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MyDeficiencies

Pancrelipase

pancreatic enzyme replacement, non-absorbed

Also sold as Creon, Zenpep, Pancreaze, Pertzye, Viokace.

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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.

Pancrelipase has no classical depletion machinery. The enzymes are not substrates of CYP enzymes or transporters, and the labels state they are not absorbed from the gastrointestinal tract in appreciable amounts [1][2][3][4]. The drug treats a malabsorption state, so most nutrient deficits seen in people who take it come from exocrine pancreatic insufficiency (EPI) or cystic fibrosis, not from the drug. Under Hard Rule 6 that confounding by indication is presumed, and it shapes every entry below. The four current labels opened here (Creon, Zenpep, Viokace, Pancreaze) contain no statement about folic acid, iron, vitamins or nutritional status, as reported by a summarizing fetch tool [1][2][3][4].

pancreatic enzyme replacement, non-absorbed · ATC A09AA02, multienzymes (WHO ATC/DDD Index [5]) · also sold as Creon and Zenpep and Pancreaze and Pertzye and Viokace · reviewed 2026-10-04. 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 Pancrelipase 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 elevation: excess/retention direction, high doses only

Orange — Moderate

See study details

The purine content of porcine pancreatic extract can raise blood and urine uric acid at high doses; this is a retention-direction risk, not a dietary deficiency, and standard-dose data show no significant change.

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

  • Null findings: [7] found no significant uric acid change at standard dosing and concluded dangerous hyperuricemia or hyperuricosuria do not usually occur. The enzyme product was not named in the abstract opened.
  • At-risk subgroups: People with gout, renal impairment, existing hyperuricemia, and those on high lipase doses (cystic fibrosis).

Regulatory status

Listed in all four labels opened (Creon, Zenpep, Viokace, Pancreaze) in Warnings and Precautions: pancreatic enzyme products contain purines that may increase blood uric acid levels, and high dosages have been associated with hyperuricosuria and hyperuricemia [1][2][3][4]. The Pancreaze label adds a suggestion to consider monitoring blood uric acid in patients with gout, renal impairment or hyperuricemia [4]. Label text reached through a summarizing fetch tool.

Population evidence

Israel, 1980 [6]: 16 cystic fibrosis patients on pancreatic enzyme supplements had elevated blood and urine uric acid; hyperuricosuria increased with age and when the dose exceeded 10,000 lipase units/kg body weight. Read from a PubMed search-listing summary only; the single record was rate limited. No effect estimate or confidence interval was available. Wiersbitzky 1989 [7]: 16 cystic fibrosis patients aged 7 to 23, serum uric acid after a standard meal with enzyme replacement over 8 hours, no significant change.

Mechanism

Named: exogenous purines in the animal-derived extract (label) [1][2]. Dose dependence is plausible and supported by the 1980 report [6].

Cohort test

Labels are for this drug. Both studies used "pancreatic enzyme supplements" of unnamed brand [6][7]; product identity could not be confirmed, so they are used as supporting and contradicting context, and the grade rests on the label.

Counter-evidence held on record

Counter-evidence and confounding The standard-dose null study [7] and the dose threshold in [6] bound the claim. Cystic fibrosis and pancreatitis themselves may alter uric acid handling; neither study had an untreated comparison group. Not a nutrient entry: uric acid is a metabolite, included because it is label-listed. Framing caution This is an excess or retention risk, not a deficiency. Nothing here suggests increasing intake of any nutrient. Dose changes for the enzyme belong to the prescriber.

Fat-soluble vitamin status in EPI: reverse direction, indication-linked

Yellow — Low

See study details

Vitamin D and other fat-soluble vitamin deficits belong to the untreated disease; in uncontrolled data, enzyme therapy is associated with improvement, but deficits also persist in treated people.

