Olsalazine

aminosalicylate, azo-bonded 5-ASA dimer (colonic prodrug)

Also sold as Dipentum.

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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.

Olsalazine has no documented classical depletion machinery in the label text read, but it has one documented functional effect on water and electrolyte handling: it causes a dose-related, reversible secretory diarrhea. Intact olsalazine is about 2.4% absorbed, more than 99% protein bound, 98 to 99% of the dose reaches the colon, and colonic bacteria cleave each molecule into two 5-ASA molecules [1]. The US label text read states no CYP450 effect, and none on folate, iron, hemoglobin, G6PD, zinc, copper or microbiome [1]. In healthy volunteers, perfusing the jejunum with olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride and potassium absorption, with rapid reversal [5]; the drug also inhibited human ileal and colonic sodium pump activity in tissue (IC50 4.1 and 4.8 mM) [6]. This is the only orange entry. It is a functional absorption disturbance of electrolytes (an excess-loss effect, not a dietary deficiency), and no study located measured serum sodium or potassium in treated patients.

aminosalicylate, azo-bonded 5-ASA dimer (colonic prodrug) · ATC A07EC03 (WHO ATC/DDD Index [2]) · also sold as Dipentum; generic olsalazine sodium · reviewed 2026-10-06. 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 Olsalazine 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

Sodium, chloride, potassium and water: reversible reduction in small-intestinal absorption and secretory diarrhea (functional finding; body-status deficit not shown)

Orange — Moderate

See study details

In healthy volunteers, olsalazine in the perfused jejunum reduced water, sodium, chloride and potassium absorption, and the effect reversed quickly. Direction: reduced absorption and intestinal loss (a fluid and electrolyte disturbance, not a dietary shortfall). No study located measured serum sodium or potassium in olsalazine-treated patients.

Full detail and limits

What the grade means here: 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. Orange

Limits on what this shows

Key null / negative: Ireland 1988 [16]: 164 patients with colitis in remission, double-blind double-dummy comparison of olsalazine 500 mg twice daily with sulphasalazine 1 g twice daily; "No haematological or biochemical abnormalities were detected" (the abstract as relayed does not itemize the biochemistry). No source located reports serum sodium, potassium or magnesium in olsalazine-treated patients.
At-risk subgroups: People starting olsalazine or increasing the dose, and those with severely inflamed mucosa [6][10]. Older adults are discussed in the drug-induced diarrhea review [11], which was read only as a PubMed listing abstract.

Regulatory status

US label [1]: diarrhea is the most common adverse reaction (2% or more) and diarrhea or loose stools (6%) led to discontinuation in controlled trials, as relayed by the summarizing tool; the text read had no statement about secretory diarrhea, sodium, potassium or other electrolytes. UK SmPC [3]: "The most common side effect is diarrhoea which is usually transient"; dose adjustment or taking the drug at the end of meals typically helps; stop if it persists. Dutch SmPC [4] agrees that diarrhea is the most common effect and usually transient.

Population evidence

Tier A, this drug. Raimundo 1991 [5]: steady-state intestinal perfusion in normal human subjects (number of subjects not in the text read). In the jejunum olsalazine at 1.0 g/l "significantly inhibited water, sodium, chloride, potassium" absorption (p < 0.05); in the ileum 0.5 g/l inhibited water and sodium uptake (p < 0.04) (abstract reconstructed from OpenAlex and partly garbled; the PubMed listing summary adds inhibition of ileal glucose uptake and states that all inhibitory effects were rapidly reversible). Clinical frequency: a pharmacology review reports diarrhea in about 17% of patients, watery and without blood, typically early or after a dose increase and usually transient [10] (PubMed listing abstract); a rat paper puts it at up to 10% [7]; in a 37-patient double-blind trial in first attacks of distal colitis intolerance occurred in two olsalazine and four sulphasalazine patients [18].

Mechanism

Named, two parts. (1) Inhibition of the sodium pump: olsalazine inhibited human ileal and colonic (Na+ + K+)-ATPase with IC50 4.1 mM (ileum) and 4.8 mM (colon), maximal inhibition not above 80% [6]. (2) Chloride-dependent water secretion at high luminal concentration, described as an induction of secretion rather than a decrease in absorption [8]. A review of drug-induced diarrhea classes olsalazine as a secretory-diarrhea drug [11][12] (PubMed listing abstracts). The sources differ on mechanism emphasis (absorption inhibition [5][7] versus secretion [8]); they agree on the outcome, net luminal water and electrolyte load.

