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Molybdenum

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Molybdenum
Molybdenum supplements
Molybdenum food sources
Molybdenum deficiency
Molybdenum toxicity

Molybdenum

Molybdenum is an essential trace element, a metal that is naturally present in many foods and is also available as a dietary supplement. Molybdenum exists as a dark-gray or black powder with a metallic luster or as a silvery-white mass 1. Molybdenum does not occur naturally in the pure metallic form, but principally as oxide or sulfide compounds 2. In humans, molybdenum functions as a cofactor for at least 4 enzymes: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime reducing component (mARC) 3. In each case, molybdenum is bound to a complex, multiring organic component called molybdopterin, forming the entity molybdenum cofactor (Figure 1). These enzymes metabolize sulfur-containing amino acids and heterocyclic compounds including purines and pyrimidines 4. Xanthine oxidase catalyzes the oxidation of purines to uric acid 5. The aldehyde oxidase in humans is involved in the metabolism of various endogenous and exogenous N-heterocyclic compounds 6. Sulfite oxidase catalyzes the terminal reaction in the degradation of sulfur amino acids cysteine and methionine 7. Mitochondrial amidoxime reducing component (mARC) was just recently discovered and it is presumed to form the catalytic portion of a 3-component enzyme system with heme/cytochrome b5 and reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide–dependent cytochrome b5 reductase 8. The structure of mARC along with its high abundance in liver and kidney suggests that mARC could play a role in detoxification of N-hydroxylated substrates 9. Xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime reducing component (mARC) are also involved in metabolizing drugs and toxins 10. Molybdenum is widely used in industry for metallurgical applications; some of these applications include high temperature furnaces, as a support wire for tungsten filaments in incandescent light bulbs, and as a component of steel used in solar panels and wind turbines 11.

The kidneys are the main regulators of molybdenum levels in your body and are responsible for its excretion 4. The average concentration of urinary molybdenum is 69 ng/mL, but urinary molybdenum does not reflect molybdenum status 3. Molybdenum, in the form of molybdopterin, is stored in the liver, kidney, adrenal glands, and bone 4.

The amount of molybdenum in food depends on the amount of molybdenum in the soil and in the water used for irrigation 4. Drinking water generally contains only small amounts of molybdenum 12. However, according to 2017 data from the U.S. Environmental Protection Agency, 0.8% of drinking water samples had molybdenum levels above 40 mcg/L 13. The U.S. Department of Agriculture’s (USDA’s) FoodData Central 14 does not list the molybdenum content of foods or provide lists of foods containing molybdenum. Therefore, the amount of information on molybdenum levels in foods is quite limited.

Legumes are the richest sources of molybdenum, with lima beans providing 87 mg molybdenum per 100 g 15. Other foods high in molybdenum include whole grains, nuts, and beef liver 12. The top sources of molybdenum in U.S. diets are legumes, cereal grains, leafy vegetables, beef liver, and milk 12. Milk and cheese products are the main sources of molybdenum for teens and children 16.

Molybdenum appears to be absorbed via a passive nonmediated process, though where absorption occurs in the intestinal tract is not known 3. Adults absorb 40% to 100% of dietary molybdenum 17. Infants absorb almost all of the molybdenum in breast milk or formula 18.

The amount of molybdenum you need depends on your age. Average daily recommended amounts are listed in Table 1 below in micrograms (mcg). The Food and Nutrition Board of the United States Institute of Medicine established that the average minimum molybdenum requirement is 22 mcg/day plus an additional 3 mcg/day for miscellaneous losses for a minimum requirement of 25 mcg/day. Further accounting for bioavailability (assumed to be 75%) and interindividual variability in molybdenum metabolism (additional 30%), the recommended daily allowance for molybdenum in the United States was set at 45 mcg/day for both men and women 3. The World Health Organization (WHO) has established a slightly higher daily molybdenum requirement of 100 to 300 mcg/day for adults 19, although it has acknowledged that lower intake levels could be adequate. The Food and Nutrition Board established a Tolerable Upper Intake Level (UL) of 2 mg/d for molybdenum (see Table 3 below) 3. Agencies outside the United States have set upper limit values for molybdenum intake that are much lower, including the Health and Consumer Protection Directorate General of the European Commission, which recommended an upper limit of 600 μg/d16 and The Expert Group on Vitamins and Minerals of the United Kingdom, which recommended an upper limit of 230 mcg/day 20.

