Molybdenum for Copper Toxicity
Molybdenum is an essential trace element and plays an important role in all living organisms as a constituent of numerous metalloenzymes. However, just like all other elements, high doses of molybdenum are also known to be toxic.
A deficiency of Molybdenum is rare, but has been associated with impaired reproductive functions and retardation of growth (Merian, Anke, Ihnat, & Stoeppler, 2004).
Deficiency of molybdenum often also indicates decreased blood, and uric acid concentrations in the urine, as well as increased xanthine and hypoxanthine excretion (Tornlund, Keyes, & Peiffer, 1995).
Metabolism
Molybdenum is most commonly found in a complex with copper in the blood. It concentrates in the liver, kidney, and bone. A significant amount of molybdenum can be found in the hair and dental enamel. The primary route of excretion of molybdenum is through the kidneys (ARLTMA, n.d.).
Molybdenum is transported into cells via Mot1 at the cell and endoplasmic reticulum membrane, and Mot2 transports molybdenum from cellular compartments into the cytoplasm (Tejada-Jiménez M, 2011).
Once inside the cell, molybdate bonds with tricyclic pterin creating molybdopterin or Moco cofactor. This form of molybdenum performs catalytic functions in the active site of enzymes (Mendel, 2011).
Sources
The average molybdenum intake differs between men and women. Women consume about 76 mcg while men consume 109 mcg each day. The recommended level of molybdenum intake is between 75-250 mcg/day. Molybdenum can be found in nutritional supplements in various forms including; sodium molybdate, molybdenum aspartate and ammonium molybdate.
Good sources of molybdenum are generally grains, nuts or legumes; such as beans, lentils and peas. Other foods, such as fruit, vegetables, and animal products, are generally low in molybdenum (Food and Nutrition Board, Institute of Medicine, 2001), although Kale can be quite high in molybdenum (Turnlund JR, 1999).
The animal organs which are highest in molybdenum are the liver and kidneys of the animal. As with most elements, the amount of molybdenum found within plants depends on the content in the soil and other environmental factors, therefore the content found in foods can have large variances.
Occupational sources of exposure to molybdenum are usually from working around metal fumes; molybdenum is used to make stainless steel, photographic chemicals, lubricants, pigments and reagents (ARLTMA, n.d.).
Molybdenum-Copper Nutrient Antagonism
Copper is an essential nutrient, however, just like all elements in excess, it can have toxic effects on the nervous system. Copper is an essential nutrient for all biogenic amines, and when copper is elevated, there can be an increase in the production of these biogenic amines; namely, epinephrine, norepinephrine, dopamine, and serotonin.
The toxic effects of copper have been becoming more prevalent since the early ’80s. However, we have reached a point where the potential for copper excess is paramount. Estrogens, xenoestrogens, and increased copper retention in the kidneys, can contribute to a vicious cycle of estrogen dominance. As copper levels increase beyond healthy levels, the function of the liver becomes disrupted and can therefore no longer neutralise toxic chemicals or estrogen in the blood.
Some sources of xeno-estrogens include: pesticides, plastic, volatile organic compounds (VOC’s) growth hormones in animals, petrochemical waste, and the list goes on. One of the major sources of exposure, in my experience, is from plastic. Just as we live in the age of aluminium, we also live in a plastic dominant world.
Risk Factors for Elevated Copper Levels
There are many risk factors for elevated copper levels. They include:
Excessive supplementing of copper without a clear indication for it.
The use of estrogen-containing oral contraceptives, or “birth control pills”
Contaminated food and drinking water, due to copper pipes and copper cooking materials.
Stress – aldosterone increases the retention of copper and depletes zinc and magnesium.
Low dietary zinc, leading to low “zinc to copper” ratio or a very high copper intake relative to zinc creating a secondary deficiency of zinc. This is quite commonly found with in those that are on a plant-based vegan diet.
Deficiency of manganese or molybdenum
Exposure to copper through copper Intrauterine Device’s (IUD’s). Hormonal IUD’s may also play a role if they function through raising estrogen.
Agricultural sprays in conventional and organic foods.
High exposure to xenoestrogens and VOC’s.
Nutritional antagonism is an excellent way to lower excess copper levels. Molybdenum is a powerful copper antagonist. It has been shown to increase the amount of copper that is excreted through the urine, while antagonising the absorption of copper in the intestine (Vyskocil & Viau, 1999). A unique property of molybdenum is that it binds directly with copper, forming insoluble complexes of copper molybdate and copper thiomolybdate, in the gastrointestinal lumen. This prevents the absorption of copper and its incorporation into plasma proteins, such as ceruloplasmin and other important copper-containing proteins, while facilitating its removal. Molybdenum can enhance copper detoxification without the common side effects that are associated with copper dumping. When copper is being eliminated, it is common for sodium levels to drop and zinc levels rise. Molybdenum raises sodium and off-sets these changes on a Hair Tissue Mineral Analysis.
