Mo – Molybdenum is found in igneous rocks at 1.5 ppm; shale at 2.6 ppm; sandstone at 0.02 ppm; limestone 0.4 ppm; fresh water at 0.00035 ppm; sea water at 0.01 ppm; soil at 2 ppm (strongly concentrated by humus, especially in alkaline soils; a few soils worldwide are rich enough in Molybdenum to cause Mo poisoning in animals consuming the plants; numerous soils are known for Mo deficiency); marine plants at 0.45 ppm; land plants at 0.9 m; marine animals at 0.6 to 2.5 ppm; land animals at 0.2 ppm (highest levels in the liver and kidney).
Molybdenum is essential to all organisms as a constituent of numerous metalloenzymes. Molybdenum is known to be an integral part of no less than three essential enzymes:
1- Xanthine oxidase
2- Aldehyde oxidase
3- Sulfite oxidase
The average American daily intake in food ranges from 76 to 109 mcg per day – the RDA for Mo is 250 mcg per day.
Toxicity occurs at 10 mg per day as a gout-like disease and interference with copper metabolism.
Molybdenum is a trace mineral nutrient present in all body tissues. Only minute amounts of this mineral are required for health. Molybdenum possibly helps to retard degenerative diseases, cancer and aging. A molybdenum-containing enzyme of the liver (sulfite oxidase) destroys sulfite, used as a preservative in foods and drugs. In this role molybdenum acts as a detoxification agent. The production of uric acid from the degradation of purines (building blocks of RNA and DNA) requires molybdenum.
A Recommended Dietary Allowance (RDA) has not been determined for molybdenum, and the requirement for optimal health is not known. A safe and adequate daily intake for adults is estimated to be 75 to 250 mcg. People who rely on a diet of refined and processed foods, who have high levels of uric acid and are prone to gout-like symptoms, or who are copper deficient can potentially be deficient in this trace mineral. High copper intake antagonizes molybdenum uptake; very high levels of molybdenum increase copper losses.
Molybdenum – Biochemical function
Aspects of the biochemistry and biological significance of molybdenum have been reviewed elsewhere. In plants and lower organisms, molybdenum dependent enzymes are involved in nitrogen fixation, in the conversion of nitrate to ammonia and in a series of other oxidation-reduction reactions. The three principal molybdenum-containing enzymes of human and animal tissues, namely xanthine dehydrogenase/oxidase, aldehyde oxidase and sulfite oxidase share a common cofactor, molybdopterin, a substituted pterin to which molybdenum is bound by two sulfur atoms.
Discovery of molybdenum in the enzyme xanthine dehydrogenase/oxidase involved in the conversion of tissue purines to uric acid provided the first evidence of the essentiality of this element. Normally the enzyme acts as a dehydrogenase but, when reacting with oxygen, it initiates the production of a series of highly reactive oxygen-rich free radicals believed to be responsible for some features of tissue damage induced by physical injury and a wide variety of toxins, including excess molybdenum.
A reduced tissue activity of this enzyme has been associated with xanthinuria, a genetic defect characterized by a low output of uric acid and high concentrations of xanthine and hypoxanthine in blood and urine. Clinical manifestations become apparent only after renal calculi have formed or after deposition of xanthine and hypoxanthine in muscles has resulted in a mild myopathy.
Low molybdenum intakes also reduce tissue xanthine dehydrogenase activity, but there is no convincing evidence that changes in molybdenum intake from conventional diets sufficiently influence enzyme activity to cause clinical changes in mammals. Furthermore, while a low xanthine dehydrogenase activity in tissues or changes in its substrate/product relationships (e.g. of the xanthine + hypoxanthine/uric acid ratio in plasma) may reflect a low molybdenum status, such responses are insufficiently specific to be of diagnostic value. Thus xanthine dehydrogenase activity also decreases if protein intake is low and in cases of hepatoma. Conversely, activity increases if protein intake is high, if vitamin E status is low, or if interferon or agents stimulating its release are given. Claims that high intakes of molybdenum stimulate tissue xanthine dehydrogenase activity await verification. The molybdenoenzyme aldehyde oxidase is structurally and chemically similar to xanthine oxidase exhibits a similar distribution between tissues and shares some substrates. However, other biochemical properties differ and its principal metabolic roles are not known.