Animal and tissue support

Scheurlen 1992 [7], rats given olsalazine for 0 to 32 days: water and electrolyte absorption inhibited in all segments, with a 61% reduction in proximal small-intestinal sodium absorption; effects fully reversible after brief withdrawal; absorption capacity remained compromised after one month of dosing, so no true adaptation. Berglindh 1988 [8]: in rats at 150 mg/kg "a total adaptation occurs within 3-4 days", with similar adaptation "noted in other species including man". Mohsen (Gut 1987) [9]: rat jejunum, olsalazine at 5 and 10 mmol/l significantly inhibited fluid transport and glucose appearance (p < 0.001). The two rat papers disagree on whether adaptation occurs.

Boundary

Functional absorption measured in a perfusion model at luminal concentrations of 0.25 to 2.0 g/l; how those concentrations relate to the small-intestinal lumen after a 500 mg capsule was not established in the sources read. Effect is dose-related, early in treatment, and reversible. The authors of [6] suggest relevance mainly in severely damaged mucosa.

Counter-evidence held on record

Counter-evidence and confounding Diarrhea in ulcerative colitis has its own causes (active disease, infection, other drugs). A watery, bloodless pattern early after starting or raising the dose points to the drug [10], but no study separated drug-induced from disease-driven electrolyte change in patients. The finding is a handling disturbance, not a measured deficit (Hard Rules 2 and 5). Framing caution Excess-loss disturbance, not a dietary deficiency. Do not suggest sodium or potassium supplements or increased intake on this basis; persistent watery diarrhea should be reported to the prescriber, who may adjust the dose or stop the drug [3]. Kept separate from ATP production: the (Na+ + K+)-ATPase result concerns an ATP-consuming pump, not ATP synthesis.

Folate: inhibition of folic acid transport in human small-intestinal tissue (ex vivo); no olsalazine study shows a folate deficit

Yellow — Low

See study details

Olsalazine inhibited folic acid transport in human small-intestinal tissue samples in one study. Direction if real: depletion by reduced absorption. No olsalazine study located measured serum or red-cell folate, and the one trial that reported blood and biochemical safety found no abnormality.

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

Key null / negative: Ireland 1988 [16]: "No haematological or biochemical abnormalities were detected" in 164 patients on olsalazine or sulphasalazine (folate not itemized in the text read). Kiilerich 1992 [17] (227 randomized): 7% withdrew for adverse reactions equally across arms, no hematologic data in the abstract read.
At-risk subgroups: Patients with small-bowel Crohn disease, resection, poor intake or other folate-lowering drugs would carry deficiency risk from the disease or circumstances; not attributable to olsalazine on current evidence.

Regulatory status

No folate, iron, hemoglobin or G6PD statement in the US label text read [1]; none in the UK or Dutch SmPC text read [3][4]. Drugs.com lists no vitamin or mineral interaction for olsalazine (Tier D) [40].

Population evidence

No olsalazine study measuring serum, red-cell or tissue folate against a comparator was located with certainty. Meenan 1996 [15] measured colonic epithelial folate in colitis patients on sulfasalazine (7), "olsalamine" (11) and controls (8): 20.1, 19.1 and 18.7 pg/ug DNA, with lower serum folate only in the sulfasalazine group (p < 0.04). The record spells the second drug "olsalamine"; whether it is olsalazine was not verifiable, so this is not relied on for olsalazine.

Mechanism

Tier B, this drug. Zimmerman 1992 [13]: in small-intestinal tissue samples, sulfasalazine and olsalazine inhibited folic acid transport similarly; olsalazine did not inhibit methotrexate uptake (abstract read in a PubMed record and listing; concentrations, tissue origin and sample size not in the text read). Sharon 1992 [14] tested olsalazine in bovine endothelial cells; the two summaries of that abstract disagreed (one said olsalazine inhibited the folate-dependent thymidine process, the other that olsalazine showed no such effect), so it is not relied on. Intact olsalazine is 2.4% absorbed and 98 to 99% reaches the colon [1], so small-intestinal exposure to the intact molecule is brief.

CLASS EXTRAPOLATION

Sulfasalazine, a related azo compound: absorption of folic acid fell from 76.7% to 69.4% after three months of sulphasalazine in colitis patients, and "this only becomes significant if other reasons for folate deficiency are also present" [19] (abstract read). Cohort test: olsalazine was not in that study; Tier C, not borrowed as a finding for olsalazine.

Counter-evidence held on record

Counter-evidence and confounding Folate deficiency is common in inflammatory bowel disease from intake, malabsorption and inflammation, so confounding by indication is presumed (Hard Rule 6). The ex vivo finding was never followed by a clinical olsalazine folate study in the sources read. The sulfasalazine folate literature is not transferred to olsalazine: olsalazine releases no sulfapyridine [1][3]. Framing caution Not a clinical folate-deficiency claim for olsalazine. No folic acid dose or supplement is recommended here; folate testing is a clinical decision for the treating team.

No ungraded entries

Not graded — disclosed evidence gap

See study details

All seven required categories and both classical entries had at least one Tier B or Tier C source, so none met the dual condition for ungraded status.