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 and contrary findings: From PubMed listing summaries only: a cross-sectional study of 101 cystic fibrosis subjects and 177 controls reported 90 percent versus 74 percent vitamin D insufficiency despite routine supplementation [16]; a newborn-screening cohort (99 completers) reported low vitamin D in about half of the EPI group despite enzyme and vitamin supplementation [17]. Neither full text was opened.
  • At-risk subgroups: Cystic fibrosis, chronic pancreatitis, pancreatectomy, pancreatic cancer, children.

Regulatory status

No vitamin statement in the four labels retrieved [1][2][3][4]. The Pancreaze label describes trial endpoints including improvement in signs and symptoms of malabsorption with measures of nutritional status, with no specific vitamin monitoring recommendation (via summarizing fetch) [4].

Population evidence

Bideeva 2020 [9]: prospective observational study, 58 chronic pancreatitis patients (30 and 28 in two groups), 8 to 12 months of adjusted-dose microencapsulated pancreatin; vitamin D, B12, albumin, transferrin, iron and magnesium improved, with vitamin D rising from 10.6 to 17.1 ng/mL in the group with abnormal baseline nutrition. No control group. Haas 2015 [15]: 50 male chronic pancreatitis patients, 28 with EPI; serum 25-OH-cholecalciferol was decreased overall and patients on enzyme therapy had higher bone density (DXA) values. Bone density is an outcome, not vitamin D status, and is not filed as one (Hard Rule 2).

Mechanism

Named: restoring fat digestion allows absorption of fat-soluble vitamins. This is the intended pharmacology, not a depletion.

Cohort test

Enzyme therapy was in both cohorts [9][15] but the product was named only as "microencapsulated pancreatin" [9] and as "PERT" [15]. Listed as indication-linked context with reverse-direction signal, which is yellow by definition.

Counter-evidence held on record

Counter-evidence and confounding The improvement in [9] is uncontrolled, with unknown co-interventions such as dietary change or concurrent vitamin supplements; it cannot show that the enzyme alone corrected vitamin status. Persistent deficiency in treated cystic fibrosis [16][17] shows enzyme therapy does not reliably normalize status. A pediatric case report in which enzymes plus iron and vitamins normalized hemoglobin and red-cell indices is context only [18]. Framing caution This does not say pancrelipase causes a vitamin deficiency, and it does not say it restores vitamin levels. It is a monitoring prompt for people with EPI. Any supplementation decision belongs to the prescriber; no dose is given here.

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 pancrelipase-specific or class-level 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 claim of pancrelipase mitochondrial damage was found (the consumer pages opened raise none: the interaction page [14], a professional monograph [21] and a consumer page [22]). The consumer-claim audit was limited by exhausted search. A disclosed gap, not a finding of safety. Likely a thin literature with a tooling-limited search; re-check.

What was searched

PubMed search listing "pancrelipase mitochondria": one result, a diabetes mitochondria review that merely carried pancrelipase as an index term; no enzyme administration. The four DailyMed labels contain no mitochondrial content.

Channel outcomes

One phrasing on PubMed only in the original pass. Repair pass: no additional mitochondrial phrasing could be run, because PubMed listings were rate limited (HTTP 429) and web search budget was exhausted; the repair-pass oxidative stress listing returned no mitochondrial record either. Crossref, Europe PMC, Semantic Scholar and Unpaywall were not queried because direct access is blocked by network policy. Mixed result: a clean null on one phrasing, plus tooling limits.

Oxidative Stress

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

Oxidative stress

Not graded — disclosed evidence gap

See study details

No study was found in which pancrelipase was given and redox or antioxidant markers were measured as a drug effect.

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: A lead exists but is unread. A grade needs the cohort test (was a named pancrelipase product given), the measured parameters and the direction, none of which could be confirmed from the title-level record; a yellow cannot be assigned on a title. No circulating oxidative stress claim for pancrelipase was found. This is a tooling-limited gap with a specific next step: open the abstract or full text of PMID 9667502 [23]; if a pancreatic enzyme product was administered and glutathione peroxidase or selenium was measured against dose or no treatment, the entry would move to yellow (Tier B or C, mechanism untested, cystic fibrosis confounding stated) and would be reverse- or forward-direction according to the result. Do not read this as a finding of safety.

