Ciprofloxacin

Limits on what this shows

• Null findings: Acute bioenergetic readouts (NAD(P)H, ATP/ADP) unchanged in mouse islets [38]; basal oxygen consumption rose rather than fell in MIO-M1 cells [37]; Hangas measured no respiration or ATP [35]; Sailer 2025 found respiration effects only at concentrations of about 100-fold or more above therapeutic peaks and complex IV unaffected [54].
• Dose relevance: Concentrations used (25 to 120 ug/mL; 0.3 mM is about 100 ug/mL) are far above peak serum levels after ordinary oral doses; the label 12.3 pharmacokinetic text was not available in the fetched label pages, so no clinical peak concentration is quoted here.

Direction

Drug-to-cell injury (a mechanistic toxicity signal). Not a nutrient deficiency and no supplementation implication (Hard Rule 2).

Regulatory status

No mitochondrial statement was found in the label text read [1]. Tendinitis, peripheral neuropathy and other serious reactions are listed outcomes, not mitochondrial findings.

Population evidence

None in humans. A review lists ciprofloxacin among drugs that inhibit hepatic mtDNA replication (Fromenty 2020; review, cited studies not opened) [42].

In vitro and cell evidence (Tier B)

Hangas 2018 [35]: human HeLa and HEK293 cells and mouse C2C12 myotubes, ciprofloxacin 80 ug/mL; mtDNA copy number fell 18% within 3 days in HeLa; replication initiation nearly completely inhibited in myotubes (OH-bubble intermediates 18% and y-shaped intermediates 33% of control); mechanism: inhibition of Top2 (Top2 beta in myotubes). ATP, respiration and membrane potential were not measured; the paper does not relate 80 ug/mL to clinical levels. Read via a summarizing fetch of the journal page. Kozieł 2006 [36]: human Jurkat cells, 25 ug/mL for several days: mtDNA content fell 60%, respiratory chain inhibition and membrane potential loss followed (listing summary only). Salimiaghdam 2022 [37]: human retinal MIO-M1 cells, 30, 60 and 120 ug/mL: 120 ug/mL lowered cellular metabolism, membrane potential and mtDNA copy number; basal oxygen consumption rose (listing summary only). Lowes 2009 [39]: normal human Achilles tendon cells, 0 to 0.3 mM: loss of mitochondrial membrane potential, prevented by the mitochondria-targeted antioxidant MitoQ (listing summary only). Liu 2026 [41]: human cortical organoids, chronic low-dose two-week exposure: excess ROS and lower membrane potential (abstract-level; concentration not in the abstract). Ghaly 2014 [38]: mouse pancreatic islets: ciprofloxacin did not significantly change glucose-induced NAD(P)H or ATP/ADP ratio, though it changed mitochondrial morphology and reduced insulin granules at 10 and 100 uM (listing summary only). Sailer 2025 [54]: permeabilized human HEK 293T cells, high-resolution respirometry, ciprofloxacin titrated 0.01 to 2 mg/mL (serum peaks under therapy 2.4 to 5 ug/mL): leak respiration rose (more than 2-fold at 1 mg/mL in the Discussion; the Results text says 2 mg/mL, a disagreement within the paper); N-linked OXPHOS capacity fell 39% when the drug was added in the leak state (16% when added in the OXPHOS state); NS-linked OXPHOS fell 26% (18%); NS electron transfer capacity fell 37% (25%); no significant direct effect on complex IV; ATP not measured; membrane potential could not be measured because ciprofloxacin interfered with the safranin dye; the 0.1 N HCl solvent itself slightly lowered respiration. The authors say the 1 mg/mL effect is far above therapeutic serum peaks and may matter only in high-dose or overdose situations. Read from the MDPI article page through a summarizing fetch tool; Tier B.