Most Americans appear to consume adequate amounts of molybdenum. Although national surveys no longer collect data about molybdenum intake, the U.S. Food and Drug Administration (FDA) 1984 Total Diet Study estimated that average daily molybdenum intakes from foods were 109 mcg in men and 76 mcg in women 21. According to the 1988–1994 National Health and Nutrition Examination Survey (NHANES) 22, molybdenum intakes from dietary supplements averaged 23 mcg/day for men and 24 mcg/day for women. Intakes of molybdenum from drinking water collected from the 100 largest cities in the United States are estimated to be about 3 mcg/day based on intakes of 2 liters of water per day 23. Another study in the United States suggested intakes of 76 mcg/day for women and 109 mcg/day for men 24.

Estimates of molybdenum intake among different countries vary, because of both dietary differences and also analytical methodology differences. In Japan, molybdenum intake has been estimated to be 225 mcg/day, with primary sources being rice and soy products 25. In Korea, molybdenum intake was estimated to be 136 mcg/day for men and 123 mcg/day for women 26. In France, mean molybdenum intake was estimated to be 275 mcg/day 27. The International Atomic Energy Agency (IARC) sponsored a study of the molybdenum content of representative total diets from 11 countries 28 and from these data the World Health Organization estimated that adults consume about 100 mcg molybdenum per day 19.

Because molybdenum deficiency is rare 9, molybdenum status is not assessed in clinical settings. According to a small study of 30 healthy men and women 29, serum levels of molybdenum range from 0.28 ng/mL to 1.17 ng/mL, and their average is 0.58 ng/mL. In another small study of four healthy young men, plasma levels of molybdenum reached 6.22 ng/mL with a molybdenum intake of 1,490 mcg per day for 24 days 17.

Table 1. Recommended Dietary Allowances (RDAs) for molybdenum

AgeMaleFemalePregnancyLactation
Birth to 6 months2 mcg*2 mcg*
7–12 months3 mcg*3 mcg*
1–3 years17 mcg17 mcg
4–8 years22 mcg22 mcg
9–13 years34 mcg34 mcg
14–18 years43 mcg43 mcg50 mcg50 mcg
19+ years45 mcg45 mcg50 mcg50 mcg

Footnote: * Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA. Adequate Intake (AI) based on mean molybdenum intakes of infants fed primarily human milk.

[Source 3 ]

Figure 1. Molybdenum cofactor

molybdenum cofactor
[Source 9 ]

Molybdenum supplements

Molybdenum is also available in dietary supplements containing molybdenum only, in combination with other minerals, and in multivitamin/multimineral products. Amounts range from about 50 mcg to 500 mcg. Forms of molybdenum in dietary supplements include molybdenum chloride, sodium molybdate, molybdenum glycinate, and molybdenum amino acid chelate 30. No studies have compared the relative bioavailability of molybdenum from these different forms.

Molybdenum food sources

Molybdenum is widespread in the diet. In plant foods, molybdenum content is primarily determined by the regional richness of the soil and in the water used for irrigation and the content in meat depends on forage of the animals 4 and molybdenum uptake by plants is promoted by neutral or alkaline soils 31. Legumes are the richest sources of molybdenum, with lima beans providing 87 mg molybdenum per 100 g 15. Other foods high in molybdenum include wholegrains, nuts, and beef liver 12. The top sources of molybdenum in U.S. diets are legumes, cereal grains, leafy vegetables, beef liver, and milk 12. Milk and cheese products are the main sources of molybdenum for teens and children 16.

Drinking water generally contains only small amounts of molybdenum 12. However, according to 2017 data from the U.S. Environmental Protection Agency, 0.8% of drinking water samples had molybdenum levels above 40 mcg/L 13, although concentrations as high as 200 μg/L have been reported in areas near mining sites 32. The U.S. Department of Agriculture’s (USDA’s) FoodData Central 14 does not list the molybdenum content of foods or provide lists of foods containing molybdenum. Therefore, the amount of information on molybdenum levels in foods is quite limited.

