Drug & supplement interaction

Gossypol + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Updated July 2026 · Pair last verified Sep 13, 2026

The bottom line No known interaction

We found no known interaction between Gossypol and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Gossypol and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Gossypol in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Gossypol safety at a glance

Gossypol overall Avoid Gossypol is toxic and is not approved as a safe dietary supplement.

Pregnancy Likely Unsafe When used orally; gossypol seems to have abortifacient and uterine stimulant effects, avoid using. Read the full pregnancy detail

Breastfeeding Possibly Unsafe When used orally; avoid using. Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Gossypol? Ask Dr. Brian Staiger, PharmD, BCPS directly ›

How we checked

Why No Interaction Is Listed for Methotrexate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Gossypol has documented interactions with 4 drug classes — the most serious being digoxin (lanoxin) (moderate), diuretic drugs (moderate) and stimulant laxatives (moderate) — and none of Methotrexate’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Gossypol Does Interact With Other Medications

Gossypol has 104 moderate known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.

Moderate 104 No known interaction 2,726 (incl. Methotrexate)

Taking anything else?

Check Another of Your Medications Against Gossypol

Covers the 2,830 medications we’ve checked against Gossypol. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Gossypol and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 3 of them are worth acting on rather than waiting out — marked below.

A low platelet count Worth acting on Additional detail
Gossypol
“Orally, two cases of mild thrombocytopenia have been reported after taking high doses of gossypol.”

Gossypol · Natural Medicines adverse-effect record, reported in thrombocytopenia.
1 source cited

52616. Bushunow, P., Reidenberg, M. M., Wasenko, J., Winfield, J., Lorenzo, B., Lemke, S., Himpler, B., Corona, R., and Coyle, T. Gossypol treatment of recurrent adult malignant gliomas. J.Neurooncol. 1999;43(1):79-86. PubMed
Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›
Liver problems Worth acting on Additional detail

Gossypol

“Orally, gossypol seems to be well-tolerated when used at doses below 20 mg daily, short-term. Using gossypol long-term or in doses greater than 20 mg daily may be unsafe.

Most Common Adverse Effects:

Orally: Diarrhea, hypokalemia, nausea, and vomiting.

Serious Adverse Effects (Rare):

Orally: When used long-term or in high doses, circulatory problems, dermatologic toxicity, heart failure, hepatotoxicity, infertility (…”

Gossypol · Natural Medicines adverse-effect record, reported in congestive heart failure (chf).

Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›
Bleeding or bruising Worth acting on Additional detail
Gossypol
“Orally, gossypol has been reported to cause nausea in 30% of subjects, vomiting in 15% of subjects, and diarrhea in 10% of subjects in one clinical study. High doses may cause mucosal sloughing, mucosal necrosis, and intestinal hemorrhage. Gossypol has also been reported to cause anorexia, malnutrition, and altered taste sensation.”

Gossypol · Natural Medicines adverse-effect record, reported in anorexia.
6 sources cited

52634. Van Poznak, C., Seidman, A. D., Reidenberg, M. M., Moasser, M. M., Sklarin, N., Van Zee, K., Borgen, P., Gollub, M., Bacotti, D., Yao, T. J., Bloch, R., Ligueros, M., Sonenberg, M., Norton, L., and Hudis, C. Oral gossypol in the treatment of patients wit

166. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.

8290. Coutinho EM, Athayde C, Atta G, et al. Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study. Contraception 2000;61:61-7. PubMed

52824. Aitken, R. J., Liu, J., Best, F. S., and Richardson, D. W. An analysis of the direct effects of gossypol on human spermatozoa. Int.J.Androl 1983;6(2):157-167. PubMed

8292. Herve JC, Pluciennik F, Bastide B, et al. Contraceptive gossypol blocks cell-to-cell communication in human and rat cells. Eur J Pharmacol 1996;313:243-55. PubMed

52665. Randel, R. D., Chase, C. C., Jr., and Wyse, S. J. Effects of gossypol and cottonseed products on reproduction of mammals. J.Anim Sci. 1992;70(5):1628-1638. PubMed
Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›
Reduced appetite Additional detail

Gossypol

Recorded for Gossypol in the same Natural Medicines adverse-effect record shown under Bleeding or bruising above.

Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›
Tiredness reported in 6.7% of FDA reports for Methotrexate Additional detail
Gossypol
“Orally, several studies have found a limited association between gossypol use and fatigue, while another study found no correlation.”

Gossypol · Natural Medicines adverse-effect record, reported in fatigue.
5 sources cited

52819. Liu, G. Z. Clinical study of gossypol as a male contraceptive. Reproduccion. 1981;5(3):189-193.

52749. Coutinho, E. M. and Melo, J. F. Clinical experience with gossypol in non-Chinese men: a follow-up. Contraception 1988;37(2):137-151. PubMed

52634. Van Poznak, C., Seidman, A. D., Reidenberg, M. M., Moasser, M. M., Sklarin, N., Van Zee, K., Borgen, P., Gollub, M., Bacotti, D., Yao, T. J., Bloch, R., Ligueros, M., Sonenberg, M., Norton, L., and Hudis, C. Oral gossypol in the treatment of patients wit

52824. Aitken, R. J., Liu, J., Best, F. S., and Richardson, D. W. An analysis of the direct effects of gossypol on human spermatozoa. Int.J.Androl 1983;6(2):157-167. PubMed

46316. Liu, G. Z., Lyle, K. C., and Cao, J. Clinical trial of gossypol as a male contraceptive drug. Part I. Efficacy study. Fertil.Steril. 1987;48(3):459-461. PubMed
Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›
Nausea / Diarrhea / Vomiting reported in 5.9% of FDA reports for Methotrexate Additional detail

Gossypol

Recorded for Gossypol in the same Natural Medicines adverse-effect record shown under Liver problems above.

Methotrexate

Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

Reported for Gossypol but not commonly for Methotrexate: a change in taste, heart failure, low potassium and changes to your period.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Gossypol come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Gossypol in Pregnancy & Breastfeeding

Pregnancy Likely Unsafe

When used orally; gossypol seems to have abortifacient and uterine stimulant effects, avoid using.

Lactation Possibly Unsafe

When used orally; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Overlapping uses

What Methotrexate Is Prescribed For, and What Gossypol Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Gossypol is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord). Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Gossypol has been studied for:

Lung cancer studied, not established Gossypol has been studied for this. Natural Medicines rates the evidence: Possibly Ineffective Read what the research shows

Gossypol for lung cancer

Several clinical studies suggest that oral gossypol does not improve survival rates or reduce tumor progression in patients with advanced or recurrent non-small cell lung cancer (NSCLC).
Head and neck cancer studied, not established Gossypol has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

Gossypol for head and neck cancer

It is unclear if oral gossypol is beneficial in patients with head and neck cancer.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Gossypol for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Gossypol or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Gossypol or Methotrexate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methotrexate

This page covers Gossypol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

How much people look this up

Where Gossypol and Methotrexate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Gossypol

Top 25%

#346 of 1,452 supplements looked up here in the last 7 days

29 days ago today

Medication Methotrexate

Top 5%

#49 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?

Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Gossypol reference on this page ↓
Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Gossypol and Methotrexate records this page draws on were last updated July 11, 2026.
What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.

Data structure & sourcing designed and verified by Dr. Brian Staiger, PharmD, BCPS.

Supplement

About Gossypol

What is Gossypol?

Male contraception (research interest)
Reduction of sperm production
Endometriosis (historical/research)
Antiviral and antiparasitic research
Cancer cell research

Gossypol is a toxic yellow pigment from cotton plants that has been studied mainly as an experimental male contraceptive because it can lower sperm production. It is not an approved or safe over-the-counter supplement, and it carries serious risks including possibly permanent infertility, low potassium, and organ toxicity. It should not be used for self-treatment.

Gossypium hirsutum · Malvaceae · Seeds (cottonseed) and seed oil; the pigment gossypol is extracted from these · Purified compound used in research; not commonly sold as a standardized consumer supplement

An interaction check asks whether these two react with each other — it does not ask whether Gossypol is a good idea for someone in your situation. Here is what our Gossypol record says about it on its own.

