Two Overlooked Mycotoxins on Your Panel:Where Citrinin and Mycophenolic Acid Come From — and How to Work Them Up

When a mycotoxin profile flags citrinin (reported as its urinary metabolite dihydrocitrinone) or mycophenolic acid, the reflex in many clinics is to assume a water-damaged building and reach for binders. That reflex is sometimes right and often premature. Both of these toxins carry a substantial dietary and pharmacologic footprint that can drive a positive result with no indoor mold source at all. Sorting exposure into three buckets — environmental, dietary, and pharmacologic — before intervening is the difference between a targeted plan and a client committed to remediation and a binder protocol they may not need.

Two Toxins, Three Questions

Citrinin and mycophenolic acid both appear on the expanded LC–MS/MS mycotoxin panels (such as the Mosaic Diagnostics MycoTOX Profile) rather than the smaller antibody-based panels. Both are produced predominantly by Penicillium and Aspergillus species — the same genera that dominate water-damaged indoor environments. That shared microbial origin is exactly why they are so easy to over-interpret: a genuine building source and a jar of supplements can produce the same line on a report. Every elevated result deserves the same three questions before anything else happens:

• Environmental — Is there a water-damaged building or occupational exposure?
• Dietary — Fermented foods, stored grains, aged cheeses, or fungal-fermented supplements?
• Pharmacologic — Is the client taking a medication that IS the toxin, or that alters its clearance?

Citrinin / Dihydrocitrinone: The Red Yeast Rice Trap

Citrinin is a nephrotoxic mycotoxin produced by Penicillium (notably P. citrinum, P. verrucosum, P. expansum), Aspergillus (including A. terreus, A. niveus), and Monascus species.¹ It contaminates cereals, grains, nuts, spices, fruits, and fermented foods.¹˒² After oral exposure it is extensively biotransformed to dihydrocitrinone (DHC), its major urinary metabolite — which is what the panel actually measures.² Human biomonitoring surveys across Europe detect citrinin and DHC in urine frequently, indicating widespread low-level exposure that is largely dietary in origin.³

The mechanism worth respecting

The kidney — specifically the proximal tubular epithelium — is citrinin's target organ, with mitochondrial dysfunction and oxidative stress central to its toxicity.¹˒⁴ The European Food Safety Authority identifies nephrotoxicity as the critical effect and derived a no-observed-adverse-effect level of 20 µg/kg body weight per day from a 90-day rat study, alongside residual uncertainty about genotoxicity and carcinogenicity.⁴ Citrinin also co-occurs with ochratoxin A because Penicillium and Aspergillus produce both, and the two toxins act additively or synergistically — a reason to read the whole panel rather than a single analyte.⁵

The single highest-yield question

Ask directly about red yeast rice. Red yeast rice — rice fermented with Monascus purpureus and marketed for cholesterol support — is a classic hidden citrinin source, because some Monascus strains produce citrinin as a secondary metabolite.⁶ A Taiwanese survey of 302 products found citrinin in 69% of raw red yeast rice and 35% of dietary supplements.⁷ The U.S. NCCIH explicitly warns that red yeast rice products can carry citrinin capable of damaging the kidneys, and independent analyses continue to find products exceeding regulatory limits.⁸˒⁹ A client taking red yeast rice for lipids can light up the citrinin line with no building involvement whatsoever.

• Other dietary contributors: stored or spoiled grains and cereals, peanuts and other nuts, spices, and some aged cheeses and fermented Asian foods (miso, sake).¹˒²

Mycophenolic Acid: Rule Out the Prescription First

Mycophenolic acid (MPA) is produced mainly by Penicillium species — P. brevicompactum, P. roqueforti, P. bialowiezense.¹⁰˒¹¹ Because P. roqueforti is the ripening organism for blue-veined cheeses, MPA has been proposed as a marker for Penicillium-infected food.¹¹ Before treating an elevated MPA as environmental, two confounders have to be excluded.

Confounder 1: The medication that IS the toxin

MPA is the active moiety of the immunosuppressant drugs mycophenolate mofetil (CellCept) and mycophenolate sodium (Myfortic). These prodrugs are rapidly hydrolyzed to MPA in the body.¹²˒¹³ Any client taking one of these will show high urinary MPA — and that is the drug, not mold. There is no way to interpret an MPA result without a medication reconciliation first.

