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MyDeficiencies

Guaifenesin

expectorant (oral, OTC)

Also sold as Mucinex, C'rcle.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Guaifenesin has no classical nutrient-depletion machinery in any source retrieved. It is absorbed from the gut, mostly converted in the liver (O-demethylation and oxidation to beta-(2-methoxyphenoxy)lactic acid), has a plasma half-life of about 1 hour, and leaves in urine as inactive metabolites with no unchanged drug [3]. The US OTC label read for this review names no nutrient, no enzyme induction or inhibition and no drug interaction [1]. No source retrieved measured a vitamin or mineral in guaifenesin users, so red and orange are empty and the literature is thin rather than reassuring.

expectorant (oral, OTC) · ATC R05CA03 (WHO ATC code as shown on Wikipedia [4]; WHO index not opened) · also sold as Mucinex and Robitussin (as DM and other combinations) and C'rcle and store brands · reviewed 2026-10-08. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Guaifenesin in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Uric acid and urinary effects: non-nutrient pharmacologic effect and high-dose toxicity

Yellow — Low

See study details

Guaifenesin lowers serum uric acid by a renal route in humans and, at very high or chronic doses, can precipitate as metabolite crystals in the urinary tract; uric acid is a metabolite, not a nutrient, so neither finding is a nutrient deficiency.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: Neither case-report PDF [8][9] reports any link to uric acid; Cockerill states no uricosuric content and measured no urate. No source linked urate lowering to a clinical harm.
  • At-risk subgroups: For stones: people taking large or chronic doses, misuse with dextromethorphan or ephedrine, low fluid intake, prior stone history [8][9][10]. For urate: not defined in sources retrieved.

Direction

Pharmacologic effect (urate lowering through renal handling) and drug toxicity (metabolite stones). Not depletion, retention or excess of any nutrient. No supplement is implied in either direction.

Regulatory status

The US OTC label read [1] and MedlinePlus [2] state nothing about uric acid, urate or kidney stones; MedlinePlus advises drinking plenty of fluids [2]. The label gives a maximum of 2,400 mg per 24 hours for adults [1]. The PubChem/HSDB excerpts returned no uric acid toxicity information (summarizer statement) [3].

Population evidence, urate

Ramsdell and Kelley 1973 [5]: 6,629 consecutive serum urate measurements at two large hospitals; hypouricemia (below 2 mg/100 mL) in 0.97%. In about two thirds of those patients drugs appeared responsible, listed as aspirin, allopurinol, X-ray contrast agents and glyceryl guaiacolate; altered renal tubular handling of uric acid seemed the cause in many; poor dietary protein and purine intake and hypo-osmolality were also common. The number of guaifenesin users, the urate values and any confidence interval were not retrievable (abstract only, via a reconstructed OpenAlex record read through a summarizing fetch tool). Ramsdell, Postlethwaite and Kelley 1974 [6]: a controlled clinical trial with placebo in male gout patients, with urate measured in blood and urine (record type and subject headings only; no abstract in PubMed or OpenAlex, so sample size, dose and effect size are not retrieved). Matheson et al. 1982 [7]: a study of acute guaifenesin administration and serum uric acid over time (record headings and reference list only; abstract absent; the SAGE page is restricted access), so the direction and size in that study are not retrieved. Repair pass: the PubMed records for PMIDs 4617771, 7067625 and 5130709 were re-fetched in one combined query and show subject headings only (4617771: Clinical Trials as Topic, Gout/drug therapy, Uricosuric Agents/therapeutic use; 7067625: Guaifenesin/adverse effects, Uric Acid/blood), with no abstract; the OpenAlex records for 4617771 and 7067625 also have a null abstract [23]. OpenAlex lists 13 works citing 4617771, but the cited-by listing could not be fetched, so no secondary report of the effect size was obtained.

Population evidence, urinary

Case reports only. Nguyen 2005 [9]: a 38-year-old man taking at least 12 OTC tablets daily (2,400 mg per day) with low fluid intake had a 9 by 6 mm ureteral stone on CT; the stone was never analysed, a prior stone had been identified as guaifenesin metabolites with trace ephedrine, and the stone was gone on CT 3 weeks later after stenting and hydration. Cockerill 2013 [8]: a 23-year-old who took about 6 g of guaifenesin once (10 tablets of a 600 mg guaifenesin with dextromethorphan product) developed acute bilateral ureteral obstruction from sludging of guaifenesin metabolites; creatinine 2.5 mg/dL on arrival and 1.2 mg/dL at follow-up; the article reports no serum or urine uric acid and no urinary pH. Kim 2023 [10]: misuse of guaifenesin with dextromethorphan led to acute renal failure from bilateral nephrolithiasis, with new small stones after stenting. Kolbach-Mandel 2017 [11]: one patient's stone-like urine sediment was about 60% protein and 40% guaifenesin plus its metabolite guaiacol; 156 proteins identified. Secondhand through [8]: Assimos et al. (7 patients taking 10 to 20 g per day, stones about 70% guaifenesin metabolites) and Pickens et al. (27 of 30 stones were 100% MPLA); neither primary was opened. A review is cited as saying ephedrine plus guaifenesin accounts for over 35% of drug-metabolite stones (secondhand via HSDB, not opened) [3].

