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MyDeficiencies

Colesevelam

Bile Acid Sequestrant

Also sold as Welchol, Cholestagel.

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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.

Colesevelam is a nonabsorbed, nonmetabolized polymer that stays in the gastrointestinal tract; roughly 0.05% of an administered dose is recovered unchanged in urine, and the drug does not induce or inhibit cytochrome P450 enzymes. That pharmacokinetic profile removes most of the classical depletion machinery seen with renally cleared or hepatically metabolized drugs. The one clear, drug-specific mechanism is local: nonspecific binding in the gut lumen that can reduce absorption of co-administered fat-soluble vitamins A, D, E, and K, which is why the FDA label instructs a 4-hour dosing separation. That said, the only controlled trial that actually measured fat-soluble vitamin levels in colesevelam-treated patients (an adolescent familial hypercholesterolemia trial) found no significant difference from placebo; a single 2025 case report describes symptomatic vitamin A deficiency after long-term use. Folic acid is named as an absorption target only in a secondary pharmacology reference (StatPearls), not in the FDA label itself, and no primary study of colesevelam and folate was located.

Bile acid sequestrant · ATC C10AC04 · also sold as Welchol and Cholestagel · reviewed 2026-09-23. 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 Colesevelam in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
severe: two or more independent Tier A sources, this drug in the studied cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
moderate: at least one Tier A source with this drug in the cohort showing a real deficit, but bounded by exposure window, subgroup, low frequency, or a functional (not circulating) deficit.
Yellow — Low
low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where another class member has real data but this drug does not; also used for context flags and reverse-direction findings.
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: evidence gap: no Tier B/C evidence to support even a yellow grade, and no circulating claim exists to rebut as white. A disclosed absence of evidence, not a finding of safety.

What the research found

Fat-soluble vitamins A, D, E, K

Yellow — Low

See study details

Bile acid sequestration mechanistically can reduce absorption of co-administered fat-soluble vitamins, and the FDA label requires a 4-hour dosing separation, but the one controlled trial that measured vitamin levels in colesevelam-treated patients found no significant deficit.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where another class member has real data but this drug does not; also used for context flags and reverse-direction findings. Yellow

Limits on what this shows

  • Key negative/null findings: The pediatric RCT (Tier A, colesevelam in the cohort) found no significant reduction in fat-soluble vitamin levels versus placebo — the most direct, drug-specific counter-evidence available.
  • At-risk subgroups: Long-term users (per the single case report), patients not observing the 4-hour dosing separation, and those with low baseline vitamin stores or additional malabsorptive conditions.
  • Counter-evidence: Controlled pediatric trial found no significant vitamin-level deficit; this is a bounded population (adolescents, familial hypercholesterolemia) and may not generalize to long-term adult use, which is exactly where the one positive case report arose.

Regulatory status

FDA label Section 5.3, "Vitamin K or Fat-Soluble Vitamin Deficiencies": colesevelam "may decrease the absorption of fat-soluble vitamins A, D, E, and K"; vitamin supplements should be taken at least 4 hours before colesevelam.

Population evidence

Randomized, placebo-controlled pediatric trial (adolescents 10–17y, heterozygous familial hypercholesterolemia; drug and dose per label): no significant difference vs placebo in growth, sexual maturation, fat-soluble vitamin levels, or clotting factors (DailyMed label). One case report (Andreyev, Gopakumar & Andreyev, Frontline Gastroenterology, 2025) describing symptomatic vitamin A deficiency in a patient on long-term colesevelam; full case detail (duration, dose, exact retinol level) could not be independently confirmed beyond bibliographic metadata during this review because the full text could not be opened.

Mechanism

Named: colesevelam's polymer binds bile acids and, by class-level pharmacology of anion-exchange/bile-acid-sequestering resins, can nonspecifically reduce micellar solubilization of co-administered lipophilic vitamins in the gut lumen.

