Zinc

In cases of pronounced zinc deficiency, it can happen that even moderate doses (for example, 30–50 mg of elemental zinc per dose) can cause nausea. This is related to the fact that the stomach and digestive system react sensitively to the sudden influx of a large amount of zinc, especially when the mucosa has not yet adapted to the increased level.

This phenomenon occurs quite often and is considered a normal side effect during the correction of deficiency.

As the level of zinc in the body normalizes, tolerance usually improves, and nausea subsides.

To reduce the severity of this effect:

• it's better to take zinc after meals rather than on an empty stomach;

• sometimes breaking the daily dose into several intakes helps.

Optimal forms: organic zinc salts

The most preferable in terms of bioavailability and tolerability are organic forms of zinc – primarily citrate and gluconate:

Zinc citrate. Organic salt of citric acid. Easily absorbed, gently affects the gastrointestinal tract. High bioavailability, excellent tolerability.

Zinc gluconate. Salt of gluconic acid. Commonly used in cold medications, proven to reduce the duration of infection. High bioavailability, good tolerability.

These forms do not irritate the stomach lining, are absorbed without additional stimulation of hydrochloric acid secretion, and are suitable for long-term use.

Other good organic forms include:

• Zinc picolinate – has high bioavailability, but may cause nausea in some;

• Zinc monomethionine – an amino acid chelate, especially effective for inflammations;

• Zinc acetate – used in acute conditions (ARVI), but may irritate the gastrointestinal tract.

Inorganic forms of zinc: low absorbability and potential toxicity

Zinc sulfate (ZnSO₄) – is an inorganic salt, often found in cheap supplements and pharmacy preparations. In water, it quickly dissociates, releasing ionic zinc Zn²⁺, which enters biological reactions.

However, this ion, in excess, can have cytotoxic effects:

• inhibit enzymatic processes;

• cause oxidative stress;

• block the absorption of copper, iron, and calcium;

• irritate the stomach lining.

Moreover, zinc sulfate:

• is poorly absorbed by the body (bioavailability is significantly lower than that of organic forms);

• often causes nausea, stomach discomfort, diarrhea;

• at high doses can lead to copper deficiency and reduced immunity.

Other undesirable inorganic forms include:

• Zinc oxide (ZnO) – nearly insoluble, absorbed extremely poorly;

• Zinc chloride (ZnCl₂) – aggressive, used in industry, not intended for long-term use.

Why the dose of zinc is increased during illness

Immunomodulatory action. Zinc plays a key role in the formation and activation of innate and adaptive immune cells:

• enhances the activity of T-lymphocytes, which destroy viral and tumor cells;
• promotes the production of interferons — proteins that suppress the replication of viruses;
• strengthens the barrier function of mucous membranes (especially the respiratory tract), reducing the risk of pathogen entry.

Anti-inflammatory action. High doses of zinc suppress the production of pro-inflammatory cytokines (e.g., IL-6 and TNF-α), reducing systemic inflammation and the risk of a "cytokine storm" during severe infections.

Antiviral activity. Zinc directly inhibits the activity of RNA polymerases in many viruses (e.g., coronaviruses, rhinoviruses), slowing their replication inside the cell.

Antioxidant protection. During infection, the level of free radicals sharply increases. Zinc is a component of the enzyme superoxide dismutase, which neutralizes these radicals and protects cells from destruction.

Safety of high doses

Short-term (up to 10 days) doses of up to 100 mg of elemental zinc per day are considered acceptable for treating acute conditions.

This refers to elemental zinc, not the mass of the salt (for example, 220 mg of zinc sulfate contains only 50 mg of elemental zinc).

With prolonged use >40 mg/day, copper deficiency may develop. Therefore, after the illness, it is important to reduce the dose or add copper (1–2 mg/day).

Why fractional intake of zinc is more effective

Ensuring stable concentration in blood and tissues. Zinc does not accumulate in the body and is excreted through the intestines and kidneys quite quickly. With a single high dose, the concentration in plasma increases only for a few hours.

Inhibition of viral replication — only with stable presence. Studies have shown that zinc slows the replication of RNA viruses (including coronaviruses, rhinoviruses, influenza) only with a stable presence in the cell. Periodic spikes (as with a single intake) are ineffective — zinc needs to continuously suppress viral polymerases.

Better absorption at lower doses. Zinc transporters in the intestines (ZIP1, ZIP4) become saturated quickly. When taking a large dose at once, only part will be absorbed, the rest will be excreted. However, with fractional intake (e.g., 10–15 mg of zinc every 1–2 hours), bioavailability is higher, and the overall effect is stronger.

Fewer gastrointestinal side effects. High single doses (especially 50+ mg) often cause nausea, especially on an empty stomach. Smaller doses taken frequently are better tolerated and do not irritate the stomach lining.