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. None

Limits on what this shows

Why no grade is needed: Ungraded requires both no Tier B or C evidence and no circulating claim. Oxidative stress, Gut microbiome and Folate have olsalazine-specific Tier B data [13][20][21][33][34]; Mitochondrial burden, Copper, Iron, Oxygen delivery and ATP production each have at least one labeled Tier C class source [27][28][29][30][31], which sets a yellow floor. This does not mean the evidence is strong; it means the weakest grade applies.

Residual gaps (disclosed, not entries)

No olsalazine-specific study of copper, iron indices, hemoglobin, ATP, mitochondrial function, serum electrolytes or drug-to-microbiome effects was located. Channels tried: PubMed search-listing pages (term=olsalazine+folate, olsalazine+diarrhea+secretion, olsalazine+hemolytic, olsalazine+oxidative, and several others); OpenAlex single-record lookups by PMID and DOI; WebSearch with three or more phrasings per theme (hemolytic anemia and iron, microbiota and azoreductase, faecal flora, folate status, oxidative stress, mitochondria and ATP, copper and zinc chelation, nutrient depletion lists) until its shared budget ran out; DailyMed, UK and Dutch SmPCs, WHO ATC. Tooling-limited in part: PubMed listings for olsalazine+microbiota, olsalazine+anemia, olsalazine+haematological, olsalazine+electrolyte and the unrestricted olsalazine listing were rejected with 429 (not retried against the same page), Europe PMC and OpenAlex keyword search returned 429, PMC article pages returned bot verification, and a 2009 FDA label URL returned 404. These are partly tooling gaps and partly genuine gaps. Re-check priority: serum sodium and potassium and folate or hemoglobin data in olsalazine trials (Ireland 1988 and Kiilerich 1992 full texts were not opened), the Sousa 2014 abstract, and the Sharon 1992 abstract.

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: class extrapolation only (mesalazine in isolated rat heart mitochondria; 5-ASA in colitis mice); no olsalazine mitochondrial study

Yellow — Low

See study details

No study located tested olsalazine on mitochondrial structure or function. Mesalazine impaired isolated rat heart mitochondria in vitro, while pure 5-ASA increased spare respiratory capacity in cultured epithelial cells; olsalazine was in neither.

Full detail and limits

Limits on what this shows

Key null / negative: No olsalazine cellular mitochondrial assay located.
At-risk subgroups: None identified.

Regulatory status

No mitochondrial statement in the label text read [1][3][4].

Population evidence

No human or olsalazine data. A PubMed listing returned olsalazine-loaded nanoparticles said to attenuate mitochondrial dysfunction in colitis mice (ACS Appl Mater Interfaces 2025) [37]; that is an engineered formulation, not the marketed capsule, and is not used for grading.

Mechanism

Not named for olsalazine.

CLASS EXTRAPOLATION

Salimi 2020 [28]: mesalazine produced concentration- and time-dependent rises in mitochondrial ROS, succinate dehydrogenase inhibition, membrane potential collapse, swelling and cytochrome c release in isolated rat heart mitochondria (concentrations not read). Cevallos 2021 [27]: in cultured epithelial cells "5-ASA stimulation increased the spare mitochondrial respiratory capacity." Cohort test: mesalazine and pure 5-ASA only; olsalazine was not tested (Tier C); the two studies point in opposite directions.

Counter-evidence held on record

Counter-evidence and confounding Isolated-organelle toxicity at unknown concentrations of a different molecule is not evidence of mitochondrial burden in patients; systemic exposure to olsalazine is about 2.4% of the dose [1]. Framing caution Not a mitochondrial toxicity finding. Do not use as a basis for CoQ10 or other mitochondrial supplement advice.

Oxidative Stress

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

Oxidative stress: no olsalazine antioxidant activity in one assay and uncertain direction in an animal cancer model; pro-oxidant chemistry is class extrapolation

Yellow — Low

See study details

Olsalazine showed no measurable antioxidant activity in a DPPH assay, and an animal study combining olsalazine with gemcitabine reports oxidative-stress markers without a clear direction in the text read. No study located measured blood or tissue antioxidant capacity in olsalazine-treated patients.

Full detail and limits

Limits on what this shows

Key null / negative: The DPPH result [33] is a null for antioxidant activity. No blood glutathione, superoxide dismutase or malondialdehyde study in olsalazine-treated patients was located.
At-risk subgroups: None identified.

Regulatory status

No oxidative-stress or antioxidant statement in the US label, UK SmPC or Dutch SmPC text read [1][3][4].

