EFSA's Panel on Dietetic Products, Nutrition and Allergies (DPNA) found that supplements that contained zeaxanthin at levels up to 20mg would exceed average intakes by up to 100 times and therefore said a safe limit of 20mg could not be established. "The proposed levels of use of up to 20 mg/person/day of synthetic zeaxanthin as an ingredient in food supplements would lead to intake levels that would substantially increase the average dietary intake of synthetic zeaxanthin resulting in up to 100 times higher intakes for adults," the DPNA said. "These intake levels are within the range of the group ADI 0-2 mg/kg body weight for lutein and synthetic zeaxanthin as established by JECFA. However, in the opinion of the Panel, the toxicological data on synthetic zeaxanthin are not sufficient to derive an acceptable daily intake." Hardly damning science DPNA's conclusion came despite it acknowledging animal toxicity studies showed no effects other than "discolouration of the faeces and adipose tissue". "In studies on embryotoxicity and teratogenicity using rats and rabbits there were no indications of maternal toxicity, embryotoxic or teratogenic effects," it said. There was no indication for genotoxicity, but DPNA noted no studies on chronic toxicity and carcinogenicity had been performed. A study involving healthy human volunteers dosing on 10-30mg of zeaxanthin per day for 4-6 months also showed no adverse effects. The panel noted similarities between zeaxanthin and a-carotene and ß-carotene but stated it was not possible to extrapolate health benefits attributed to the use of those nutrients such as lung cancer reduction among heavy smokers to zeaxanthin in the form of supplements for a lack of evidence. The average European intake level of zeaxanthin via food is between 0.2 and 0.9 mg/day, rising to 1.8mg per day for those consuming zeaxanthin-rich vegetables and fruits such as cabbage, corn, broccoli, Brussels sprouts, green beans, kale, mandarins, oranges, peas, pumpkins, spinach and squash. Commerical sources include the marigold flower, red peppers and goji berries. Egg yolk was another good source of the nutrient that has been shown, like lutein, to be beneficial in the prevention and treatment of advanced macular degeneration, an eye condition common among over-50s. The safety applicant stated its synthetic version of zeaxanthin would be offered in three formats: two spray-dried powders of either gelatine or starch base 'beadlets' each containing five per cent zeaxanthin with a-tocopherol and ascorbyl palmitate added as antioxidants, and a corn oil suspension containing 20 per cent zeaxanthin with added a-tocopherol. DPNA noted the bioavailability of zeaxanthin varies depending on factors such as the food matrix in which it is ingested as well as the effects of co-ingested food. Research indicated zeaxanthin plasma levels jumped from 50 nmo/L to 920 nmo/L when 10mg of zeaxanthin was consumed in the form of a food. If doses were pushed to 30mg animal studies indicated zeaxanthin accumulated in the macula of the eye, where it could be beneficial to the onset of AMD. "In rats zeaxanthin accumulated in adipose tissue, the liver and several other organs, whereas in monkeys zeaxanthin accumulated in the adipose tissue, liver and eye." A US company, Chrysantis, had been granted GRAS (generally regarded as safe) status by the Food and Drug Administration (FDA) for its zeaxanthin ingredient in doses up to 2mg. The US raw materials market is believed to be worth $2-3m per year, but growing at double digit rates.