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Mold 107: Ochratoxin A - Part 3

Updated: Mar 17

This article is not medical advice. Before starting any health related regimen, seek the advice of your Primary Care Physician or an M.D.

This article summarizes some of the effects by Ochratoxin A prevalent in the existing literature, and then lists potential ways to mitigate these effects that exist in the literature as well. There are a number of factors listed below that point to benefits from anti oxidants themselves (e.g. Vit E) as well as supporting the body's natural antioxidant systems. Understanding your nutritional status of various anti oxidants and your genetic status for various anti oxidant genes may be something to consider. Lastly, a number of probiotics show absorption capability of OTA and others show biotransformation ability. One potential way to focus and narrow the scope of things to consider is to see where nutritional and genetic weakness exists most profoundly, and to start there in terms of supports.

  • OTA down regulates important anti oxidant enzymes NrF2, through Keap 1

    • Sulfurophane modulates the Keap 1 / NrF2 pathway

  • Inhibits HMOX1 - stores iron into ferritin, controls NADPH/NOX/Mast Cell Activation

    • Hops upregulates HMOX1

  • Upregulates iNOS (POTS), NFKB, and NADPH Oxidase, all NAD consuming

    • iNOS is calmed by Andrographis, Oregano, Sage, Resveratrol, Fenugreek

    • NFKB is calmed by Resveratrol and Hops

    • NADPH Oxidase is calmed by Blueberry extract, Rosemary, Fisetin, Quercetin,

  • Excess nitrosation - peroxynitrite, damaging free radical

    • Hydroxy B12, Rosemary, Witch Hazel, Pycnogenol are peroxynitrite scavengers

  • Lowered amino acid catabolism - higher amino levels, lower fatty acid oxidation, higher carnitine, and lowered Alinine

    • Phenylainine helps recover the suppressed gene function PHEN

  • Mitochondrial Dysfunction (membrane potential compromise - phospholipid and cell membrane oxidations)

  • ER Stress, Super Oxide, and Calpain production have recently become a focus in research related to cell death.

    • OTA induces calpain activity, and apocynin attenuates this stress.[10] It is also a potent inhibitor of NADPH Oxidase[29].

  • Metabolic dysfunction (amino acid and fatty acid metabolism effected)

  • Glial cell reactivity, brain inflammation

  • Mast cells are stimulated by elevated iNOS, NADPH Oxidase, and impairment of HMOX1

  • Induction of Aryl Hydrocarbon Receptor - AHR - NMDA Receptor Activation

    • AHR is calmed by Rosemary and Milk Thistle (which inhibits Glucuronidation)

  • Induction of HIF1a - Hypoxia

    • Which can be calmed by Astragulus and Rhodiola

  • Induction of Ferroptosis (unmitigated cell death) via GPX4 and FXR Inhibition and Iron Dysregulation - upregulation of iron importers and down regulation of iron exporters.

    • GPX4 is upregulated by : Andrographis, Astragulus, and Rosemary

    • FXR is induced by Reishi and Physlium Husk

    • Circumin is a potent iron scavenger

  • Major CYP 450 Phase 1 Pathways for Ochratoxin A:

    • CYP1A1

    • CYP1A2

    • CYP2C9

    • CYP3A4

    • Dill upregulates CYP1A2, CYP2C19, NAT2, and SULT1A1 [31]

    • "In addition to induction of CYP3A4 by St. John's wort, common valerian and Ginkgo biloba increased the activity of CYP3A4 and 2D6 and CYP1A2 and 2D6, respectively. A general inhibitory potential was observed for horse chestnut, Echinacea purpurea and common sage.'[32]

    • "St. John's wort inhibited CYP3A4 metabolism at the highest applied concentration. Horse chestnut might be a herb with high inhibition potentials in vivo and should be explored further at lower concentrations."[32]

    • We show for the first time that G. biloba may exert opposite and biphasic effects on CYP1A2 and CYP2D6 metabolism. Induction of CYP1A2 and inhibition of CYP2D6 were found at low concentrations; the opposite was observed at high concentrations. CYP2D6 activity, regarded generally as non-inducible, was increased by exposure to common valerian (linear to dose) and G. biloba (highest concentration).[32]

  • Major Phase 2 detoxification pathways for OTA (Glutathione, Amino Acid, Glucuronidation)

  • Uses the glutathione gene GSTA1 for glutathione detoxification. [15]

    • Glutathione gene GSTA1 used by OTA is upregulated by Andrographis (inhibits glucuronidation somewhat)

    • Amino Acid conjugated is supported by Glycine, Glutamine

    • Glucuronidation is supported by Rosemary, Astaxanthin, Pterostilbene, Calcium D Glucorate, Dandelion, and Ellagic Acid. Milk Thistle is potent inhibitor of many glucuronidation genes, and Andrographis has some glucuronidation inhibition properties as well.