Population evidence

No human data. Tier B, this drug: Jelicic 2019 [33], a congress abstract comparing aminosalicylates in a DPPH radical assay: "oxidative nature of 1mM olsalazine was not detected", while 5-ASA showed stronger antioxidant activity than sulfasalazine and balsalazide (read through a summarizing tool; the page was a conference abstract, and the wording is ambiguous between "not antioxidant" and "not pro-oxidant"). Sharma 2024 [34]: olsalazine pretreatment with gemcitabine in a rat model of liver carcinoma induced by N-nitrosodiethylamine and carbon tetrachloride; tissue oxidative-stress markers were measured; the PubMed listing summary says they were reduced, while the reconstructed abstract names no marker or direction (doses not read). The drug in that paper is studied as a DNA-methylation inhibitor in cancer, not as a colitis therapy.

Mechanism

No olsalazine redox mechanism established. The paper [34] attributes effects to DNMT1 interaction.

CLASS EXTRAPOLATION

Pro-oxidant direction: 5-ASA with Fe3+ at 20 uM each generated hydroxyl radical and lipid peroxidation in solution [29]; aminophenols including mesalamine sustained copper-dependent reactive oxygen species in permeabilized yeast [30]. Protective direction: Simmonds 1999 [35] found balsalazide and 5-ASA (20 mM) inhibited inflamed rectal biopsy chemiluminescence by 93% and 100%; olsalazine was not tested (reconstructed abstract). Cohort test: olsalazine was not in any of these; all Tier C.

Counter-evidence held on record

Counter-evidence and confounding The class results point in opposite directions and none used olsalazine; the animal cancer model is unrelated to colitis therapy and its direction was inconsistent between summaries. Disease inflammation itself changes redox markers. Framing caution Not an antioxidant deficiency claim and not a reason to add antioxidant supplements. Direction is unresolved for olsalazine.

Copper and Iron Balance

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

Iron: in vitro chelation and redox chemistry of 5-ASA (class extrapolation); iron deficiency in ulcerative colitis is disease-driven

Yellow — Low

See study details

5-ASA chelates and reduces ferric iron in solution. No study located shows that olsalazine lowers iron absorption or stores, and iron deficiency in UC has strong disease causes.

Full detail and limits

Limits on what this shows

Key null / negative: No label iron interaction [1][3][4]; Drugs.com lists no vitamin or mineral interaction for olsalazine (Tier D) [40].
At-risk subgroups: People with active UC, children and anyone with chronic blood loss. These are disease groups, not drug-attributable groups.

Regulatory status

No iron statement and no iron interaction in the US label, UK SmPC or Dutch SmPC text read [1][3][4]; no separation interval documented.

Population evidence

No iron-status study stratified by olsalazine located. Disease context: the ECCO consensus [32] states that about two-thirds of IBD patients have anaemia at diagnosis, about 30 to 40% of adults and about 70% of children during follow-up, with iron deficiency, chronic disease and mixed anemia the main forms.

Mechanism

CLASS EXTRAPOLATION. Grisham 1992 [29]: "5-ASA was very effective at chelating ferric iron (Fe3+), and it rapidly reduced Fe3+ to the ferrous form," with maximal hydroxyl radical formation at 20 uM 5-ASA and 20 uM Fe3+. Cohort test: only 5-ASA was tested; olsalazine was not (Tier C). Olsalazine delivers two 5-ASA molecules to the colon [1], but no study located tested iron binding by olsalazine itself or its effect on intestinal iron uptake.

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication is presumed (Hard Rule 6). Anemia or iron deficiency in a person with UC is not an iron-deficiency finding caused by olsalazine. The chemistry is in a test tube with a different molecule. Framing caution Do not tell patients olsalazine causes iron deficiency. Iron decisions belong to the IBD care team; no iron dose is recommended here. Copper is a separate entry.

Copper: in vitro redox interaction of an aminophenol class member (mesalamine, class extrapolation); no copper status data

Yellow — Low

See study details

Mesalamine, a 4-aminophenol derivative, supported copper-dependent reactive oxygen species in a yeast cell system. Nothing located shows that olsalazine changes copper status in either direction.

Full detail and limits

Limits on what this shows

Key null / negative: None for olsalazine.
At-risk subgroups: None identified.

Regulatory status

No copper statement in the label text read [1][3][4].

Population evidence

No copper-status study stratified by olsalazine located.

Mechanism

CLASS EXTRAPOLATION. Murakami and Yoshino 2022 [30]: 2- and 4-aminophenol isomers, but not the 3-isomer, produced reactive oxygen species with cupric ion in permeabilized yeast cells (aconitase inactivation); the abstract names mesalamine as a 4-aminophenol derivative; concentrations not read. Cohort test: mesalamine is the relevant class member; olsalazine was not tested (Tier C, in vitro). No mechanism of copper loss, malabsorption or retention was found. Copper-olsalazine metal-organic frameworks studied as colorectal cancer nanocatalysts [36] (PubMed listing abstract) are synthetic materials, not the drug as given, and are not used for grading.