Mechanism

Urate: altered renal tubular handling is stated in the 1973 abstract for the drug group as a whole; no transporter or guaifenesin-specific mechanism was retrieved. Stones: poor solubility of the metabolite MPLA at high urinary load plus dehydration, per the case authors [8][9]. These are metabolite stones, not uric acid stones.

Counter-evidence held on record

Counter-evidence and confounding The 1973 survey was hospital-based and multi-cause (disseminated cancer, liver disease, other drugs, low protein intake), so guaifenesin's share is unknown. Stone cases involve doses at or above the label maximum, co-ingestants and dehydration, and one stone was never analysed. The urate evidence base (1973 to 1982) is old and not replicated in any retrieved modern cohort. Framing caution Do not present this as a nutrient deficiency or as a reason to add or avoid any supplement. It is a laboratory-interpretation and high-dose safety note only.

Dietary intake (nausea and appetite)

Not graded — disclosed evidence gap

See study details

Nausea and vomiting are listed as uncommon adverse effects, but no study linked them to reduced intake of any nutrient.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: the mechanism class (changed intake) is present only as a low-frequency side effect with no nutrient implicated, so no Tier B or C evidence supports a nutrient entry, and no circulating claim exists. Disclosed gap.

What was searched

Label [1] and MedlinePlus [2] read: MedlinePlus lists headache, nausea and vomiting and advises continuing the normal diet; the AMA Drug Evaluations 1977 excerpt (via HSDB) says nausea and drowsiness may occur rarely [3]. The 1973 hypouricemia survey noted poor dietary protein and purine intake as a common co-factor in hypouricemic patients [5], which is a confounder of the urate entry, not evidence of a guaifenesin effect on intake. Repair pass: PubMed export listing "guaifenesin AND (appetite OR nausea OR vomiting OR nutrition)" returned 13 records (first 10 read) [21]. Relevant human items: PMID 22895922 (2012 review of OTC cough medicines; nausea and vomiting listed among minor adverse effects at low incidence), PMID 18654069 (2008 randomized placebo-controlled trial of guaifenesin with pseudoephedrine; nausea 2.3% among the commonest treatment-related adverse effects, combination product so not attributable to guaifenesin alone) and PMID 15243011 (2004 dysmenorrhea trial; nausea one of ten symptoms scored, no separate result). No record measured appetite, food intake or any nutrient intake. Abstract-level summaries only.

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. Appetite, nausea, vomiting and nutrition were run on PubMed. Nausea is a documented low-frequency adverse effect, but no intake outcome was found. Genuine gap on the phrasings tried.

Directly measured vitamin and mineral status

Not graded — disclosed evidence gap

See study details

No study retrieved measured a vitamin, mineral or electrolyte in guaifenesin users, apart from urate and creatinine in case reports.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C nutrient-status evidence, and no circulating depletion claim was located. This entry holds the place for classical nutrients; it is not a finding of safety.

What was searched

Label [1], MedlinePlus [2] and the PubChem excerpts [3]: no nutrient statements (the granule magnesium-diet caution is a formulation note). Web search "guaifenesin nutrient depletion vitamin mineral deficiency" returned patient information pages in several languages and an herbal-interaction page (not opened), none documenting a depletion. PubMed "glyceryl guaiacolate" visible titles included no nutrient-status study. Case reports [8][9] measured creatinine only. A 2024 commentary [19] reports no nutrient or adverse-effect data. Repair pass: PubMed export listing "guaifenesin AND (deficiency OR vitamin OR magnesium OR zinc OR serum electrolytes)" returned 27 records (first 10 read) [21]; none measured a nutrient or electrolyte in guaifenesin users. Closest items: PMID 33206684 (Indonesian infant cohort in which vitamins and zinc are co-used medicines, with no serum levels) and PMID 25170357 (fibromyalgia supplement-use survey: guaifenesin ever-used by 11.5%, magnesium by 19.2%, no level measured). The other items were analytical chemistry, veterinary or non-nutrient clinical records.

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. The remaining 1,023 results of the PubMed "glyceryl guaiacolate" listing and the unread 17 records of the repair query were not visible. Genuine gap on what was read; partly tooling-limited for the unread records.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden

Not graded — disclosed evidence gap

See study details

No guaifenesin-specific evidence on mitochondrial structure, electron transport or biogenesis was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source supports even a yellow grade, and no circulating consumer claim of guaifenesin mitochondrial damage was found. A disclosed gap, not a finding of safety.