Biotdetoxification of OTA by Absorption[15]:

  • Sacromyces Boulardii/Cervaisae

  • Lactobacillus plantarum LOCK 0862, L. brevis LOCK 0845, and L. sanfranciscensis LOCK 0866 reduced the absorption of OTA - perhaps potential binders

  • bacillus lichenformis (in MegaSpore Biotic)

Astaxanthin alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, mff), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance.[16]

  • Astaxanthin upregulates NrF2, and PON1 which is a Super Oxide scavenging gene.

Selenium combined with other antioxidants, such as CoQ10, L-carnitine, Zn, Mg, N-acetyl cysteine, vitamin C, vitamin E or tamoxifen, to intervene in apoptosis induced by OTA in livers of mice was also investigated. [17]

  • Selenium is the cofactor for many of the glutathione enzymes (GPX, GST's)

  • High dose selenium (dose TBD) has been shown to induce ferroptosis - so care must be taken on dosing (generally 100mcg or less).

OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA and could alleviate oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.[18]

  • Circumin also upregulates NrF2, scavenges iron, and regulates TNFA.

The degradation of OTA to OTα (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3-R-methylisocoumarin) is the most important mechanism of OTA biodegradation, OTα is considered much less toxic than OTA. Bacillus subtilis degrades OTA. [15]

  • Bacillus subtilis CW 14 could degrade 97.6% of OTA (6 μg/mL) within 24 h, and is a common spore based probiotic species found in Megaspore, Just Thrive, and many others.

Melatonin exhibits a preventive effect against OTA-induced oxidative stress, and structural damage in the kidney through its role in the scavenging of free radicals and/or the prevention of lipid peroxidation. Alpha-tocopherol (vitamin E) in the diet decreased by 58% the total DNA adduct provoked in kidney by a single administration of OTA in mouse and rat kidney. Vit C, Artichoke extract and sesame seeds given to laying hens in their diet showed protection against decreased egg production and toxic effect on various organs due to ochratoxin. Vitamins A, C, E with pre treatment showed reduced number of DNA adducts in kidney by 70%, 90%, 80% for Vitamins A, C, E. [17,26]

  • Melatonin scavenges hydroxyl radicals, Vit E helps lipid peroxidation, artichoke and sesame are interesting

Selenium blocks the increases of DNMT1, DNMT3a and HDAC1 mRNA and protein expression, reversed the decreases of glutathione peroxidase 1 (GPx1) mRNA and protein expression, and promoted the increases of SOCS3 mRNA and protein expression induced by OTA.[27]

  • Selenium is the cofactor for most of the GPX and GST genes (glutathione peroxidase, and s transferese).

  • GPX1 is upregulated by Panax Gensing

Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. Lycopene is found in red, pink and orange colored foods, including tomatoes, watermelon, pink grapefruit, asparagus, red cabbage, guava, papaya, red bell pepper, persimmon, and mango. Green Tea (EGCG) has also been shown to be effective in offering protection from OTA.[28]

  • Lycopene up regulates GSR, which recycles glutathione

  • EGCG protects GPX4 from being downregulated, by blocking the GPX4 inhibition site from RS3. EGCG is a potent inhibitor of COMT, so consideration of COMT status should be given.

The cyanidin 3-O-β-D-glucoside (C3G), an anthocyanin with anti oxidant effects found in beans, fruits, vegetables and red wine, might counteract oxidative damage from OTA.[25]

  • Consistent with Catalase, GPX4, SOD - anti oxidant support may be helpful.

Licorice extract showed a protective effects from OTA in rats. [22]

  • Licorice downregulates iNOS / NOS2; NOS2 can produce super oxide (a free radical)

  • Licorice can raise blood pressure significsntly.