Cohort test: Kalghatgi 2013

Kalghatgi et al. (Sci Transl Med 2013; PMID 23825301) tested three bactericidal classes (quinolones, aminoglycosides, beta-lactams) in mammalian cells and mice, with mitochondrial dysfunction, ROS and oxidative damage reversed by N-acetylcysteine. The abstract names the classes, not individual drugs; the full text could not be opened (PMC returned a bot-verification page; Science returned 403), so this review could NOT confirm that ciprofloxacin was among the drugs tested. It is therefore used only as CLASS EXTRAPOLATION (quinolone class), capped at yellow, and ciprofloxacin is not claimed to be in the cohort [34].

Mechanism

Named: inhibition of mitochondrial topoisomerase 2 (replication initiation) and, in other cell studies, ROS and membrane potential loss [35][39].

Counter-evidence held on record

Counter-evidence and confounding Cell lines, supraphysiologic concentrations, short exposures and no human tissue. Mixed bioenergetic outcomes (null ATP/ADP, higher oxygen consumption) argue against reading structural findings as functional impairment. Framing caution A mechanistic signal, not a deficiency and not a finding that therapeutic courses damage mitochondria in people. No antioxidant or mitochondrial supplement is recommended by this entry.

Limits on what this shows

• Null findings: In MIO-M1 cells ROS was lower at 72 hours at 120 ug/mL with ciprofloxacin (opposite direction) [37]. Hangas measured no ROS [35]. In vivo animal null: Jijie 2023 [57] exposed zebrafish to ciprofloxacin alone (5 mg/L, 96 hours, n = 5 per group) and reported no effect on MDA, SOD or GPx (numbers are in a figure not seen); only the lead-containing mixtures changed them (Tier B, OpenAlex abstract and MDPI article page via a summarizing tool).

Direction

Drug-to-cell redox burden (mechanistic). Not an antioxidant-nutrient deficiency.

Regulatory status

No oxidative stress statement in the label text read [1].

Population evidence

None in humans. No human trial or cohort measuring MDA, glutathione or antioxidant enzymes in ciprofloxacin users was retrieved; the one in vivo marker study found (zebrafish) is a null (see Null findings).

Cell evidence (Tier B)

Lowes 2009 [39]: normal human Achilles tendon cells, 0 to 0.3 mM for 24 hours and 7 days: up to a 3-fold rise in the rate of DCF oxidation (ROS marker), reduced by 1 uM MitoQ or idebenone. Zeng 2024 [40]: primary human aortic smooth muscle cells, 110 ug/mL for 72 hours with angiotensin II: ROS higher (MitoSOX and DCFH-DA), membrane potential lower, AMPK phosphorylation suppressed; an AMPK activator partly reversed it. Liu 2026 [41]: cortical organoids, excess ROS.

Cohort test: Kalghatgi 2013

Mouse blood oxidative stress markers and tissue damage after quinolone class exposure are reported in the abstract, but ciprofloxacin was not confirmed to be in the cohort (full text unopened); CLASS EXTRAPOLATION, yellow cap [34].

Counter-evidence held on record

Counter-evidence and confounding Supraphysiologic concentrations, no in vivo ciprofloxacin marker study retrieved, and mixed direction across cell types. Framing caution A mechanistic signal only. No antioxidant supplement is recommended; NAC and MitoQ results are cell or mouse findings, not treatment advice.

Limits on what this shows

• Null findings: None found for oral iron with oral ciprofloxacin. Related animal study: Wong 2000 [10] gave rats intravenous ciprofloxacin 5 mg/kg with oral ferrous sulfate 100 mg/kg (no gut contact): AUC was higher with iron (1.89 versus 1.00 mg.h/L), distribution volume about 2-fold and half-life about 4-fold higher, yet the microbiological-to-HPLC ratio fell (0.7 versus 1.1), which the authors read as reduced antimicrobial activity. Different route and species, so not counted toward the grade; it shows the interaction is not purely a gut-absorption effect in that model.
• At-risk subgroups: People taking iron tablets, mineral-containing multivitamins or iron-fortified products near ciprofloxacin doses; infections with organisms of moderate susceptibility, where a lower peak matters more (Polk) [7].