A Note on Glyphosate…
Glyphosate disrupts sulphur metabolism, and since sulphur can be a molybdenum synergist, we can extrapolate and say that a modern cause for copper toxicity is through glyphosate exposure disrupting the metabolic pathways of sulphur and thus negatively effecting molybdenum’s biological function.
Hair Tissue Mineral Analysis (HTMA) Notes
Assessing molybdenum levels through an HTMA may be better than blood levels such as serum and plasma.
Molybdenum should be in the range of 0.002 - 0.006 mg% and reflects the cellular level of molybdenum.
The ideal ratio of “copper to molybdenum” is 625. If it is lower, it can indicate a molybdenum deficiency relative to copper. Though this is not always the case.
Dr Paul Eck used molybdenum to lower high copper levels on a Hair Tissue Mineral Analysis. We have found that you do not need to use molybdenum to lower copper in many instances, though it still can be helpful for individuals who have had high copper for many years that have been unsuccessful lowering it with their Mineral Balancing Programs.
Genes and Enzymes
As an ultra-trace mineral, molybdenum plays an integral part of no less than three essential enzymes (which are listed first), for a total of eight genes in humans:
Xanthine oxidase (XDH)
Aldehyde oxidase (AOX1)
Sulphite oxidase (SUOX)
Gephyrin (GPHN)
Molybdenum cofactor sulfurase (MOCOS)
Aldehyde oxidase (AOX1)
Mitochondrial MOSC domain-containing protein 1 (MOSC1)
Mitochondrial MOSC domain-containing protein 2 (MOSC2)
Molybdenum’s Synergistic Nutrients
Iron and sulphur.
B1, B3, and B6.
Known to raise sodium levels on a Hair Tissue Mineral Analysis, but is not extremely meaningful in my experience.
The “copper to molybdenum” ratio may be used to identify a secondary deficiency of molybdenum in copper toxicity.
Molybdenum’s Antagonistic Nutrients
Absorption of molybdenum is antagonised by copper, sulphur and perhaps methionine.
Molybdenum’s metabolic antagonists include; manganese, zinc, sometimes sulphur, tungsten, lead and perhaps sodium.
Elevated Levels of Copper
There are several useful indicators for identifying a person’s copper level. Most of the body’s copper is bound to copper proteins, and unbound (free) copper ions in the blood are toxic.
Typically, a low ceruloplasmin (Cp) level indicates that the total serum copper is low and that free (unbound) copper is usually increased.
The calculation for free copper is determined by subtracting the amount of copper in Cp from the total serum copper. Free copper can also be measured directly at some labs.
Molybdenum can be used to reduce free copper levels in as low as 540 mcg daily. This dose can encourage the elimination of copper through the urine (John N. Hathcock).
A Possible Cancer Connection
Copper, just like iron, is a well-known co-factor in promoting physiological and malignant angiogenesis, which is critical to tumour growth, invasion and metastasis (Yu Yu, 2006). Thus copper chelators such as tetrathiomolybdate have been under investigation due to its ability to quickly deplete copper stores. However, it is most commonly used to treat the hereditary copper metabolism disorder Wilson’s disease, where it is used due to its ability to not only antagonise copper absorption, but also to aid in the excretion of copper.
Tetrathiomolybdate has been shown to block angiogenesis and reduce tumour growth by chelating copper from the bloodstream and suppressing the signalling cascade of nuclear factor-kappa B (NFκB) (Yu Yu, 2006; Quintin Pan, 2003). Reducing the expression of angiogenic mediators such as vascular endothelial growth factor-1 (VEGF-1), fibroblast growth factor-1 (FGF-1), interleukin (IL)-1α, IL-6, and IL-8 (Yu Yu, 2006; Quintin Pan, 2003). Thus making tetrathiomolybdate treatment an interesting avenue which may become a novel treatment for diseases such as cancer, age-related macular degeneration, and other diseases featuring excessive blood vessel deposition (George J. Brewer, 2000).
