Cephalexin

Limits on what this shows

• Negative or null findings: Cohort test for the broader antibiotic-mitochondria literature: a 2025 respirometry study tested gentamicin, ciprofloxacin and amoxicillin in human cells and included no cephalosporin, so it is not used for cephalexin. [24] The widely cited 2013 cell and mouse study of bactericidal antibiotics and mitochondrial dysfunction was not opened in this review (PubMed 429), so whether it included cephalexin is unknown and it is not used.
• At-risk subgroups: Not defined. Renal impairment raises cephalexin exposure but no mitochondrial consequence was studied. [10]
• Counter-evidence on record: The in vivo rabbit result is itself the counter-evidence to a class-wide cephalosporin mitochondrial toxicity claim.

Direction

Neutral to mild in vitro inhibition; no human signal. Not a nutrient deficiency.

Regulatory status

Not addressed in any label opened. [1][4]

Population evidence

None in humans. Tier B (animal and isolated mitochondria with cephalexin itself), seen as listing-level summaries: in vivo (the protocol in one study was 300 mg/kg intravenously one hour before sacrifice), cephalexin did not reduce succinate uptake or respiration; in vitro, exposure of 300 to 3,000 ug/mL for 2 to 6 hours reduced respiration only slightly and inhibited succinate uptake; fatty-acid-substrate respiration was mildly reduced in vitro and stimulated in vivo; the nephrotoxic comparator cephaloglycin reduced net succinate uptake by 70%. Numeric values for cephalexin were not available in the lines read. [22]

Mechanism

Named for the toxic cephalosporins (cephaloridine, cephaloglycin): inhibition of mitochondrial uptake of anionic substrates such as succinate. Cephalexin is the weak or inactive comparator. [22]

Counter-evidence held on record

Boundary The in vitro concentrations (up to 3,000 ug/mL) are far above the plasma peaks in the US label (about 9 to 32 ug/mL), although urinary levels reach several thousand ug/mL. [1] Listing-level data only. Framing caution Animal and isolated-organelle work with a negative in vivo result; it does not describe human mitochondrial function.

Limits on what this shows

• Negative or null findings: The rabbit result above. No human antioxidant capacity, MDA or glutathione study with cephalexin was returned by the PubMed listing. The 2013 study often cited for antibiotic-induced oxidative damage was not opened and is not used. [23]
• At-risk subgroups: Not defined.
• Counter-evidence on record: The rabbit null result against any mammalian oxidative signal.

Direction

Neutral in the mammalian study; oxidative stress rises at high exposure in fish and in a wastewater microbial system. Not a nutrient deficiency.

Regulatory status

Not addressed in any label opened.

Population evidence

None in humans. Rabbit renal cortex (Biochem Pharmacol 1989, cephaloridine and cephaloglycin versus cephalexin): cephalexin "no oxidative changes except for a slight increase of mitochondrial conjugated dienes" (no numbers in the line read). Rainbow trout exposed to cephalexin showed oxidative stress rising with concentration in gill and intestine (no values in the line read). In an anaerobic digestion system, 200 mg/L cephalexin raised ROS by 61.74%. [23]

Mechanism

Not established for cephalexin. A listed cephalexin plus radiation study implicates ROS in a tumor-cell setting only. [23]

Counter-evidence held on record

Boundary Fish and wastewater exposures are far removed from oral dosing in people. Listing-level data only; one mammalian line. Framing caution No evidence that cephalexin changes oxidative stress or antioxidant nutrient needs in people.

Limits on what this shows

• Negative or null findings: The PubMed copper listing returned no study of copper status, ceruloplasmin or absorption with cephalexin (10 of 16 records seen). [30]
• At-risk subgroups: Not defined.
• Counter-evidence on record: None; the evidence is chemistry only.

Direction

Metal affects the drug in vitro (reduced antibacterial activity). There is no evidence for the drug lowering or raising body copper.

Regulatory status

Copper is not mentioned in any label opened. [1][2][4]

Population evidence

None in humans or animals. Tier B in vitro, listing-level summaries: cephalexin forms a stable 1:1 complex with Cu(2+) (Free Radic Biol Med 2018, eight beta-lactams, copper weakened several against E. coli and S. aureus); copper(II) and zinc(II) cephalexin complexes were made and tested (J Pharm Pharmacol 1999, a rat paw edema test of the copper complex); metal chlorides often raised cephalexin MIC (Pak J Pharm Sci 2007). No concentrations were retrieved. [30]

Mechanism

Chelation chemistry in vitro; physiological relevance not studied.

Counter-evidence held on record

Boundary and overlap This is Tier B chemistry, kept distinct from iron. The in vitro metal findings are the same type of evidence as the zinc mechanism and are cross-listed in the overlap map. Framing caution No evidence that cephalexin changes copper status. Do not infer a need for copper supplementation.