Table 2. Molybdenum content of selected foods

FoodMicrograms (mcg) per servingPercent DV*
Black-eyed peas, boiled, ½ cup288640
Beef, liver, pan fried (3 ounces)104231
Lima beans, boiled, ½ cup104231
Yogurt, plain, low-fat, 1 cup2658
Milk, 2% milkfat, 1 cup2249
Potato, baked, flesh and skin, 1 medium1636
Cheerios cereal, ½ cup1533
Shredded wheat cereal, ½ cup1533
Banana, medium1533
White rice, long grain, cooked, ½ cup1329
Bread, whole wheat, 1 slice1227
Peanuts, dry roasted, 1 ounce1124
Chicken, light meat, roasted, 3 ounces920
Egg, large, soft-boiled920
Spinach, boiled, ½ cup818
Beef, ground, regular, pan-fried, 3 ounces818
Pecans, dry roasted, 1 ounce818
Corn, sweet yellow, cooked, ½ cup613
Cheese, cheddar, sharp,1 ounce613
Tuna, light, canned in oil, 3 ounces511
Potato, boiled without skin, ½ cup49
Orange, medium49
Green beans, boiled, ½ cup37
Carrots, raw, ½ cup24
Asparagus, boiled, ½ cup24

Footnote: *DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for molybdenum is 45 mcg for adults and children age 4 years and older 33. FDA does not require food labels to list molybdenum content unless molybdenum has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

[Source 16 ]

Molybdenum deficiency

Molybdenum deficiency has not been reported, except in people with a genetic mutation that prevents the synthesis of molybdopterin and therefore of sulfite oxidase 9. In this rare metabolic disorder, known as molybdenum cofactor deficiency, mutations in one of several genes prevent the biosynthesis of molybdopterin 34. The absence of molybdopterin impairs the function of enzymes that metabolize sulfite, leading to encephalopathy and seizures 35; the neurological damage is severe and usually leads to death within days after birth 36. Until recently, therapy has been symptomatic, with no effective cure available. However, very recently it was reported that one type of molybdenum cofactor deficiency could be treated with substitution therapy. In this case study, purified cyclic pyranopterin monophosphate was administered intravenously, resulting in normalization of clinical markers 37. This represents the first real potential therapy for this devastating disorder.

A single reported incident of acquired molybdenum deficiency occurred in 1981 in a patient with Crohn’s disease receiving total parenteral nutrition that was devoid of molybdenum 38. The patient developed irritability, tachycardia, tachypnea, headache, night blindness, and coma. These effects resolved with molybdenum (300 μg ammonium molybdate per day) administration 38.

Molybdenum toxicity

Acute molybdenum toxicity is rare, but it can occur with industrial mining and metalworking exposure. Exposure to excess molybdenum levels has been associated with adverse health outcomes. The most sensitive effects appear to be respiratory effects following inhalation exposure to molybdenum trioxide and decreases in body weight, kidney damage, decreases in sperm count, and anemia following oral exposure 12. A systematic review of the available human and laboratory animal health effects database resulted in the following hazard identification conclusions:

  • Respiratory effects are a presumed health effect for humans for molybdenum oxides. Decreases in lung function, dyspnea, and cough were reported in a study of workers exposed to fine or ultrafine molybdenum trioxide dust 39. Another study of workers at a molybdenite roasting facility exposed to molybdenum trioxide and other oxides did not have alterations in lung function 40. In studies of rats and mice exposed to molybdenum trioxide for 2 years, hyaline degeneration of the nasal epithelium, squamous metaplasia of the epiglottis, and chronic inflammation (rats only) were observed 41. However, no effects were observed following a 13-week exposure to similar concentrations 41.
  • Renal effects are a presumed health effect for humans. Several studies have reported renal effects in rats exposed to ≥60 mg/kg/day 42. The effects included hyperplasia of the renal proximal tubules, degeneration, increases in total lipid levels in the kidney, and diuresis and creatinuria.
  • The data were inadequate to conclude whether hepatic, uric acid level, reproductive, or developmental effects will occur in humans.
    • Liver Effects. Liver effects, which consisted of decreases in glycogen content, increases in aminotransferase activities, and increases in lipid content, have been observed at higher doses (≥300mg/kg/day) that are often associated with body weight losses 43. No hepatic effects have been observed at lower (≤60 mg/kg/day) doses 42.
    • Reproductive Effects. Cross-sectional epidemiological studies have reported significant associations between blood molybdenum levels and sperm concentration and morphology 44 or testosterone levels 45. No significant alterations in sperm parameters or estrous cycling were observed in a 90-day rat study 42 or in a 2- generation reproductive toxicity study 46. Studies providing limited information on molybdenum doses and/or the copper content of the diet have reported reproductive effects. Decreases in sperm motility and concentration and increases in sperm morphological changes have been observed in rats exposed to approximately 25 mg molybdenum/kg/day as sodium molybdate 47. Degeneration of the seminiferous tubules was also observed at similar molybdenum doses 48. Effects have also been observed in the female reproductive system (oocyte morphological alterations, abnormal rate of ovulation, and irregularities in the estrous cycle) at ≥1.5 mg molybdenum/kg/day in rats 49.
    • Developmental Effects. Mixed results have been observed in animal developmental toxicity studies. Decreases in the number of live fetuses and fetal growth were observed in rats administered 14 mg molybdenum/kg as sodium molybdate 50. Interpretation of the results of this study is limited by the lack of information on the copper content of the diet and the lack of developmental effects reported in two high-quality studies in which rats were exposed to doses as high as 40 mg molybdenum/kg/day as sodium molybdate 46.
    • Uric Acid Levels. A study of workers at a molybdenite roasting facility exposed to molybdenum trioxide and other oxides reported an increase in serum uric acid levels 40. An increased occurrence of gout-like symptoms and increased blood uric acid levels were also observed in residents living in an area of high molybdenum levels in the soil 51; no alterations in urinary uric acid levels were found in a 10-day experimental study in men 52.
  • Cancer Effects. No increases in the risk of lung cancer were reported in workers who self-reported exposure to molybdenum 53. An increase in alveolar/bronchiolar adenomas or carcinomas was observed in mice exposed to molybdenum trioxide for 2 years 41; in rats chronically exposed to airborne molybdenum trioxide, the incidence of alveolar/bronchiolar adenoma/carcinoma was within the range of historical controls 41. The potential carcinogenicity of molybdenum in humans has not been evaluated by the Department of Health and Human Services or the EPA. The International Agency for Research on Cancer 54 categorized molybdenum trioxide as possibly carcinogenic to humans (Group 2B).

