Zinc: anti-estrogen, -prolactin, steroidogenesis, pro-dopamine

Zinc, a very important water-soluble trace mineral, is involved in over 300 enzymatic reactions and even more proteins. Zinc regulates neurotransmitters, behavior, learning & memory, neural development, fuel metabolism, RNA/DNA synthesis, muscle protein synthesis (increase mTOR), growth, hormone production, insulin (involved in the synthesis, storage and release of insulin), fatty acid oxidation, improve hypertension (by lowering angiotensin) etc…  (123)

It also lowers lactate by inhibiting the lactic dehydrogenase enzyme, which can lead to more energy, better sleep etc… (4)

Also increases the bodies pH by regulating carbonic anhydrase, which catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons.

Aids in proper digestion as it plays a role in the enzyme carboxypeptidase which breaks protein down, and also the digestive enzymes made in the pancreas is zinc-dependent. (5)

Zinc increases dopamine synthesis and is anti-anxiety

Zinc regulates levels of neurotransmitters in the brain, such as dopamine and serotonin, and antagonize the excitatory neurotransmitters’ receptor, namely NMDA, and reduces glutamate release. (6) Zinc activates glycine receptors, antagonizes GABA-A receptor, which has a nootropic effect, but increases overall GABA, and activates purinergic receptors as well. (78)

Zinc increases dopamine receptors and extracellular dopamine and inhibits dopamine uptake by neurons, which result in dopamine exerting a more powerful effect. (9101112)

Zinc also increases serotonin uptake, weakening its action, further amplifying dopamines’ effect. (13) Zinc is an agonist to the 5-HT1a receptor. (59) Activation of the 5-HT1a receptor actually has a negative feedback mechanism on serotonin release and increases dopamine release and lower adrenaline. (w)

Zinc supplementation also increases BDNF, which increases the growth of new neurons in the brain and ensures your brain stay healthy. (14)

A high Cu/Zn ratio has been found to increase anxiety, and that supplementing Zn significantly reduces anxiety. (15) Zinc did not negatively influence Cu levels, but rather normalized the Cu/Zn ratio. But don’t go and avoid Cu rich foods, as low Cu is associated with low dopamine. (16)

This leads to better sensitivity and signaling for dopamine and less activity for serotonin. This all has a powerful relaxing, anti-anxiety, motivating, energetic, focused, etc… effect.

Zinc is anti-inflammatory and increases immunity

Zinc protects the body from oxidative stress by strengthening the bodies defense systems, namely catalase, superoxide dismutase and glutathione.

It also boosts the immunity by increasing thymulin, a thymic hormone involved in T-lymphocyte maturation. (17)

Zinc is anti-inflammatory, as it induces A20 (a zinc finger protein) which inhibits NF-kappaB activation resulting in decreased generation of inflammatory cytokines (TNF-alpha, IL-1beta, and IL-8 ) and increase in IL-2 and IL-2Ralpha mRNAs.  (1819)

A zinc deficiency may decrease the generation of new CD4+ T cells from the thymus. (20)

Lipid peroxidation (oxidative degradation of lipids) causes inflammation in the body, which zinc inhibits very well. So zinc protects the body from the harmful effect of poly-unsaturated fatty acids.

Furthermore, zinc inhibits the metabolism of COX-2 and prostaglandins, prevent the inflammation and damage these would cause (21).

Zinc inhibits the aromatase & lowers estrogen

It’s been shown, that rats that are deficient in zinc have significantly more estrogen receptors, low testosterone and high estrogen, indicating high aromatase activity. (22)

Also, a zinc deficiency increases estrogen sensitivity, indicating more estrogen receptors. Supplemental zinc reverses the sensitivity. (23)

If you are deficient in zinc, aromatase will be increased, and by fixing the deficiency will reduce excess unregulated aromatase. Look at the end of the article for supplementation recommendations.

Zinc is Androgenic

Zinc intake is significantly correlated with total and free testosterone and DHT. (242526)

Zinc increases the enzyme, 17 β-hydroxysteroid dehydrogenase (17β-HSD), which converts androstenedione to testosterone. (27) Androstenedione is much more susceptible to aromatase than testosterone.

A zinc deficiency results in significantly fewer androgen bindings and significantly less DHT conversion from testosterone (lower 5 alpha reductase). (28) Less binds can also be due to less receptors, as Zn-finger proteins are involved in genetic expression of various growth factors and steroid receptors. (29) Without zinc, you get an abundance of estrogen receptors and a lack of androgen receptors.

Zinc supplementation (120mg twice daily) significantly increased DHT (19%), and also slightly increased testosterone (8%) in eugonadal men (490 to 750ng/dl), showing an upregulation of 5 alpha reductase even at a very high dose zinc. (30)

However, in this in vitro study, high zinc concentrations significantly inhibit 5 alpha reductase. This decrease was mediated by both a non-competitive inhibition of the binding of testosterone to the 5 alpha-reductase enzyme and by a reduction in the formation of the NADPH cofactor. (31) As shown above, a high dose of zinc (240mg daily) increased 5-a reductase, and such a dose is anyway way too high and totally unnecessary unless trying to quickly reverse a deficiency.

