Gossypol Interactions Overview

Additional Details

Is Gossypol Safe? Are There Any Warnings?

Gossypol is considered possibly safe when used orally and appropriately in the short-term, at doses less than 20 mg daily, for up to one year. However, it is potentially unsafe when used orally in doses greater than 20 mg daily or for more than one year. High doses of gossypol can cause toxic effects such as liver, gastrointestinal, and cardiovascular problems, as well as hypokalemia.

There is also a risk of permanent infertility in males with long-term use of gossypol. It is important to note that there is insufficient information available about the safety of gossypol when applied topically. Pregnant women and lactating women should avoid using gossypol orally.

How Is Gossypol Thought To Work? What Is the Mechanism of Action?

Gossypol is a pigment that occurs naturally in certain plants. It has a racemic mixture of enantiomers. Gossypol has different mechanisms of action depending on its use:

• Abortifacient effects: Gossypol disrupts estrous cycles, pregnancy, and early embryo development. It is believed to work mainly by acting as a luteolytic agent, but it may also affect decidual cells and cytotrophoblasts.
• Anticancer effects: Gossypol slows the growth of cancer cells by inducing apoptosis (cell death) and inhibiting tumor cell proliferation. It has been studied for its potential effectiveness against lung cancer and prostate cancer, but the results have been inconclusive.
• Antifertility effects: Gossypol is widely studied as a male contraceptive. It reduces sperm count and inhibits sperm motility, effectively preventing fertilization. Gossypol also affects hormones and enzymes involved in reproduction.
• Antimalarial effects: In laboratory studies, gossypol has shown antimalarial activity.
• Antiviral effects: Gossypol has been found to inhibit the replication of the human immunodeficiency virus type 1 (HIV-1) in vitro. It may also have antiviral activity against herpes viruses.

Pharmacokinetics

After oral administration, gossypol is absorbed through the intestine and the stomach lining. It is highly bound to amino acids and dietary iron. Gossypol is mainly eliminated through feces, with a long elimination half-life in humans. The concentrations and activity of the enantiomers of gossypol can vary. (-)-Gossypol tends to have greater effects in antifertility and anticancer activity compared to (+)-gossypol.

Interaction Overview

Gossypol may interact with certain drugs and supplements:

• Drug Interactions: Gossypol may have moderate interactions with digoxin, diuretic drugs, stimulant laxatives, and theophylline. Special caution should be taken when using gossypol along with these medications.
• Supplement Interactions: Gossypol may interact with cardiac glycoside-containing herbs, horsetail, licorice, and stimulant laxative herbs. These interactions are due to the potassium-depleting effects of gossypol.

Common Side Effects To Watch For

The most common side effects reported during the use of gossypol include diarrhea, hypokalemia (low potassium levels), nausea, and vomiting. In rare cases, more serious side effects such as circulatory problems, dermatologic toxicity, heart failure, hepatotoxicity, infertility in males, intestinal hemorrhage, and mucosal necrosis may occur with long-term or high-dose use.

Are Supplements Standardized?

Gossypol is usually provided as gossypol acetic acid or gossypol monoacetic acid. It is derived from cotton and is a racemic mixture of (+) and (-) enantiomers. There is a clinically studied product called AT-101 that is standardized to contain only the R-(-)-enantiomer of gossypol.

What Is Gossypol Typically Used For?

Gossypol has been studied for various purposes, including:

• Contraception: Gossypol has shown potential as a male contraceptive by reducing sperm count and inhibiting sperm motility. It is reversible in most cases, but permanent infertility is possible.
• Lung cancer: Although some studies have suggested that gossypol may have anticancer effects against lung cancer, clinical research has not found it to be effective in improving survival rates or reducing tumor progression.
• Prostate cancer: Clinical research has not shown gossypol to be effective in improving survival rates or prostate-specific antigen (PSA) levels in patients with prostate cancer.
• Other uses: Gossypol has been studied for its potential effects on endometriosis, head and neck cancer, HIV/AIDS, and various forms of advanced cancer. However, more research is needed to determine its effectiveness for these uses.

Drugs that interact with Gossypol