In healthy people, consumption of a diet high in molybdenum usually does not pose a health risk because the molybdenum is rapidly excreted in urine 9. One study assessed the effect of high dietary intakes of molybdenum (10–15 mg/day) in an area of Armenia where the soil contains very high levels of molybdenum 55. The affected individuals experienced achy joints, gout-like symptoms, and abnormally high blood levels of uric acid 9.

In 2005, a case study 56 was reported of an individual with high molybdenum exposure. An electrician with high occupational molybdenum exposure presented with hyperuricemia and gouty arthritis, which was ascribed to the molybdenum exposure 56. During an exposure-free period, his symptoms lessened, but then again worsened when he was once again exposed to high levels of environmental molybdenum. The authors noted that the association could be circumstantial.

In 2008, Meeker et al 57 reported an association between male infertility (impaired sperm motility) and blood molybdenum levels, based on volunteers attending infertility clinics. In a follow-up study published 2 years later, it was reported that circulating testosterone levels were inversely associated with blood molybdenum levels in the same study population 58.

Given the absence of human studies, the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine 3 established Upper Intake Levels (ULs) for molybdenum for healthy individuals based on levels associated with impaired reproduction and fetal development in rats and mice.

Table 3. Tolerable Upper Intake Levels (ULs) for Molybdenum

AgeMaleFemalePregnancyLactation
Birth to 6 monthsNone established*None established*
7–12 monthsNone established*None established*
1–3 years300 mcg300 mcg
4–8 years600 mcg600 mcg
9–13 years1,100 mcg1,100 mcg
14–18 years1,700 mcg1,700 mcg1,700 mcg1,700 mcg
19+ years2,000 mcg2,000 mcg2,000 mcg2,000 mcg

Footnote: * Breast milk, formula, and food should be the only sources of molybdenum for infants.

[Source 3 ]

Human data: Mining and metallurgy workers chronically exposed to 60 to 600 mg molybdenum/m3 reported an increased incidence of nonspecific symptoms that included weakness, fatigue, headache, anorexia, and joint and muscle pain 59.

Immediately Dangerous to Life or Health Concentrations: 5,000 mg molybdenum/m3

The available toxicological data contain no evidence that an acute exposure to a high concentration of insoluble molybdenum compounds would impede escape or cause any irreversible health effects within 30 minutes. However, the revised Immediately Dangerous to Life or Health Concentrations for insoluble molybdenum compounds is 5,000 mg molybdenum/m3 based on being 500 times the Occupational Safety and Health Administration permissible exposure limit (legal limit in the United States for exposure of an employee to a chemical substance) of 10 mg molybdenum/m3 (500 is an assigned protection factor for respirators and was used arbitrarily during the Standards Completion Program for deciding when the “most protective” respirators should be used for particulates).

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