What was searched

Web search "guaifenesin oxidative stress OR mitochondrial OR antioxidant study cells" (generic patents and oxidative-stress papers, none on guaifenesin). PubMed listing "guaifenesin mitochondria" returned a 404 page with no list, so it is unconfirmed whether it was a zero-result page. PubMed listing "glyceryl guaiacolate" (1,070 results; 47 titles visible) contained no mitochondrial title. Repair pass: PubMed export listing "guaifenesin AND (mitochondria OR mitochondrial)" returned 1 record (PMID 23597204, a 2013 review of herb-induced nephrotoxicity); its abstract mentions guaifenesin only as a stone-forming agent after abuse, and the mitochondrial ATP synthesis inhibition it reports belongs to a different compound (carboxyatractyloside). The broader listing "guaifenesin AND (mitochondria OR mitochondrial OR respiration)" returned 67 records; the first 10 (horse, donkey and calf anaesthesia papers, a 1977 cough review, the same 2013 review) reported no mitochondrial outcome for guaifenesin. The listing "guaifenesin AND (antioxidant OR glutathione OR oxidative)" (94 records, first 10 read) also held no mitochondrial finding [21]. These are abstract-level summaries; no full text was opened.

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. The earlier 404 on "guaifenesin mitochondria" is superseded by a clean PubMed result. Assessment: a near-zero result on a working PubMed channel with two phrasings, plus a clean zero on the original open web search. Largely a genuine gap; the unread 66 records of the broad query are mostly veterinary anaesthesia and are not expected to hold a mitochondrial study.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress

Not graded — disclosed evidence gap

See study details

No evidence on systemic or tissue redox markers or antioxidant capacity in guaifenesin users was retrieved.

Full detail, limits and 1 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source supports a signal in either direction, and no circulating oxidative-stress or antioxidant-depletion claim for guaifenesin was found. The Tier B source [20] is a null chemistry measurement (the drug itself does not scavenge radicals in the TEAC assay); it does not measure oxidative stress in drug users, shows no pro-oxidant effect and so gives no basis for even a yellow flag. It is recorded here as the only drug-specific redox datum. A disclosed gap, not reassurance. Do not infer redox effects from the guaiacol chemical class; no source supporting that was retrieved.

What was searched

Web search as for Mitochondrial burden (ROS, antioxidant terms). PubMed listing "guaifenesin oxidative stress" returned 2 records, both HPLC stability-method papers for related compounds (PMID 33395699 and 23781462, titles only, not opened; one is for methocarbamol), neither a redox study. Repair pass: PubMed export listing "guaifenesin AND (antioxidant OR glutathione OR oxidative)" returned 94 records; the first 10 were read [21]. One is a drug-specific measurement: Seagrave et al. 2012, Respir Res 13:98 (PMID 23113953), opened on the BioMed Central page [20]. In primary differentiated human airway cells, the authors ran a Trolox equivalent antioxidant capacity (TEAC) assay on the drugs themselves. Reported slopes: N-acetylcysteine -0.316 against Trolox -0.155 (about twice Trolox), guaifenesin 0.032 and ambroxol 0.025, both described as having no evident antioxidant capacity; the abstract states that only N-acetylcysteine exhibited antioxidant capacity. The cell experiments used 10 to 300 micromolar and viability was unaffected. The other 9 records were anaesthesia, chemistry, mucus reviews or non-guaifenesin records.

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. The two original PubMed hits are analytical chemistry. The new antioxidant, glutathione and oxidative phrasing was run on PubMed; MDA and SOD terms were not run separately. Largely a genuine gap on the phrasings tried.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No evidence on guaifenesin and copper status, absorption, chelation or ceruloplasmin was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C copper source and no circulating copper claim for guaifenesin. Disclosed gap.

What was searched

PubMed listing "guaifenesin copper" returned 2 records: a 2014 spectroscopy study of a methocarbamol degradation product complexed with copper(II) (PMID 24674917) and a 1986 paper on oxidation of lignin model compounds by inorganic complexes (PMID 3767993). Both are titles only, not opened, and neither is a human or guaifenesin copper-status study. Web search "guaifenesin nutrient depletion vitamin mineral deficiency" returned patient information pages only. Repair pass: PubMed export listing "guaifenesin AND (ceruloplasmin OR copper OR iron OR ferritin OR transferrin)" returned 4 records, the same four seen before, now read at abstract-summary level: PMID 24674917 (methocarbamol degradation product trapped by copper(II), a chemistry study in which guaifenesin is a decomposition product, not a status study), PMID 3767993 (copper peroxydisulfate as an oxidant for lignin model compounds), PMID 41545455 and PMID 9063550 (no copper content). No ceruloplasmin or serum copper record appeared [21].

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. Kept independent of Iron (Hard Rule 7). Ceruloplasmin and serum copper terms were run on PubMed with a clean negative; Wilson-disease phrasing was not run. Genuine gap on the phrasings tried.

Iron

Not graded — disclosed evidence gap

See study details

No evidence on guaifenesin and iron absorption, ferritin or iron deficiency was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C iron source and no circulating iron claim for guaifenesin. Anemia would be an outcome, not iron deficiency. Disclosed gap.

