Summary
Data from animal studies suggests that copper deficiency harms testosterone and reproductive function. Even worse, ultimately it results in death! At a certain level, (human equivalent of 9.5mg) a study found that copper supplementation could boost testosterone, but going higher seems to harm reproductive function. Negative effects were demonstrated at a human-equivalent level of 19mg. Unfortunately, human experimental data regarding copper and testosterone is lacking, furthermore although some observational studies exists, unfortunately their results are contradictory - but then observational studies don't tell you a whole lot on their own.
What further research is needed? A human experimental study, looking at copper supplementation and hormones (T, E, LH, FSH, DHT, GNRH)
Animal studies - Deficiency
Rat study: Copper deficiency harms fertility
https://www.ncbi.nlm.nih.gov/pubmed/15501388
Ram study: Induced copper deficiencies (by molybdenum sulfate administration) lowers testosterone and other reproductive markers
https://www.ncbi.nlm.nih.gov/pubmed/2724283
Effect may be on the sertoli cells
https://www.ncbi.nlm.nih.gov/pubmed/2724285
Also a marked loss of spermatogenic cells was observed in Zn and Cu deficient rats.
https://www.ncbi.nlm.nih.gov/pubmed/2599557
Copper deficiencies kill rats
https://www.ncbi.nlm.nih.gov/pubmed/3671356
Animal studies - Supplementation
Rat study: High copper boosts testosterone, LH and sperm motility. Very high dose has reverse effects
https://www.ncbi.nlm.nih.gov/m/pubmed/16449843/
Researchers gave rats either 0, 1mg, 2mg, or 3mg of copper (as copper chloride) per kg body weight to rats. These are all very high doses! The 1mg dose significantly boosted testosterone, LH and sperm motility. For a 70kg man, this gives a 70mg at a simple scale up. Using the 7.4 rat to human conversion gives a dose of 9.5mg dose. That's relatively high, but still reasonable. The equivalent doses in the other groups would be 19mg and 28.5mg.
Rat study: Very high copper has no effect on rat reproduction… Extremely high dose has adverse effect
https://www.ncbi.nlm.nih.gov/pubmed/10656160
Rat study: Absolutely massive dose of copper sulfate harms fertility
https://www.ncbi.nlm.nih.gov/pubmed/27129317
control group (CG, 0 mg/kg BW), low-dose group (LG, 100 mg/kg BW), mid-dose group (MG, 200 mg/kg BW), and high-dose group (HG, 400 mg/kg BW)
- Even the low dose is incredibly, incredibly high! Copper sulfate is approx 40% copper. Simple scaling the dose up to a 70kg man gives a dose of 7000mg. Using scaling for rat to human dose, gives a human dose of 946mg. Compare this to the RDA for copper is 1 (yes, one) mg! Why they wanted to study such huge doses, I cannot tell!
In Vitro Studies
copper-amino acid complexes are potent stimulators of the release of luteinizing hormone-releasing hormone from isolated rat hypothalamic granules.
https://www.ncbi.nlm.nih.gov/pubmed/6378607
Mechanism study
https://www.ncbi.nlm.nih.gov/pubmed/6358411
- Also of note that glutathione suppressed the effect.
The impact of different copper chelates
https://www.ncbi.nlm.nih.gov/pubmed/6390443
Copper, PGE2, and Potassium
https://www.ncbi.nlm.nih.gov/pubmed/2432612
Copper's effects are with PGE2 and potassium.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC304254/?page=1
https://www.ncbi.nlm.nih.gov/pubmed/3539258
https://www.ncbi.nlm.nih.gov/pubmed/3282877
Extracellular calcium is required for copper-amplified prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from median eminence explants.
https://www.ncbi.nlm.nih.gov/pubmed/3015573
https://www.ncbi.nlm.nih.gov/pubmed/3525128
https://www.ncbi.nlm.nih.gov/pubmed/2861081
https://www.ncbi.nlm.nih.gov/pubmed/3900787
https://www.ncbi.nlm.nih.gov/pubmed/3908962
Human Observational Studies
Observational studies look for correlations between variables. Unfortunately, they cannot be used to determine causation. This is especially true in the case of copper, where serum copper generally rises *in response* to inflamation - suggesting that copper may often be the fire engine, not the cause of the fire.
Observational study: Higher copper associated with higher testosterone in men
https://www.ncbi.nlm.nih.gov/m/pubmed/18990371/
Observational study: Serum copper inversely associated with serum testosterone
https://www.ncbi.nlm.nih.gov/m/pubmed/25439796/?i=2&from=/18990371/related
Interestingly… lead and Cadmium were postively correlated with testosterone! (Please do not supplement with these metals!!! - Even moderate exposure to lead and cadmium can significantly reduce human semen quality https://www.ncbi.nlm.nih.gov/pubmed/10620523)
Observational study: no significant correlation with copper?
https://www.ncbi.nlm.nih.gov/pubmed/23791927
Observational study: Decreased serum testosterone is significantly associated with a high level of Cu and elevated Cu/Zn ratio in hair tissue
https://www.ncbi.nlm.nih.gov/pubmed/21671089
READ: Iron and copper in male reproduction: a double-edged sword. https://www.ncbi.nlm.nih.gov/pubmed/25245929
READ: https://www.ncbi.nlm.nih.gov/pubmed/10620523
THIS study requires further reading.
Is magnesium deficiency related to copper deficiency?
Copper in semen = bad semen
http://www.bioline.org.br/pdf?rm10011
But…
https://www.ncbi.nlm.nih.gov/pubmed/3242372
Decreases in Mg and P in all organs and blood serum is characteristic of Cu deficiency and molybdenosis.
https://www.ncbi.nlm.nih.gov/pubmed/10813454
Copper required in the anterior pituitary
http://pubs.rsc.org/en/content/articlelanding/2016/mt/c6mt00079g#!divAbstract
Dihydrotestosterone
Copper inhibits Type 1 5AR by 50% at 1.9microM and Type 2 at 19.2 microM
https://www.ncbi.nlm.nih.gov/pubmed/7738354
- Unsure of relevance. Are these doses actually within normal physiological ranges
Copper unrelated to 5AR activity in prostates
https://www.ncbi.nlm.nih.gov/pubmed/6182394
Prolactin
Serum copper inversely related to prolactin
http://www.sciencedirect.com/science/article/pii/S0013935109001121
Depletion of copper by other nutrients
22mg of Zinc reduces copper and iron satus in adolescents
https://www.ncbi.nlm.nih.gov/pubmed/19277992
Lipolysis - Breakdown of Fat
Copper increases cyclic-AMP-dependent lipolysis.
https://www.ncbi.nlm.nih.gov/pubmed/27272565
Copper downregulates PDE3 which itself downregulates cAMP dependent lipolysis. Essentially, this increases cAMP dependent lipolysis by putting a break on the break!
Non-alcoholic fatty liver disease
Copper deficiency in a murine model of nonalcoholic fatty liver disease
https://www.ncbi.nlm.nih.gov/pubmed/27911810