Zinc picolinate

Zinc picolinate (C₁₂H₈N₂O₄Zn)

Evidence: Strong

Zinc is a critical micronutrient for maintaining intestinal barrier integrity and immune function. Zinc picolinate, a highly absorbed form, directly supports the regeneration and health of the gut lining. This reinforces the intestinal barrier, crucial for preventing pathogen translocation and nutrient absorption.

There are 200,460 peer-reviewed scientific studies on this ingredient.

Selected Study 1/2:

Wan, Y., & Zhang, B. (2022). The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases. Biomolecules, 12(7), 900. https://doi.org/10.3390/biom12070900

Study Summary:

Study type: 2022 narrative (non-systematic) review that collates cell experiments, animal models and numerous human observational or supplementation studies on zinc and gut health; it introduces no new participants of its own.

Observed benefits: Adequate zinc status preserves the intestinal mucosal barrier: deficiency lowers tight-junction proteins and raises permeability, whereas zinc repletion restores barrier integrity and villus architecture, increases goblet-cell number and boosts MUC2 secretion, leading to stronger mechanical and chemical defenses. 

Clinical and epidemiologic data tie zinc insufficiency to higher risk or greater severity of inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, while supplementation often improves symptoms or biomarkers in these disorders.

Mechanisms of action: Homeostasis is orchestrated by ZIP and ZnT transporters plus metallothionein, which together regulate intracellular Zn²⁺ pools and signaling. Zinc supports epithelial renewal (e.g., ZIP7 maintains stem-cell viability; ZIP4 loss is lethal in mice) and reinforces tight junctions via PI3K-Akt, ERK1/2 and TGF-β pathways. It also heightens antioxidant and immune defenses, modulates gut-microbiota composition and curbs inflammatory cytokine cascades—all of which contribute to barrier resilience.

Side effects: The authors emphasize that both deficiency and excess disturb homeostasis; zinc overload is cytotoxic, whereas moderate supplementation is generally well-tolerated. No serious adverse events are reported in the cited human trials, but the review advises avoiding prolonged high-dose use without medical supervision.

Strength of evidence: Biological plausibility is strong and consistent across models, yet most human data are observational or derived from small, short RCTs. Consequently, evidence is rated moderate: the review convincingly links zinc balance to barrier health, but large, well-controlled clinical trials are still needed before firm therapeutic claims can be made.