Counter-evidence held on record

Counter-evidence and confounding A redox interaction in permeabilized yeast is neither depletion nor excess, and it concerns a different molecule from the one given to patients. Framing caution Kept separate from Iron. Not a copper deficiency or excess claim; no copper supplementation is supported.

Gut Microbiome Risk

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

Gut microbiome risk: the drug depends on the microbiota for activation; no olsalazine study of its effect on microbiome composition

Yellow — Low

See study details

Olsalazine is cleaved by colonic bacteria into two molecules of 5-ASA, a dependence of the drug on the microbiome, not a harm to it. Olsalazine-specific data on drug-to-microbiome effects were not located; the class data are sparse and mixed.

Full detail and limits

Limits on what this shows

Key null / negative: The sulphasalazine mucosal-flora study [24] is a class-level null; the olsalazine rat probiotic study [20] found no change in the azoreductase-bearing community.
At-risk subgroups: Patients on concurrent antibiotics might alter activation; this is a hypothesis from mechanism and was not tested for olsalazine in any source read.

Regulatory status

US label [1]: "Colonic bacteria convert olsalazine into 5-aminosalicylic acid"; each molecule is rapidly converted into two molecules of 5-ASA by colonic bacteria and the low prevailing redox potential (summarizer paraphrase of the label). The text read does not mention antibiotics or microbiome effects. UK SmPC [3]: "Bacteria split olsalazine in the colon into two molecules of 5-ASA."

Population evidence

Direction 1, microbiota to drug (Hard Rule 4, filed as an efficacy and pharmacokinetic dependence, not a depletion). Tier B, this drug: Li 2022 [20], olsalazine in ulcerative colitis rats, Lactobacillus acidophilus "barely had an influence" on olsalazine, 5-ASA and N-acetyl-5-ASA pharmacokinetics and did not change the total abundance of azoreductase and N-acetyltransferase gut microbiota enzymes; the authors report "no potential medication risks" with the combination. Sousa 2025 [21]: in rat faecal bioreactors, half-lives were 29.1 min (sulfasalazine), 47.9 min (balsalazide) and 84.1 min (olsalazine), so olsalazine was the slowest of the three. Sousa 2014 [22] covers olsalazine bacterial metabolism but its abstract was not opened. Crouwel 2020 [23], a review whose abstract names olsalazine, states that bacterial enzymes cleave the azo bond in sulfasalazine, balsalazide and olsalazine. Direction 2, drug to microbiota: no olsalazine study located.

Mechanism

Dependence: named (azoreductase cleavage) [1][20]. Effect of the drug on the microbiota: no olsalazine-specific mechanism found. The unabsorbed prodrug (98 to 99% of the dose) and its cleavage products reach the colon [1].

CLASS EXTRAPOLATION

Xu 2018 [26]: mucosal 16S study, 57 UC patients (20 untreated, 37 treated with 5-ASA) plus a 10-patient validation cohort; treated patients had higher Firmicutes (Enterococcus) and lower Proteobacteria (Escherichia-Shigella), and "5-ASA treatment significantly decreased the bacterial alpha diversity" in the validation cohort. Formulations were not named and olsalazine is not mentioned, so olsalazine cannot be confirmed in the cohort (Tier C). A SHIME in vitro model study (2024) [25] found that 5-ASA and sulfasalazine "significantly reduced the growth of the faecal microbiota" from six healthy donors; olsalazine was not included (Tier C, summary read). Hartley 1996 [24]: sulphasalazine caused "only minor disturbance" to mucosa-associated flora in 84 colitis patients; olsalazine was not in the cohort (Tier C, null).

Counter-evidence held on record

Counter-evidence and confounding Treated and untreated UC patients differ in disease activity, so [26] cannot separate drug effect from inflammation, and the formulation is unknown. Reduced Proteobacteria in the treated group points toward a less dysbiotic profile, not a harm signal. The Xu diversity result comes from a 10-patient validation cohort. Framing caution Not a finding that olsalazine harms the microbiome. Do not suggest probiotics or other supplements on this basis.

Oxygen and ATP Output

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

Oxygen delivery/utilization: hematologic adverse events listed on the label, not a nutrient finding; no olsalazine hemoglobin or hemolysis study located

Yellow — Low

See study details

The labels list anemia, hemolytic anemia and other blood dyscrasias as rare adverse reactions and warn of myelosuppression with thiopurines. These are drug adverse events, not an oxygen-delivery deficiency (Hard Rule 2). The one trial that screened blood and biochemistry found no abnormality.

Full detail and limits

Limits on what this shows

Key null / negative: The Ireland trial [16] screened hematology and biochemistry and found no abnormality; the US label states that safety and effectiveness in pediatric patients have not been established [1].
At-risk subgroups: Patients co-treated with azathioprine, 6-mercaptopurine or thioguanine [1][3]. G6PD status is not addressed in the label text read.