What was searched

PubMed listing "pancrelipase oxidative stress": six results, none an enzyme administration study (mouse, cell-line and plant-extract papers carrying pancrelipase as an index term). A longer phrasing combining pancreatic enzymes with antioxidant status and cystic fibrosis returned a PubMed home page, not results; a second phrasing hit a 429. Repair pass, listing "pancreatin antioxidant cystic fibrosis": ten records, mostly historical cystic fibrosis reviews and uric acid papers with no antioxidant measurement. One title is on point: Winklhofer-Roob et al., "Effects of pancreatic enzyme preparations on erythrocyte glutathione peroxidase activities and plasma selenium concentrations in cystic fibrosis", Free Radic Biol Med 1998 (PMID 9667502) [23]. The OpenAlex record confirmed title, authors, year and DOI but carries no abstract. The PubMed record, a PubMed uid listing, the Crossref DOI record and the ScienceDirect page for it all returned HTTP 429, so the cohort (which enzyme products, how many patients), the direction of the glutathione peroxidase and selenium result, and any effect size could not be read.

Channel outcomes

Tried this pass: PubMed listing (one success, several 429s), OpenAlex single record (success, no abstract), OpenAlex keyword search (429), PubMed single record (429, three attempts across waits of up to 3 minutes), Crossref single DOI (429), ScienceDirect (429), web search (budget exhausted). Other bibliographic hosts blocked by policy. EPI-related loss of antioxidant vitamins is a disease effect and is covered under the fat-soluble vitamin entry, not here. Cystic fibrosis confounding applies: selenium and antioxidant enzyme activity are altered by the disease and by malabsorption itself, so even a readable result would need an untreated or dose-contrast comparison before it could be attributed to the drug.

Copper and Iron Balance

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

Iron: acute absorption, single small study, product unnamed

Yellow — Low

See study details

A 1989 study found reduced iron absorption after a pancreatic enzyme preparation in both cystic fibrosis patients and healthy controls; no iron status effect in treated patients has been shown, and iron deficiency is common in the underlying disease.

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 and contrary findings: A prospective observational study of microencapsulated pancreatin in 58 chronic pancreatitis patients with EPI, followed 8 to 12 months, reported improved iron among other nutritional markers [9]. That study had no untreated control and an unnamed product, so it cannot offset [8], but it points the other way for chronic exposure.
  • At-risk subgroups: Cystic fibrosis (iron deficiency is documented in about one third per the [8] abstract), menstruating women, people with low intake.

Regulatory status

No iron statement in the Creon, Zenpep, Viokace or Pancreaze label text retrieved [1][2][3][4].

Population evidence

Zempsky 1989 [8]: 13 young adults with cystic fibrosis and 9 healthy controls; iron absorption measured over 3 hours with and without a pancreatic enzyme supplement. Baseline hemoglobin was normal in all. Absorption was significantly impaired after the enzyme preparation in both groups, and absorption correlated inversely with iron stores. The authors suggested chronic enzyme use may contribute to iron deficiency. No effect size or confidence interval was available in the abstract text opened. The abstract (OpenAlex record) reports elevated serum ferritin in patients versus controls, while the PubMed listing summary described depleted stores; the two retrievals disagree and the full text was not opened.

Mechanism

Not established in the text opened. The study reports the functional absorption result only.

Cohort test

The intervention was "a preparation of pancreatic enzymes", the same drug category, but the abstract does not name the product or confirm lipase, protease and amylase content. Treated as unconfirmed cohort identity, so capped at yellow. Not a class extrapolation to a different drug.

Counter-evidence held on record

Counter-evidence and confounding Iron deficiency is a known feature of cystic fibrosis and EPI, so any deficiency in treated people is presumed disease-driven (Hard Rule 6). The absorption effect in healthy controls in [8] argues against pure confounding for the acute effect, but this is one 3-hour study from 1989 with no replication located. A 3-hour absorption test is functional, not a status measure. Framing caution This is a monitoring prompt, not a deficiency claim. Iron deficiency is not anemia, and anemia is not iron deficiency (Hard Rule 2). Iron supplementation is not recommended by this entry; excess iron carries its own risks.

