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Lutein and lycopene, two prevalent carotenoids in the human diet have become increasingly popular ingredients in dietary supplements. A large body of human and animal research suggests that oral forms of these carotenoids may provide benefits in the areas of eye, prostate, skin and cardiovascular health. The increased awareness and use of these ingredients in dietary supplements warrants a comprehensive review of their safety. Systematic evaluation of the research designs and data provide a basis for risk assessment and the usual tolerable Upper Level of Intake (UL) derived from it if the newer methods described as the Observed Safe Level (OSL) or Highest Observed Intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 20 mg/d for lutein, and 75 mg/d for lycopene, and these levels are identified as the respective OSL. Although much higher levels have been tested without adverse effects and may be safe, the data for intakes above these levels are not sufficient for a confident conclusion of long-term safety.