Regulatory status

US label [1]: postmarketing hematologic reactions listed as aplastic anemia, anemia, eosinophilia, hemolytic anemia, leukopenia, lymphopenia, neutropenia, pancytopenia, reticulocytosis and thrombocytopenia; with azathioprine or 6-mercaptopurine, "may increase the risk for blood disorders, bone marrow failure." UK SmPC [3]: "Serious blood dyscrasias have been reported very rarely"; thrombocytopenia uncommon; aplastic anaemia, haemolytic anaemia, leukopenia and others "not known"; myelosuppression risk with 6-mercaptopurine or thioguanine. Dutch SmPC [4] lists the same events.

Population evidence

Tier A, null: Ireland 1988 [16], 164 colitis patients in remission, assessments at 0, 3 and 6 months, olsalazine 500 mg twice daily versus sulphasalazine 1 g twice daily: "Adverse events were minor and were similar in both groups" and "No haematological or biochemical abnormalities were detected" (abstract as relayed; hemoglobin not itemized). Kiilerich 1992 [17]: 227 randomized, 7% withdrawn for adverse reactions equally across arms. No olsalazine hemoglobin, hematocrit, reticulocyte or hemolysis study stratified to olsalazine was located.

Mechanism

Idiosyncratic hypersensitivity or marrow suppression; no nutrient mechanism and no oxygen-transport mechanism is named.

CLASS EXTRAPOLATION

Dore 2023 [31]: 453 IBD patients; none of 78 G6PD-deficient patients receiving mesalamine was hospitalized or treated for acute hemolytic anemia, chronic hemolysis markers did not differ in 30 cases versus 112 controls on mesalamine up to 4500 mg/day, and ex vivo hemolysis occurred only above 2500 ug/mL (about 1000-fold above clinical levels per the paper). Cohort test: mesalamine, with sulfasalazine in three patients; olsalazine and balsalazide were not mentioned (Tier C). The ECCO consensus [32] states that sulphasalazine or 5-ASA "have been related to a minor degree of hemolysis or aplasia"; olsalazine is not named (Tier C).

Counter-evidence held on record

Counter-evidence and confounding Anemia in ulcerative colitis is common and disease-driven (see Iron) [32]. A drug blood-cell toxicity is monitored with a blood count, not corrected with nutrients. Kept separate from ATP production. Framing caution Recorded as an outcome entry. No nutrient or supplement action is implied; unexplained bruising, bleeding, fever, sore throat or anemia symptoms are a prescriber matter [3].

ATP production: restoration signal for 5-ASA in colitis mice (class extrapolation); no olsalazine ATP synthesis data

Yellow — Low

See study details

The only ATP-synthesis finding located is for pure 5-ASA, which restored epithelial ATP in a mouse colitis model. Olsalazine inhibits an ATP-consuming enzyme (the sodium pump) in human tissue, which is not an ATP-production deficit.

Full detail and limits

Limits on what this shows

Key null / negative: None for olsalazine.
At-risk subgroups: None identified.

Regulatory status

No energy-metabolism statement in the label text read [1][3][4].

Population evidence

No human data. No olsalazine study measured ATP, oxygen consumption or fatigue as an energy outcome.

Mechanism

CLASS EXTRAPOLATION. Cevallos 2021 [27]: C57BL/6J mice with DSS colitis fed pure 5-ASA (2.5 g/kg chow); DSS "reduced epithelial ATP levels" and 5-ASA treatment restored them in control mice but not in mice lacking epithelial PPAR-gamma. Cohort test: pure 5-ASA was used and olsalazine was not mentioned (Tier C, reverse direction). Related but distinct: olsalazine inhibited human ileal and colonic (Na+ + K+)-ATPase [6]; that enzyme consumes ATP, so this is filed under Electrolytes and not as an ATP-production finding. One review abstract worded the olsalazine effect as inhibiting ATPase-mediated ATP breakdown [11] (PubMed listing summary).

Counter-evidence held on record

Counter-evidence and confounding The mouse finding is tissue restoration during inflammation and may reflect remission. Whether 5-ASA released from olsalazine acts the same way was not tested. Framing caution Kept separate from Mitochondrial burden and Oxygen delivery/utilization. Not an energy-deficit claim; no supplement is supported.

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.