Copper

Not graded — disclosed evidence gap

See study details

No evidence was found that pancrelipase alters copper absorption, status or handling.

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 evidence for a copper effect, and no circulating copper claim for pancrelipase found. Copper is kept independent of Iron (Hard Rule 7). Not a finding of safety.

What was searched

PubMed listing "pancrelipase copper": the one relevant record is a 1983 in vitro analysis of low-molecular-weight metal-binding ligands in Viokase, a porcine pancreatic extract used in acrodermatitis enteropathica; it focused on zinc-binding ligands, used copper-containing buffers as an analytical tool, and reported amino-acid ligands, with no copper status, absorption or depletion result [13]. It does not support a copper effect, so it is not used as a Tier B source for one. The four labels contain no copper content.

Channel outcomes

Original pass: one PubMed phrasing plus an OpenAlex single-record lookup of [13]. Repair pass: PubMed listings "cystic fibrosis copper zinc pancreatic enzyme" and "pancreatic enzyme therapy serum copper selenium zinc" both returned HTTP 429 (the second twice, after waits up to 3 minutes), so no new copper record was read. The one related item surfaced anywhere in this review is the selenium and glutathione peroxidase study [23], which concerns selenium, not copper, and is not used for this entry. Confounding by cystic fibrosis and EPI (zinc, copper and selenium malabsorption) would apply to any copper finding in treated people. Genuine thin literature, with limited retrieval depth.

Gut Microbiome Risk

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

Gut microbiome risk: reverse direction, indication-linked

Yellow — Low

See study details

EPI is associated with gut dysbiosis, and enzyme replacement shifts the microbiome toward healthy composition in one minipig study and one small human cohort; no harmful microbiome effect of the drug has been shown.

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 and contrary findings: A 2024 veterinary review (dogs and cats) as seen in a PubMed listing summary noted enteric dysbiosis can persist despite enzyme therapy [19]; not opened. No human study showing enzyme-induced harm was located.
  • At-risk subgroups: Not defined by the sources.

Regulatory status

Not mentioned in the four labels retrieved [1][2][3][4].

Population evidence

Ritz 2020 [10]: duct-ligated minipigs (animal, Tier B). Alpha diversity fell after EPI induction and returned to a nearly healthy state after enzyme replacement; pathobionts such as Escherichia/Shigella, Acinetobacter and Stenotrophomonas fell. Animal numbers and the enzyme product were not given in the abstract. Halle-Smith 2026 [11]: prospective observational cohort, 25 patients with pancreatic disease; pathogenic genera including Viridans group Streptococcus and Campylobacter were higher in PEI than controls and fell after at least 4 weeks of enzyme therapy (shotgun metagenomics). Product not specified; no effect estimate in the abstract.

Mechanism

Named in [10]: reversal of EPI-induced dysbiosis and bacterial overgrowth by restored digestion. The direction is protective or normalizing.

Cohort test

Enzyme replacement was the intervention in both studies, but neither abstract names the product. Treated as unconfirmed cohort identity; yellow regardless because the finding is reverse-direction.

Counter-evidence held on record

Counter-evidence and confounding The dysbiosis is attributed to EPI, not to the drug, and the human study has no untreated comparison after baseline, a small sample, and no control for diet or antibiotics. Concurrent PPI use, common in this population, may itself alter the microbiome and is not separated in the abstracts. Framing caution Not a deficiency or harm claim. Do not present enzyme therapy as a microbiome treatment; the evidence is preliminary.

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

No evidence was found that pancrelipase lowers hemoglobin, red-cell mass or tissue oxygen delivery through a route independent of the iron entry.

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 evidence of a drug effect on oxygen delivery, and no circulating oxygen-carrying claim for pancrelipase found. Any iron-mediated effect is carried by the Iron entry and not double-counted (see Overlap map).