Counter-evidence held on record

Do not present this as "colesevelam depletes vitamin A/D/E/K." The only controlled measurement in colesevelam-treated patients found no significant reduction; the evidence for a real-world deficit rests on a single case report after long-term use. No dosing recommendation is made for this yellow-graded entry; the 4-hour separation is the label's own instruction, not a dose the dossier is recommending.

Folic acid

Yellow — Low

See study details

Folic acid is named as an absorption-interference target of colesevelam only in a secondary pharmacology reference; the current FDA label does not mention folic acid at all.

Full detail and limits

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where another class member has real data but this drug does not; also used for context flags and reverse-direction findings. Yellow

Limits on what this shows

  • Key negative/null findings: None identified; this is an absence of data rather than a negative trial.
  • At-risk subgroups: Theoretical only: patients with elevated folate needs (e.g., pregnancy) if the class-level mechanism applies to colesevelam, which is not established.
  • Counter-evidence: The FDA label's own fat-soluble vitamin warning (Section 5.3) names only vitamins A, D, E, and K; folic acid's absence from that same section, despite the label being the most authoritative colesevelam-specific source, weakens the claim.

Regulatory status

Not mentioned. A full-text search of the current colesevelam prescribing information for "folic acid" returned no matches.

Population evidence

None identified for colesevelam specifically. Multiple Crossref API queries ("colesevelam folate folic acid," "cholestyramine folate folic acid") returned no primary interventional or observational study connecting colesevelam, or the older bile acid sequestrant class, to folate status.

Mechanism

Proposed by class analogy to nonspecific intestinal binding by bile-acid-sequestering resins (StatPearls: Patel & Can, 2023), not corroborated by any colesevelam-specific pharmacokinetic or clinical study located in this review.

Counter-evidence held on record

Single secondary-source mention, not corroborated by the regulatory label or by any primary study found in this review. Should not be presented to consumers as an established effect of colesevelam.

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

Mitochondrial burden

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: No Tier B or Tier C evidence connecting colesevelam to mitochondrial structure, membrane integrity, electron transport, or biogenesis was located, and no circulating consumer claim exists to rebut as white. Searched via DailyMed, StatPearls, and the Crossref API (queries: "colesevelam mitochondrial," "bile acid sequestrant mitochondrial bile acid receptor TGR5 energy") across more than one phrasing; results returned unrelated general mitochondrial-biology papers, not colesevelam-specific or bile-acid-sequestrant-class findings. A dedicated general web search for this category could not be completed because this session's search quota was exhausted before it was reached, and PubMed/PMC listing pages were blocked by bot-verification during the same period; this is a genuine tooling limitation on top of an apparent true evidence gap. Biological plausibility is also low: colesevelam is not absorbed from the gut, so it has no direct systemic route to mitochondria.

Oxidative Stress

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

Oxidative stress

Not graded — disclosed evidence gap

See study details

Oxidative stress

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: No Tier B or Tier C evidence connecting colesevelam to systemic or tissue-level redox/antioxidant-capacity markers was located, and no circulating consumer claim exists to rebut as white. Searched via DailyMed, StatPearls, and the Crossref API ("colesevelam oxidative stress") with no relevant drug-specific or class-level result; general web search for this category could not be completed before the session's search quota was exhausted. Biological plausibility is low given the drug's lack of systemic absorption.

Copper and Iron Balance

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

Copper

Not graded — disclosed evidence gap

See study details

Copper

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: No Tier B or Tier C evidence connecting colesevelam to copper status was located, and no circulating consumer claim exists to rebut as white. Searched via DailyMed, StatPearls, and the Crossref API ("colesevelam copper," "colesevelam mitochondrial oxidative stress copper") across more than one phrasing; all relevant results were general copper/mitochondrial biology unrelated to colesevelam or bile acid sequestrants. General web search for this category could not be completed before the session's search quota was exhausted. Copper is graded independently of iron, per protocol, even though both were negative here.

