Are There Adverse Effects of Lycopene Exposure? Dr. Paula Trumbo, U.S. Food and Drug Administration Dr. Trumbo presented a review of literature on the evidence for adverse effects of lycopene exposure. Animal studies evaluating the safety of lycopene can be classified using the following six categories: acute toxicity studies; subchronic and chronic safety studies; reproductive studies; genotoxicity studies; hepatic uptake studies; and absorption, distribution, metabolism, and excretion studies. Most of the studies used crystalline lycopene—a synthetic form that is sensitive to light and oxygen, insoluble in water, and not suitable for commercial use. In addition, the lycopene formulations used in the majority of studies included ascorbic acid and/or vitamin E to prevent lycopene oxidation. These were small toxicology studies, with 6 to 10 animals per group. Lycopene did not have any adverse effect in the acute toxicity study. The subchronic and chronic safety studies—which monitored factors such as body weight, hematology, blood chemistry, histology, food consumption, and motor activity—found no evidence of clinically significant adverse effects of lycopene (although some reported very minimal effects on food consumption, slightly suppressed appetite and growth rate, and slight changes in hematological measures and enzymes). The reproductive studies found no evidence of maternal or developmental toxicity with lycopene, and no signs of aborted pregnancies, malformations, or teratogenic effects. One genotoxicity study suggested that pure crystalline lycopene, when exposed to light and air, is degraded to compounds with some mutagenic activity. The other genotoxicity studies, however, found no increase in mutant frequency compared to controls, no increase in DNA damage, and no evidence of chromosome damage. Lastly, the hepatic uptake studies indicated that: 1) hepatic levels of lycopene are 2.5 times higher in rats fed a supplement versus tomato concentrate, with the highest concentrations in liver; and 2) although lycopene deposits were observed in liver, they had no effect on liver pathology. In summary, these data suggest that there are no serious adverse effects of lycopene intake. Rats have been shown to accumulate lycopene in different tissues at levels similar to humans; thus, it appears that animals can be used as a reference for assessments of human health as well as for safety analyses. In terms of safety assessment, lycopene has a No Observed Adverse Effect Level (NOAEL) of 3 g/kg/day. According to NHANES-III data, the 50 % of lycopene intake from food is reported at 5.2 mg/d, whereas the 99 % is 123 mg/d. Tomato products/watermelon provide 5 to 30 mg of lycopene per serving and supplements contain 5 to 15 mg of lycopene per capsule; therefore, it would require a high level of food/supplement consumption to reach the NOAEL or the 99th percentile of intake. No tolerable upper intake level was set for lycopene in the 2001 Institute of Medicine’s Dietary Reference Intake Antioxidant Report because there are no observed adverse effects. In addition, the FDA had no questions in response to a notice that the use of synthetic lycopene as a food ingredient is Generally Recognized as Safe. Discussion A recommendation was made to study the biologic activity of the breakdown products of lycopene. The breakdown products of beta-carotene, for example, have been implicated in increased carcinogenesis. Absorption of lycopene seems low. One participant asked what happens to the unabsorbed lycopene, particularly what metabolism occurs in the colon. Dr. Trumbo replied that much is excreted in feces. Although a large amount of lycopene is still intact, some metabolites do occur. A comment was made that one of the unanticipated problems in the beta-carotene trials was that the carrier (oil) enhanced the absorption and bioavailability of beta-carotene, resulting in beta-carotene blood levels that were unexpected on the basis of absolute concentration. When designing lycopene clinical trials, attention should be paid to the lycopene formulation being administered and to changes in circulating levels, despite evidence that most lycopene is excreted. 2/05 NIH Meeting Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.