Direction

Nutrient-to-drug TIMING INTERACTION, filed yellow under Hard Rule 4 (the nutrient affects the drug, so it is a timing interaction with a separation interval, not a depletion). Nutrient-to-drug: Iron salts chelate ciprofloxacin in the gut and lower its absorption. Ciprofloxacin is not shown here to lower iron status (Hard Rules 2 and 4); the drug-to-mineral question is carried in the ungraded entry on systemic mineral status and in the Overlap map.

Regulatory status

Label section 2.4 names "other products containing calcium, iron or zinc"; the section 7 table row "Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent Cations" says these "decrease ciprofloxacin absorption, resulting in lower serum and urine levels" and that ciprofloxacin should be taken "at least two hours before or six hours after" such products [1][2]. Drugs.com patient text lists iron supplements with the same 2 hour and 6 hour interval [21]. The NIH iron fact sheet does not mention quinolones [20].

Population evidence

Polk 1989 [7]: 12 healthy men, four-way crossover, ciprofloxacin 500 mg after an overnight fast. AUC alone 14.5 +/- 2.3 ug.h/mL (repeat control 15.7 +/- 2.8); with ferrous sulfate 325 mg three times a day for 7 days, dose taken with the last iron dose, 5.4 +/- 1.7 ug.h/mL (63% lower, calculated from the printed means); with a multivitamin with zinc 11.3 +/- 2.4. The authors state that peak concentrations with iron were below the MIC for 90% of strains of many normally susceptible organisms. Abstract read through an OpenAlex reconstruction and a PubMed listing. Lehto 1994 [8]: three two-period crossover trials, 8 healthy volunteers each; ciprofloxacin 500 mg with ferrous sulphate containing 100 mg elemental iron: AUC reduced 57% (P < 0.001), peak concentration reduced 54% (P < 0.01). The same paper gives norfloxacin 73% and ofloxacin 25% for AUC. Abstract read via a PubMed listing summary (confidence intervals not printed in the abstract). Kara 1991 [9]: randomized crossover in 8 healthy subjects; ferrous sulphate 300 mg lowered ciprofloxacin Cmax from 3.0 to 2.0 mg/L (about 33% lower) and AUC from 12.3 to 6.7 mg/L.h (about 46% lower), both significant; ferrous gluconate 600 mg lowered Cmax by 1.3 mg/L and AUC by 4.1 mg/L.h, and a Centrum Forte tablet by 1.4 mg/L and 5.4 mg/L.h (baselines not printed in the abstract, so no percent). The authors propose a ferric iron-ciprofloxacin complex at a 3:1 ratio. Abstract read via a PubMed listing summary. Note: the assignment attributed iron to Frost 1992 and antacids to Kara 1991; the retrieved records show the reverse (Frost 1992 is aluminum and calcium antacids, Kara 1991 is iron).

Independence

Three different research groups (Polk, Lehto, Kara), designs (7 day iron loading versus single doses), populations and years. Both measured the drug level directly, so the "nutrient" measured is the antibiotic exposure, not iron status.

Mechanism

Named: chelation (complex formation) between the multivalent cation and the quinolone. In vitro, aluminum, calcium and iron ions each slowed ciprofloxacin release across a membrane [14].

What is not shown

Whether the label separation interval fully restores exposure was not retrieved for iron specifically; no iron-status (ferritin, hemoglobin) measurement in ciprofloxacin users was found.

Separation interval

Label: ciprofloxacin at least 2 hours before or 6 hours after products containing calcium, iron or zinc, multivitamins and antacids [1]. This is the action the entry supports; it is not a nutrient recommendation.

Counter-evidence held on record

Counter-evidence and confounding Studies used healthy volunteers, fasting dosing and single doses of ciprofloxacin; real-world meals reduce but are not shown here to remove the effect. The clinical consequence (treatment failure) is an inference from reduced exposure, not a measured outcome in these trials. Framing caution This is a timing rule for the antibiotic, not an iron-deficiency finding. Do not stop or start iron because of it, and take no action beyond following the label spacing from the prescriber or pharmacist. No iron dose is recommended here.

