Zinc

Zinc
Chemical formula	Zn
Solubility	Zinc salts vary: zinc sulfate and zinc gluconate are water-soluble; zinc oxide is poorly soluble in water. Zinc bisglycinate (glycinate) has increased oral bioavailability (~43% higher than gluconate).
Bioavailability	Dependent on phytate intake as the overwhelming factor absorption. Animal protein (especially amino acid composition) enhances absorption; plant proteins inhibit it. A vegan needs twice as much zinc as an omnivore due to inhibitory phytate and lack of animal protein's beneficial effects. Egg yolk enhances zinc absorption.
Dietary sources	Oysters are by far the best source, followed by beef and cheese. Liver is relatively higher in copper than zinc, so pairing liver with oysters helps balance the zinc-to-copper ratio.
RDA (adults 19–50 y)	Men: 11 mg/day; Women: 8 mg/day. The RDA assumes vegetarians need ~50% more zinc due to phytate inhibition. Some computer modeling suggests very high phytate diets may require up to 100 mg to compensate.
Upper limit	40 mg/day (Institute of Medicine). Chronic high-dose zinc can induce copper deficiency by increasing metallothionein, which sequesters copper. Dietary zinc-to-copper ratio should be at least 2:1 but no more than 15:1.

Zinc is one of the two most prevalent mineral deficiencies on Earth (alongside iron), and on a population level, deficiency is extremely correlated with the plant-to-animal ratio of the diet. Anywhere where there's endemic iron or zinc deficiency, it's in populations that mostly eat plants. Unlike many nutrients where status markers are controversial, zinc has been exceptionally well-studied through depletion-repletion trials, particularly Janet King's elegant experiments that remain the gold standard for understanding zinc deficiency progression.

History

Etymology

The name's origin is disputed. The most-cited theory traces it to German Zink, possibly related to Zinke ("prong, point"), describing the needle-like appearance of zinc crystals after smelting, a usage credited to Paracelsus around 1526. Other proposed origins include a Persian word for stone (zinc ore often has a rocky appearance) or a compound of German zinn ("tin") with a diminutive suffix; the German word's ultimate root remains genuinely unclear.

Zinc was produced and used, in impure alloyed form (as brass), since antiquity, but wasn't isolated as a distinct metal in Europe until the 16th century; India had been smelting relatively pure zinc since around the 12th century.

Structure/Chemical properties

Zinc (Zn) is a transition metal, atomic number 30. It exists as a divalent cation (Zn²⁺) in biological systems.

Key chemical behaviors:

Forms coordination complexes with proteins. Zinc is a structural component of over 300 enzymes

The positive charge of zinc can form coordination bonds with amino acid side chains (histidine, cysteine, aspartate, glutamate)

Different salt forms have different properties: sulfate and gluconate are water-soluble; oxide is poorly soluble

Function/Mechanism of Action

Zinc is a cofactor for carbonic anhydrase, which regulates pH and taste sensitivity. Zinc deficiency is associated with smell and taste loss.

Stress increases metallothionein, which binds zinc and other metals. Lower available zinc may then impair carbonic anhydrase in sensory organs.

Acid-base regulation:

Carbonic anhydrase depends on zinc. Correcting deficiency can improve exercise-related acidosis in some people (community report; not a controlled trial).

Testosterone and thyroid support:

• In trained athletes, zinc supplementation prevented exercise-induced decline in T3, T4, and testosterone (human study).
• Marginally zinc-deficient elderly men given zinc for 6 months roughly doubled serum testosterone (human study).
• In elite wrestlers, exhaustion exercise significantly lowered thyroid hormones and testosterone, but 4 weeks of oral zinc supplementation (3 mg/kg/day) prevented this exercise-induced decline in both resting and post-exercise T3, T4, and testosterone levels.
• Low-testosterone groups tend to have lower zinc levels than normal-testosterone groups in observational work.
• Zinc given for 6 months to 37 infertile men raised testosterone and DHT in those starting below 480 ng/dL testosterone (DHT rose regardless of baseline); 9 subjects' partners conceived during the study.

Immune function:

Zinc deficiency causes immune dysfunction, but so does zinc excess. The mechanisms differ. Zinc is needed for immune function, but excess zinc induces copper deficiency, which also impairs immunity.