What was searched

PubMed listing "pancreatic enzyme replacement therapy hemoglobin anemia iron": one result, a pediatric case report of EPI presenting with bruising, in which enzymes plus iron and fat-soluble vitamins normalized hemoglobin and red-cell indices [18]. This is disease-driven anemia treated with co-interventions, not a drug effect on oxygen delivery, and it was seen only as a listing summary. Anemia is an outcome, not a nutrient (Hard Rule 2).

Channel outcomes

Original pass: one PubMed phrasing. Repair pass: PubMed listing "pancreatic enzyme supplementation hemoglobin anemia cystic fibrosis" returned HTTP 429 and was not repeated; web search budget exhausted; other hosts blocked. No new record was read. Any hemoglobin finding in treated people would be confounded by cystic fibrosis or pancreatitis (iron deficiency, inflammation, blood loss, vitamin malabsorption) and would be an outcome, not a nutrient (Hard Rule 2). Tooling-limited with a likely thin literature.

ATP production

Not graded — disclosed evidence gap

See study details

No evidence was found that pancrelipase affects mitochondrial ATP synthesis or cellular energy output.

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 evidence and no circulating "low energy from pancrelipase" claim found. Kept independent of Mitochondrial burden and Oxygen delivery/utilization. Not a finding of safety.

What was searched

The same "pancrelipase mitochondria" PubMed listing as the Mitochondrial burden entry returned nothing on energy output. No separate ATP phrasing was run (budget and rate limits). The labels contain no ATP or energy-metabolism content.

Channel outcomes

Shared with Mitochondrial burden; the gap is one gap viewed twice (see Overlap map). Repair pass: no separate ATP or energy-metabolism phrasing could be run (HTTP 429 on PubMed listings, web search budget exhausted). Tooling-limited.

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 (reduced absorption)

    Where it comes from: A Drugs.com food/nutrient interaction page (Tier D) states pancrelipase may reduce the effectiveness of folic acid and iron by interfering with their absorption and advises separating dosing times; it cites no source [14].

    Why it fails: None of the four current labels retrieved mentions folic acid [1][2][3][4]. PubMed listings for "pancrelipase folate" and "pancreatin folic acid" returned no study of folate absorption or serum folate with enzyme therapy; one 1985 chronic pancreatitis record (PMID 4018710) mentions folic acid measured with pancreatin but its results were not shown and the record was not opened. No mechanism for folate was found. Re-check needed because of limited retrieval depth. The iron half of the same claim is graded separately (yellow).

How the body handles this medication

Metabolism and enzymes
The lipases, proteases and amylases are not substrates of CYP enzymes or transporters. CYP or transporter mediated drug interactions are not expected. No CYP induction or inhibition is described.[1][2][4] DailyMed Creon, Zenpep, Pancreaze, sec 12.3 (via summarizing fetch)
Absorption and site of action
Not absorbed from the gastrointestinal tract in appreciable amounts. The enzymes act in the gut lumen. No absorption transporter applies. Crushing, chewing, or mixing capsule contents with foods of pH above 4.5 can disrupt the enteric coating.[1][2][3][4] sec 12.3, 5.2
Elimination and accumulation
No renal or hepatic elimination pathway is described in the label text retrieved. The Zenpep label states pancrelipase is minimally absorbed systemically. Accumulation in renal or hepatic impairment is not described in the retrieved text.[2] sec 8.1 (via summarizing fetch)
Source and purine content
Extract of porcine pancreatic glands. The labels state that pancreatic enzyme products contain purines that may increase blood uric acid levels, and that high dosages have been associated with hyperuricosuria and hyperuricemia. Pancreaze adds a suggestion to consider monitoring uric acid in patients with gout, renal impairment or hyperuricemia.[1][2][3][4] sec 5.3
Acid dependence and co-therapy
Viokace (non-enteric-coated) is indicated in combination with a proton pump inhibitor for EPI due to chronic pancreatitis or pancreatectomy in adults; its label cites omeprazole in the clinical study. Acid suppression is therefore a common co-prescription, and its own nutrient signals belong to the PPI and H2 blocker dossiers, not here.[3] indications and administration (via summarizing fetch)
Food, mineral and nutrient interactions
No folic acid, iron, vitamin, calcium or nutritional-status statements were found in the Creon, Zenpep, Viokace or Pancreaze label text retrieved. Dose-related safety: doses above 6,000 lipase units/kg/meal have been associated with colonic stricture (fibrosing colonopathy) in children under 12. Pertzye label: not opened.[1][2][3][4] sec 5.1, 7, 12.3

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.

