Chloroquine

Limits on what this shows

• Null findings: No therapeutic-dose study measuring potassium on chloroquine was found. The Riou 1988 NEJM series of severe poisoning [4] does not mention potassium in its abstract. The Borba 2020 high-dose COVID trial (reconstructed abstract only) does not report potassium or magnesium in the abstract. Hydroxychloroquine overdose case reports and an hydroxychloroquine cohort with hypokalemia linked to QTc (aOR about 5) were seen and are not borrowed, since chloroquine was not in them.
• At-risk subgroups: Deliberate or accidental overdose, including children (the label reports fatalities after accidental ingestion), and patients on catecholamine infusions per the authors [3][1].

Regulatory status

The overdosage section lists hypokalemia among the features and advises potassium monitoring alongside arrhythmia and convulsion management. The QT warning names uncorrected hypokalemia as a reason for caution [1].

Population evidence

Clemessy et al., Lancet 1995 [3]: retrospective study of 191 consecutive acute chloroquine poisoning cases. Mean blood chloroquine 20.1 umol/L (SD 14.3). Mean admission plasma potassium 3.0 mmol/L (SD 0.8); lower in patients who died than in survivors (p=0.0003); inversely related to blood chloroquine (Kendall tau -0.42, p=0.0001) and to QRS and QT intervals; directly related to systolic blood pressure. No confidence intervals are given in the abstract. Potassium was directly measured. Read as a PubMed record through a summarizer; two separate PubMed views returned the same numbers.

Mechanism

Named and plausible. The authors propose a transport-dependent mechanism (a shift of potassium into cells); toxicology reviews list potassium channel blockade in chloroquine poisoning (listing-level summary of PMID 7629896 [36]). In Drosophila, a chloroquine diet reduced total potassium by about 10% [20] (animal data, weak support).

Direction

Excess-loss from serum by redistribution during acute poisoning (Hard Rule 5). Not a dietary deficiency. The authors warn that overzealous repletion risks hyperkalemia. Supplementation would be the hazard.

Counter-evidence held on record

Counter-evidence and confounding Single retrospective series, no comparison group, and severity of poisoning confounds the potassium to mortality link. A second independent chloroquine cohort with measured potassium was not found, so red is not met. Framing caution This is not a reason to take potassium. In poisoning, potassium is managed by clinicians with monitoring. Do not generalize to people on malaria prophylaxis or treatment doses.

Limits on what this shows

• Null findings: Cross-sectional studies with chloroquine use recorded: 30 children and adolescents with lupus versus 30 controls, no association between chloroquine use and 25-hydroxyvitamin D [17]; 137 Mexican women with lupus, no association found (abstract-level, PMID 27084269 [18]). Both are lupus populations, not sarcoidosis, and 25-hydroxyvitamin D is not the converted hormone.
• At-risk subgroups: Sarcoidosis or other granulomatous disease with raised 1,25-dihydroxyvitamin D. Not defined elsewhere.

Regulatory status

Not mentioned in the label [1].

Population evidence

O'Leary et al., NEJM 1986 [15]: two sarcoidosis patients, chloroquine phosphate 500 mg/day, a 6-month and a 10-month course each over 3 years while steroid dose was held fixed. Serum 1,25-dihydroxyvitamin D and urinary calcium fell significantly; serum 25-hydroxyvitamin D did not change; the two hormone and calcium measures correlated. No values in the abstract. Adams, Diz, Sharma, Ann Intern Med 1989 [16], titled as short-course chloroquine reducing 1,25-dihydroxyvitamin D and calcium in sarcoid hypercalcemia; only a partial reconstructed abstract was read, with no patient count or values. A 2013 case report [18] describes calcium falling from 11.5 to 10.8 mg/dL over 6 months after chloroquine was added to prednisone, with 1,25-dihydroxyvitamin D normal (record-level only). These are Tier B case reports and small series.

Mechanism

Proposed by the authors: inhibition of conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, in sarcoidosis, where 1,25-dihydroxyvitamin D is made outside the kidney [15]. A reconstructed abstract of [16] states chloroquine and hydroxychloroquine were reported to reduce extrarenal synthesis.

Direction

Reverse/reduction of the active hormone in a disease where it is in excess. Not a deficiency (Hard Rule 2). The hypocalciuria and lower calcium are the intended effect in hypercalcemic sarcoidosis.

Counter-evidence held on record

Counter-evidence and confounding Case-level evidence only, no controlled cohort, and sarcoidosis is itself the driver of 1,25-dihydroxyvitamin D excess. The Ann Intern Med 1963 report on chloroquine and hypercalcemia in sarcoidosis (PMID 14067478) has no abstract in the listing and was not opened. Framing caution Do not read this as chloroquine causing low vitamin D. Whether to supplement or restrict vitamin D in sarcoidosis is a clinician decision; this entry makes no such recommendation.

