: 339-353.

7 Gregory J, Foster K, Tyler H, Wiseman M. The Dietary and Nutritional Survey of British Adults. London: HMSO, 1990.

8 Buss D H, Ruck N. The amino acid pattern of the British diet. J Hum Nutr 1977; 31: 165-169.

9 McCreanor G M, Bender D A. The metabolism of high intakes of tryptophan, nicotinamide and nicotinic acid in the rat. Br J Nutr 1986; 56: 577-586.