An additional molybdenoenzyme, sulfite oxidase, responsible for the conversion of sulfite derived from cysteine, methionine and related compounds into inorganic sulfate, has been isolated from the liver of humans and other species. Instances of genetic “deficiency” of sulfite oxidase have been detected in early human infancy and have a lethal outcome at the age of 2-3 years. The lesion results in severe neurological abnormalities, mental retardation and ectopy of the lens. Urinary outputs of sulfite, thiosulfate and S-sulfo-L-cysteine all increase and urinary sulfate decreases. These pathological changes may result either from the accumulation of toxic concentrations of sulfite in some critical organs or from inadequate production of the sulfate required for synthesis of sulfolipids, proteins and sulfate-conjugates. Other inborn metabolic disorders are associated with genetically related deficiencies of aldehyde oxidase, xanthine oxidase and sulfite oxidase caused by failure to synthesize their molybdopterin cofactor.
A nutritional deficiency of molybdenum giving rise to clinical symptoms suggestive of a deficiency of sulfite oxidase has been reported by Abumrad et al. in a human patient subjected to prolonged total parenteral nutrition. The clinical symptoms included irritability leading to coma, tachycardia, tachypnea and night blindness. A reduced intake of protein and sulfur-containing amino acids alleviated the symptoms, whereas they were exacerbated by infusion of sulfite. Tissue sulfite oxidase activity was low; thiosulfate excretion increased 25-fold, sulfate output declined by 70% and plasma methionine increased markedly. The clinical symptoms of molybdenum deficiency were totally eliminated by supplementation with 300 mcg of ammonium molybdate (147 mcg of molybdenum) daily. Further evidence of the essentiality of molybdenum came from a study of two young adults with Crohn disease maintained on total parenteral nutrition after ileal resection. Both had extensive losses of trace minerals including molybdenum (350-530 Mg of molybdenum/day) from the intestinal tract. Parenteral infusion of 500 mcg of ammonium molybdate (225 mcg of molybdenum) increased uric acid levels in the plasma and urine of these patients.
It has been claimed that molybdenum status influences susceptibility to certain forms of cancer and that the high incidence of esophageal cancer among the Bantu in Transkei (South Africa) is associated with a deficiency of this element in locally available food. Studies in Henan province, China, suggest that a high incidence of esophageal cancer is associated with lower than normal contents of molybdenum in drinking water and food as well as in serum, hair and urine. Esophageal cancer tissue also had lower molybdenum content than normal. It may well be relevant that inclusion of 2 or 20 mcg of molybdenum/g in the diet of rats has been found to inhibit esophageal and stomach cancer following the administration of N-nitrososarcosine ethyl ester. Molybdenum in the drinking water of rats at a concentration of 10 mg/l inhibited mammary carcinogenesis induced by N-nitroso-N-methylurea.
In 1973, a WHO Expert Committee suggested that 2 mcg of molybdenum per kg of body weight per day would be adequate to maintain normal health.
Am J Clin Nutr 1980 May;33(5):1103-1107
Molybdenum in the diet: an estimate of average daily intake in the United States.
Tsongas TA, Meglen RR, Walravens PA, Chappell WR
Previous studies have estimated the average intake of molybdenum (Mo) from the diet at approximately 300 to 400 micrograms/day. Foods collected in a grocery basket sampling program was analyzed for Mo content. The Mo concentration of these foods was combined with published United States Department of Agriculture estimates of food consumption to estimate the average daily dietary intake of Mo in the United States. This estimate is less than those previously reported and varies between 120 and 240 micrograms Mo/day, depending on age, sex, and income.
Molybdenum absorption, excretion, and retention studied with stable isotopes in young men at five intakes of dietary molybdenum.
Turnlund JR, Keyes WR, Peiffer GL
US Department of Agriculture, ARS/Western Human Nutrition Research Center, Presidio of San Francisco, CA 94129, USA.