Limits on what this shows

• Null findings: No human chloroquine B12, methylmalonic acid or homocysteine study was found in PubMed listings.

Regulatory status

Not mentioned in the label [1].

Population evidence

None in humans. Zhao et al., Biosci Rep 2014 [8] (reconstructed OpenAlex abstract): HT1080 fibroblasts and SH-SY5Y neurons treated with chloroquine or leupeptin for up to 48 hours; the lysosomal share of labeled cobalamin rose about fourfold in fibroblasts and tenfold in neurons, cytosolic and mitochondrial cobalamin fell, and methylmalonyl-CoA mutase-linked propionate incorporation fell. Tier B. A rat kidney tubule cell study (PMID 3715376) reports chloroquine inhibits transcobalamin II degradation, and PMID 4005299 reports raised transcobalamin II secretion; both are listing-level only.

Mechanism

Named in vitro: impaired lysosomal export of cobalamin. Physiologic relevance at human tissue concentrations is not shown.

Counter-evidence held on record

Counter-evidence and confounding In vitro conditions may exceed human exposure. The consumer claim attached to this drug family concerns intestinal absorption of B12 (hydroxychloroquine page, no source [31]), which is a different mechanism from the cell data here. Framing caution A cell-model signal, not a deficiency claim. Do not recommend B12 supplementation from this entry.

Limits on what this shows

• Null findings: A 2020 J Med Microbiol retrospective of zinc added to hydroxychloroquine and azithromycin in 411 versus 521 patients did not report serum zinc and involved hydroxychloroquine, not chloroquine; it is not used. No human serum zinc after chloroquine was found.

Regulatory status

Not mentioned in the label [1].

Population evidence

None in humans. Xue et al., PLoS One 2014 [19] (reconstructed OpenAlex abstract): in A2780 ovarian cancer cells chloroquine increased zinc uptake in a dose-dependent way by fluorescent probe, TPEN reduced the effect, zinc localized to lysosomes, and zinc plus chloroquine increased cytotoxicity; the authors concluded it is a zinc ionophore. Campos-Blazquez et al., Metallomics 2022 [20] (reconstructed abstract): Drosophila larvae fed chloroquine lost up to half their stored zinc and about 10% of total potassium; in MDCK cells a short high-dose exposure raised Fluozin-3 fluorescence but total zinc fell about 36%; the authors state chloroquine should not be considered a zinc ionophore. Tier B.

Mechanism

Lysosomal dysfunction altering zinc compartmentalization is plausible and shown in vitro in both directions. The relevance of either result to human zinc status is not established.

Counter-evidence held on record

Counter-evidence and confounding The circulating claim treats chloroquine as a zinc delivery vehicle. The cell data conflict, the Drosophila study suggests loss rather than gain, and no human zinc status data exist. Efficacy questions are out of scope here. Framing caution Not a deficiency claim and not an instruction to take zinc with chloroquine. Zinc has an NIH upper limit for adults and none is recommended or dosed here.

Limits on what this shows

• Null findings: PubMed 'chloroquine hypomagnesemia': no chloroquine magnesium measurement. The healthy-volunteer QT study in the label (116 subjects) reports QTcF changes only [1].

Regulatory status

QT warning: use with caution in patients with uncorrected hypokalemia and/or hypomagnesemia [1]. The label does not claim chloroquine lowers magnesium.

Population evidence

None measuring magnesium on chloroquine. A prospective Iranian multicenter study of 2,403 COVID-19 patients (2,365 analyzed) on chloroquine, hydroxychloroquine and other drugs found QTc of 500 ms or more in 11.2% and torsades in 0.38%, with hypokalaemia during treatment among predictors; chloroquine-specific numbers and magnesium were not reported in the record read (Haghjoo 2021 [29], record-level). A hydroxychloroquine study of 500 patients and a hydroxychloroquine cohort on potassium are not chloroquine and are not used.

Mechanism

Direction is nutrient status modifying the drug's cardiac risk (Hard Rule 4 style context), not the drug lowering magnesium. No mechanism for chloroquine-induced magnesium loss was found.

Counter-evidence held on record

Counter-evidence and confounding A label caution on pre-existing hypomagnesemia is not evidence of depletion. Overlaps with the potassium entry for the QT narrative (see Overlap map). Framing caution Do not recommend magnesium supplementation. Antacids containing magnesium also reduce chloroquine absorption (next entry).

Limits on what this shows

• Null findings: Dimethicone did not adsorb chloroquine in vitro. No study found that chloroquine lowers calcium or magnesium status through this route.

Regulatory status

Label: antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between these agents and chloroquine should be observed [1].