Melatonin helped to protect rats who were exposed to OTA for 28 days. [22]

Green coffee powder protected rats from OTA effects. [24]

  • Caffeine induces sulfation

Catalase and SOD have protective effect in rats exposed to OTA. [22]

  • Exogenous Catalase (SuperSmart), SOD Booster By Life Extension, NrF2 / Keap1 / NQO1 support all helpful too.

N-acetyl Cysteine has  been shown to combine directly with OTA or metabolites and is removed in the urine.

  • NAC is usually the rate limiting ingredient in glutathione production.

Resveratrol is used by grapes to control Aspergillus carbonarius growth and ochratoxin A biosynthesis, and has also been used in research to attenuate damage from OTA.

  • Resveratrol upregulates NrF2 / Keap 1 / NQO1, Sulfurophane much stronger.

Phenylalinine prevents poisoning in mice from OTA.[20]

Three herbs, Silybum marianim - Milk thistle, Withania somnifera - Ashwaghanda, and Centella asiatica - Gotu kola were all shown to protect young chicks from OTA toxicity.[21]

  • Interestingly Milk Thistle downregulates glucuronidation, so this one has conflicting information.

SLC7A11 - Important for Using Cysteine To Create Glutathione

"System Xc- is an important antioxidant system composed of solute carrier family 7 member 11 (SLC7A11) and solute carrier family 3 member 2 (SLC3A2) subunits in the cell membrane, which is essential for the synthesis of glutathione . It can take up extracellular cystine in the cell in a 1:1 ratio and is rapidly reduced to cysteine while pumping out glutamate. Furthermore, a study found that tumor suppressor gene p53 could inhibit the absorption of cystine by System Xc- via down-regulating the expression of SLC7A11, which ultimately triggered ferroptosis. Therefore, GSH, GPX4, and system Xc- are important targets for regulating ferroptosis by medicines"[30]

Fucoidan - Rescues SLC7A11

"Ferroptosis is caused by lipid peroxidation, and Chinese herbal medicine can be used to treat ferroptosis-related diseases. Some researchers showed that fucoidan inhibited iron overload induced by long-term alcohol exposure and protected hepatocytes from ferroptosis. Specifically, fucoidan attenuated alcohol-induced liver oxidative damage in rats by upregulating the p62/Nrf2/SLC7A11 pathway and lowering serum ferritin levels, thereby inhibiting ferroptosis. The environmental pollutant di (2-ethylhexyl) phthalate (DEHP) is a threat to human health. In rats, Dai found that DEHP exposure disrupted iron ion homeostasis, increased lipid peroxidation, and inhibited cysteine/glutamate antiporter, whereas lycopene supplementation dramatically suppressed these ferroptosis characteristics"[30,33]


  1. Ochratoxin A-mediated DNA and protein damage: roles of nitrosative and oxidative stresses

  2. Peroxynitrite scavenger reference

  3. Curcumin Modulates Nitrosative Stress, Inflammation, and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats. by Consiglia Longobardi, Sara Damiano, et. al. Department of Mental, Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Largo Madonna delle Grazie 1, 80138 Napoli, Italy. Antioxidants 2021, 10(8), 1239;

  4. Differential modification of inflammatory enzymes in J774A.1 macrophages by ochratoxin A alone or in combination with lipopolysaccharide. By M C Ferrante 1G Mattace Raso. Toxicol Letters. . 2008 Sep;181(1):40-6. doi: 10.1016/j.toxlet.2008.06.866. Epub 2008 Jul 5.

  5. Unusual astrocyte reactivity caused by the food mycotoxin ochratoxin A in aggregating rat brain cell cultures. By M-G Zurich 1S Lengacher, et. al. Neuroscience. 2005;134(3):771-82.

  6. An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling. By Muhamed N. H. Eeza, Narmin Bashirova, et. al. Nature. Scientific reports. Published: 15 April 2022. Scientific Reports volume 12, Article number: 6341 (2022)

  7. Nrf2: a main responsive element in cells to mycotoxin-induced toxicity. By Marta Justyna Kozieł,# Karolina Kowalska. Arch Toxicol. 2021; 95(5): 1521–1533. Published online 2021 Feb 8. doi: 10.1007/s00204-021-02995-4. PMCID: PMC8113212. PMID: 33554281

  8. A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity. By Alice Limonciel, Paul Jennings, et. al.

  9. Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway. By Gengyuan Cui,Lin Li,Weixiang Xu. Oxidative Medicine and Cellular Longevity. 2020. Article ID 7639109 |

  10. Ochratoxin A induces ER stress and apoptosis in mesangial cells via a NADPH oxidase-derived reactive oxygen species-mediated calpain activation pathway. By Meei-Ling Sheu, Chin-Chang Shen, et. al. Oncotarget. 2017 Mar 21; 8(12): 19376–19388.

