Meta Information
ID:zinc
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/chelating-antibiotics
Target name:
Chelating Antibiotics (Tetracyclines, Quinolones)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Zinc ions bind to tetracycline and quinolone antibiotics in the gut, forming non-absorbable complexes that significantly reduce the bioavailability and effectiveness of the antibiotic.
Actionable advice:
Doses of zinc and these specific antibiotics should be separated by at least 4 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Many of these tetracycline-metal complexes are either insoluble or otherwise poorly absorbable from the gastro-intestinal tract.
Label source:
PubMed: Interactions with the absorption of tetracyclines. (PMID 946598)
Action type:
separate
Target id:
/intervention/copper
Target name:
Copper
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic high-dose zinc intake (over 50 mg/day) stimulates the production of metallothionein in intestinal cells, which binds strongly to dietary copper and prevents its absorption, leading to a risk of copper deficiency.
Actionable advice:
If taking high-dose zinc long-term, ensure adequate copper intake (e.g., 1-2 mg copper for every 15-30 mg zinc) or monitor copper levels.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We report a unique case of severe anemia in a patient with copper deficiency caused by zinc supplement use.
Label source:
PubMed: Severe copper deficiency anemia caused by zinc supplement use. (PMID 37640593)
Action type:
monitor
Target id:
/intervention/iron-supplements
Target name:
Iron Supplements
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Zinc and non-heme iron compete for the same absorption pathways (like DMT1) in the small intestine, reducing the uptake of both minerals when taken together.
Actionable advice:
Zinc and iron supplement doses should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effect of inorganic zinc on the absorption of inorganic iron (Fe+2) from a solution was assessed in two studies on healthy male volunteers.
Label source:
PubMed: Inorganic zinc and the intestinal absorption of ferrous iron. (PMID 2502004)
Action type:
separate
Target id:
/intervention/calcium-supplements
Target name:
Calcium Supplements
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High concentrations of supplemental calcium in the gut can interfere with zinc absorption pathways, reducing its bioavailability.
Actionable advice:
High-dose calcium supplements (over 600mg) and zinc should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development.
Label source:
PubMed: Zinc balance in adolescent females consuming a low- or high-calcium diet. (PMID 9129477)
Action type:
separate
Target id:
/dietary/phytate-rich-foods
Target name:
Phytate-Rich Foods (Grains, Legumes, Nuts)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Phytic acid, present in plant-based foods like whole grains and legumes, forms insoluble complexes with zinc, significantly reducing its absorption from a meal.
Actionable advice:
Zinc supplements are best taken at least 2 hours away from meals high in phytates for optimal absorption.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Phytate, which is present in staple foods like cereals, corn and rice, has a strong negative effect on zinc absorption from composite meals.
Label source:
PubMed: The Journal of nutrition (2000)
Source url:
Exact phrase from label:
Most phytic acid-rich food-feeding studies (13 of 17, 77%) showed compromised iron and zinc bioavailability.
Label source:
PubMed: Nutrients (2024)
Source url:
Exact phrase from label:
The addition of 50 mg phytate-P or more significantly decreased zinc absorption (p=0.01) as compared to absorption from the test meals with no added phytate.
Label source:
PubMed: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (2006)
Action type:
separate
Target id:
/dietary/calcium-rich-foods
Target name:
Dairy and Calcium-Fortified Foods
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Calcium and casein protein found in dairy products compete with or inhibit the intestinal absorption of zinc.
Actionable advice:
Zinc supplements and dairy products or calcium-fortified foods should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability.
Label source:
PubMed: Role of zinc in health and disease. (PMID 38367035)
Action type:
separate
Target id:
/dietary/meal
Target name:
Any Caloric Food or Meal
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Zinc supplements, particularly zinc sulfate, can irritate the gastric lining when taken on an empty stomach, commonly causing nausea and stomach upset.
Actionable advice:
Zinc is best taken with a meal to prevent stomach upset, preferably one low in phytates and calcium.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The subjects were asked to take 50 mg of elemental zinc (as 220 mg zinc sulphate) or placebo, three times a day for six weeks. Venous blood was collected for the analysis of plasma levels of copper and zinc. Symptoms, which included headaches, abdominal cramps, nausea, loss of appetite and vomiting, were registered from 84% of women and 18% of men. Six female volunteers discontinued the trial; five owing to gastric irritation and one owing to consistent headaches.
Label source:
PubMed: The Medical journal of Australia (1987)
Source url:
Exact phrase from label:
The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea.
Label source:
PubMed: Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition (2012)
Source url:
Exact phrase from label:
Appropriate dosing helps to avoid acute zinc toxicity involving nausea and vomiting.
Label source:
PubMed: Cutis (2022)
Action type:
informational_none
Target id:
/class/thiazide-diuretics
Target name:
Thiazide Diuretics
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Thiazide diuretics increase the amount of zinc lost through urine, which over long-term use can contribute to zinc depletion.
Actionable advice:
If taking thiazide diuretics long-term, monitor zinc status and consider supplementation if necessary.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Serum Zn levels remained normal in the majority of subjects on long term thiazide therapy, but the occasional finding of subnormal levels suggests that long term thiazide therapy carries with it the hazard of Zn deficiency.
Label source:
PubMed: The effects of thiazides on serum and urinary zinc in patients with renal calculi. (PMID 804069)
Action type:
monitor
Target id:
/condition/alcohol-chronic
Target name:
Chronic Alcohol Use (Alcohol Use Disorder)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic alcohol intake damages the intestinal lining, impairing zinc absorption, and also increases the amount of zinc lost in the urine.
