Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake

Abstract

Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission.

Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products

“…This dose of lutein (equivalent to 30–40 mg/day for adults weighing 60–75 kg) is attainable from the diet [ 36 ] but is more commonly achieved through supplementation in humans. In Cynomolgus monkeys, no adverse effects were observed when oral doses of lutein up to 35 μmol/kg body weight per day were given for 52 weeks [ 37 ]. Additionally, no adverse effects of lutein have been reported in humans [ 38 ] and no tolerable upper intake levels for lutein have been established by the Institute of Medicine.…”

Sea Buckthorn Oil as a Valuable Source of Bioaccessible Xanthophylls

“…Furthermore, it has been proposed that they may improve cognitive function [6]. In the human diet, lutein is the dominant xanthophyll, and even though some good few sources of zeaxanthin are known such as egg yolk, corn and orange pepper [7,8], the usual dietary ratio of lutein to zeaxanthin is approximately 5:1 [9]. Sea buckthorn oil is of special interest for human nutrition, because of the fruits' high content of carotenoids, in particular zeaxanthin (present in an esterified form with one or two fatty acids), and can be considered a noteworthy contributor of this ophthalmo-protective xanthophyll to dietary intake [10].…”

Non‐Provitamin A and Provitamin A Carotenoids as Immunomodulators: Recommended Dietary Allowance, Therapeutic Index, or Personalized Nutrition?

“…On the contrary, non-provitamin A carotenoids could have a safer profile (20 mg/d for lutein, 75 mg/d for lycopene, and 53 mg/d for zeaxanthin) [ 13 , 105 ] than β -carotene. The latter is converted to RA with immunomodulatory effects ( Figure 1 ).…”

“…The overall mortality increased after β -carotene supplementation [ 102 – 104 ] at a dose of >9.6 mg/d [ 104 ]. On the contrary, for non-provitamin A carotenoids, an Observed Safe Level (OSL) of 20 mg/d for lutein and 75 mg/d for lycopene [ 13 ] has been suggested and an acceptable daily intake (ADI) of 53 mg/d has been proposed for zeaxanthin [ 105 ]. The positive effect of lutein and zeaxanthin on age-related macular degeneration is well known [ 106 ].…”