A study of molybdenum absorption, excretion, and balance was conducted in four young men fed five amounts of dietary molybdenum, ranging from 22 to 1490 micrograms/day, for 24 days each. The study was conducted to obtain scientific data on which to base a recommendation on dietary molybdenum intake for healthy young men. Stable isotopes of molybdenum were used as tracers. 100Mo was fed five times during the study and 97Mo was infused three times. 94Mo was used to quantify the molybdenum isotopes and total molybdenum in urine, fecal collections, and diets by isotope dilution. Adverse effects were not observed at any of the dietary intakes. Molybdenum was very efficiently absorbed, 88-93%, at all dietary molybdenum intakes, and adsorption was most efficient at the highest amounts of dietary molybdenum. The amount and percentage of molybdenum excreted in the urine increased as dietary molybdenum increased, suggesting that molybdenum turnover is slow when dietary molybdenum is low and increases as dietary molybdenum increases. We conclude from these results that dietary intakes between 22 and 1500 micrograms/d by adult men are safe for > or = 24 days and that molybdenum retention is regulated by urinary excretion. Molybdenum is conserved at low intakes and excess molybdenum is rapidly excreted in the urine when intake is high.
United States Department of Agriculture, Grand Forks Human Nutrition Research Center, ND 58202-7166.
Molybdenum (Mo) supplementation reduces the incidence of nitrosamine-induced tumors in the esophagus and forestomach of laboratory animals, and the incidence of mammary cancer in female rats induced by N-nitroso-N-methylurea (NMU). The present study was conducted to evaluate the effect of graded amounts of Mo on NMU-induced mammary carcinogenesis, and on the excretion of Mo and copper (Cu). Female Sprague-Dawley rats aged 5 wk were given as needed a low-Mo (0.026 mg/kg) diet and deionized water. After 15 d, a single SC injection of 50 mg NMU/kg body wt was administered to each of 30 rats in groups 2-5. Eight rats in group 1 served as untreated control. One week after the carcinogen treatment, 0.1, 1.0, or 10 mg Mo from sodium molybdate was added to each liter of drinking water for groups 3, 4, and 5, respectively. Groups 1 and 2 did not receive any Mo supplementation. After the rats had been Mo-supplemented for 38, 67, and 85 d, 48-h urine and fecal samples were collected from the same 48 rats, and Mo and Cu were determined. Molybdenum seemed to have little effect on Cu excretion. At each time interval, animals fed 0 or 0.1 mg Mo/L excreted more Mo in feces than in urine, whereas rats fed 1 and 10 mg Mo/L water excreted more Mo in urine than in feces, which indicates that Mo absorption was not easily saturated as the amount of Mo increased. However, the liver became saturated with Mo when 0.1-1 mg Mo/L was fed. The total number of palpable tumors per group 101 d after NMU administration was 109, 115, 101, and 81, and the total carcinomas per group were 92, 96, 86, and 65 for the animals in groups 2-5, respectively. The results indicate that supplemental Mo in the amount of 10 mg/L of drinking water inhibited mammary carcinogenesis.
Essential and Toxic Tace Elements in Human Health: An Update,pages 355-376, 1993.
Ultratrace Elements of Possible Importance for Human Health: An Update
Forrest H. Nielsen
USDA, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202
The importance of molybdenum for three mammalian enzymes, xanthine oxidase/dehydrogenase, aldehyde oxidase and sulfite oxidase is well established (Rajagopalan, 1988). However, there is no evidence that molybdenum is of significant nutritional concern. A patient receiving prolonged parenteral nutrition therapy developed a syndrome described as acquired molybdenum deficiency (Abumrad et al., 1981). This syndrome, exacerbated by methionine administration, was characterized by hypermethioninemia, hypouricemia, hyperoxypurinemia, hypouricosemia and very low sulfate excretion. In addition, the patient suffered mental disturbances that progressed to coma. Supplementation of the patient with ammonium molybdate improved the clinical condition, reversed the sulfur-handling defect, and normalized uric acid production. Thus, an excessive intake of methionine, or other situations requiring the enhanced activity of the molybdoenzyme sulfite oxidase, may be the stressors that could make molybdenum a nutritional concern.
Epidemiologic and experimental findings have implicated molybdenum deficiency as a factor in the occurrence of esophageal cancer (Luo et al., 1983; Komada et al., 1989). Cancer is often caused by xenobiotic compounds. The molybdoenzymes xanthine oxidase, aldehyde oxidase, and sulfate oxidase may be involved in the detoxification of xenobiotic compounds (Rajagopalan, 1980). Possibly humans exposed to certain xenobiotics also will demonstrate an enhanced need for molybdenum.