Limits on what this shows

• Null findings: None needed; no measurement exists to be null.

Direction

Drug-to-copper chelation (chemistry only). Not a copper deficiency or excess finding. Kept separate from the Iron entry (Hard Rule 7).

Regulatory status

The label text read lists calcium, iron and zinc, magnesium and aluminum as cations; copper is not named [1].

Population evidence

None. No human copper, ceruloplasmin or urinary copper measurement in ciprofloxacin users was retrieved.

Chemistry and formulation evidence (Tier B)

Cu(II)-ciprofloxacin complexes characterized by X-ray crystallography (Drevensek 2003, PMID 12944650; Yang 2012, PMID 22412472), mixed-valence complexes with about the same gyrase activity as free drug (Drevensek 2005, PMID 15621275), and copper-complex inhaled formulations tested against Pseudomonas aeruginosa in rats (Tewes 2020, PMID 32442738; 2023, PMID 36970713) [48]. Abstract-level listing summaries only; the studies concern the drug acting with copper as a pharmaceutical complex, not body copper.

Mechanism

Named: metal-ion coordination by the quinolone keto-carboxylate group. No copper-handling mechanism in the body was shown.

Counter-evidence held on record

Counter-evidence and confounding The complexes were made for antibacterial formulation research; they say nothing about copper status in treated patients. Framing caution No copper supplement or restriction is implied. This is a chemistry note.

Limits on what this shows

• Why no grade: Dual condition met: no Tier B or C source found for a systemic mineral status effect, and no circulating claim of that direction found. Not a finding of safety. Re-check with PubMed restored for single-mineral listings (for example "ciprofloxacin serum iron", "ciprofloxacin urinary calcium", "ciprofloxacin ferritin"), each run as its own simple query because a combined Boolean query returned nothing.

What was searched

Label text read: cations listed only as agents that lower ciprofloxacin absorption [1]. StatPearls: no mineral loss statement [3]. Consumer pages (Drugs.com, GoodRx) and Wikipedia fluoroquinolone toxicity: mineral claims run nutrient-to-drug only [21][22][52]. PubMed listings: "ciprofloxacin copper complex" (chemistry, copper entry above); an attempted listing "ciprofloxacin copper zinc iron serum levels chelation" returned unrelated records because the "patients" term dominated; a cleaner re-run ("ciprofloxacin copper zinc chelation status") was rate limited (429) and not read. The animal magnesium-deficiency literature (Magnesium and tendon entry) concerns local cartilage and tendon magnesium, and the ofloxacin rat study found unchanged total tissue magnesium [46].

Repair search (2026-10-08)

PubMed listing "ciprofloxacin hypomagnesemia" opened (5 records) [56]: two case reports in which low magnesium (with low phosphate and potassium in one) occurred in people given ciprofloxacin for diarrhea; the abstracts attribute the magnesium loss to chronic proton pump inhibitor use (PMID 36506733, confirmed on a second channel: OpenAlex abstract, magnesium normalized after the PPI was stopped) or give no cause (PMID 37791144, OpenAlex abstract: ciprofloxacin mentioned only as the initial treatment and not implicated), so ciprofloxacin was the intercurrent drug, not the proposed cause; two geriatric safety reviews (PMIDs 12641485, 20210367) list low magnesium as a reason for caution, not a measurement; and the Daya hypocalcemia torsade case (already cited) is a dialysis patient. A combined Boolean query for serum magnesium, zinc, iron and urinary zinc returned no matching records. The "ciprofloxacin zinc deficiency" PubMed listing opened (4 records, after two rate-limited attempts with other wording): a zinc review mentioning only that oral zinc lowers ciprofloxacin absorption, two bacterial in vitro papers, and one animal study. That animal study, Jijie 2023 [57] (zebrafish, ciprofloxacin alone 5 mg/L for 96 hours, n = 5 per group for element analysis, whole-body Ca, K, Mg, Na, Zn, Cu and Fe), is the only direct measurement of body minerals with ciprofloxacin found: the paper states no significant difference from control (Ca 4963.5 +/- 71.3 ug/g and Mg 355.8 +/- 12.7 ug/g in the ciprofloxacin group, values for K, Na, Zn, Cu and Fe are only in a figure not seen) and that ciprofloxacin alone had no effect on AChE, MDA, SOD or GPx. The mineral shifts in that paper (lower Ca, K, Mg, Na and higher Zn) occurred only with lead plus ciprofloxacin, so they are a lead effect. This is a Tier B animal null at a high exposure, not support for a deficiency; it reads OpenAlex abstract plus the MDPI article page via a summarizing tool. Iron and calcium listings ("ciprofloxacin serum iron", "ciprofloxacin urinary calcium") were not run, because the limited PubMed access allowed only one further query.