Gossypol: dosing

There is no established safe or standardized dose of gossypol for supplement use. The doses studied in research were used under medical supervision and still carried serious risks.Because gossypol is toxic and not approved as a dietary supplement, we cannot recommend any specific amount. If you encounter a product that lists gossypol, do not use it without first speaking to a pharmacist or doctor, and follow any professional guidance rather than a product label alone.

From our Gossypol monograph — the full record covers uses, side effects and every documented interaction.

Read the full Gossypol monograph & all interactions

Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports

Arthralgia 40,830 reports

Fatigue 33,049 reports

Nausea 28,999 reports

Joint swelling 25,026 reports

See full Methotrexate drug information

Keep checking

Other Drugs & Gossypol

Browse every other medication we’ve checked against Gossypol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major

104Moderate

0Minor

2,725No known interaction

104 Moderate 2,725 No interaction

Moderate

104 interactions

Showing 60 of 104 moderate interactions — see all 104 on the Gossypol page.

No interaction 2,725 drugs checked — show the list

We also checked Gossypol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,725 medications checked with no known interaction — see the full Gossypol list.

See the full Gossypol interactions page

See every supplement checked against Methotrexate, ranked by severity

Evidence & sources

Gossypol References

The 53 references that drive our Gossypol monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
Cowart CL, London SN, Vernon MW, Pedigo NG. The effects of cyclic adenosine monophosphate, forskolin, and theophylline on motility parameters in gossypol-treated human sperm. Fertil Steril 1994;61:929-34. PubMed
Coutinho EM. Gossypol: a contraceptive for men. Contraception 2002;65:259-63. PubMed
Guo J, Reidenberg MM. Inhibition of 11beta-hydroxysteroid dehydrogenase by bioflavonoids and their interaction with furosemide and gossypol. J Lab Clin Med 1998;132:32-8.
Coutinho EM, Athayde C, Atta G, et al. Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study. Contraception 2000;61:61-7. PubMed
Herve JC, Pluciennik F, Bastide B, et al. Contraceptive gossypol blocks cell-to-cell communication in human and rat cells. Eur J Pharmacol 1996;313:243-55. PubMed
Taylor GT, Griffin MG, Bardgett M. Search for a male contraceptive: the effect of gossypol on sexual motivation and epididymal sperm. J Med 1991;22:29-44.
Woolley, R. J. Contraception--a look forward, Part II: Mifepristone and gossypol. J.Am.Board Fam.Pract. 1991;4(2):103-113.
Liu, G. Z., Lyle, K. C., and Cao, J. Clinical trial of gossypol as a male contraceptive drug. Part I. Efficacy study. Fertil.Steril. 1987;48(3):459-461. PubMed
Qian, S. Z. and Wang, Z. G. Gossypol: a potential antifertility agent for males. Annu.Rev.Pharmacol.Toxicol. 1984;24:329-360. PubMed
Qian, S. Z., Jing, G. W., Wu, X. Y., Xu, Y., Li, Y. Q., and Zhou, Z. H. Gossypol related hypokalemia. Clinicopharmacologic studies. Chin Med.J.(Engl.) 1980;93(7):477-482.
Flack, M. R., Pyle, R. G., Mullen, N. M., Lorenzo, B., Wu, Y. W., Knazek, R. A., Nisula, B. C., and Reidenberg, M. M. Oral gossypol in the treatment of metastatic adrenal cancer. J.Clin.Endocrinol.Metab 1993;76(4):1019-1024. PubMed
Bushunow, P., Reidenberg, M. M., Wasenko, J., Winfield, J., Lorenzo, B., Lemke, S., Himpler, B., Corona, R., and Coyle, T. Gossypol treatment of recurrent adult malignant gliomas. J.Neurooncol. 1999;43(1):79-86. PubMed
Reidenberg, M. M. Environmental inhibition of 11beta-hydroxysteroid dehydrogenase. Toxicology 4-3-2000;144(1-3):107-111.
