Molybdenum

Background

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Molybdenum acts as a cofactor for the enzymes sulphite oxidase, xanthine oxidase and aldehyde oxidase. These enzymes are involved in catabolism of sulphur amino acids and heterocyclic compounds including purines and pyridines. No clear deficiency syndrome has been seen in animals even with major reductions in molybdoenzymes. Molybdenum is absorbed very efficiently over a wide range of intakes by passive transport and urinary excretion reflects intake (Turnlund et al 1995a,b).

Molybdenum is found in plant foods and reflects the soil content in which they grow . Legumes are major contributors of molybdenum in the western diet, as are grain products and nuts (Pennington & Jones 1987, Tsongas et al 1980). Animal foods, fruits and vegetables are low in molybdenum. Little is known about bioavailability from various foods. There are no data for Australia or New Zealand either for dietary or supplemental intake. One US study reports dietary intakes from 120-240 µg/day, averaging 180 µg/day (Tsongas et al 1980). The US Total Diet study showed dietary intakes of 76 µg/day for women and 109 µg/day men (Pennington & Jones 1987).

Deficiency has not been seen in otherwise healthy people. Evidence of essentiality relates to a specific genetic defect that prevents the synthesis of sulphite oxidase and can lead to severe neurological damage and to the demonstration of amino acid intolerance in a long-term parenterally fed patient where molybdenum was omitted from the feed (Abrumrad et al 1981, Johnson 1993). There is some limited and inconclusive epidemiological data that low intakes may be associated with increased incidence of oesophageal cancer (WHOWorld Health Organization of the United Nations 1996).

Plasma, serum or urinary concentrations of molybdenum or indicators can be used to assess requirements, as plasma levels are generally low and difficult to measure, and urinary measures alone do not reflect status. Molybdenum balance studies are therefore used to establish homeostasis and changes in body stores. Two such studies have been done in men (Turnlund et al 1995a,b), and one in pre-adolescent girls (Engel et al 1967).

1 mmol molybdenum = 96 mg molybdenum

Recommendations by life stage and gender

Infants

Rationale: The AIAdequate intake for infants 0-6 months was based on the average volume of breast milk (0.78 L/day) and the average concentration of molybdenum in breast milk of 2 µg/L (Anderson 1992, Aqulio et al 1996, Biego et al 1998, Bougle et al 1988, FNB:IOMFood and Nutrition Board: Institute of Medicine 2001, Krachler et al 1998, Rossipal & Krachler 1998). The AIAdequate intake for older infants was extrapolated using a body weight ratio from the AIAdequate intake for younger infants. Cow's milk contains more molybdenum (50 µg/L) than human milk, as does soy milk, but there are no data on bioavailability in cow's milk or infant formula.

Children & adolescents

Rationale: There are no specific age-related data on which to base EAREstimated average requirements for children and adolescents. The EAREstimated average requirements are extrapolated from adult EAREstimated average requirements on a metabolic body weight basis allowing for growth needs (FNB:IOMFood and Nutrition Board: Institute of Medicine 2001). For this and all other age and gender groups, RDIRecommended dietary intakes were set as the EAREstimated average requirement plus twice the CVCoefficient of variations, which were set at 15%.

Adults

Rationale: The adult EAREstimated average requirement is based on the results of controlled balance studies in young men (Turnlund et al 1995a,b, FNB:IOMFood and Nutrition Board: Institute of Medicine 2001) using an average bioavailability of 75%. As there are no data for older men and women, the same EAREstimated average requirement was set for these groups. As the number of available studies was limited and subject numbers were low, RDIRecommended dietary intakes were derived assuming a CVCoefficient of variation of 15% for the EAREstimated average requirement.

Pregnancy

Rationale: There are no direct data for needs in pregnancy. The EAREstimated average requirement was determined by extrapolating from the requirements for adolescent and adult women on a body weight basis, assuming an average additional 16 kg weight. The RDIRecommended dietary intake was set using a CVCoefficient of variation of 15% for the EAREstimated average requirement and rounding to the nearest 10 µg.

Lactation

Rationale: The EAREstimated average requirements were based on that of the non-pregnant, non-lactating women plus the molybdenum intake required to replace molybdenum secreted in human milk. The RDIRecommended dietary intake was set using a CVCoefficient of variation of 15% for the EAREstimated average requirement and rounding to the nearest 10 µg.

Upper Level of Intake

Rationale: Toxic effects seen in animals have included decreased haemoglobin concentration, depression of growth, mild renal failure, diuresis and proteinuria, histological changes in kidney and liver and body weight loss. Other effects included impaired copper utilisation, prolonged oestrus cycle, failure to breed, decreased gestational weight gain, deaths in litters and adverse effects on embryogenesis (FNB:IOMFood and Nutrition Board: Institute of Medicine 2001).