  • Lab / baseline and periodic

    Fat-soluble vitamins

    25-OH vitamin D, vitamin A, vitamin E and a vitamin K marker (such as prothrombin time) are worth checking in people with EPI or cystic fibrosis, as a disease-management step. A 2023 AGA clinical practice update, seen only as a PubMed listing summary, recommends supplementation and monitoring of fat-soluble vitamin levels alongside enzyme therapy [20]. This is a monitoring prompt, not a finding of drug-caused deficiency.

  • Lab / symptoms

    Iron indices

    Complete blood count and ferritin if fatigue, pallor or heavy menstrual loss; interpret ferritin with inflammation in cystic fibrosis. A consumer interaction page advises separating iron and enzyme doses [14]; no label establishes a separation interval, so any timing question belongs to a pharmacist.

  • Lab / high dose or gout

    Serum uric acid

    Consider checking in people with gout, renal impairment or hyperuricemia, and in those on high lipase doses, consistent with the Pancreaze label wording [4].

  • Safety outcome, not a nutrient

    Dose ceiling and colonic symptoms

    Labels link doses above 6,000 lipase units/kg/meal to colonic stricture (fibrosing colonopathy) in children under 12 [1][2][3][4]. A 1997 case-control study (29 cases, 105 controls) found relative risks of 10.9 for 24,001 to 50,000 and 199.5 for above 50,000 lipase units/kg/day, with no association for product strength, coating or manufacturer, as read from a PubMed listing summary [12]. Persistent abdominal pain or distension should be reported to the prescriber. This is an outcome and is not filed as a nutrient finding.

  • Co-prescription

    Acid suppression

    Viokace is labeled for use with a PPI [3]. PPI and H2 blocker nutrient signals (B12, magnesium, iron) are covered in those drugs' dossiers and should not be attributed to pancrelipase. Same-batch ursodiol, whose fat-soluble vitamin absorption is a related topic, was not opened for this dossier.

Overlap map, to prevent double counting

  • Iron

    Shares evidence with: Fat-soluble vitamin status

    Note: The same observational study [9] reports iron and vitamin D changes. One study, not two confirmations.

  • Iron

    Shares evidence with: Fails verification: folic acid

    Note: One Tier D page [14] makes both claims. It is one unsupported source, with iron carrying a real (yellow) study [8] and folic acid carrying none.

  • Iron

    Shares evidence with: Oxygen delivery/utilization (ungraded)

    Note: Any anemia effect would run through iron. The pediatric case report [18] is cited only in the oxygen and vitamin context, not as iron evidence.

  • Fat-soluble vitamin status

    Shares evidence with: Gut microbiome risk

    Note: Common upstream mechanism: restoring fat digestion in EPI. The sources are separate [9][15] versus [10][11], but the improvements may reflect one underlying effect, not independent signals.

  • Uric acid elevation

    Shares evidence with: None

    Note: Rests on the repeated label warning [1][2][3][4], which is one regulatory text family, plus two studies [6][7] that disagree.

  • Mitochondrial burden

    Shares evidence with: ATP production

    Note: Both ungraded from the same search outcome. One gap viewed twice.

  • Copper

    Shares evidence with: Iron

    Note: No shared source. The only copper-related record [13] is in vitro ligand chemistry and is used for neither. Graded separately per Hard Rule 7.