What was searched

PubMed listing "guaifenesin iron" returned 2 records: a 2026 electrochemical sensor paper for oxeladin citrate in mixtures with guaifenesin (PMID 41545455) and a 1997 survey of adolescents on OTC drug toxicity knowledge (PMID 9063550). Titles only, not opened, no iron-status content. Web search for depletion claims found none. Repair pass: the combined listing "guaifenesin AND (ceruloplasmin OR copper OR iron OR ferritin OR transferrin)" returned the same 4 non-status records (iron appears only as an electrode material and as a perceived-lethality survey item). The listing "guaifenesin AND (hemoglobin OR methemoglobin OR ferritin OR anemia OR hemolysis)" returned 24 records; the first 10 were read and none reported iron, ferritin or hemoglobin status in guaifenesin users (they are horse, cattle, bear and mule anaesthesia papers, a methocarbamol hemolysis study and an in vitro albumin and hemoglobin binding study) [21].

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. Kept independent of Copper (Hard Rule 7). Ferritin, transferrin and anemia terms were run on PubMed with no iron-status hit. Genuine gap on the phrasings tried.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Not graded — disclosed evidence gap

See study details

No evidence on guaifenesin and gut microbiota composition, diversity or function was retrieved.

Full detail, limits and 1 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C evidence for human gut effects and no circulating microbiome claim. Disclosed gap. The environmental paper is not a gut-microbiome source and was not graded.

What was searched

Web search "guaifenesin gut microbiome OR fecal microbiota OR dysbiosis" (generic microbiome reviews, none on guaifenesin). PubMed listing "guaifenesin microbiota" returned 1 record: a 2019 paper on pharmaceuticals transformed by anaerobic microbiomes in the environment (PMID 30883883; title only, not opened; environmental, not human gut). Repair pass: PubMed export listing "guaifenesin AND (microbiome OR dysbiosis OR feces OR intestinal flora)" returned 3 records [21]. PMID 30883883 (2019) reports that anaerobic environmental microbial consortia O-demethylated guaifenesin to a novel metabolite (abstract-level summary); this is microbes acting on the drug, outside the human gut, and is not a depletion mechanism (Hard Rule 4 direction). PMID 5548215 (1971, methocarbamol metabolism in rat, dog and human) is not about guaifenesin. PMID 989543 (Brown, JAMA 1976) tests guaifenesin against the guaiac stool occult blood test, a laboratory interference question [22], not a microbiome study.

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. Microbiome, dysbiosis, feces and intestinal flora were run on PubMed (3 records, none a human gut study); 16S and C. difficile phrasings were run on the original web search only. Genuine gap on the phrasings tried.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization: animal red-cell data and in vitro hemoglobin binding only, route not applicable to oral use

Yellow — Low

See study details

Animal studies with this drug touched red blood cells or arterial oxygenation (rat osmotic fragility, horse and cattle haemolysis with concentrated intravenous solutions, transient hypoxaemia in horses) and one in vitro study showed guaifenesin binding human hemoglobin; no human in vivo hemoglobin, hematocrit or oxygenation data were found for oral guaifenesin.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: A PubMed listing for "guaifenesin anemia" returned only the 1971 rat study [18]. Searches for methemoglobin and hemoglobin in humans returned no guaifenesin-specific case or trial (web search) or were rate limited (PubMed "guaifenesin hemoglobin" and "guaifenesin methemoglobin" returned 429). Repair pass: the listing "guaifenesin AND (hemoglobin OR methemoglobin OR ferritin OR anemia OR hemolysis)" returned 24 records and the first 10 held no human in vivo hemoglobin, hematocrit or methemoglobin outcome for guaifenesin; the one human-subject hemolysis record in the list (PMID 837639, 1977) concerned methocarbamol, not guaifenesin, so it fails the cohort test.
  • At-risk subgroups: None defined for oral use.

Direction

Not a nutrient. A possible red-cell hazard under veterinary intravenous exposure. No deficiency or excess is claimed.

Regulatory status

The OTC label [1] and MedlinePlus [2] mention no blood effects.

Population evidence

None in humans. Giri 1971 [16]: rat study of glyceryl guaiacolate ether and erythrocyte osmotic fragility (Life Sciences 10:1059 to 1063); no abstract exists in OpenAlex or Crossref, so the direction and size of the effect are not known. Schatzmann et al. 1978 [17]: horses given glyceryl guaiacolate by rapid intravenous infusion as a casting agent; higher concentrations caused transient mild hypoxaemia and, in two cases, aseptic jugular thrombosis; haemolysis occurred only with unstabilised solutions, with a threshold between 16% and 20% (abstract only, via OpenAlex and a summarizing fetch tool). Repair pass, abstract-level summaries from PubMed export listings, full texts not opened [21]: Giri 1971 [16] PubMed indexing terms include Anemia, Hemolytic/etiology, Hemolysis and Osmotic Fragility/drug effects (direction still not stated; abstract absent from PubMed on re-fetch). Cattle (PMID 2318045, 1990): hemolysis depended on concentration, diluent and plasma level, with 5% in 5% dextrose most suitable. Horse (PMID 6989792, 1980): a 10% solution in sterile water was judged most suitable, with no clinically significant hemolysis. Horse (PMID 7212404, 1980): intravenous guaifenesin lowered arterial pressure and transiently reduced arterial oxygen tension. Donkeys (PMID 24961870, 2014, crossover, 8 animals): both anaesthesia protocols, one of them guaifenesin-ketamine-xylazine, caused significant hypoxaemia; guaifenesin was part of a combination, so the effect is not attributable to it. Human in vitro (PMID 23471625, 2013): guaifenesin and metoprolol each bound human serum albumin and hemoglobin at about one site and altered protein secondary structure; no oxygen affinity or oxygen delivery measurement was reported in the summary.