  11. Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells. By Hyun Jung Lee 1Min Cheol Pyo Food Chem Toxicol. . 2018 Dec:122:59-68. doi: 10.1016/j.fct.2018.10.004. Epub 2018 Oct 3. PMID: 30291945. DOI: 10.1016/j.fct.2018.10.004

  12. Ochratoxin A Induces Renal Cell Ferroptosis by Disrupting Iron Homeostasis and Increasing ROS. By Sen Wang, Hui Ren. J. Agric. Food Chem. 2024, 72, 3, 1734–1744. Publication Date:December 22, 2023.

  13. Farnesoid X Receptor Plays a Key Role in Ochratoxin A-Induced Nephrotoxicity by Targeting Ferroptosis In Vivo and In Vitro. Jiangyu Tang, Junya Zeng,et. al. FOOD SAFETY AND TOXIcology. J. Agric. Food Chem. 2023, 71, 39, 14365–14378. Publication Date:September 26, 2023.

  14. Is increased susceptibility to Balkan endemic nephropathy in carriers of common GSTA1 (*A/*B) polymorphism linked with the catalytic role of GSTA1 in ochratoxin a biotransformation? Serbian case control study and in silico analysisZorica Reljic 1, Mario Zlatovic . Toxins (Basel). . 2014 Aug 8;6(8):2348-62.doi: 10.3390/toxins6082348. PMID: 25111321. PMCID: PMC4147586DOI: 10.3390/toxins6082348

  15. Advances in Biodetoxification of Ochratoxin A-A Review of the Past Five Decades Wenying Chen,1,2,† Chen Li. Front Microbiol. 2018; 9: 1386. Published online 2018 Jun 26. doi: 10.3389/fmicb.2018.01386 PMCID: PMC6028724 PMID: 29997599

  16. Protective Effects of Astaxanthin on Ochratoxin A-Induced Liver Injury: Effects of Endoplasmic Reticulum Stress and Mitochondrial Fission–Fusion Balance by Yiting Zou, Shiyi Zhang, et. al. Toxins 2024, 16(2), 68;

  17. Toxicity of Ochratoxin A and Its Modulation by Antioxidants: A Review Valeria Sorrenti,1,* Claudia Di Giacomo. Toxins (Basel). 2013 Oct; 5(10): 1742–1766. Published online 2013 Oct 11. doi: 10.3390/toxins5101742 PMCID: PMC3813909 PMID: 24152986

  18. Protective effect of curcumin on ochratoxin A–induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota S.S. Zhai,∗ D. Ruan. Poult Sci. 2020 Feb; 99(2): 1124–1134. Published online 2019 Dec 12. doi: 10.1016/j.psj.2019.10.041 PMCID: PMC7587726 PMID: 32036964

  19. Is increased susceptibility to Balkan endemic nephropathy in carriers of common GSTA1 (*A/*B) polymorphism linked with the catalytic role of GSTA1 in ochratoxin a biotransformation? Serbian case control study and in silico analysis Zorica Reljic 1, Mario Zlatovic, et. al. Toxins (Basel), . 2014 Aug 8;6(8):2348-62. doi: 10.3390/toxins6082348. PMID: 25111321. PMCID: PMC4147586 DOI: 10.3390/toxins6082348

  20. Phenylalanine prevents acute poisoning by ochratoxin-A in mice. By Edmond E. Creppy a b, Monique Schlegel, et. al. Toxicology Letters. Volume 6, Issue 2, July 1980, Pages 77-80 .

  21. Selected herbal feed additives showing protective effects against ochratoxin A toxicosis in broiler chicks. By S.D. Stoev. World Mycotoxin Journal: 12 (3)- Pages: 257 - 268.