There are limited toxicity data in humans. The relevance to the general population of data on the effects tetrathiomolybdate treatment on copper metabolism in subjects with Wilson's disease, a condition in which copper accumulates in the body (Brewer 2003, Goodman et al 2004), is unclear. The limited toxicity data may relate in part to the rapid excretion of molybdenum in urine, particularly at higher intake levels. One study of supplemental intakes up to 1.5 mg/day in humans showed no adverse effects on copper utilisation (Turnlund & Keyes 2000). There are limited and inconclusive data to suggest that high molybdenum intakes may be associated with increased dental caries.

Because of the limited human data, ULUpper level of intakes were set on the basis of the most sensitive indicator in animals - the effect of molybdenum on reproduction and foetal development in rats and mice. These studies indicated a NOAELNo observed adverse effect level of 0.9 mg/kg/day (Fungwe et al 1990). A UF of 30 was applied for extrapolation from animal to human data and for intraspecies differences to give a ULUpper level of intake of 30 µg/kg/day for humans.

References

Abrumrad NN, Schneider AJ, Steel D, Rogers LS. Amino acid intolerance during prolonged total parenteral nutrition reversed by molybdate therapy. Am J Clin Nutr 1981;34:
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Anderson RR. Comparison of trace elements in milk of four species. J Dairy Sci 1992;75:3050-5.

Aqulio E, Spagnoli R, Seri S, Bottone G, Spennati G. Trace element content in human milk during lactation of preterm newborns. Biol Trace Elem Res 1996;51:63-70.

Biego GH, Joyeux H, Hartemann P, Debry G. Determination of mineral contents in different kinds of milk and estimation of dietary intakes in infants. Food Addit Contam 1998,15:775-81.

Bougle D, Bureau F, Foucault P, Duhamel J-F, Muller G, Drosdowsky M. Molybdenum content of term and preterm human milk during the first 2 months of lactation. Am J Clin Nutr 1988;48:652-4.

Brewer GJ. Tetrathiomolybdate anticopper therapy for Wilson's disease inhibits angiogenesis, fibrosis and inflammation. Cell Mol Med 2003;7:11-20.

Engel RW, Price NO, Mile RF. Copper, manganese, cobalt and molybdenum balance in preadolescent girls. J Nutr 1967;92:197-204.

Food and Nutrition Board: Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington DC: National Academy Press, 2001.

Fungwe TV, Buddingh F, Demick DS, Lox CD, Yang MT, Yang SP. The role of dietary molybdenum on estrous activity, fertility, reproduction and molybdenum and copper enzyme activities of female rats. Nutr Res 1990;10:515-24.

Goodman VL, Brewer GJ, Merajver SDStandard deviation. Copper deficiency as an anti-cancer strategy. Endocr Relat Cancer 2004;11:255-63.

Johnson JL. Molybdenum. In: O'Dell BL, Sunde RA, eds. Handbook of nutritionally essential mineral elements. Clinical nutrition in health and disease. New York: Marcel Dekker, 1993. Pp 413-38.

Krachler M, Li FS, Rossipal E, Irgolic KJ. Changes in the concentrations of trace elements in human milk during lactation. J Trace Elem Med Biol 1998;12:159-76.

Pennington JAT, Jones JW. Molybdenum, nickel, cobalt, vanadium and strontium in total diets. J Am Diet Assoc 1987;87:1644-50.

Rossipal E, Krachler M. Pattern of trace elements in human milk during the course of lactation. Nutr Res 1998;18:11-24.

Tsongas TA, Meglen RR, Walravens PA, Chappell WR. Molybdenum in the diet: an estimate of average daily intake in the United States. Am J Clin Nutr 1980;33:1103-7.

Turnlund JR, Keyes WR, Peiffer GL, Chiang G. Molybdenum absorption, excretion and retention studied with stable isotopes in young men during depletion and repletion. Am J Clin Nutr 1995a;61:1102-9.

Turnlund JR, Keyes WR, Peiffer GL. Molybdenum absorption, excretion and retention studied with stable isotopes in young men at five intakes of dietary molybdenum. Am J Clin Nutr 1995b;62:790-6.

Turnlund JR, Keyes WR. Dietary molybdenum: effects on copper absorption, excretion and status in young men. In: Roussel AM, Anderson RA, Favier A, eds. Trace elements in man and animals 10. New York: Kluwer Academic, 2000.

World Health Organization. Trace Elements in Human Nutrition and Health, Geneva: WHOWorld Health Organization of the United Nations, 1996. Pp 144-54.