Channel outcomes

Mixed. The magnesium listing is a genuine null for a drug-to-magnesium effect (the only human records attribute the deficit to a PPI). Zinc now has a listing plus one animal null (zebrafish); iron and calcium were covered only by the earlier listings, the label, StatPearls, consumer pages and the ODS fact sheets, so the gap is better established for magnesium and zinc than for iron and calcium.

Limits on what this shows

• Null findings: Individual C in Dethlefsen showed no significant richness change; effects "varied among individuals" and between-person differences were the largest source of variability [23]. In the placebo-controlled trial, pyrosequencing showed clindamycin with a larger impact than ciprofloxacin [25], and the saliva shift was seen only at week 1 [24]. A 3-volunteer follow-up found no change in E. coli MIC or tolerance after 14 days (de Lastours 2022, PMID 35030401; listing line only) [28].
• At-risk subgroups: Not defined by these cohorts (healthy adults only). Older adults and people with a prior disturbed gut or repeated courses were not studied in the sources read.

Direction

Disturbance of the gut microbial community (a risk entry). It implies no supplement, probiotic or fiber recommendation.

Regulatory status

Label section 5: "Clostridium difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including ciprofloxacin" [1]. In the label clinical-trial data nausea occurred in about 2.5% and diarrhea in about 1.6% of patients [1].

Population evidence

Dethlefsen 2008 [23]: 3 healthy adults, ciprofloxacin 500 mg twice a day for 5 days, five time points over 8 months. The effective number of species fell 82% (individual A), 63% (B) and 36% (C); taxonomic richness fell significantly in A and B (p < 10 to the minus 4 and p < 0.005) but not in C (p = 0.24 in the text, 0.129 in a figure legend); 30% of reference OTUs (442 of 1,450) responded; Faecalibacterium declined in all three; at 4 weeks community composition was within pretreatment variability, and several taxa had not recovered at 6 months. Read through a summarizing fetch of the PLOS article page (first 100,000 of 100,723 characters). Zaura 2015 / Rashid 2015 [24][25]: randomized, placebo-controlled trial in healthy adults; the ciprofloxacin arm that completed had 10 volunteers (Karolinska site); ciprofloxacin 500 mg twice daily for 10 days (dose from the Rashid abstract). Fecal Bray-Curtis dissimilarity from placebo was significant up to 1 month; Shannon diversity was significantly lower than baseline for up to 12 months, the longest of any antibiotic group; predicted metagenome at month 1: 612 of 4,606 functions significant (110 higher, 502 lower); butyrate-producer decline was attributed to ciprofloxacin and clindamycin together, not ciprofloxacin alone; normalization took about 1 to 12 months depending on species. No single OTU survived false-discovery correction. Zaura read through a summarizing fetch of the journal page (dose in a supplement not seen); Rashid abstract via OpenAlex only, with no sample size or index values. de Lastours 2017 [27]: 48 volunteers, ciprofloxacin days 0 to 14; enterococcal counts fell from about 5.9 to about 4.0 log cfu/g at day 7 and 3.9 at day 14; the fluoroquinolone-resistant fraction rose from 44% to 73% to 75%; at day 42, 10 of 48 (21%) still carried resistant strains. Culture-based, one genus, PubMed listing summary only. A French cohort, independent of the two above. Stewardson 2015 [53]: outpatients with urinary tract infection treated with ciprofloxacin or nitrofurantoin, compared with untreated patients and household contacts of ciprofloxacin-treated patients; V3-V4 16S pyrosequencing at three time points; groups similar at baseline. Ciprofloxacin had a significant global effect on the microbiota and nitrofurantoin did not; at the end of treatment Bifidobacterium, Alistipes, Faecalibacterium, Oscillospira, Ruminococcus and Dialister fell while Bacteroides, Blautia, Eubacterium and Roseburia rose, with substantial recovery by 4 weeks. Abstract read through a PubMed single-record listing; the OpenAlex record carries no abstract and the full text could not be opened (publisher redirect returned an empty page, ScienceDirect disallowed access), so group sizes, diversity indices and p values were NOT retrieved. A third independent human cohort (patients, with a nitrofurantoin comparator and a no-antibiotic control) in the same direction; it is supporting evidence and the red grade does not depend on it. Second-channel checks this repair : the Zaura mBio page [24] states that 10 volunteers completed each of the placebo and ciprofloxacin groups, that fecal diversity was "significantly reduced" in the ciprofloxacin group "even up to 12 months", and that the ciprofloxacin group differed from placebo (Bray-Curtis) up to 1 month; it prints no numeric Shannon values in the text (figure and supplementary text not seen) and gives no ciprofloxacin p value beyond the P < 0.05 threshold. The Rashid abstract on the OUP page [25] gives ciprofloxacin 500 mg twice daily for 10 days, "a strong effect on the diversity of the microbiome" and 1 to 12 months to normalize (a range for both antibiotics); the full text is paywalled, so no n or index values were retrievable.