  22. Effect of superoxide dismutase and catalase on the nephrotoxicity induced by subchronical administration of ochratoxin A in rats. I Baudrimont 1A M Betbeder, et. al. Toxicology. . 1994 Apr 18;89(2):101-11. doi: 10.1016/0300-483x(94)90218-6. PMID: 8197587. DOI: 10.1016/0300-483x(94)90218-6.

  23. A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis Janette H. Hope 1 ,* and Bradley E. Hope. J Environ Public Health. 2012; 2012: 835059. Published online 2011 Dec 29. doi: 10.1155/2012/835059 PMCID: PMC3255309 PMID: 22253638

  24. Protective effect of Yemeni green coffee powder against the oxidative stress induced by Ochratoxin A. By Qais A Nogaim 1, Lakshmi Sai Pratyusha Bugata, et. al. Toxicol Rep. 2020 Jan 15:7:142-148. doi: 10.1016/j.toxrep.2019.11.015. eCollection 2020. PMID: 31956515. PMCID: PMC6962656. DOI: 10.1016/j.toxrep.2019.11.015.

  25. Protective effect of cyanidin 3-O-beta-D-glucoside on ochratoxin A-mediated damage in the rat. By Claudia Di Giacomo 1, Rosaria Acquaviva, et. al. Br J Nutrition. . 2007 Nov;98(5):937-43. doi: 10.1017/S0007114507756908. Epub 2007 Jun 12. PMID: 17562227 DOI: 10.1017/S0007114507756908

  26. Retinol, ascorbic acid and alpha-tocopherol prevent DNA adduct formation in mice treated with the mycotoxins ochratoxin A and zearalenone. By Y Grosse 1, L Chekir-Ghedira, et. al. Cancer Lett. . 1997 Mar 19;114(1-2):225-9. doi: 10.1016/s0304-3835(97)04669-7. PMID: 9103298. DOI: 10.1016/s0304-3835(97)04669-7.

  27. GPx1-mediated DNMT1 expression is involved in the blocking effects of selenium on OTA-induced cytotoxicity and DNA damage. By Fang Gan 1Yajiao Zhou, et. al. Int J Biol Macromol. . 2020 Mar 1:146:18-24. doi: 10.1016/j.ijbiomac.2019.11.221. Epub 2019 Nov 29. PMID: 31790739. DOI: 10.1016/j.ijbiomac.2019.11.221.

  28. Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats. By S Sezin Palabiyik 1, Pinar Erkekoglu. Exp Toxicol Pathology. . 2013 Sep;65(6):853-61. doi: 10.1016/j.etp.2012.12.004. Epub 2013 Jan 15. PMID: 23332503 DOI: 10.1016/j.etp.2012.12.004.

  29. Apocynin: Molecular Aptitudes. By J. Stefanska and R. PawliczakMediators Inflamm. 2008; 2008: 106507. Published online 2008 Dec 2. doi: 10.1155/2008/106507 PMCID: PMC2593395. PMID: 19096513.

  30. Ferroptosis as a Potential Therapeutic Target of Traditional Chinese Medicine for Mycotoxicosis: A Review. Wenli Ding,1,† Luxi Lin. Toxics. 2023 Apr; 11(4): 395. Published online 2023 Apr 21. doi: 10.3390/toxics11040395 PMCID: PMC10142935 PMID: 37112624

  31. Dill Shows Potential for Herb-Drug Interactions via Up-Regulation of CYP1A2, CYP2C19, SULT1A1, NAT2 and ABCB1 in Caco-2 Cells. By Wachirawit Udomsak, Waranya Chatuphonprasert, Kanokwan Jarukamjorn. Pak J Biol Sci. 2022 Jan;25(1):56-66. doi: 10.3923/pjbs.2022.56.66. PMID: 35001576. DOI: 10.3923/pjbs.2022.56.66

  32. The Induction of CYP1A2, CYP2D6 and CYP3A4 by Six Trade Herbal Products in Cultured Primary Human Hepatocytes. By Bent H. Hellum, Zhuohan Hu, and Odd Georg Nilsen. 22 December 2006. Basic and Clinical Pharmacology and Toxicology.

  33. Fucoidan: Structure and Bioactivity. By Bo Li,* Fei Lu, Xinjun Wei, and Ruixiang ZhaoMolecules. 2008 Aug; 13(8): 1671–1695. Published online 2008 Aug 12. doi: 10.3390/molecules13081671. PMCID: PMC6245444. PMID: 18794778

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