Confounder 2: Blue cheese

Blue-veined cheeses routinely carry MPA. Surveys have found MPA in 37% of a worldwide blue-cheese collection, with reported levels ranging from below 10 up to 1,200 µg/kg in blue-veined cheeses — and one blue-white mold cheese as high as 11,000 µg/kg.¹⁴˒¹⁵ A client who eats blue cheese regularly has a plausible dietary explanation for a modest elevation.

Why MPA matters clinically

MPA is a potent, selective inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo guanosine nucleotide synthesis.¹²˒¹³ Proliferating T and B lymphocytes depend uniquely on that pathway, so IMPDH inhibition selectively suppresses lymphocyte proliferation — which is exactly why it is a transplant drug.¹³ Framed the other way: chronic environmental MPA exposure is a plausible contributor in a client with recurrent infections or blunted immune signaling, once diet and medication are excluded.

What Both Toxins Point Toward

If diet and medications are genuinely clean, the shared Penicillium/Aspergillus origin becomes meaningful. These are quintessential water-damage indoor molds: both genera are among the fungi most consistently recovered from damp and water-damaged buildings, in air and in settled dust.¹⁶˒¹⁷ Building material colonized by Penicillium and Aspergillus has been shown to be cytotoxic in indoor-air studies linking damp workplaces to occupant symptoms and immune effects.¹⁸ So a citrinin-plus-MPA pattern with a clean history genuinely raises the pretest probability of a building source — it just should not be the first conclusion.

A Functional-Medicine Roadmap

Once the three buckets are sorted, I work the case in roughly this order. The through-line is that source identification and removal — not binders — is the intervention that actually moves the needle.

1. Take the exposure history first. Separate environmental, dietary, and pharmacologic contributions before ordering anything else. Catching red yeast rice (citrinin) or mycophenolate/blue cheese (MPA) here can end the workup on day one.
2. Interpret the collection method. Note whether the sample was provoked (glutathione, sauna) or unprovoked. Most reference labs measure random urine and advise against provoking agents, since they can distort levels; a provoked-only elevation in a clean environment reads very differently from a spontaneous one.¹⁹ Results are creatinine-corrected to adjust for hydration, which aids longitudinal comparison.²⁰
3. Assess the environment. ERMI/HERTSMI-2 dust analysis plus a visual and moisture inspection of home and workplace. Marker compounds in dust may indicate risk better than culturable counts alone, and no single test proves a space is safe.²¹
4. Consider colonization if the picture fits. Chronic sinus symptoms or GI dysbiosis can reflect nasal or gut Penicillium/Aspergillus, which can sustain a positive urine result independent of ongoing environmental exposure.
5. Open drainage and detox pathways before aggressive binding. Hydration, bowel regularity, glutathione/NAC, and support for Phase II and biliary flow. Glutathione, antioxidants, and induced sweating are among the supportive measures reviewed in the water-damaged-building literature.²¹
6. Add binders matched to the toxin. Activated charcoal, bentonite clay, and chlorella have the broadest applicability for this Penicillium/Aspergillus cluster.²¹ A pharmacologic aside worth knowing: cholestyramine interrupts the enterohepatic recirculation of MPA and reduces its absorption — relevant to clearance kinetics, though cholestyramine is better evidenced for ochratoxin and trichothecenes than for these two specifically.¹³
7. Monitor the target organs. For citrinin, baseline and follow-up renal function (eGFR, urinalysis, consider cystatin C) given its tubular toxicity.⁴ For MPA, watch immune resilience.
8. Retest after source control. Repeat in roughly three months to confirm a downtrend rather than chasing a single value.

References

1. Faisal Z, et al. Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin. Mycotoxin Res. 2019. PubMed 30426325.

2. Molecules 2019;24:1328. Interaction of Dihydrocitrinone with Native and Chemically Modified Cyclodextrins (citrinin sources; DHC as major urinary metabolite). PMC6479545.