Mechanism

Named: antibacterial activity against susceptible commensal bacteria, with selection of resistant strains, as interpreted by the cohort authors; the label itself states only the C. difficile warning [1].

Cohort test

Not independent: Zaura 2015 and Rashid 2015 (same antibiotics and doses, placebo comparator and one-year sampling; Zaura is a coauthor of Rashid; treated as the same trial) and Card 2015 (PMID 25987611, E. coli decreased and returned in 1 to 4 months; ciprofloxacin-resistant Veillonella persisted 12 months in saliva; listing line only) appear to report the same ciprofloxacin and clindamycin placebo-controlled volunteer trial (same antibiotics, placebo comparator, one-year sampling; not confirmed from full text), so they are treated as one trial [26]. Combination exposures, not counted: Lankelma 2017 (16 men, 7 days of ciprofloxacin plus vancomycin plus metronidazole; diversity lower in all treated) and Haak 2019 (13 men, same three drugs; diversity dropped, butyrate producers reduced, composition often still altered at 8 to 31 months) [29][30]. These are Tier C for ciprofloxacin alone. Raymond 2016, named in the assignment, was checked on two channels (PubMed listing and an OpenAlex single-record abstract): it studied the second-generation cephalosporin cefprozil (18 exposed participants, shotgun metagenomics; ciprofloxacin not mentioned), so it fails the cohort test and is not used [31]. A 2011 follow-up from the Dethlefsen group is likely to reuse the same three volunteers; it was not opened and is not counted. A repair-pass PubMed listing ("ciprofloxacin microbiome diversity volunteers", 5 records) returned no further ciprofloxacin-alone cohort beyond those above: de Lastours 2012 (PMID 22930806) is the same ciprofloxacin 14-day, 48-volunteer design as the 2017 report, tracks resistant E. coli by culture (no diversity measure) and is not counted separately; Card 2015, Rashid 2015, Haak 2019 and Lankelma 2017 are as described.

