Reduced Carotenoid and Retinoid Concentrations and Altered Lycopene Isomer Ratio in Plasma of Atopic Dermatitis Patients

Abstract

Carotenoids and retinoids are known to alter the allergic response with important physiological roles in the skin and the immune system. In the human organism various carotenoids are present, some of which are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors such as the retinoic acid receptor and the retinoid X receptor. In this study, we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n = 20) compared to healthy volunteers (HV, n = 20). The study indicated that plasma levels of the carotenoids lutein (HV 198 ± 14 ng/mL, AD 158 ± 12 ng/mL, p = 0.02; all values in mean ± SEM), zeaxanthin (HV 349 ± 30 ng/mL, AD 236 ± 18 ng/mL, p ≤ 0.01), as well as the retinoids retinol (HV 216 ± 20 ng/mL, AD 167 ± 17 ng/mL, p = 0.04) and all-trans-retinoic acid (HV 1.1 ± 0.1 ng/mL, AD 0.7 ± 0.1 ng/mL, p = 0.04) were significantly lower in the AD-patients, while lycopene isomers, α-carotene, and β-carotene levels were comparable to that determined in the healthy volunteers. In addition, the ratios of 13-cis- vs. all-trans-lycopene (HV 0.31 ± 0.01, AD 0.45 ± 0.07, p = 0.03) as well as 13-cis- vs. all-trans-retinoic acid (HV 1.4 ± 0.2, AD 2.6 ± 0.6, p = 0.03) were increased in the plasma of AD-patients indicating an AD-specific 13-cis-isomerisation. A positive correlation with SCORAD was calculated with 13-cis- vs. all-trans-lycopene ratio (r = 0.40, p = 0.01), while a negative correlation was observed with zeaxanthin plasma levels (r = −0.42, p = 0.01). Based on our results, we conclude that in the plasma of AD-patients various carotenoids and retinoids are present at lower concentrations, while the ratio of selected lycopene isomers also differed in the AD-patient group. An increase in plasma isomers of both lycopene and retinoic acid may cause an altered activation of nuclear hormone receptor signaling pathways and thus may be partly responsible for the AD-phenotype.

β-Carotene in the human body: metabolic bioactivation pathways – from digestion to tissue distribution and excretion

“…(B) Direct correlation newly calculated based on of serum ATβC to ATRA in children in Germany with different ethical backgrounds (183,184) . (C) Direct correlation based on serum ATβC to ATRA levels in Hungarian adults (n 40, Lucas et al (187) ) This figure is just present in the original study in ng/ml, while 1 ng/ml ATRA corresponds to 3.3 nM and 1 ng/ml ATβC to 1.86 nM. (D) Distribution of BCO1 mRNA expression in human tissues, as published previously in Lindqvist and Andersson (144) (PBLperipheral blood lymphocytes).…”

“…It should be noted that serum and tissue levels do not represent freely available carotenoids, but mainly carotenoids attached to binding proteins and carotenoids associated in lipid vesicles in the membranes and lipid accumulating vesicles such as in the adipose tissue (13) . In one study examining children (182)(183)(184) , a direct correlation between all-transβ-carotene (ATβC) and ATRA serum levels was observed, resulting in a linear correlation with r 0·68, while in adults (185)(186)(187) no such correlation was observed (r −0·14), likely due to auto-regulative processes. The highest relevant level of ATβC in serum of children was 756 nM (Fig.…”

Bioactive Properties of Carotenoids in Human Health

“…The author shows that patients with atopic dermatitis present an overall reduction of key carotenoids such as lutein and β-carotene, accompanied by a reduction in all-trans retinoic acid. These results indicate that low levels of carotenoids/retinoids, together with an altered ratio of some of their isomers, could be associated to the maintenance or the development of atopic dermatitis [25].…”

Allergy Modulation by N-3 Long Chain Polyunsaturated Fatty Acids and Fat Soluble Nutrients of the Mediterranean Diet

“…The exact contribution of pro-vitamin A and non-pro-vitamin A carotenoids in relation to allergy risk remains to be revealed. Although the total amount of ß-carotene and lycopene were comparable between healthy volunteers and AD patients, levels of retinol (VitA) and all trans retinoic acid as well as lycopene metabolites lutein and zeaxanthin, were significantly reduced in plasma of AD patients ( Lucas et al, 2018 ). Asthma patients with AHR had reduced ß-carotene and tocopherol blood levels ( Wood and Gibson, 2010 ), while in stable asthma patients serum lycopene concentrations were reduced ( Riccioni et al, 2006 ).…”