Mechanism

Present at a membrane level for concentrated intravenous exposure; not established for oral human exposure. In vitro hemoglobin binding is a physicochemical observation, not a demonstrated change in oxygen carriage.

Counter-evidence held on record

Counter-evidence and confounding The horse data are an anaesthesia-adjunct setting with different species, route, concentration and co-drugs, so they cannot be extrapolated to oral OTC dosing. Anemia or hemolysis would be a clinical outcome, not a nutrient (Hard Rule 2). Kept independent of ATP production (Hard Rule 7). Framing caution This is a disclosed animal-only flag, not a statement about oral guaifenesin and oxygen-carrying capacity in people.

ATP production

Not graded — disclosed evidence gap

See study details

No evidence on guaifenesin and mitochondrial ATP synthesis or cellular energy output was retrieved.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source supports a grade and no circulating "low energy" claim for guaifenesin was found. Disclosed gap.

What was searched

PubMed listing "guaifenesin ATP" returned 1 record, a 2013 review of herb-induced nephrotoxicity (PMID 23597204, title only, not opened, not a guaifenesin study). A PubMed listing summary of a horse study (PMID 28404362; guaifenesin used only for anaesthetic induction with propofol and ketamine, detomidine as the studied drug, post-anaesthesia fall in muscle energy stores) was seen but not opened and is confounded by the anaesthetic regimen, so it was not used. Repair pass: PubMed export listing "guaifenesin AND (ATP OR adenosine triphosphate OR phosphorylation)" returned 1 record, again PMID 23597204 (a 2013 herb nephrotoxicity review whose only ATP content concerns carboxyatractyloside, not guaifenesin); "guaifenesin AND (mitochondria OR mitochondrial)" returned the same single record; the 67-record respiration query (first 10 read) held equine, donkey and calf cardiopulmonary papers with no cellular energy outcome [21].

Channel outcomes

Original review: web search budget exhausted partway, PubMed listing fetches intermittently 429, Europe PMC and Semantic Scholar 429, OpenAlex listing queries 429. Repair pass 2026-10-08: web search was still unavailable (budget used up), Europe PMC returned 429 again, and PubMed export-format listings (?term=...&format=pubmed, read through a summarizing fetch tool) were run one at a time, 3 to 5 minutes apart; a query with six OR terms or bracketed field tags returned the PubMed home page and was discarded; direct database APIs were not routed around. Kept independent of Mitochondrial burden and Oxygen delivery/utilization (Hard Rule 7). ATP, adenosine triphosphate, phosphorylation and respiration phrasings were run on PubMed; membrane-potential phrasing was not. Largely a genuine gap; the shared search record with Mitochondrial burden is a shared gap, not shared evidence.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • None located

    Where it comes from: Consumer depletion lists were searched with "guaifenesin nutrient depletion vitamin mineral deficiency" and the seven category phrasings. Results were patient information pages (several languages), generic reviews and patents; none asserted a guaifenesin-specific nutrient depletion that was read.

    Why it fails: No claim to rebut. This is a documented null, not a white entry, and nothing here is counted in the chip. A hit for a carob-guaifenesin interaction page appeared in the results but was not opened and is a herb-drug interaction claim, not a nutrient depletion. Web search budget was then exhausted, so a Tier D depletion-handbook page could exist and was not seen.

How the body handles this medication

Absorption
Readily absorbed from the gastrointestinal tract. No named absorption transporter was found. The OTC label allows dosing regardless of meals, with a full glass of water.[1][3] DailyMed C'rcle label; PubChem record (Micromedex excerpt via summarizer)
Metabolism and enzymes
After a 400 mg oral dose, over 60% is hydrolysed within about 7 hours. Hepatic oxidation gives beta-(2-methoxyphenoxy)lactic acid (MPLA), the major urinary metabolite; microsomal O-demethylase gives a demethylated metabolite (about 40% of the dose in urine within 3 hours). Both are described as inactive. No CYP450 isoform, induction or inhibition is named in the sources read. Barbiturate enzyme induction shortens the half-life.[3] DrugBank, HSDB and T3DB excerpts via PubChem (summarized by the fetch tool); label [1] lists no interactions
Elimination and kinetics
Renal, as inactive metabolites (glucuronides and sulfates per an older source); no parent drug in urine. Plasma half-life about 1 hour. Geometric mean volume of distribution 116 L and clearance about 94.8 L/h in healthy adults.[3] PubChem record
Renal tubular handling
Sources do not describe tubular handling of water or electrolytes. A 1973 hospital survey reported altered renal tubular handling of uric acid as the apparent cause of hypouricemia in drug-associated cases, including glyceryl guaiacolate [5]. No transporter was identified in sources retrieved.[5] Ramsdell and Kelley 1973 (abstract via OpenAlex, summarized)
Renal and hepatic impairment
No accumulation data were found in the label read or the other sources. Gap, not a finding of safety.[1][3]
Food, mineral and laboratory interactions
No food, antacid or mineral interaction is stated on the label read [1]. A dissolving-granule product carries a low-magnesium-diet caution on MedlinePlus, which concerns the formulation [2]. Laboratory interference: a metabolite falsely raises urinary 5-HIAA [12][14]; Brazilian leaflets add false VMA elevation, with discontinuation 48 hours before urine collection [13].[1][2][12][13][14]