Gut Microbiome Risk

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

Gut microbiome composition

Yellow — Low

See study details

In a colesevelam-treated cohort with bile acid diarrhoea, overall gut bacterial diversity was unchanged, but specific bacterial taxa shifted differently between clinical responders and non-responders.

Full detail, limits and 1 references

What the grade means here: low/theoretical: mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where another class member has real data but this drug does not; also used for context flags and reverse-direction findings. Yellow

Limits on what this shows

  • Key negative/null findings: The study explicitly reports that "colesevelam did not alter bacterial alpha/beta-diversity" overall — a reassuring null finding for global microbiome disruption.
  • At-risk subgroups: Findings were most evident in the idiopathic BAD cohort at the 8-week timepoint; not established as generalizing to colesevelam's on-label lipid-lowering or glycemic-control populations, who do not have bile acid diarrhoea.
  • Counter-evidence: This cohort's underlying condition (bile acid diarrhoea, often post-surgical or idiopathic) differs from colesevelam's on-label hyperlipidemia/type 2 diabetes indications, so confounding by indication cannot be excluded; taxa shifts tracked with clinical response rather than appearing as a uniform adverse drug effect, and no non-colesevelam comparator arm was available to isolate the drug effect from the underlying bile acid disorder.

Regulatory status

Not addressed in the FDA label.

Population evidence

Kumar et al., Frontiers in Microbiology, 2023 (PMID 37007510): prospective study, 257 stool samples from 135 patients across four cohorts (idiopathic bile acid diarrhoea [BAD], post-cholecystectomy BAD, post-operative Crohn's disease BAD, and 75SeHCAT-negative controls), sampled at baseline, 4 weeks, 8 weeks, and 6–12 months after starting colesevelam.

Mechanism

Named: colesevelam alters the luminal bile acid pool and composition, which shapes the bacterial taxa involved in converting primary to secondary bile acids. Clinical responders showed increased Fusobacteria and Ruminococcus (taxa that aid primary-to-secondary bile acid conversion); non-responders showed increases in CAG-352 and Coprococcus.

Counter-evidence held on record

This is a compositional/functional shift associated with treatment response in bile acid diarrhoea, not an established dysbiosis or nutrient-depletion risk from colesevelam's on-label lipid or glycemic use. Overall bacterial diversity was preserved; do not present this as "colesevelam disrupts your gut microbiome."

Oxygen and ATP Output

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

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

Oxygen delivery/utilization

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: No Tier B or Tier C evidence connecting colesevelam to hemoglobin, hematocrit, red-cell mass, arterial oxygenation, or tissue oxygen delivery was located, and no circulating consumer claim exists to rebut as white. Searched via DailyMed, StatPearls, and the Crossref API ("colesevelam anemia hemoglobin oxygen") with no colesevelam-specific results returned; a dedicated general web search for this category could not be run before the session's search quota was exhausted, which is disclosed as a genuine access limitation. Graded independently of ATP production, per protocol.

ATP production

Not graded — disclosed evidence gap

See study details

ATP production

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: No Tier B or Tier C evidence connecting colesevelam to mitochondrial ATP synthesis or cellular energy output was located, and no circulating consumer claim (e.g., "low energy" claims) exists to rebut as white. Searched via DailyMed, StatPearls, and the Crossref API ("colesevelam ATP energy metabolism fatigue") with no colesevelam-specific results; general web search for this category could not be completed before the session's search quota was exhausted. Graded independently of mitochondrial burden and oxygen delivery/utilization, per protocol, though all three share the same underlying negative-plausibility basis (see Overlap map).

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.

  • Iron

    Where it comes from: Automated consumer drug-interaction checkers (e.g., Drugs.com) list a "Moderate" interaction between colesevelam and "multivitamin with iron."

