Gossypol

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Apogossypol, apogossypol 1b, apogossypol hexaacetate, chiral gossypol, cottonseed, cottonseed flour, cottonseed oil, cottonseed protein, DDG, DDGA, deoxyhemigossypol, DHG, DHGA, GAA, GIL, GOS, gossylic iminolactone, gossylic lactone, gossylic nitrile, gossypium, Gossypium herbaceum, Gossypium hirsutum, gossypium oil, gossypol 1a, gossypol 1c, gossypol acetic acid, gossypol dimethyl ether, gossypol ethylamine, gossypol formic acid, gossypol hexamethyl ether, gossypol Schiff’s base, gossypol tetramethyl ether, gossypolone, GP, naphthaldehyde, O-hydroxylnaphthaldehyde, polyphenolic bianphthyl gossypol, racemic gossypol.

Background

  • Gossypol is a pigment that is most commonly produced by the stem, seeds, and roots of the cotton plant. Gossypol was first identified as an infertility agent when studies were conducted in China to explain extremely low birth rates in a particular geographic region. The phenomenon was attributed to the use of crude cottonseed oil for cooking; further investigation revealed that the antifertility agent was gossypol.

  • Gossypol may cause infertility in men, potentially making it a promising alternative to surgical vasectomy. In early research, gossypol shows some evidence of benefit as a treatment for endometriosis and certain cancers, but further research is necessary.

  • At low doses and for short durations, gossypol is well tolerated. However, its use is limited by the fact that it may cause potassium depletion and infertility.

  • In traditional medicine practices, gossypol has been used to treat nasal polyps, uterine fibroids, and other types of cancer. A tea of fresh or roasted seeds has been used to treat bronchitis, diarrhea, dysentery, and hemorrhage. Cottonseed oil was used by early American slaves for abortion.

  • Further research is needed to determine if lower doses, possibly in combination with other therapies, may be effective and safe.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Contraceptive (males)

According to human studies, gossypol has been found to suppress fertility in Chinese men. Gossypol may be an effective method of birth control for men and women, although some individuals have experienced irreversible infertility after using gossypol for more than two years.

Cancer

Limited research suggests that gossypol may slow the growth of cancer in humans. However, gossypol may also promote cancer formation and may not be effective against all types of cancer. Further research is needed before a firm conclusion can be made.

Endometriosis

Limited research suggests that gossypol may prevent the growth of endometrial cells (those that line the inside of the uterus) and prevent ovulation. Further research is needed before a firm conclusion can be made.

Vaginal contraceptive

Limited research suggests that, when applied to the vagina, gossypol may prevent the movement of spermatozoa. This may make it useful in preventing pregnancy or sexually transmitted diseases. Further research is needed before a firm conclusion can be made.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Abortion, ACE-inhibitor activity, acne, aflatoxin toxicity, alcoholism, allergy, alopecia, analgesic, anemia, angina (chest pain), anthelmintic, antiaging, antiandrogen, antianorectic activity, antibacterial, antifungal, antihistamine, anti-inflammatory, antimalarial, antimicrobial, antioxidant, antiseptic, antiviral, arthritis, asthma, autism, beriberi, bronchitis, canker sores, cardiovascular disease, chemotherapy adjuvant, chilblains, cirrhosis, coagulation disorders, convulsions, cosmetic, Crohn’s disease, dandruff, dental conditions, depression, diabetes, diarrhea, diuretic, dizziness, emmenagogue, encephalitis, endocrine disorders, epilepsy, expectorant, eye disorders, fatigue, flavoring, flu, fragrance (detergents, perfumes, soaps), gastrointestinal disorders, gynecological disorders, hangover remedy, headache, heartburn, hemorrhoids, herpes simplex virus-2, HIV, hyperactivity, hypercholesterolemia (high cholesterol), hypertension (high blood pressure), hypotension (low blood pressure), immunomodulation, inhibition of platelet aggregation, insecticide, insomnia, joint problems, laxative, Lyme disease, melanoma, Ménière’s syndrome, menopausal symptoms, menorrhagia (abnormally heavy periods), mitochondrial diseases, multiple sclerosis (MS), neurologic disorders, neuroprotective, obesity, obstetric and gynecological disorders, Parkinson’s disease, pneumonia, premenstrual syndrome (PMS), psychiatric disorders, rabies, radiation protection, Raynaud’s disease, sedative, skin care, spermicide, spine problems, stimulant, streptococcal infections, sunscreen, tranquilizer, ulcer, uterus problems, vasoregulator.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • The maximal tolerated dose of gossypol is reported to be 40 milligrams daily when taken by mouth.

  • To treat cancer, 10-70 milligrams of gossypol has been given daily by mouth for 4-78 weeks.

  • To function as a birth control agent, 7.5-20 milligrams of gossypol has been given daily by mouth for 10-44 weeks. A maintenance dose of 20 milligrams gossypol, given 2-3 times weekly for 8-22 months, has also been used. Also, 20 milligrams of gossypol has been given with 1.5 grams of potassium chloride or 50 milligrams of triamterene for 12 months.

  • To treat endometriosis (abnormal growth of uterine cells in other parts of the body), 20 milligrams of gossypol has been given twice daily by mouth for 20 days, followed by 20 milligrams twice weekly for six months.

