Requirements and Signs of Deficiency

As for most other micronutrients, the requirement of niacin to prevent or reverse the clinical deficiency signs is not known very precisely, and probably depends on ancillary dietary deficiencies or other insults occurring in natural human populations. For the purpose of estimating niacin requirements for dietary reference values, the criterion of restoration of urinary excretion of NMN during controlled human depletion-repletion studies has been selected, and on this basis, the average adult requirement has been estimated as 5.5 mg (45 mmol) of niacin equivalents per 1000 kcal (4200 kJ). Adding a 20% allowance for individual variation this needs to be increased to 6.6 mg (54 mmol) per 1000 kcal, (4200 kJ), which is the current reference nutrient intake (UK). Niacin requirements were, by convention, expressed as a ratio to energy expenditure. For subjects with very low energy intakes, the daily intake of niacin equivalents should not fall below 13 mg, however. If dietary protein levels and quality are high, it is possible for tryptophan alone to provide the daily requirement for niacin equivalents. Dietary niacin deficiency is now rare in most Western countries.

The appearance of severe niacin deficiency as endemic pellagra, especially in North America in the nineteenth and early twentieth centuries, has been ascribed to the very poor availability of bound forms of niacin (in niacytin, a polysacchar-ide/glycopeptide/polypeptide-bound form, which is 90% indigestible), together with the relatively low content of tryptophan occurring in grains (see Table 1). However, the lack of available niacin and tryptophan may not have been the whole story, since coexisting deficiencies or imbalances of other nutrients, including riboflavin, may also have contributed to this endemic disease. It appears also that the choice of cooking methods may have been critical, since the Mexican custom of cooking maize with lime in the preparation of tortillas helps to release the bound niacin from its carbohydrate complex and to increase the bioavailability of trypto-phan-containing proteins, and thus to reduce the prevalence of clinical deficiency disease. In parts of India, pellagra has been encountered in communities whose main staple is a form of millet known as 'jowar', which is rich in leucine. It was proposed, and evidence was obtained from animal and in vitro studies, that high intakes of leucine can increase the requirements for niacin. However, other evidence is conflicting (this interaction is not fully understood). In parts of South Africa, iron overload has been reported to complicate the metabolic effects of low niacin intakes.

The average content of niacin in human breast milk is 8 mg (65.6 mmol) per 1000 kcal (4200 kJ), and this is the basis for the recommendations (and dietary reference values) for infants up to 6 months. In the UK, the Reference Nutrient Intake niacin increment during pregnancy is nil, and during lactation it is 2 mg per day.

The most characteristic clinical signs of severe niacin deficiency in humans are dermatosis (hyper-pigmentation, hyperkeratosis, desquamation - especially where exposed to the sun), anorexia, achlorhydria, diarrhea, angular stomatitis, cheilosis, magenta tongue, anemia, and neuropathy (headache, dizziness, tremor, neurosis, apathy). In addition to the pellagra caused by dietary deficiency or imbalance, there are also reports of disturbed niacin metabolism associated with phenylketonuria, acute intermittent porphyria, diabetes mellitus, some types of cancer (carcinoid syndrome), thyrotoxicosis, fever, stress, tissue repair, renal disease, iron overload, etc. The picture in other species is not radically different; however, deficient dogs and cats typically exhibit 'black tongue' (pustules in the mouth, excessive salivation) and bloody diarrhea, pigs exhibit neurological lesions affecting the ganglion cells, rats exhibit damage to the peripheral nerves (cells and axons), and fowl exhibit inflammation of the upper gastrointestinal tract, dermatitis, diarrhea, and damage to the feathers. All species exhibit reduction of appetite and loss of weight; however, it is of interest that the skin lesions seen in humans are rare in most other species.

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