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Laboratory interference

    Urinary 5-HIAA and VMA tests

    A guaifenesin metabolite falsely raises urinary 5-HIAA, a carcinoid-syndrome marker; the 1970 JAMA note advised stopping 24 hours before the 24-hour collection [12], and a laboratory test catalog lists guaifenesin cough syrup among items to avoid [14]. Brazilian leaflets state false elevation of VMA, with discontinuation 48 hours before urine collection [13]. The Mayo Clinic Laboratories VMA page lists L-dopa and trimethoprim-sulfamethoxazole but not guaifenesin [15]. A 1976 JAMA study examined whether guaifenesin causes false-positive guaiac stool occult blood tests in 31 healthy volunteers; the result was not retrieved [22]. Tell the ordering clinician and laboratory about guaifenesin use before these tests. This is a test artifact, not a nutrient effect.

  • Laboratory interpretation

    Unexplained low serum urate

    Guaifenesin has been listed among drugs associated with low serum urate [5]. Where urate is unexpectedly low, a medication history that includes cough and cold products is reasonable context. No threshold or action level comes from these sources.

  • Safety / renal

    High-dose and misuse exposure

    Case reports link a single 6 g dose, chronic 2,400 mg per day with low fluid intake, and misuse with dextromethorphan to ureteral sludging or stones [8][9][10]. The OTC label maximum is 2,400 mg per 24 hours and says to swallow tablets with a full glass of water [1]. Flank pain, blood in urine or reduced urine output in a heavy user warrants medical review.

  • Nutrient labs

    No routine nutrient panel indicated

    No source retrieved shows a nutrient change that would justify routine vitamin or mineral monitoring for guaifenesin alone. Nutrient status testing should follow the person's other drugs and conditions. Combination cough products add other active ingredients (dextromethorphan, ephedrine, pseudoephedrine) that need their own review.

  • Special populations

    Pregnancy, children, formulation

    The label read says not to use under age 12 and to ask a health professional if pregnant or breastfeeding [1]. A first-trimester exposure study of 197 mother-child pairs reported more inguinal hernias in neonates, with congenital defects not strongly associated (Micromedex excerpt via HSDB, secondhand) [3]. A dissolving-granule product carries a low-magnesium-diet and kidney-disease caution [2]. No supplement separation interval applies; no supplement dose appears in this dossier.

Overlap map, to prevent double counting

Entries that rest on the same source or mechanism.

  • Uric acid and urinary effects

    Shares evidence with: Dietary intake (nausea and appetite)

    Note: The 1973 survey [5] supplies both the urate finding and the observation that low protein and purine intake co-occurred with hypouricemia. One source, counted once.

  • Uric acid and urinary effects

    Shares evidence with: Directly measured vitamin and mineral status

    Note: The urinary case reports [8][9] provide the only measured values (creatinine) and are used only in the urinary entry.

  • Oxygen delivery/utilization

    Shares evidence with: None

    Note: Rests on animal studies [16][17] and PubMed abstract-level records [21] (cattle, horse, donkey, in vitro hemoglobin binding) used nowhere else. The haemolysis and hypoxaemia records come from veterinary anaesthesia settings and are one family of evidence, not independent confirmations. Independent of ATP production and Mitochondrial burden.

  • Mitochondrial burden, Oxidative stress, ATP production, Copper, Iron, Gut microbiome risk

    Shares evidence with: None

    Note: All ungraded on the same empty PubMed and web-search channels; the shared search record is a shared gap, not shared evidence. PMID 23597204 is the single PubMed hit for both Mitochondrial burden and ATP production and is a non-guaifenesin finding in both. The Oxidative stress null [20] is used only in that entry.

