The dark side of curcumin

➡️Curcumin is a yellow–orange pigment obtained from the plant Curcuma longa

➡️Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies (outside the living body and in an artificial environment).

➡️The chemotherapy potential of oral curcumin is limited in real world (in humans). Eg: When 15 patients with advanced colorectal cancer were treated with curcumin at daily doses of 3.6 g for up to 4 months, no partial responses to treatment or decreases in tumor markers were observed.

➡️A strategy to increase curcumin absorption includes using the black pepper alkaloid piperine (bioperine) to increase the bioavailability of curcumin. This strategy, however, should be used cautiously, as piperine is a potent inhibitor of drug metabolism and may cause toxicity in people taking other essential drugs.

➡️Any strategy that increases the levels of curcumin in tissues will not only increase the effectiveness of curcumin, but also its toxicity.

➡️A relatively high number of reports suggests that curcumin may cause toxicity under specific conditions.

➡️In 1976 Goodpasture and Arrighi found that turmeric caused a dose- and time-dependent induction of chromosome changes and genetic damage in cells and tissues in lab studies.

➡️Accumulating data have demonstrated since then that curcumin can induce DNA damage and chromosomal alterations both in vitro (cells and tissues) and in vivo (in animals) at concentrations similar to those reported to exert its beneficial effect.

➡️For instance, curcumin concentrations of 2.5 and 5 μg/mL were shown to induce DNA damage to both the mitochondrial and nuclear genomes in cells. These reports raise concern about curcumin safety, as the induction of DNA alterations is a common event in cancer formation.

➡️Rats and mice were fed diets containing several concentrations of turmeric oleoresin (79-85% curcumin) for 3 months and 2 years, and the possible toxic and cancer causing effects were evaluated. In the 2-year feeding studies there was increased incidences of ulcers, tissue damage and inflammation of the stomach, large bowel of male rats and of the lower colon in female rats.

➡️Curcumin also increased incidences of clitoral gland tumors in female rats, liver tumors in female mice, and cancers of the small intestine and liver tumors in male mice. A recent report has also shown that curcumin can promote lung cancer in mice.

➡️Experimental studies have demonstrated that, although low concentrations of curcumin induce antioxidant effects, higher concentrations of this compound increase reactive oxygen species. This lower concentrations have poor absorption in humans and no benefits, but higher concentrations have more toxicity than benefits.

➡️Curcumin was recently found to be an active iron binder and induce a state of iron deficiency anemia in mice fed with diets poor in iron. This suggests that curcumin has the potential to affect iron absorption and lead to iron deficiency anemia, particularly in people consuming low amounts of iron-rich foods.

➡️Curcumin has also been shown to inhibit the activity of the drug-metabolizing enzymes cytochrome P450, glutathione-S-transferase, and UDP-glucuronosyltransferase. The inhibition of these enzymes (in liver) in people taking curcumin may lead to an undesired increase blood concentrations of other essential drugs they are on and and cause toxicity.

➡️Based on human studies, it is generally recognized that curcumin does not cause significant short-term toxicity at doses up to 8 g/day. This dose of curcumin is not completely harmless, however, as human studies have shown that curcumin at doses ranging from 0.9 to 3.6 g/day for 1–4 months originates some adverse effects including nausea and diarrhea and causes an increase in blood enzyme levels of serum alkaline phosphatase and lactate dehydrogenase.

➡️The lack of long-term toxicity studies in humans should not only be considered by health professionals, but also by people taking supplements of curcumin (with and without piperine) that are readily available in the market.

➡️It is unfortunate that curcumin is regarded in the scientific literature as efficient and safe when its efficiency and safety have not yet been proven.

➡️The fact that curcumin is a common dietary constituent is not enough to prove its safety, as other common dietary constituents have shown toxicity when used as dietary supplements. Eg: Use of beta-carotene has been associated with an increased risk of lung cancer.

➡️The fact that no major toxicity has been found in short-term studies in humans is not a proof of curcumin safety either. For a drug to be safe, it must also be devoid of long-term toxicity, and the most complete long-term toxicity study conducted to date raises concern about curcumin safety.

➡️Finally, the fact that the number of studies showing positive effects of curcumin is much higher than that showing negative effects does not necessarily mean that the benefit-risk ratio of curcumin is shifted towards the benefit; it may just indicate that there are more researchers evaluating the beneficial effects of curcumin than evaluating its toxicity.