  • Oxidative stress

    Shares evidence with: Fat-soluble vitamin status

    Note: No shared evidence; vitamin E and carotenoids were not measured in any opened source, so the vitamin entry does not stand in for an oxidative stress finding. The unread glutathione peroxidase and selenium lead [23] supports no entry at present and, if later opened, would belong to Oxidative stress only; it would not count as copper evidence.

All references used above
  1. CREON (pancrelipase) delayed-release capsules, DailyMed label (setid 073201aa), AbbVie. — Regulatory label (Tier A). Revised 2/2024 per the retrieved page. Indication, sec 5.1 to 5.5, adverse reactions, 12.3, excipients. Read through a summarizing fetch tool, not as raw label text. A second DailyMed Creon record (setid c29a4461, label update 4/1/2026) was a bulk-ingredient manufacturing label with no clinical sections and was not used.
  2. ZENPEP (pancrelipase) delayed-release capsules, DailyMed label. — Regulatory label (Tier A). Revised 7/2025. Sec 5.1 to 5.5, 8.1, 12.3. Summarizing fetch.
  3. VIOKACE (pancrelipase) tablets, DailyMed label. — Regulatory label (Tier A). Revised 7/2025. Indication in combination with a PPI, fibrosing colonopathy, hyperuricemia, 12.3. Summarizing fetch.
  4. PANCREAZE (pancrelipase) delayed-release capsules, DailyMed label. — Regulatory label (Tier A). Revised 5/2025. Hyperuricemia monitoring wording, 12.3. Summarizing fetch. Pertzye label (setid 481eec00) was not opened.
  5. WHO Collaborating Centre, ATC/DDD Index: A09AA02, multienzymes (lipase, protease etc.). — Reference index. No DDD defined for enzyme preparations. Summarizing fetch.
  6. Hyperuricosuria in cystic fibrosis patients treated with pancreatic enzyme supplements. A study of 16 patients in Israel. Isr J Med Sci 1980. — Observational series, 16 cystic fibrosis patients. PMID 6901713.Seen only in a PubMed search-listing summary; the single record lookup was rate limited. Product not named.
  7. Wiersbitzky S, Ballke EH, Wolf E, Paul W. Uric acid serum concentrations in CF-children after pancreatic enzyme supplementation. Padiatr Grenzgeb 1989;28(3):171-173. — Meal-test study, 16 cystic fibrosis patients aged 7 to 23. PMID 2761994. Abstract opened via OpenAlex record; no DOI provided.Enzyme product not named in the abstract. Summarizing fetch.
  8. Zempsky WT. Effect of pancreatic enzyme supplements on iron absorption. Am J Dis Child / Arch Pediatr Adolesc Med 1989. — Absorption study, 13 young adults with cystic fibrosis and 9 controls. PMID 2756973. DOI 10.1001/archpedi.1989.02150200131032. Abstract opened via OpenAlex record.Product not named. Retrievals disagreed on ferritin direction; full text not opened. Summarizing fetch.
  9. Bideeva TV, Maev IV, et al. Effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in correction of nutritional status in chronic pancreatitis: a prospective observational study. Ter Arkh 2020. — Prospective observational, 58 patients (30 and 28), 8 to 12 months. PMID 32598660. DOI 10.26442/00403660.2020.01.000488. Abstract via OpenAlex record.No untreated control; product class "microencapsulated pancreatin", brand not stated in retrieved text. Summarizing fetch.
  10. Ritz S, Hahn DEE, Wami HT, Tegelkamp K, Dobrindt U, Schnekenburger J. Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency. Microb Cell Fact 2020. — Animal study (Tier B), duct-ligated minipigs, 16S rRNA sequencing. DOI 10.1186/s12934-020-01482-2. PMID 33272255.Abstract via OpenAlex record; animal numbers and product not stated in retrieved text. Summarizing fetch.
  11. Halle-Smith JM, Fung KSW, Efstathiou E, et al. The effect of pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy on gut microbiome composition in pancreatic disease: a prospective cohort study. Pancreas 2026. — Prospective observational, 25 patients. DOI 10.1097/mpa.0000000000002709. Abstract via OpenAlex record.Product not specified. Summarizing fetch.