    Why it fails: The mechanism text on these checkers is a verbatim restatement of the FDA label's fat-soluble vitamin (A/D/E/K) warning, not an iron-specific mechanism; the same checker returns "no interactions found" for colesevelam plus vitamin B12 alone. No primary or secondary pharmacology source located in this review (FDA label, StatPearls, or Crossref searches for "colesevelam iron" and "colesevelam iron absorption") documents an iron-specific binding or chelation mechanism for colesevelam, and no case reports of iron-deficiency anemia attributed to colesevelam were found.

All references used above
  1. DailyMed. COLESEVELAM HYDROCHLORIDE tablet, film coated — full prescribing information. — U.S. National Library of Medicine, DailyMed. Regulatory label. Includes Clinical Pharmacology, Warnings and Precautions 5.1–5.6, Drug Interactions (Section 7, with quantified AUC changes), and the pediatric familial hypercholesterolemia trial (fat-soluble vitamin, growth, and clotting-factor endpoints).
  2. Patel PH, Can AS. Colesevelam. — StatPearls [Internet]. NCBI Bookshelf, StatPearls Publishing. Last updated May 1, 2023. NBK557815. Tier B pharmacology reference; source of the proposed TGR5/GLP-1 glycemic mechanism and the folic-acid mention not present in the FDA label.
  3. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index: C10AC04 Colesevelam. — Regulatory classification source. Defined Daily Dose 3.75 g, oral.
  4. Brown KS, Armstrong IC, Wang A, et al. Effect of the bile acid sequestrant colesevelam on the pharmacokinetics of pioglitazone, repaglinide, estrogen estradiol, norethindrone, levothyroxine, and glyburide. — J Clin Pharmacol. 2010. PMID 19789374. Colesevelam-specific pharmacokinetic interaction study; underlies the label's quantified AUC changes and the levothyroxine timing interaction.Full abstract could not be opened during this review: PubMed and the publisher's Wiley page returned bot-verification/403 responses. Title, authors, journal, year, and the list of drugs studied were confirmed via the Europe PMC REST API and corroborating web search results, not from the full abstract text.
  5. Weitzman SP, Ginsburg KC, Carlson HE. Colesevelam hydrochloride and lanthanum carbonate interfere with the absorption of levothyroxine. — Thyroid. 2009;19(1). PMID 19119983. Case report, colesevelam specifically.Full text could not be opened during this review (PubMed and PMC returned bot-verification challenges). Title, authors, journal, and year confirmed via the Europe PMC REST API search index.
  6. Andreyev DA, Gopakumar V, Andreyev HJN. Symptomatic vitamin A deficiency in a patient on long-term colesevelam. — Frontline Gastroenterology. 2025. DOI 10.1136/flgastro-2024-102919. Case report, colesevelam specifically; the only individual patient-level evidence of a fat-soluble vitamin deficiency in a colesevelam user identified in this review.Full text could not be opened during this review (429 rate-limit responses from the publisher and from ResearchGate). Title, authors, journal, year, and DOI confirmed via the Crossref API.
  7. Kumar A, et al. The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam. — Front Microbiol. 2023;14. PMID 37007510. Prospective study, 257 stool samples from 135 patients, colesevelam-treated. Source for the gut microbiome composition entry.
  8. Drugs.com. Drug interaction report: colesevelam + multivitamin with iron. — Tier D consumer interaction checker. Used only for the circulating-claim audit of the iron entry; states "Moderate" interaction with the fat-soluble-vitamin mechanism text, not an iron-specific mechanism.
  9. Drugs.com. Drug interaction report: colesevelam + vitamin B12. — Tier D consumer interaction checker. Returns "no interactions found"; used as supporting context for the iron rebuttal.
  10. Ubie Doctor's Note. "Urgent Warning: How Bile Acid Sequestrants Block Vitamins." — Tier D consumer health content. Used only to characterize the circulating consumer narrative, which conflates colesevelam with older, chemically distinct bile acid sequestrants (cholestyramine, colestipol) without differentiation.