  • To be used as a topical birth control agent, a gel containing 0.5 milligrams of gossypol per milliliter of gel has been applied to the vagina one hour before intercourse.

Children (under 18 years old)

  • There is no proven safe or effective dose for gossypol in children

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with a known allergy or sensitivity to gossypol, cottonseed oil, or any of their parts.

Side Effects and Warnings

  • Gossypol may cause abnormal heart beats, altered sense of taste, anorexia, breathing difficulty, burning sensation, diarrhea, disruption of menstrual cycles and damage to testes, fatigue, hair discoloration, increased levels of certain hormones, liver damage, malnutrition, nausea, potassium depletion (particularly in Chinese men), reduced appetite, reduced growth rate, stomach and intestinal disorders, and tissue swelling.

  • Use cautiously when giving more than 40 milligrams of gossypol daily or for periods longer than one year.

  • Use cautiously in people of Chinese heritage or those with asthma or other breathing disorders, heart disorders, kidney disease, liver disorders, sensitive skin, or stomach disorders.

  • Use cautiously in people also taking nonsteroidal anti-inflammatory drugs (NSAIDs), theophylline, forskolin, steroids, or androgenic agents.

  • Use cautiously in people driving or operating machinery, due to the risk for fatigue.

  • Avoid in people consuming alcohol, in people with low potassium levels, or in those taking diuretics, laxatives, or other agents that may reduce potassium levels.

  • Avoid in men or women that may wish to have children in the future, due to the risk of infertility.

  • Avoid use in children, due to a lack of safety information.

  • Avoid in pregnant or breastfeeding women, due to a risk of spontaneous abortion.

Pregnancy and Breastfeeding

  • There is currently a lack of scientific evidence on the use of gossypol during pregnancy or lactation.

  • Although not well studied in humans, gossypol may cause spontaneous abortions.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Gossypol may interact with agents that affect hormone levels, agents that affect potassium levels (particularly ACE inhibitors or angiotensin receptor blocking agents (ARBs)), alcohol, beta-blockers, birth control or fertility agents, cyclosporine, diuretics (agents that increase urination; particularly those that affect potassium levels), laxatives, metyrapone, nonsteroidal anti-inflammatory agents (NSAIDS), phenobarbital, steroids, sulfadiazine, and theophylline.

Interactions with Herbs and Dietary Supplements

  • Gossypol may interact with herbs and supplements that affect hormone levels, antioxidants, birth control or fertility agents, diuretics (particularly those that affect potassium levels), forskolin, and laxatives.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Dodou K, Anderson RJ, Small DA, and Groundwater PW. Investigations on gossypol: past and present developments. Expert.Opin.Investig.Drugs 2005;14(11):1419-1434. View Abstract
  2. Final report on the safety assessment of Hydrogenated Cottonseed Oil, Cottonseed (Gossypium) Oil, Cottonseed Acid, Cottonseed Glyceride, and Hydrogenated Cottonseed Glyceride. Int J Toxicol. 2001;20 Suppl 2:21-29. View Abstract
  3. Kalla NR. Gossypol. Acta Eur.Fertil. 1990;21(1):5-6. View Abstract
  4. 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. View Abstract
  5. Le Blanc M, Russo J, Kudelka AP, and Smith JA. An in vitro study of inhibitory activity of gossypol, a cottonseed extract, in human carcinoma cell lines. Pharmacol.Res. 2002;46(6):551-555. View Abstract
  6. Liu GZ, Lyle KC. Clinical trial of gossypol as a male contraceptive drug. Part II. Hypokalemia study. Fertil.Steril. 1987;48(3):462-465. View Abstract
  7. Liu GZ, Ch’iu-Hinton K, Cao JA, Zhu CX, and Li BY. Effects of K salt or a potassium blocker on gossypol-related hypokalemia. Contraception 1988;37(2):111-117. View Abstract
  8. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch.Intern.Med 11-9-1998;158(20):2200-2211. View Abstract
  9. Porat O. Effects of gossypol on the motility of mammalian sperm. Mol.Reprod.Dev. 1990;25(4):400-408. View Abstract
  10. Qian SZ. Gossypol-hypokalaemia interrelationships. Int.J.Androl 1985;8(4):313-324. View Abstract
  11. Royer RE, Mills RG, Deck LM, Mertz GJ, and Vander Jagt DL. Inhibition of human immunodeficiency virus type I replication by derivatives of gossypol. Pharmacol.Res. 1991;24(4):407-412. View Abstract
  12. Stein RC, Joseph AE, Matlin SA, Cunningham DC, Ford HT, and Coombes RC. A preliminary clinical study of gossypol in advanced human cancer. Cancer Chemother.Pharmacol. 1992;30(6):480-482. View Abstract
  13. Waites GM, Wang C, and Griffin PD. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int.J.Androl 1998;21(1):8-12. View Abstract
  14. Wu D. An overview of the clinical pharmacology and therapeutic potential of gossypol as a male contraceptive agent and in gynaecological disease. Drugs 1989;38(3):333-341. View Abstract
  15. Wu YW, Chik CL, and Knazek RA. 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. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.