All references used above
  1. C'rcle Guaifenesin Extended-Release Tablets 600 mg and 1200 mg, DailyMed label (Innovus Pharmaceuticals; label updated April 8, 2023). — Regulatory label (Tier A), OTC. Read through a summarizing fetch tool. Used for uses, warnings, directions, maximum daily dose and the absence of a drug-interaction or nutrient section. A second label (365 Whole Foods Market) was listed but not opened.
  2. MedlinePlus. Guaifenesin drug information. — Established drug reference (Tier B). Side effects (headache, nausea, vomiting), diet and fluids advice, granule magnesium caution. Read through a summarizing fetch tool.
  3. PubChem compound record for guaifenesin (CID 3516), PUG-View sections Pharmacology and Biochemistry, Metabolism/Metabolites, Human Toxicity Excerpts, Interactions. — Aggregator of DrugBank, HSDB and T3DB excerpts (Tier B at best). Read through a summarizing fetch tool; excerpts attribute to Micromedex, AMA Drug Evaluations 1977, Bennett 2004 and Nguyen 2005. Those primaries were not all opened.
  4. Wikipedia. Guaifenesin. — Tier D for evidence; used only for the ATC code R05CA03, brand names and as a reference-list pointer. WHO ATC/DDD Index itself was not opened.
  5. Ramsdell CM, Kelley WN. The clinical significance of hypouricemia. Ann Intern Med 1973;78(2):239-242. PMID 4683752. DOI 10.7326/0003-4819-78-2-239. — Observational survey, 6,629 consecutive serum urate measurements at two hospitals (Tier A for the drug-class finding; guaifenesin n not retrieved). Abstract only, reconstructed from OpenAlex and paraphrased by the fetch tool; full text not opened.
  6. Ramsdell CM, Postlethwaite AE, Kelley WN. Uricosuric effect of glyceryl guaiacolate. J Rheumatol 1974;1(1):114-116. PMID 4617771. — Controlled clinical trial with placebo in gout (from PubMed publication types and headings). Record metadata only; no abstract in PubMed or OpenAlex; full text not opened.Effect size, sample size and dose not retrieved. A jrheum.org page guess returned 404.
  7. Matheson CE, Murphy JE, Gibson SH, Moffitt S. The effect of acute guaifenesin administration on serum uric acid. Drug Intell Clin Pharm 1982;16(4):332-334. PMID 7067625. DOI 10.1177/106002808201600414. — Human study (design and size not retrieved). PubMed record (headings: Guaifenesin/adverse effects, Uric Acid/blood, Time Factors) and Crossref reference list read. No abstract in any record.SAGE full text is restricted access; direction and size of the uric acid effect not retrieved.
  8. Cockerill PA, de Cogain MR, Krambeck AE. Acute bilateral ureteral obstruction secondary to guaifenesin toxicity. Can J Urol 2013;20(5):6971-6973. PMID 24128843. — Case report (Tier B). PDF opened through a summarizing fetch tool and abstract read via OpenAlex.
  9. Nguyen, Fallon and Winfield. Case report of a ureteral stone in a patient taking guaifenesin 2,400 mg per day. Can J Urol 2005;12(4):2769-2771. PMID 16197601. — Case report (Tier B). PDF opened through a summarizing fetch tool. The article title and author initials were not retrieved; authors and citation are taken from the HSDB excerpt and the PDF file name, so verify against the journal.
  10. Kim E, Perlmutter MC, Zweber H, Resch JC. Bilateral nephrolithiasis following ingestion of guaifenesin and dextromethorphan. Urol Case Rep 2023;50:102481. DOI 10.1016/j.eucr.2023.102481. — Case report (Tier B). Abstract only, reconstructed from OpenAlex.
  11. Kolbach-Mandel AM, Mandel NS, Cohen SR, Kleinman JG, Ahmed F, Mandel IC, Wesson JA. Guaifenesin stone matrix proteomics: a protocol for identifying proteins critical to stone formation. Urolithiasis 2017;45(2):139-149. DOI 10.1007/s00240-016-0907-4. — Single-patient protocol study (Tier B). Abstract read on the Springer page via a summarizing fetch tool; full text not opened.
  12. Pedersen AT. False-positive tests for urinary 5-hydroxyindoleacetic acid. JAMA 1970;211(7):1184. PMID 5466975. DOI 10.1001/jama.1970.03170070054016. — Laboratory note (Tier B). Abstract reconstructed from OpenAlex and paraphrased by the fetch tool; full text not opened.
  13. bula.com.br. Guaifenesina EMS and Expectoflui, interacao medicamentosa pages (Brazilian leaflet text). — Regulatory leaflet text reproduced by a commercial aggregator (Tier A-equivalent only if it matches the ANVISA original, which was not opened). Source of the VMA false-elevation statement and 48-hour discontinuation advice. Portuguese text read through a summarizing fetch tool.A US-source statement on VMA interference was not found. Secondary source.
  14. National Reference Laboratory test catalog file (5-HIAA patient preparation text). — Laboratory catalog (Tier B/D for evidence). States that L-dopa, acetaminophen, salicylates and cough syrup containing guaifenesin must be avoided for the 5-HIAA test. Read through a summarizing fetch tool.