Zinc deficiency first impairs angiotensin-converting enzyme (ACE) activity, and this, in turn, leads to depletion of testosterone and low DHEA. (32) Copper antagonizes ACE, so too much copper and too little zinc can lead to low T and hypotension.

Zinc also significantly increases undercarboxylated osteocalcin, which is the hormonally active form, stimulates testosterone synthesis. (A)

Zinc blocks cortisol

Zinc administration at doses between 25-50mg acutely inhibits cortisol secretion. (33) Cortisol is known to cause frustration and anger, and is catabolic, increases the aromatase, inhibit liver and thyroid function and lowers testosterone. More on lowering cortisol here

Zinc increases growth hormone & lowers prolactin

For normal growth hormone (GH) secretion, sufficient amount of zinc is required for the biogenesis of GH-containing secretory granules. (34)

Zn(2+) binding to GH through amino acid residues His18, His21, and Glu174 are essential for GH dimerization and might mediate its aggregation and storage in secretory granules. (35)

Thus, zinc is essential for the synthesis of GH.

Zinc is very important for adequate growth, as it increases IGF-1, IGFBP-3 and GH levels in short stature and normal children. (363738) As an interesting side note, zinc also stimulates the desire for protein and fats. (39) Protein and fats are the most important for muscle growth and androgen synthesis.

In most cases, prolactin also increases with GH, but zinc also decreases prolactin in a dose-dependent manner. (40)

Zinc promotes proper thyroid function

Zinc supplementation boosts metabolism, resting metabolic rate by increasing thyroid function. It does so by increasing thyroid hormone production. Zinc supplementation increases, total T4 and T3 and also free T3. (4142)

Zinc also lowers parathyroid hormone (PTH), which further increases metabolism and thyroid. (43) Elevated PTH leads to osteoporosis, soft tissue calcification, muscular and nerve dysfunction and hyperaldosteronism, which increases urinary excretion of calcium, magnesium and potassium.

Absorption & utilization & nutrient interaction

A high fiber diet containing phytic acid (an anti-nutrient that binds strongly to Zn) significantly inhibits Zn absorption.

Protein intake and increased physiologic demand (e.g. exercise) positively impact Zn absorption. (444546)

Vitamin B6 helps the body to utilize Zn. (47)

High zinc intake (140mg) decreased the intestinal absorption of calcium during a low calcium intake (230mg) but not during a normal calcium intake (800mg). (48)

Inorganic iron (25-75mg) decreased zinc (25mg) uptake in a dose-dependent manner. However, there is no inhibition between the nutrients at lower doses. The recommended daily allowance (RDA) for iron is 8mg daily and 15mg for zinc. Iron in food will not prevent zinc absorption. The study used inorganic iron, which is not naturally found in plants or meat and will not have the same effect as organic iron.

High dose zinc (50mg/day) can decrease copper uptake over a period of time. (4950)


a) Help recover faster from the common cold.

b) Zinc can help stop diarrhea by lowering inflammation and increasing immunity (51)

c) Aids in wound healing.

d) Zinc aids in vitamin A transport through the blood and also converts vitamin A to its active form, retinoic acid, via the zinc-dependent retinol dehydrogenase enzyme. (52) A deficiency in zinc can lead to night blindness.

e) Serum ferritin concentration declined in a zinc deficiency, leading to anemia. (53)

f) progesterone has a zinc raising effect.

g) eNOS (which causes vasodilation) are zinc dependent.


Severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated.

A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation.

A mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia.


Absorption of zinc from zinc citrate is 61.3%,  zinc gluconate is 60.9% and zinc oxide is 49.9%. However, during this study, a few participants had little or no absorption from zinc oxide, making Zn oxide the least effective form. (54)

Zinc picolinate seem better absorbed than Zn citrate and gluconate, however, the body excretes is faster, just like Zn sulfate. (55) Picolinic acid is also an agonist to the NMDA receptors, which has excitatory actions. Glycine is antagonistic to NMDA receptors.

Zinc glycinate is better than zinc sulfate and gluconate. (5657) This is my personal favorite.

I don’t think high doses, >100mg daily, should be used for a long period of time, unless you still have a severe deficiency, or when you want to build good quality muscle, but only when there are adequate co-factors also present. A lower dose, <30mg daily would be better long term.

Excessive zinc intake will eventually affect the balance and proper ratios with numerous other nutrients, which includes iron, calcium, selenium, nickel, phosphorus, copper, as well as Vitamin A, B1, C, and others.

Zinc synergists:

Magnesium, chromium, cobalt, tin, vitamin B2, D, E, A (small amounts)

Zinc antagonists:

Iron, calcium, phosphorus, selenium, sodium, nickel, copper, vitamin A (large amounts) B1, C, B3, B9, choline, lecithin, alcohol, phytic acid, oxalic acid.


  • Zinc biglycinate – 22mg per serving, 250 caps

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