Limits on what this shows

• Why no grade: Dual condition met: (1) no Tier B or Tier C evidence that cephalexin changes iron status or absorption was found, and (2) no circulating claim about cephalexin and iron was found on the consumer pages read. The class-level iron finding with a different drug (cefdinir with iron salts, the largest mineral effect in a beta-lactam absorption review) runs from iron to the drug and concerns a third-generation agent, so it does not support a yellow iron-status entry for cephalexin. [11]

Direction

Not determined.

Channels tried

PubMed listing "cephalexin iron" (45 results, 10 shown: environmental degradation chemistry, an iron-complex mass spectrometry study, a moxifloxacin trial, one record without an abstract); the beta-lactam food and mineral systematic review abstract; six cephalexin labels (no iron text); Drugs.com and Antidote pages (no iron claim). [31][11][1][4][36][35]

Genuine gap or tooling

Mostly a genuine gap; partly tooling-limited: only 10 of 45 PubMed records were visible and the abstract of the systematic review gave no cephalexin-iron figure. A further iron phrasing ("cephalexin ferritin", "cefalexin anaemia iron deficiency") was not run. Ferrous fumarate was associated with higher C. difficile odds in the Ontario cohort (OR 1.71) but that is an iron product and CDI, not a cephalexin and iron finding. [13]

Counter-evidence held on record

Re-check Re-check the full PubMed listing and the full text of the beta-lactam mineral review for a cephalexin and iron row. Framing caution This is a disclosed gap, not a finding of no effect.

Limits on what this shows

• Negative or null findings: Buckley 2021 [15] (in vitro): C. difficile (RT027, 10^7 spores/mL) did not germinate or produce toxin under cefalexin, whereas ceftriaxone (150 mg/L daily) produced simulated infection with toxin; the authors concluded a low propensity to induce CDI. Counts were three technical replicates of one biological replicate. Sehgal 2025 [16]: 54 Peruvian children, stool at 3 to 16 months; recent cefalexin use did not affect richness, Shannon diversity or genus abundance in the published abstract (cefalexin rate 4.1 courses per 100 child-months in the preprint; a marginal Intestinibacter difference, log2 fold change 0.44, FDR 0.05, is contradicted by the same text; the beta-lactam resistance gene change was not significant, beta -1.02, 95% CI -2.05 to 0.01). Elvers 2020 [17]: systematic review of primary-care antibiotics; cephalexin was not among the antibiotics with results.
• At-risk subgroups: Older adults are the group shown (the Ontario cohort was aged over 65 and not recently hospitalized); no cephalexin-specific subgroup analysis was retrieved. The Ontario authors note possible protopathic bias in the 1 to 90 day window (the 7 to 90 day estimate was slightly lower) and that adjusted and unadjusted estimates correlated only moderately (R=0.68), indicating confounding. [13]
• Counter-evidence on record: Class context points lower for first-generation agents but is Tier C and does not name cephalexin: cephalosporins pooled with monobactams and carbapenems OR 5.68 (2.12 to 15.23) for community CDI [18]; second-, third- and fourth-generation cephalosporins 2.23, 3.20 and 2.14 for hospital-acquired CDI, with a first-generation figure of 1.36 quoted secondhand and not verified [19][15]. Hospital-based studies of first-generation cephalosporins as a class mostly found no association or a lower risk (for example OR 0.86 in a matched case-control of 36 cases; reduced risk in a 401,234-patient cohort; one cohort listed them among risk factors), without naming cephalexin and in settings where the first-generation agent is probably often perioperative cefazolin (an inference, not verified) [34]. A 1986 healthy-volunteer study of cephradine (first-generation, not cephalexin) found no significant fecal flora change except near-elimination of staphylococci [20]. Cephalexin was not in any of these cohorts.

Direction

Disturbance and infection risk (an outcome entry). It is not a nutrient deficiency and implies no supplementation. Colonization resistance is the named mechanism; the evidence is on infection, not on diversity.

Regulatory status

US label 5.2: C. difficile-associated diarrhea "has been reported with nearly all antibacterial agents"; it "must be considered in any patient with diarrhea after antibiotic use"; 5.6: prolonged use "may result in the overgrowth of nonsusceptible organisms". Diarrhea is the most common adverse reaction in the labeled list. No incidence figure was on the page read. [1][2]

Population evidence

Brown 2026 [13][33]: case-cohort, Ontario adults over 65, 2018 to 2023, 16,196 incident CDI cases and 549,831 controls. Cephalexin (cefalexin) in the 1 to 90 days before the index day: adjusted OR 3.05 (95% CI 2.86 to 3.25); exposed in 2,112 cases (13.0%) versus 10,285 controls (1.9%); population attributable fraction 8.8%. Restricted to 7 to 90 days: OR 2.96 (2.75 to 3.20). Same study, for scale: clindamycin 16.83, amoxicillin-clavulanate 6.05, ciprofloxacin 3.83. Levy 2000 [14]: retrospective cohort of 358,389 enrollees in four US health plans (1992 to 1994) with a nested case-control analysis; cephalexin OR 7.5 (95% CI 1.8 to 34.7), cefixime 6.4 (1.2 to 39.0); no other antibiotic showed an increased association; prevalence 12 per 100,000 person-years; case and control numbers not in the abstract read.