  15. Mayo Clinic Laboratories VMA random urine test page; ARUP hotline note 3018863. — Opened as counter-checks. Neither mentions guaifenesin (the Mayo page lists L-dopa and trimethoprim-sulfamethoxazole). Null result for US VMA interference.
  16. Giri SN. The influence of glyceryl guaiacolate ether on the osmotic fragility of erythrocytes in rats. Life Sci II 1971;10(18):1059-1063. PMID 5130709. DOI 10.1016/0024-3205(71)90300-6. — Animal study (Tier B). Metadata only from OpenAlex and Crossref; neither has an abstract.Direction and size of effect not retrieved.
  17. Schatzmann U, Tschudi P, Held JP, Muhlebach B. An investigation of the action and haemolytic effect of glyceryl guaiacolate in the horse. Equine Vet J 1978;10(4):224-228. PMID 33040. DOI 10.1111/j.2042-3306.1978.tb02266.x. — Animal study (Tier B). Abstract only, via OpenAlex and a summarizing fetch tool.
  18. PubMed search-listing pages retrieved 2026-10-08: "glyceryl guaiacolate" (1,070 results, 47 titles visible), "guaifenesin uric acid", "guaifenesin oxidative stress", "guaifenesin microbiota", "guaifenesin anemia", "guaifenesin iron", "guaifenesin copper", "guaifenesin ATP". — Title lists only, read through a summarizing fetch tool. Records seen only as titles are not cited as evidence: PMIDs 33395699, 23781462, 30883883, 41545455, 9063550, 24674917, 3767993, 23597204, 28404362, 38227627, 4638115, 5056642, 5766107. The "guaifenesin mitochondria" listing returned 404.Boolean combined queries returned the PubMed home page; PubMed "guaifenesin hemoglobin", "guaifenesin methemoglobin" and "guaifenesin hypouricemia" were rate limited (429) and not retrieved.
  19. Eyassu DG, McCoul ED. Guaifenesin: the ubiquitous orphan. Otolaryngol Head Neck Surg 2024;171(4):1260-1261. PMID 38804670. DOI 10.1002/ohn.834. — Commentary (Tier C context). Abstract only via OpenAlex; it reports no adverse-effect or nutrient data and was used only to confirm the literature is sparse on safety detail.
  20. Seagrave J, Albrecht HH, Hill DB, Rogers DF, Solomon G. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells. Respir Res 2012;13:98. PMID 23113953. DOI 10.1186/1465-9921-13-98. — In vitro study with guaifenesin as a studied agent (Tier B). Opened on the BioMed Central page through a summarizing fetch tool. Used only for the Trolox equivalent antioxidant capacity result (guaifenesin slope 0.032, no evident antioxidant capacity; N-acetylcysteine -0.316; Trolox -0.155). Not a human oxidative stress study.
  21. PubMed export-format listings (?term=...&format=pubmed) run 2026-10-08 in the repair pass: "guaifenesin AND (mitochondria OR mitochondrial)" (1 record), "... OR respiration" (67), "guaifenesin AND (antioxidant OR glutathione OR oxidative)" (94), "guaifenesin AND (hemoglobin OR methemoglobin OR ferritin OR anemia OR hemolysis)" (24), "guaifenesin AND (deficiency OR vitamin OR magnesium OR zinc OR serum electrolytes)" (27), "guaifenesin AND (microbiome OR dysbiosis OR feces OR intestinal flora)" (3), "guaifenesin AND (ceruloplasmin OR copper OR iron OR ferritin OR transferrin)" (4), "guaifenesin AND (ATP OR adenosine triphosphate OR phosphorylation)" (1), "guaifenesin AND (appetite OR nausea OR vomiting OR nutrition)" (13), and a combined fetch of PMIDs 4617771, 7067625 and 5130709. — Record listings read through a summarizing fetch tool; only the first 10 records of each long listing were visible. Abstract-level summaries, full texts not opened; records are Tier B (animal or in vitro with this drug) where cited in the Oxygen delivery entry (PMIDs 2318045, 6989792, 7212404, 24961870, 23471625), and otherwise listed only as search outcomes: 23597204, 22895922, 18654069, 15243011, 33206684, 25170357, 30883883, 5548215, 24674917, 3767993, 41545455, 9063550, 837639, 23113953.Cohort test: PMID 24961870 involved guaifenesin only as part of a drug combination, and PMID 837639 (human hemolysis) concerned methocarbamol, so neither supports a guaifenesin-specific finding. Queries with six or more OR terms or bracketed field tags returned the PubMed home page and were discarded. Europe PMC returned 429 and web search was unavailable.
  22. Brown JR. Guaifenesin effects on the guaiac test for occult blood. JAMA 1976;236(16):1881. PMID 989543. DOI 10.1001/jama.1976.03270170047028. — Laboratory interference study (Tier B). Only a truncated abstract fragment was read from OpenAlex (31 healthy volunteers, 28 men and 3 women, ages 22 to 31); the result is not retrieved. Not a nutrient source.Result not retrieved.
  23. OpenAlex single-record lookups for PMIDs 4617771 and 7067625 (works/pmid:N), 2026-10-08. — Both records return a null abstract; the 4617771 record shows 13 citing works. Used only to confirm that no abstract exists in that channel.