Curcumin may be one of the most medicinal herbs thus far investigated for use as a potent natural medicine.

In fact, in a search of, the electronic database of the National Institutes of Health, “curcumin” yields more than 6,100 studies listed.

However, curcumin has a significant challenge: it is poorly absorbed. Curcumin is extracted from the spice turmeric, but turmeric has very little curcumin. Only about 2 to 5% of this spice is the compound curcumin. Therefore, doctors and researchers do not generally use turmeric in medical research, they use curcumin in their studies when looking at health applications.

Because curcumin is hard to absorb, there have been attempts to enhance its absorption. While there are safe and effective curcumin extracts in the market with clinically document enhanced absorption, there is one method that is particularly problematic, because the compound used to enhance absorption is a highly concentrated extract of black pepper called piperine. While it is fine to consume black pepper as a spice, there are safety considerations with the highly concentrated extract, piperine.

Piperine is incompatible with many prescription medications, as it magnifies effects on P-glycoprotein and CYP3A4 1 which can affect a wide spectrum of prescription medications, including digoxin (heart rhythm drug), verapamil (high blood pressure and angina) , cyclosporine (anti-rejection drug for transplant patients), phenytoin (anti-seizure), rifampin  (anti-tuberculosis) and more.

1Bhardwaj R, Glaeser H, Becquemont L, Klotz U, Gupta S,  Fromm M. Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4. The Journal of Pharmacology and Experimental Therapeutics. Vol. 302, Issue 2, 645-650, Aug 2002.

Additionally, piperine has demonstrated toxicity at higher dosages, and also increases the absorption of dietary toxins such as aflatoxin, which is a known carcinogen.


  1. Toxicity

Toxic to mice, rats and hamsters. LD50 for a single i.v., i.p., s.c., i.g., and i.m. administration to mice were: 15, 43, 200, 330 and 400 mg/kg, resp. Most animals given a lethal dose died of respiratory paralysis within 3-17 min. In subacute toxicity studies, rats died within 1-3 days (Toxicol Lett, 1983, 16:351-59)

2. Promotes DNA damage and cytotoxicity induced by benzo[a]pyrene

In cultured V-79 fibroblast cells, piperine pretreatment caused an increased covalent binding of B[a]P-diol epoxide to DNA, 2.3 times greater than without pretreatment. Lowest activities of GST and UDP-Gtase after 30-60 min of pretreatment. (Food Chem Toxicol, 1994, 32:373-77).

3. Potentiates aflatoxin B1 in rat tissues

Rats pretreated with piperine accumulated considerable [3H]-AFB1 radioactivity in plasma and tissues compared to controls. Piperine-treated rat liver microsomes demonstrated a tendency to enhance aflatoxin binding to calf thymus DNA in vitro. (Cancer Lett, 1992, 61:195-99)

4. Potentiates carbon tetrachloride hepatotoxicity

Piperine potentiated CCl4-induced hepatotoxicity (liver toxicity) in a dose-dependent manner. Also induced CCl4-induced lipid peroxidation. The extent of potentiation correlated well with the rise in hepatic enzyme activity in the plasma (Drug Chem Toxicol, 1995, 18:333-44)

5. Cytotoxic to cultured rat hippocampal cells

Exposure to piperine induced marked injuries to cultured hippocampal brain cells. SOD and catalase were ineffective in affording protection against piperine toxicity. Involvement of free radicals is indicated (Biol Pharm Bull, 1997, 20:958-61).

6. Reduction of neurite extension on hippocampal and septal neurons

In addition to its cytotoxic effects on neuronal survival, piperine also suppressed neurite extension in developing neurons (Bio Pharm Bull, 1994, 17:898-901).

7. Death of cerebellar granule neurons induced by piperine

Death of cerebellar granule neurons by piperine by non-apoptic mechanism, and may involve lipid peroxidation (Neurochem Res, 1998, 23:97-102)

8. Piperine lowers serum concentrations of thyroid hormones, glucose and hepatic 5’D activity in mice (Hormone Metab, 2003, 35:523-26).

9. Increases gastric acid secretion

Stimulation of histamine H2 receptors may be involved in the increased acidity induced by piperine (Afr J Med Sci, 2002, 31:293-95)

10. Immunotoxicological effects

Mice gavaged at doses of 1.12, 2.25 or 4.5 mg/kg bw - at the highest dose significant reduction in the weight of spleen, thymus and mesenteric lymph nodes. Caused a significant reduction in leukocyte (white blood cell) count. Differential leukocyte counts showed an increase in neutrophils. The number of primary antibody (IgM) forming cells in the spleen and the level of primary antibody in the serum was decreased (Toxicology, 2004, 15:229-36)

11. Effect on sperm capacitation and fertilization

Hamster sperm incubated in a capacitation medium with added piperine reduced both the percentage of eggs fertilized and the degree of polyspermia (Int J Androl, 1991, 14:283-90).


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Terry is happy to provide his opinion on diet and nutrition, supplements and lifestyle choices. This information is for educational purposes only. It is not meant to replace the advice of your physician and is not to be considered medical advice, diagnosis or treatment. Should you have any concerns please contact your physician directly.

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