Folic acid "depletion" by 5-ASA drugs, stated as an established effect. Direction if real: depletion
Where it comes from: Tier D practitioner page listing "5-Aminosalycyclic acid (for bowel inflammation)" with Sulfasalazine, Colaza1 (as printed) and Mesalamine and the line "Depletes: Folic acid"; no primary citation seen; olsalazine and Dipentum do not appear on the page [38]. A separate Tier D page asserts folic acid supplementation for sulfasalazine users with no references [39].
Why it fails: As a claim about olsalazine it has no source: neither page names olsalazine, and the US label, UK SmPC and Dutch SmPC text read contain no folate statement [1][3][4]. Olsalazine releases no sulfapyridine [1], and the clinical folate findings cited for this group belong to sulfasalazine [19]. The only olsalazine-specific folate data are an ex vivo transport inhibition [13], graded yellow in its own entry; no olsalazine study shows low folate, and a controlled trial found no haematological or biochemical abnormalities [16]. The claim fails as an established clinical depletion; the narrower mechanistic signal is not rebutted here, and this is not a finding that no effect exists.
Folic acid supplementation advised for olsalazine users (transfer of the sulfasalazine advice)
Where it comes from: Tier D page on sulfasalazine and folic acid, citing "many doctors" and unreferenced colon-cancer risk figures [39].
Why it fails: No olsalazine label, trial or review read advises folic acid supplementation, and the studies behind the sulfasalazine advice did not include olsalazine [19]. No dose is recommended here.

How the body handles this medication

Activation and metabolism: Taken as intact prodrug; colonic bacteria and the low redox potential split the azo bond into two molecules of 5-ASA. About 0.1% of an oral dose is metabolized in the liver to olsalazine-S; 5-ASA is acetylated to N-acetyl-5-ASA in the colonic epithelium and liver.[1] DailyMed label sec 12; [3] UK SmPC 5.2
CYP450: The US label text read states nothing on CYP450 induction or inhibition. Absence was reported by a summarizing tool and is not independently confirmed.[1] DailyMed label
Absorption and exposure: About 2.4% of a single 1 g dose is absorbed; 98 to 99% reaches the colon. Olsalazine is more than 99% plasma-protein bound (5-ASA 74% and N-acetyl-5-ASA 81%). Serum half-life about 0.9 hour. UK SmPC: uptake 1.3% or 1.6% with or without food; at 500 mg twice daily steady-state aminosalicylate 0.8 to 2.9 mcg/ml.[1]; [3] UK SmPC 5.2
Elimination: Urinary recovery of olsalazine is below 1%; total recovery of 14C-labeled olsalazine ranged from 90 to 97%. About 20% of total 5-ASA is recovered in urine, over 90% of it as N-acetyl-5-ASA. The UK SmPC reports a metabolite half-life of 6 to 10 days.[1]; [3] UK SmPC 5.2
Renal and hepatic handling: Renal impairment (minimal change disease, interstitial nephritis, renal failure) is reported; discontinue if renal function deteriorates. UK SmPC contraindicates use in significant renal impairment and sets a monitoring schedule. Hepatic failure evaluation and nephrolithiasis with adequate hydration are listed in the US precautions. No renal or hepatic PK table was found in the text read.[1]; [3] UK SmPC 4.3, 4.4
Food, mineral and drug interactions: Documented: nephrotoxic agents and NSAIDs; azathioprine or 6-mercaptopurine (blood disorders, bone marrow failure); low molecular weight heparins (bleeding risk after neuraxial anesthesia); varicella vaccine (avoid for six weeks); warfarin (raised prothrombin time reported in the UK SmPC). No iron, calcium, antacid, folate or other mineral interaction and no separation interval in the text read. The US label does not state a food effect; the UK SmPC advises taking it at the end of meals if diarrhoea occurs.[1] sec 7; [3] UK SmPC 4.4, 4.5

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.

Label / renal
Kidney function
The US label asks to discontinue if renal function deteriorates [1]. The UK SmPC requires baseline renal function and a monitoring schedule (before treatment, every 3 months in year one, every 6 months in years two to five, then annually) and contraindicates use in significant renal impairment [3]. This is drug toxicity, not a nutrient finding.
Label / blood counts
Complete blood count with thiopurines
With azathioprine, 6-mercaptopurine or thioguanine, the labels warn of blood disorders and bone marrow suppression [1][3]. Unexplained bleeding, bruising, fever, sore throat or anemia warrants stopping and review per the UK SmPC [3]. A low count is a drug-interaction signal, not iron or folate deficiency.
Drug effect / fluids
Diarrhea, hydration and electrolytes
Watery diarrhea is the most common adverse effect, usually early or after a dose increase, and usually transient [3][10]. The UK SmPC suggests dose adjustment or taking the drug at the end of meals, and stopping if it persists [3]. Whether to check serum sodium and potassium when diarrhea persists is a clinical decision; no source read prescribes a schedule. Adequate fluids are advised because nephrolithiasis is reported [1].
Disease / lab
Iron indices and anemia in UC
Hemoglobin and ferritin (with transferrin saturation when inflammation is present) are standard in UC care [32]. A new deficiency is presumed disease-driven and evaluated by the IBD team, not attributed to olsalazine.
Interactions
Warfarin, vaccines and heparin
Raised prothrombin time has been reported with warfarin [3]; avoid the drug for six weeks after varicella vaccine [1]; low molecular weight heparins carry a bleeding risk with neuraxial anesthesia [1]. No mineral or vitamin separation interval is documented, and no supplement dose is recommended in this dossier.
Subgroups
Pregnancy, lactation, children
Animal reproductive toxicity occurred at 5 to 20 times the maximum human dose, and the UK SmPC reports a risk of stillbirth or preterm birth without substantial malformation risk [1][3]. Lactation data are insufficient; monitor the infant for diarrhea [1]. Pediatric safety and effectiveness are not established in the US label [1]. A pediatric trial exists [41].
Folate / B12
Only if clinically indicated
No olsalazine-specific folate or B12 deficiency signal was found. Deficiency in UC arises from disease, diet, small-bowel involvement or resection and is a clinical decision, not a drug-attributed finding.