Why red and its edge

Two independent Tier A human cohorts with ciprofloxacin alone and the microbiome directly measured by 16S sequencing: Dethlefsen 2008 (n = 3, effective species down 36% to 82%) and the Zaura 2015 randomized placebo-controlled trial (n = 10 ciprofloxacin versus 10 placebo, diversity lower for up to 12 months). The direction is the same in both, a mechanism is named, and no Tier A source contradicts it; Stewardson 2015 (patients, with controls) points the same way. Rashid 2015 and Card 2015 are the Zaura trial and are not counted again; Raymond 2016 (cefprozil) is excluded. The red grade sits at the lower edge: the two cohorts are small (n = 3 and n = 10), the surrogate is community diversity rather than a clinical outcome, and one Dethlefsen volunteer showed no significant richness change. It is kept red, not demoted to orange, because both cohorts meet the red test as written (independent, drug present, measured directly, consistent, named mechanism) and the Zaura numbers rest on a placebo comparator.

Counter-evidence held on record

Counter-evidence and confounding Infection itself, diet, and co-medication confound patient studies, but these were healthy volunteers. Effects were smaller than clindamycin in one pyrosequencing comparison. Sample sizes are small and one cohort used culture of a single genus. Framing caution This is a disturbance risk, not a deficiency. No probiotic, fiber or vitamin supplement is recommended by this entry. New severe or persistent diarrhea during or after a course needs clinical assessment (the label carries a C. difficile warning).

Limits on what this shows

• Null findings: Ghaly 2014 [38]: no significant change in ATP/ADP ratio in mouse islets. Salimiaghdam 2022 [37]: ATP not reported for ciprofloxacin; basal oxygen consumption rose. Hangas 2018 [35]: ATP not measured. Sailer 2025 [54]: ATP not measured; the respiration decreases (OXPHOS capacity down 16% to 39%) were at concentrations far above therapeutic peaks.

Direction

Drug-to-cell energy effect (mechanistic). Not a nutrient deficiency.

Regulatory status

No ATP statement in the label text read [1].

Population evidence

None in humans.

Cell evidence (Tier B)

Kozieł 2006 [36]: human Jurkat cells, 25 ug/mL: cellular ATP fell 16% on day 4 and 35% on day 7, then recovered by day 11, after a 60% fall in mtDNA content and respiratory chain inhibition (listing summary only). Liu 2026 [41]: in the abstract aspirin "restored ATP and ROS levels" in primary neurons after ciprofloxacin exposure, which implies lower ATP; no ciprofloxacin-alone figure in the abstract.

Counter-evidence held on record

Counter-evidence and confounding Different cells, concentrations and time courses; the one quantified decrease recovered while exposure continued. Framing caution A cell-level mechanistic note, not evidence that ciprofloxacin lowers energy in people. No energy or mitochondrial supplement is recommended.

Limits on what this shows

• Null findings: The G6PD cohort above is a null for major hemolysis [47]. The StatPearls chapter did not mention G6PD [3].

Direction

Adverse-outcome entry (hematologic reaction). Anemia is not iron deficiency and this is not an oxygen-delivery nutrient finding (Hard Rule 2). Distinct from the Iron entry, which concerns absorption of the antibiotic.

Regulatory status

Label section 5.6: "Anemia, including hemolytic and aplastic" is listed among hematologic reactions; no G6PD deficiency text was in the label text read [1].

Population evidence

Gronich 2024 [47]: Clalit Health Services database, 31,962 G6PD-deficient patients (G6PD below 6 U/g Hb), 71 hospitalized major hemolysis cases (0.2%), 51 linked to fava beans, 6 to infection, 3 suggested medication-related (nitrofurantoin, phenazopyridine, a pain killer). The abstract (via a PubMed listing summary) names ciprofloxacin only as a drug prescribed to many G6PD-deficient patients without major hemolysis; ciprofloxacin-specific counts were not retrieved.

Mechanism

Not retrieved for ciprofloxacin. No immune hemolysis case report for ciprofloxacin was retrieved in the listing opened.

Counter-evidence held on record

Counter-evidence and confounding A database study of hospitalized major hemolysis cannot exclude mild or subclinical hemolysis; infection in the indication is a competing explanation for anemia. Framing caution A label-listed adverse reaction. Unexplained pallor, dark urine, jaundice or marked fatigue during a course needs clinical assessment; iron supplements are not the remedy and also lower ciprofloxacin absorption.