Gu, Z. P., Mao, B. Y., Wang, Y. X., Zhang, R. A., Tan, Y. Z., Chen, Z. X., Cao, L., You, G. D., and Segal, S. J. Low dose gossypol for male contraception. Asian J.Androl 2000;2(4):283-287.
Van Poznak, C., Seidman, A. D., Reidenberg, M. M., Moasser, M. M., Sklarin, N., Van Zee, K., Borgen, P., Gollub, M., Bacotti, D., Yao, T. J., Bloch, R., Ligueros, M., Sonenberg, M., Norton, L., and Hudis, C. Oral gossypol in the treatment of patients wit
Song, D., Lorenzo, B., and Reidenberg, M. M. Inhibition of 11 beta-hydroxysteroid dehydrogenase by gossypol and bioflavonoids. J.Lab Clin.Med. 1992;120(5):792-797.
Kovacic, P. Mechanism of drug and toxic actions of gossypol: focus on reactive oxygen species and electron transfer. Curr.Med.Chem. 2003;10(24):2711-2718. PubMed
Randel, R. D., Chase, C. C., Jr., and Wyse, S. J. Effects of gossypol and cottonseed products on reproduction of mammals. J.Anim Sci. 1992;70(5):1628-1638. PubMed
Ray, S., Verma, P., and Kumar, A. Development of male-fertility-regulating agents. Med.Res.Rev. 1991;11(5):437-472. PubMed
Zhong, C. Q., Lui, Q. L., Tang, Y. J., Wang, Y., Shi, F. J., and Qian, S. Z. Study on sperm function in men long after cessation of gossypol treatment. Contraception 1990;41(6):617-622. PubMed
Porat, O. Effects of gossypol on the motility of mammalian sperm. Mol.Reprod.Dev. 1990;25(4):400-408. PubMed
Meade, V. Contraceptive development lags in U.S. Am.Pharm. 1990;NS30(5):22-23. PubMed
Gui-Yuan, Z., Meng-Chun, J., Jin-Lai, C., and Wen-Qing, Y. The effect of long-term treatment with crude cotton seed oil on pituitary and testicular function in men. Int J Androl 1989;12(6):404-410. PubMed
Xu, L. F., Wang, M., and Zhao, C. L. [Clinical effects and experimental study on gossypol in endometriosis]. Zhong.Xi.Yi.Jie.He.Za Zhi. 1989;9(8):462-4, 451.
Wu, Y. W., Chik, C. L., and Knazek, R. A. An in vitro and in vivo study of antitumor effects of gossypol on human SW-13 adrenocortical carcinoma. Cancer Res. 7-15-1989;49(14):3754-3758.
Fu, Y. F., Zhang, S. L., Lu, Z. M., and Wang, W. Effects of gossypol on the activity of kidney (Na+ + K+)-ATPase and the functions of erythrocyte membrane. Contraception 1988;37(2):179-184. PubMed
YU, T. W. [Ultrastructural study of the testis in 22 persons based on the effect of gossypol]. Zhonghua Bing.Li Xue.Za Zhi. 1987;16(1):60-61.
Fu, Y. F., Zhang, S. L., Lu, Z. M., and Wang, W. Effects of gossypol on the activity of rabbit kidney Na,K-ATPase and the functions of human erythrocyte membrane. Prog.Clin.Biol.Res. 1988;268B:385-392.
Meng, G. D., Zhu, J. C., Chen, Z. W., Wong, L. T., Zhang, G. Y., Hu, Y. Z., Ding, J. H., Wang, X. H., Qian, S. Z., Wang, C., and . Follow-up of men in the recovery period immediately after the cessation of gossypol treatment. Contraception 1988;37(2):119 PubMed
Glander, H. J. [Gossypol and other nonhormonal substances for the inhibition of male fertility]. Zentralbl.Gynakol. 1988;110(12):772-777.
Wu, D. F., Reidenberg, M. M., and Drayer, D. E. Determination of gossypol enantiomers in plasma after administration of racemate using high-performance liquid chromatography with precolumn chemical derivatisation. J.Chromatogr. 12-9-1988;433:141-148. PubMed
Wu, D. F., Yu, Y. W., and Zheng, D. K. [Determination of (+)- and (-)-gossypol in human plasma using high performance liquid chromatography with pre-column chemical derivatization]. Yao Xue.Xue.Bao. 1988;23(12):927-932.
Coutinho, E. M. and Melo, J. F. Clinical experience with gossypol in non-Chinese men: a follow-up. Contraception 1988;37(2):137-151. PubMed
Liu, G. Z. and Lyle, K. C. Clinical trial of gossypol as a male contraceptive drug. Part II. Hypokalemia study. Fertil.Steril. 1987;48(3):462-465. PubMed
Liu, G. Z., Lyle, K. C., and Cao, J. Experiences with gossypol as a male pill. Am.J.Obstet.Gynecol. 1987;157(4 Pt 2):1079-1081. PubMed