  12. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med 1997. — Case-control, 29 cases and 105 controls. PMID 9113931.Seen only in a PubMed search-listing summary; not opened as a record. Authors not captured. Used in the Monitoring panel only. The dossier assigns this a safety-outcome role and no nutrient grade.
  13. Martin MT, Jacobs FA, Brushmiller GJ. Metal-binding ligands in Viokase. J Pediatr Gastroenterol Nutr 1983. — In vitro analysis (Tier B), no clinical measures. PMID 6620061. DOI 10.1097/00005176-198302030-00026. Abstract via OpenAlex record.Does not report any copper status effect; not used to support a grade. Summarizing fetch.
  14. Drugs.com, pancrelipase food/nutrient interactions page. — Consumer reference (Tier D). Claims moderate interaction with folic acid and iron; no source cited. Accessed via summarizing fetch. Tier D never supports a grade; used for the circulating-claim audit.Tier D. Not used as evidence.
  15. Haas S, Krins S, Knauerhase A, Löhr MJ. Altered bone metabolism and bone density in patients with chronic pancreatitis and pancreatic exocrine insufficiency. JOP 2015. — Prospective, 50 male chronic pancreatitis patients, 28 with PEI. DOI 10.6092/1590-8577/2898. PMID 25640785. Abstract via OpenAlex record.Enzyme therapy was a comparison variable, product not named. Summarizing fetch.
  16. Vitamin D insufficiency in children, adolescents and young adults with cystic fibrosis despite routine oral supplementation. Am J Clin Nutr 2007. — Cross-sectional, 101 cystic fibrosis subjects and 177 controls. PMID 18065588.Seen only in a PubMed search-listing summary; not opened.
  17. Nutritional status in the first 2 years of life in cystic fibrosis diagnosed by newborn screening. J Pediatr Gastroenterol Nutr 2018. — Prospective multicenter, 105 enrolled, 99 completed. PMID 29543697.Seen only in a PubMed search-listing summary; not opened.
  18. Bruising as the first sign of exocrine pancreatic insufficiency in infancy. Med Pharm Rep 2019. — Single pediatric case report. PMID 31086851.Seen only in a PubMed search-listing summary; co-interventions (iron, vitamins) confound. Context only.
  19. Exocrine pancreatic insufficiency in dogs and cats. J Am Vet Med Assoc 2024. — Veterinary review. PMID 37944252.Seen only in a PubMed search-listing summary; not opened. Animal review, context only.
  20. AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review. Gastroenterology 2023. — Expert review. PMID 37737818.Seen only in a PubMed search-listing summary; not opened. Narrative guidance without drug-level stratification (Tier C); used for the monitoring prompt only.
  21. Drugs.com, Creon professional monograph. — Consumer-facing reference reproducing prescribing information (Tier D for this purpose). Opened through a summarizing fetch; reported no statement on folic acid, iron, vitamins or minerals.Not used as regulatory evidence; the DailyMed labels [1] to [4] are.
  22. Drugs.com, pancrelipase consumer information page. — Consumer reference (Tier D). Opened through a summarizing fetch; reported no iron, folate or vitamin statement, and a general "gout or high levels of uric acid" disclosure prompt only.Tier D. Not used as evidence.
  23. Winklhofer-Roob BM, Tiran B, Tuchschmid PE, van't Hof MA, Shmerling DH. Effects of pancreatic enzyme preparations on erythrocyte glutathione peroxidase activities and plasma selenium concentrations in cystic fibrosis. Free Radic Biol Med 1998. — Cystic fibrosis cohort (size and design not read). PMID 9667502. DOI 10.1016/s0891-5849(98)00061-6. Title, authors, year and DOI read from an OpenAlex record and a PubMed listing row; no abstract available.Abstract and results NOT opened (PubMed record, PubMed uid listing, Crossref and ScienceDirect all returned HTTP 429). Cohort test not completed; enzyme product, sample size and direction unknown. Supports no grade. Candidate lead for the Oxidative stress entry, re-check.