Dosing Recommendations
Molybdenum deficiency is quite rare. When it comes to assessing adequate levels of molybdenum in plasma and serum, it is quite difficult. The reason is that molybdenum concentrations are generally quite low. Plasma concentration is not a good indicator of molybdenum status and cannot be used as an indicator for estimating requirements (M C Cantone, 1995; Department of Health and Ageing, National Health and Medical Research Council, Ministry of Health., 2006). Serum molybdenum concentrations can reflect dietary intake, and ‘one to three month’ deficiency can result in more than 20% decrease in blood levels (Tornlund & Keyes, 2004).
Dr Paul Eck had originally formulated the product MOLY-CU which contains 100 mcg of molybdenum that is usually taken three times a day. This is within the CRN recommendations of 350 mcg (John N. Hathcock).
A daily dose of 2000 mcg is considered safe. Consuming more than 100 mg/kg may result in toxicity signs such as diarrhoea, anaemia, and elevated uric acid levels that are associated with gout (Food Standards Australia New Zealand (FSANZ), 2008).
Excessive consumption of molybdenum and zinc can induce a copper deficiency, and in turn, excessive copper and zinc can induce a molybdenum deficiency.
References
ARLTMA. (n.d.). Molybdenum. Retrieved from https://arltma.com/mineral-information/molybdenum/
Department of Health and Ageing, National Health and Medical Research Council, Ministry of Health. (2006). Nutrient Reference Values for Australia and New Zealand. Commonwealth of Australia. Retrieved from https://www.nhmrc.gov.au/about-us/publications/nutrient-reference-values-australia-and-new-zealand-including-recommended-dietary-intakes
Food and Nutrition Board, Institute of Medicine. (2001). Dietary reference intakes for vitamin A, vitamin K, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, D.C: National Academy Press.
Food Standards Australia New Zealand (FSANZ). (2008). The 22nd Australian Total Diet Study. FSANZ. Retrieved from https://www.foodstandards.gov.au/publications/documents/ATDS.pdf
George J. Brewer, R. D. (2000, January). Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study. Clinical Cancer Research, 6(1). Retrieved from https://clincancerres.aacrjournals.org/content/6/1/1.long
John N. Hathcock, P. (n.d.). Vitamin and Mineral Safety. Council for Responsible Nutrition. Retrieved from https://www.crnusa.org/sites/default/files/files/resources/CRN-SafetyBook-3rdEdition-2014-fullbook.pdf
M C Cantone, D. d. (1995). Proton activation analysis of stable isotopes for a molybdenum biokinetics study in humans. Med Phys, 22(8), 1293-98. Retrieved from https://pubmed.ncbi.nlm.nih.gov/7476716/
Mendel, R. R. (2011). Cell biology of molybdenum in plants. Plant Cell Reports, 30, 1787-1797. Retrieved from https://link.springer.com/article/10.1007/s00299-011-1100-4
Merian , E., Anke, M., Ihnat, M., & Stoeppler, M. (2004). Elements and Their Compounds in the Environment: Occurrence, Analysis and Biological Relevance (2nd ed.). WILEY‐VCH Verlag. Retrieved from https://onlinelibrary.wiley.com/doi/book/10.1002/9783527619634
Quintin Pan, L. W. (2003, August). Tetrathiomolybdate Inhibits Angiogenesis and Metastasis Through Suppression of the NFκB Signaling Cascade. Molecular Cancer Research, 1(10). Retrieved from https://mcr.aacrjournals.org/content/1/10/701
Tejada-Jiménez M, G. A. (2011). Algae and humans share a molybdate transporter. Proc Natl Acad Sci USA, 108(16), 6420-6425. Retrieved from https://www.pnas.org/content/108/16/6420
Tornlund, J., & Keyes, W. (2004). Plasma molybdenum reflects dietary molybdenum intake. 15. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0955286303001712
Tornlund, J., Keyes, W., & Peiffer, G. (1995). Molybdenum absorption, excretion, and retention studied with stable isotopes in young men at five intakes of dietary molybdenum. Am J Clin Nutr, 62(4), 790-796. Retrieved from http://europepmc.org/article/MED/7572711
Turnlund JR, W. C. (1999). Molybdenum absorption and utilization in humans from soy and kale intrinsically labeled with stable isotopes of molybdenum. Am J Clin Nutr, 69(6), 1217-1223. Retrieved from http://europepmc.org/article/MED/10357742
Vyskocil, A., & Viau, C. (1999). Assessment of molybdenum toxicity in humans. J Appl Toxicol, 19(3), 185-92. Retrieved from https://pubmed.ncbi.nlm.nih.gov/10362269/
Yu Yu, J. W. (2006). Chelators at the Cancer Coalface: Desferrioxamine to Triapine and Beyond. Clinical Cancer Research, 12(23). Retrieved from https://clincancerres.aacrjournals.org/content/12/23/6876.long