Meng, G. D., Zhu, J. C., Chen, Z. W., Wong, L. T., Zhang, G. Y., Hu, Y. Z., Ding, J. H., Wang, X. H., Qian, S. Z., Wang, C., and . Recovery of sperm production following the cessation of gossypol treatment: a two-centre study in China. Int.J.Androl 1988; PubMed
Kjaergaard, N. [Male contraception]. Ugeskr.Laeger 9-8-1986;148(37):2335-2338.
Qian, S. Z. Gossypol-hypokalaemia interrelationships. Int.J.Androl 1985;8(4):313-324. PubMed
Wang, C. and Yeung, R. T. Gossypol and hypokalaemia. Contraception 1985;32(3):237-252. PubMed
Gao, H., Yang, Z. S., and Jin, S. X. [Primary observations on distal renal tubule acidosis in 177 cases caused by gossypol intoxication]. Zhonghua Nei Ke.Za Zhi. 1985;24(7):419-21, 447.
Cao, J. and Liu, G. Z. [Reversibility of azoospermia following gossypol withdrawal]. Zhongguo Yi.Xue.Ke.Xue.Yuan Xue.Bao. 1983;5(4):227-230.
Bi, X. F., Ye, Y. X., Yang, H. F., and Zhang, Z. R. [Preliminary study on gossypol in causing hypokalemia (author's transl)]. Zhongguo Yi.Xue.Ke.Xue.Yuan Xue.Bao. 1981;3(3):175-178.
Penningroth, S. M. Pharmacological basis of therapeutics: gossypol, an oral male contraceptive? J.Med.Soc.N.J. 1984;81(8):663-665.
Demoulin, A. [Male contraception]. Rev Med Liege 4-1-1984;39(7):266-272.
Liu, G. Z. Clinical study of gossypol as a male contraceptive. Reproduccion. 1981;5(3):189-193.
Aitken, R. J., Liu, J., Best, F. S., and Richardson, D. W. An analysis of the direct effects of gossypol on human spermatozoa. Int.J.Androl 1983;6(2):157-167. PubMed
Waites, G. M. Male fertility regulation: the challenges for the year 2000. Br.Med Bull. 1993;49(1):210-221. PubMed
Reidenberg, M. M., Gu, Z. P., Lorenzo, B., Coutinho, E., Athayde, C., Frick, J., Alvarez, F., Brache, V., and Emuveyan, E. E. Differences in serum potassium concentrations in normal men in different geographic locations. Clin.Chem. 1993;39(1):72-75. DOI
Fan, L. P., Ren, C. Q., and Hou, T. X. [Emergency treatment and care of hypokalemia paralysis due to gossypol poisoning]. Zhonghua Hu Li Za Zhi. 9-5-1995;30(9):522-525.
Waites, G. M., Wang, C., and Griffin, P. D. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int.J.Androl 1998;21(1):8-12. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Related: nutrient depletion

Methotrexate Is Linked to Lower Levels of One Nutrient

Natural Medicines records Methotrexate as a medicine that can lower these. This is not an interaction with Gossypol — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:

FOLIC ACID›

Read the full Methotrexate nutrient depletion report ›

Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.

Pharmacist Counseling Corner

Taking Gossypol and Methotrexate Together: Common Questions

Is it safe to take Gossypol with Methotrexate?

We do not list a known interaction between Gossypol and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.

Do Gossypol and Methotrexate have any of the same side effects?

Yes — our sources link each of them separately to 8 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.

Are Gossypol and Methotrexate used for the same thing?

They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Gossypol in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.

How was the Gossypol and Methotrexate combination checked?

Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Gossypol has documented interactions with 4 drug classes — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.

Does Gossypol interact with any other medications?

Yes. Gossypol has 104 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.

Does Methotrexate interact with any supplements?

Yes. Methotrexate has documented interactions with 82 supplements in our database — Gossypol is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Gossypol monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 53 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.