Vitamin A activation:

Low ATP means less zinc absorption → less zinc means impaired acetaldehyde dehydrogenase (zinc-dependent) → impaired vitamin A activation

Medical uses/Effects

Deficiency symptoms (from Janet King's depletion-repletion studies: only 5% whole body zinc loss needed):

• Sore throat
• Diarrhea
• Glucose intolerance
• Dry skin, severe acne
• Eczema, seborrheic dermatitis
• Growth impairment in children
• Hair stops growing (adults)
• Lean mass loss / difficulty building muscle
• Smell and taste dysfunction (30% whole body deficit)

Therapeutic applications:

• Acute URI: Ionic zinc lozenges at throat (see below), distinct from systemic capsules
• Skin conditions: Eczema, dermatitis, acne
• Testosterone support in deficient individuals
• Exercise recovery: Prevents thyroid/testosterone decline from training
• Atheroprotection: Lowers inflammatory and lipid-peroxidation markers implicated in atherosclerosis
• Mood support in deficient individuals: See Depression

Mood and depression

Zinc plays a broad, permissive role in neurotransmitter regulation, BDNF signaling, and HPA axis control, and disruption of any of these pathways is implicated in depression. A meta-analysis of 17 studies covering 1,643 depressed patients and 804 controls found peripheral blood zinc running about 1.85 µmol/L lower in the depressed group, with lower zinc tracking greater depression severity. Zinc supplementation has shown benefit in mild-to-moderate depression and as an add-on to conventional antidepressants, including some treatment-resistant cases.

Atherosclerosis prevention (dietary dose)

In a randomized, double-blind, placebo-controlled trial, 40 healthy elderly subjects (56-83 years) took 45 mg/day zinc gluconate for 6 months. Zinc supplementation lowered plasma C-reactive protein, IL-6, MCP-1, VCAM-1, secretory phospholipase A2, and malondialdehyde+hydroxyalkenals (lipid peroxidation products) relative to placebo, with the changes in plasma zinc inversely correlated to the inflammatory/oxidative markers. At this dose, copper status should be monitored, since sustained high zinc intake can induce copper deficiency.

Zinc lozenges and colds (ionic Zn²⁺)

Zinc researcher George Eby ran early double-blind trials of zinc gluconate throat lozenges. A 1984 human RCT found 23 mg zinc gluconate dissolved every 2 wakeful hours shortened common cold duration versus placebo.

Eby's later work explains why zinc lozenge trials disagree: efficacy depends on ionic zinc (Zn²⁺) released at mouth/throat pH, not total zinc on the label. Zinc acetate tends to release more ionic zinc than zinc gluconate; lozenges with citric acid or certain additives can release little or no usable Zn²⁺ and may lengthen colds in some trials.

This is acute cold treatment at the upper respiratory tract, separate from chronic dietary zinc repletion on this page. Meta-analyses remain mixed; formulation dominates brand. See Harm reduction.

Zinc L-carnosine (polaprezinc) for reflux esophagitis

Zinc L-carnosine, sold as polaprezinc, is a chelated complex of zinc and carnosine distinct from the plain zinc salts discussed elsewhere on this page. It forms an acid-independent protective layer on stomach and esophageal mucosa. In a rat model of reflux esophagitis, oral polaprezinc lowered IL-8 and PGE2 in inflamed tissue and reduced PI3K/Akt/mTOR pathway activation, with effects on IL-8 comparable to a proton-pump inhibitor and an additive effect when combined with one. Human evidence is thinner: controlled trials support polaprezinc for radiation-induced esophagitis and infant regurgitation, but a 2022 review found no direct randomized-trial evidence yet for classical adult GERD, despite growing off-label use for its mucoprotective properties.

Side/Adverse effects

Excess zinc:

• Copper deficiency: the primary long-term risk; zinc induces metallothionein which sequesters copper
  • MT binds copper with high affinity (higher than zinc) and traps it inside the cell.
• Immune dysfunction: well-demonstrated consequence of excessive supplementation
• Insomnia: reported adverse effect; if occurring, reduce dose or change timing
• Nausea: common with high doses, especially on empty stomach

Two women had a very sudden onset of cataracts... it turned out that one of them had begun taking 500 mg of zinc daily a few months earlier, and the other had begun taking 600 mg of zinc and 250 mg of iron... just a couple of months before the cataracts appeared.

— Ray Peat

Inflammation effect:

Inflammation decreases plasma zinc by increasing tissue uptake. SIBO and other inflammatory conditions can cause plasma zinc to keep dropping despite supplementation; this reflects increased demand, not toxicity.

Dosing

General supplementation:

• Start: 7–15 mg/day
• Deficiency protocol: 10 mg three to four times daily, away from phytate foods
• Athletes (thyroid/testosterone support): 50–70 mg/day for 4 weeks (study dose)

Children off growth curve:

Give 5 mg zinc; if they shoot back onto the growth curve, they had zinc deficiency.

Timing:

• Ideal: 3 hours after eating, 1 hour before next meal
• Minimum: 40 minutes before/after meals
• Alternative: Take with a phytate-free (carnivore-style) meal
• Coffee inhibits zinc absorption, separate them

Lozenges vs. capsules:

• Lozenges: Local ionic Zn²⁺ at nose/throat during acute URI (only if formulation releases ionic zinc, see above)
• Capsules: Systemic dietary/supplement repletion

Form switching if not absorbing:

If plasma zinc stays low despite supplementation, try different forms: gluconate → acetate → citrate → glycinate → methionine.

See also

• Copper
• Immune system
• Harm reduction