Overlap map, to prevent double counting

Sodium, chloride, potassium and water; ATP production
Shares evidence with: Scheurlen 1993 [6]; Ratnaike review [11]
Note: The (Na+ + K+)-ATPase result is the named mechanism for the Electrolytes entry and is mentioned in ATP production only to state it is not ATP synthesis. One source, not two lines of evidence.
Sodium, chloride, potassium and water; Folate
Shares evidence with: Small-intestinal transport work [5][13]
Note: Both rest on olsalazine inhibiting transport in small-intestinal tissue (water and electrolyte transport; folic acid transport). Different measured analytes, similar tissue-level mechanism; do not count as mutually confirming.
Sodium, chloride, potassium and water; Folate; Oxygen delivery/utilization
Shares evidence with: Ireland 1988 [16]
Note: The same statement ("No haematological or biochemical abnormalities were detected") is a null in all three entries. One trial, one sentence.
Mitochondrial burden; ATP production; Gut microbiome risk
Shares evidence with: Cevallos 2021 [27]
Note: One mouse and cell study of pure 5-ASA supplies the respiratory-capacity, ATP and E. coli findings. Treat as one source with one cohort, not three confirmations.
Mitochondrial burden; Oxidative stress
Shares evidence with: Salimi 2020 [28]
Note: The mitochondrial ROS finding is cited in Mitochondrial burden; Oxidative stress cites it nowhere independently.
Oxidative stress; Iron; Copper
Shares evidence with: Grisham 1992 [29]; Murakami 2022 [30]
Note: Iron and copper redox chemistry in vitro is the same body of work as the pro-oxidant row in Oxidative stress. Same mechanism, not independent lines.
Iron; Oxygen delivery/utilization
Shares evidence with: ECCO consensus [32]
Note: The disease-driven anemia and iron-deficiency context is shared. Neither entry is counted as a drug effect.
Gut microbiome risk
Shares evidence with: Li 2022 [20]; Sousa 2025 [21]; Crouwel 2020 [23]; label [1]
Note: All state the same fact, azo-bond cleavage by colonic bacteria. One dependence finding, not independent confirmations.
All nine entries; Fails verification
Shares evidence with: Olsalazine labels [1][3][4]
Note: The same label text supports every "no nutrient statement" line and the sulfapyridine non-transfer statement. It is one set of sources.

All references used above

Olsalazine

Findings for this medication

What the research found

Sodium, chloride, potassium and water: reversible reduction in small-intestinal absorption and secretory diarrhea (functional finding; body-status deficit not shown)

Folate: inhibition of folic acid transport in human small-intestinal tissue (ex vivo); no olsalazine study shows a folate deficit

No ungraded entries

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: class extrapolation only (mesalazine in isolated rat heart mitochondria; 5-ASA in colitis mice); no olsalazine mitochondrial study

💥Oxidative Stress

Oxidative stress: no olsalazine antioxidant activity in one assay and uncertain direction in an animal cancer model; pro-oxidant chemistry is class extrapolation

⚖️Copper and Iron Balance

Iron: in vitro chelation and redox chemistry of 5-ASA (class extrapolation); iron deficiency in ulcerative colitis is disease-driven

Copper: in vitro redox interaction of an aminophenol class member (mesalamine, class extrapolation); no copper status data

🌿Gut Microbiome Risk

Gut microbiome risk: the drug depends on the microbiota for activation; no olsalazine study of its effect on microbiome composition

💨Oxygen and ATP Output

Oxygen delivery/utilization: hematologic adverse events listed on the label, not a nutrient finding; no olsalazine hemoglobin or hemolysis study located

ATP production: restoration signal for 5-ASA in colitis mice (class extrapolation); no olsalazine ATP synthesis data

Claims checked and not supported

Folic acid "depletion" by 5-ASA drugs, stated as an established effect. Direction if real: depletion

Folic acid supplementation advised for olsalazine users (transfer of the sulfasalazine advice)

How the body handles this medication

What the research says is worth watching

Overlap map, to prevent double counting

Mitochondrial Burden

Oxidative Stress

Copper and Iron Balance

Gut Microbiome Risk

Oxygen and ATP Output