3. Occurrence of the mycotoxin citrinin and its metabolite dihydrocitrinone in urines of German adults (human biomonitoring). ResearchGate/265690790.

4. EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on the risks for public and animal health related to citrinin in food and feed. EFSA Journal 2012 (nephrotoxicity; NOAEL 20 µg/kg bw/day).

5. Combined effects of ochratoxin A with citrinin and their metabolites on cell and zebrafish models. Food Chem Toxicol. 2021. ScienceDirect S0278691521007079.

6. Dietary Supplements Based on Red Yeast Rice — A Source of Citrinin? Toxins (Basel). 2021;13(7):497. PMC8310238.

7. Incidence of citrinin in red yeast rice and various commercial Monascus products in Taiwan, 2009–2012. Food Control. 2013. ScienceDirect S0956713513005392.

8. National Center for Complementary and Integrative Health (NCCIH). Red Yeast Rice fact sheet. nccih.nih.gov/health/red-yeast-rice.

9. Quality Control and Safety Assessment of Online-Purchased Food Supplements Containing Red Yeast Rice. PMC11202976.

10. Del-Cid A, et al. Identification and Functional Analysis of the Mycophenolic Acid Gene Cluster of Penicillium roqueforti. PLoS One 2016;11:e0147047. PMC/journals.plos.org.

11. Development and application of monoclonal antibodies against the mycotoxin mycophenolic acid (MPA as marker for Penicillium-infected food; immunosuppressive toxin). Mycotoxin Res. 2015. Springer 10.1007/s12550-015-0229-3.

12. Sintchak MD, et al. Structure and Mechanism of Inosine Monophosphate Dehydrogenase in Complex with the Immunosuppressant Mycophenolic Acid. Cell 1996. ScienceDirect S0092867400812751.

13. CellCept (mycophenolate mofetil) clinical pharmacology: MMF is a prodrug rapidly hydrolyzed to MPA, a selective uncompetitive IMPDH inhibitor; cholestyramine/colestipol reduce MPA absorption via enterohepatic recirculation. Product monograph.

14. Fontaine K, et al. Occurrence of roquefortine C, mycophenolic acid and aflatoxin M1 in blue-veined cheeses. Food Control. 2014 (MPA quantifiable in 37% of cheeses). ScienceDirect S0956713514004319.

15. Usleber E, et al. Enzyme immunoassay for mycophenolic acid in milk and cheese (MPA <10–1200 µg/kg in blue-veined cheeses). J Agric Food Chem. 2008. Summarized in PMC5076727.

16. From mold to mycotoxins: an LC–MS/MS method for quantifying airborne mycotoxins in indoor environments (Aspergillus/Penicillium in water-damaged buildings). PMC12325524.

17. Mycobiota and mycotoxin-producing fungi in water-damaged houses (Penicillium among most common indoor species). PMC9673783.

18. Toxic Indoor Air Is a Potential Risk of Causing Immunosuppression and Morbidity — A Pilot Study (Penicillium/Aspergillus building material; cytotoxicity). PMC8877819.

19. Reference-laboratory guidance on mycotoxin provocation vs. random-urine collection (US BioTek / RealTime Labs; Mosaic Diagnostics). Clinical practice guidance.

20. Mosaic Diagnostics. MycoTOX Profile overview and creatinine-correction methodology. mosaicdx.com.

21. A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins (glutathione, antioxidants, sequestering agents — cholestyramine, charcoal, clay, chlorella — induced sweating; ERMI). PMC3654247.

About Dr. Kim

Dr. Yoon Hang “John” Kim, MD, MPH is board-certified in Preventive Medicine and practices Integrative & Functional Medicine, bringing more than 20 years of clinical experience. He completed fellowship training as an Osher Fellow under Dr. Andrew Weil at the University of Arizona and holds certifications in preventive medicine, medical acupuncture, and integrative/holistic medicine. He specializes in low-dose naltrexone (LDN), autoimmune conditions, chronic pain, integrative oncology, fibromyalgia, chronic fatigue syndrome, MCAS, and mold toxicity. He is the author of three books and more than 20 peer-reviewed articles.

Learn more at www.yoonhangkim.com (professional) or www.directintegrativecare.com (clinical practice).