Mechanism

Named: loss of colonization resistance from antibiotic exposure of the colonic flora. In the human-stool chemostat, cefalexin at 15 mg/L four times daily for 7 days lowered Bifidobacterium by 2.4 log10 cfu/mL (not recovered by 2 weeks), lactose-fermenting Enterobacteriaceae by 1.0 log10 (then about 1 log10 above baseline), Lactobacillus by 1.2 log10 (recovered); Bacteroides initially fell and recovered; Enterococcus and Clostridium were unchanged. [15]

Why not red

The microbiome was not directly measured in cephalexin-treated people, one Tier A cohort (children, short exposure window, cephalexin sample size not retrievable) found no composition effect, and the in vitro model found no infection. The infection outcome is observational and confounded by indication and healthcare exposure, and first-generation cephalosporin class data in hospital cohorts point to little or no excess risk.

Counter-evidence held on record

Boundary in the title The orange grade covers the infection outcome in the cohorts named, not a proven change in the gut community and not a nutrient shortfall. The label directs that diarrhea after antibiotic use be evaluated for C. difficile. Framing caution This is an infection and disturbance risk, not a nutrient deficiency. No probiotic or supplement recommendation is made or implied.

Limits on what this shows

• Negative or null findings: No report of a hemoglobin fall in routine cephalexin courses was retrieved, which is absence of data and not evidence of absence. A second PubMed listing aimed at case series or registries of drug-induced immune hemolytic anemia with cefalexin returned one record, a cefadroxil case report, and no incidence data. [21]
• At-risk subgroups: Not defined by the evidence. Older age and renal impairment appear in individual reports only.
• Counter-evidence on record: None identified; the limitation is the absence of incidence data.

Direction

Adverse drug reaction (immune hemolysis). It is not a nutrient deficiency, not iron deficiency and not a drug-intended effect.

Regulatory status

US label 5.3: "Positive direct Coombs' tests have been reported"; acute intravascular hemolysis has been reported; if anemia develops, work up for drug-induced hemolytic anemia and stop cephalexin. Adverse reactions list hemolytic anemia, eosinophilia, neutropenia and thrombocytopenia; plain anemia is not listed separately. UK SmPC lists haemolytic anaemia in the adverse reactions. [1][2][3][4]

Population evidence

Tier B case reports with cephalexin as the suspect drug: an 85-year-old woman with hemoglobin 15.1 g/dL falling to 4.7 g/dL within three days, direct antiglobulin test positive for IgG and C3 (negative five months later), treated with transfusion, immunoglobulin and prednisone (Cureus 2026); a 48-year-old woman with hemolysis and acute kidney injury needing hemodialysis, full renal recovery in four weeks (Cureus 2025); a woman in her late fifties with acute renal failure needing emergency dialysis after one dose (BMJ Case Rep 2025); further reports from 2017, 2015 and 1987. These are listing-level summaries; the abstracts were not opened. [21] No cohort, incidence or hemoglobin-change study with cephalexin was found.

Mechanism

Named in outline: drug-dependent antibody (IgG and complement, C3) binding to red cells with extravascular or intravascular destruction; kidney injury in some reports follows pigment (hemoglobin cast) injury. Not studied beyond case reports. [21]

Counter-evidence held on record

Boundary and why not higher Orange would need either a label or cohort incidence figure or a measured hemoglobin change in cephalexin users; neither was found. Anemia is an outcome here and is never filed as a nutrient finding. Framing caution Hemolysis is an uncommon allergic-type reaction to a drug. It says nothing about iron, B12 or any nutrient intake, and no supplement is indicated.

Limits on what this shows

• Negative or null findings: In vivo respiration unchanged; fatty-acid substrate respiration stimulated in vivo. [22]
• At-risk subgroups: Not defined.
• Counter-evidence on record: Not applicable beyond the null surrogate result.

Direction

Neutral by surrogate, with a mild in vitro respiratory reduction at high concentration. Not a nutrient deficiency.

Regulatory status

Not addressed in any label opened.

Population evidence

None in humans. The surrogate data are the same rabbit studies as the mitochondrial burden entry; none of the listing lines reported ATP content or membrane potential for cephalexin. [22] A dedicated PubMed query "cefalexin adenosine triphosphate" returned a single bacterial cell-division paper in which cephalexin was only a comparator for blocking septal peptidoglycan synthesis in E. coli (PMID 32636250; abstract-level, no ATP measurement); the phrasing "cephalexin ATP oxidative phosphorylation" was rate limited and not retrieved.

Mechanism

Absent for cephalexin in the evidence read; the toxic-cephalosporin mechanism (substrate uptake inhibition) would lower respiration, not directly ATP.

Counter-evidence held on record

Boundary and overlap This entry shares its entire evidence base with mitochondrial burden (see the overlap map) and is not an independent confirmation. It is graded yellow rather than ungraded only because a respiration surrogate exists with cephalexin itself. Framing caution No evidence of lower energy output from cephalexin in people; the claim "antibiotics lower your energy" has no cephalexin-specific support.