Population evidence

Six volunteers (J Trop Med Hyg 1982 [27], abstract via summarizer): chloroquine AUC fell 18.2% with magnesium trisilicate and 28.6% with kaolin; the authors advise separating by at least 4 hours. In vitro adsorption study (same journal 1982 [27]): chloroquine adsorbed to calcium carbonate (52.8% reduction), kaolin (46.5%) and magnesium trisilicate (31.3%); dimethicone had no effect. In 7 volunteers food raised chloroquine AUC and peak without changing absorption rate [28].

Mechanism

Adsorption of chloroquine onto the antacid or clay, shown in vitro and in volunteers.

Counter-evidence held on record

Counter-evidence Small volunteer study; the in vitro percentages are not human exposure changes. Framing caution Separate calcium or magnesium antacids, and kaolin, from chloroquine by at least 4 hours per the label. This is a drug-absorption note, not a mineral deficiency. No supplement dose is given.

Limits on what this shows

• Null findings: No EGRAC or urinary riboflavin study with chloroquine found.

Regulatory status

Not mentioned in the label [1].

Population evidence

None in humans on status. PMID 21686082 (ACS Med Chem Lett 2011): chloroquine is a ligand of the riboflavin receptor, KD 2100 nM (quinacrine 264 nM). PMID 23471972 (JBC 2013): chloroquine binds reduced NQO2 flavin (1.4 Angstrom structure). PMID 34436427 (Metabolites 2021): 1H-NMR metabolomics of uninfected human red cells exposed to chloroquine; riboflavin metabolism among the disturbed pathways. PMID 11036031 (AAC 2000): riboflavin mildly antagonistic to chloroquine against P. falciparum. All listing-level [32].

Mechanism

Binding and enzyme-flavin interactions shown in vitro.

Counter-evidence held on record

Counter-evidence and confounding Receptor affinity in a binding assay does not show a status effect. Framing caution Mechanistic note only; not a deficiency claim.

Limits on what this shows

• Null findings: A PubMed search 'chloroquine hypoglycemia' returned 83 results; the only chloroquine-specific item among the first 10 was the 1987 letter. Several other records concerned hydroxychloroquine or malaria itself, which causes hypoglycemia.

Regulatory status

Label: chloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life-threatening; it may enhance the effects of a hypoglycemic treatment and a dose decrease of insulin or other antidiabetic drugs may be required; hypoglycemia is listed under metabolic adverse reactions [1].

Population evidence

Goyal and Bordia, J Assoc Physicians India 1995 [25] (PubMed record via summarizer): 10 healthy volunteers, chloroquine 800 mg intravenous over 3 hours; blood glucose fell 25.86% versus 10.47% in controls (p=0.001; control size not stated). A 1987 Lancet letter 'Chloroquine and hypoglycaemia' [26] links hypoglycemia to chloroquine poisoning (record-level).

Mechanism

Not defined in the sources read.

Direction

Intended or off-target pharmacologic glucose lowering. Outcome entry (Hard Rule 2). Not related to a nutrient shortfall.

Counter-evidence held on record

Counter-evidence and confounding Intravenous dosing in volunteers differs from oral prophylaxis; malaria and quinine are strong competing explanations in clinical hypoglycemia. Framing caution Not a nutrient claim. Relevant to people on insulin or antidiabetic drugs; discuss with the prescriber.

Regulatory status

Adverse reactions include anorexia, nausea, vomiting, diarrhea and abdominal cramps [1]. The adverse reaction list does not mention taste changes.

Population evidence

No dietary or nutrient study. The pediatric Nigerian prophylaxis study showed higher hemoglobin and no ferritin difference in protected children [11], which gives no sign of net hematologic harm in that setting.

Mechanism

Mechanism H (changed intake), generic. Food raises chloroquine absorption [28], so taking it with food is a PK matter.

Counter-evidence held on record

Counter-evidence and confounding A context flag only. The diseases treated (malaria, rheumatic disease) independently affect intake. Framing caution Not a deficiency claim.

Limits on what this shows

• Why no grade: Dual condition met: no Tier B or C source supports a yellow grade, and no circulating consumer claim exists for this nutrient. Genuine literature gap on the channels reached, with a small tooling limit (PMC blocked). This is not a finding of safety.

What was searched

PubMed listing 'chloroquine niacin OR nicotinamide OR tryptophan pellagra' (20 records, none mentioning chloroquine, read via summarizer in an earlier pass [35]). Consumer pages checked for claims: the hydroxychloroquine nutrient page [31], a pharmacy education depletion handout and a 2006 drug-depletion magazine article, none of which lists niacin or tryptophan for chloroquine.

Channel outcomes

DailyMed label opened: no niacin content [1]. PMC article pages bot-challenged; Crossref, Europe PMC, Semantic Scholar and direct PubMed API calls not used (network policy). OpenAlex and PubMed single-record lookups worked. A broader PubMed query was rate-limited (429) once and was not retried.