Actionable advice:
Excessive alcohol consumption is best avoided, as it can lead to or worsen zinc deficiency over time.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients, including glucose, amino acids, lipids, water, vitamins, and minerals within the small intestine.
Label source:
PubMed: Nutrients (2023)
Source url:
Exact phrase from label:
Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species.
Label source:
PubMed: American journal of physiology. Gastrointestinal and liver physiology (2010)
Source url:
Exact phrase from label:
Both ethanol and protein malnutrition cause muscle zinc depletion and increase urinary zinc and manganese excretion, whereas ethanol also increases urinary iron excretion and liver manganese content.
Label source:
PubMed: Alcohol (Fayetteville, N.Y.) (1998)
Action type:
avoid
Target id:
/intervention/penicillamine
Target name:
Penicillamine
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Zinc chelates with penicillamine in the gut, reducing its absorption and therapeutic effect for conditions like Wilson's disease or rheumatoid arthritis.
Actionable advice:
Zinc supplements and penicillamine should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Its bioavailability is variable and may decrease by as much as 70% in the presence of food, antacids and iron salts.
Label source:
PubMed: Clinical pharmacokinetics (1993)
Source url:
Exact phrase from label:
Food, antacids and, in particular, iron reduce absorption of the drug.
Label source:
PubMed: Clinical pharmacokinetics (1987)
Source url:
Exact phrase from label:
The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril).
Label source:
PubMed: Drugs (2002)
Action type:
separate
Target id:
/biomarker/zinc
Target name:
Zinc Blood Test
Severity:
major
Interaction type:
assay_interference
Nature:
temporal
Temporal spacing:
Hours before target:
12
Hours after target:
null
Description:
Taking a zinc supplement shortly before a blood test will result in a transiently high reading that does not reflect your true, stable zinc status.
Actionable advice:
Zinc supplements should be discontinued for at least 12-24 hours before a blood test to measure baseline zinc levels.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Plasma zinc increased in the supplemented groups, peaked at wk 4, then decreased toward initial values. The decline in plasma zinc regardless of continuing zinc administration may reflect a homeostatic response.
Label source:
PubMed: The American journal of clinical nutrition (1982)
Source url:
Exact phrase from label:
Serum zinc and total-body zinc clearance, although at normal levels, increased significantly after zinc supplementation.
Label source:
PubMed: Journal of the American College of Nutrition (2009)
Source url:
Exact phrase from label:
Serum zinc levels increased significantly both in the pre and postmenopausal women (0.88 ± 0.17 vs. 1.06 ± 0.23, p < 0.01 and 0.83 ± 0.24 vs. 0.96 ± 0.33, p < 0.01) after two weeks of daily oral zinc supplementation.
Label source:
PubMed: European journal of obstetrics, gynecology, and reproductive biology (2020)
Action type:
separate
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term use of some ACE inhibitors may increase zinc excretion or interfere with its metabolism, potentially lowering zinc levels over time.
Actionable advice:
Zinc depletion may occur with long-term ACE inhibitor use, and monitoring levels may help.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: Treatment of hypertensive patients with captopril or enalapril may result in zinc deficiency.
Label source:
PubMed: Journal of the American College of Nutrition (1998)
Source url:
Exact phrase from label:
The available evidence suggests that use of ACE inhibitors and angiotensin 2 receptor antagonists or thiazide diuretics have the potential to reduce zinc levels in hypertensive patients.
Label source:
PubMed: International journal of clinical practice (2013)
Source url:
Exact phrase from label:
This study suggests that treating heart failure patients with ACE inhibitors may result in zinc deficiency.
Label source:
PubMed: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (2007)
Action type:
monitor
Target id:
/class/immunosuppressants
Target name:
Immunosuppressant Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Zinc plays a key role in immune function and high-dose supplementation could theoretically stimulate the immune system, potentially counteracting the effects of immunosuppressant drugs.
Actionable advice:
Consulting a healthcare provider before using high-dose zinc supplements while on immunosuppressive therapy may help.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Zinc is essential for both innate and adaptive immunity, playing a pivotal role in T-lymphocyte maturation, macrophage and neutrophil function, and cytokine production.
Label source:
PubMed: Between Deficiency and Excess: The Dual Role of Selected Dietary Supplements in Immune Health. (PMID 41878172)
Action type:
informational_none
Target id:
/intervention/vitamin-a
Target name:
Vitamin A
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Zinc is a necessary cofactor for the enzyme that converts retinol (Vitamin A) to retinal, and for the synthesis of retinol-binding protein which transports Vitamin A in the blood.
Actionable advice:
Adequate zinc status is generally best maintained to support proper Vitamin A metabolism and function, particularly for vision and immunity.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
It acts as a cofactor in enzymatic reactions involved in DNA expression, membrane stabilization, vitamin A metabolism, and the gustatory and olfactory systems.
Label source:
PubMed: Zinc Toxicity (PMID 32119435)
Action type:
informational_none
Target id:
/class/antioxidant-supplements
Target name:
Antioxidant Supplements (Vitamins C & E, Carotenoids)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In the context of age-related macular degeneration (AMD), zinc works synergistically with specific antioxidants to protect retinal cells from oxidative stress, as established by the AREDS2 study.
Actionable advice:
For slowing AMD progression, zinc is most effective when combined with specific antioxidants as per the AREDS2 formula.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
In this group, those taking “antioxidants plus zinc” had the lowest risk of developing advanced stages of AMD and its accompanying visual loss.
Label source:
Anecdotal: NEI
Action type:
informational_none