Vitamin A is essential for brain function and plays an important role in vision, immunity and reproduction. Data in the literature have shown that retinoic acid (RA), the bioactive form of vitamin A, is involved in the regulation of several intracellular responses related to biological rhythms. It is reported that RA affects the circadian rhythm binding to RA receptors, such as receptors on circadian feedback loops in the suprachiasmatic nucleus of mammals.
This fat-soluble vitamin was the first described in the literature and is found mainly in animal products or converted from dietary carotenoids from plant products, and there are two forms of vitamin A. in the human diet, that is, preformed (usually from animal products) and provitamin A (including beta-carotene, usually from plant-derived foods), both have a group of derivatives that includes retinol, retinal, retinoic acid and some carotenoids according to different terminal functional groups. Commonly, vitamin A refers to retinol, while retinoid refers to a general term that includes metabolites and vitamin A compounds that exhibit biological activities similar to vitamin A.
In addition, after absorbed in the intestine, preformed vitamin A and provitamin A are converted into retinol. and then oxidized to form retinal and AR that support the biological process and are stored in the form of retinyl ester in the liver which, when necessary to use it again, is converted into retinol. It is worth mentioning that these derivatives of vitamin A are metabolized by enzymes of the CYP26 family together with their derivatives, being involved in the regulation of various activities of life, including cell proliferation and differentiation, vision, reproduction, embryogenesis and immune function.
Although vitamin A is present in the composition of a variety of foods, its deficiency is still a problem. observed in several underdeveloped countries around the world. With this, vitamin A deficiency (VAD) is associated with an abnormal RA signaling pathway, for example, study shows that a diet with vitamin A deficiency reduced the expression of retinoic acid receptors and retinoid X receptors.
Biological Rhythms and the Physiological Functions of Vitamin A
Biological rhythms regulate various physiological, biochemical, and behavioral processes in living organisms. That is, they act with a “timer”, thus may have an influence on the sleep-wake cycle, body temperature and blood pressure. Among the biological rhythms, the circadian rhythm is the best known.
Thus, the circadian system can be divided into central clock and peripheral clock. As far as the central is concerned, its control is by the suprachiasmatic nucleus, while the peripheral nucleus is composed of peripheral oscillators that are located in several peripheral tissues. Still, it is worth noting that the central can conduct or synchronize the peripheral rhythm through neurohumoral pathways, while the peripheral rhythm can affect and regulate the central rhythm through periodic activities, such as daily diet and sleep. In short, it is a two-way street.
On the other hand, when we relate biological rhythms and vitamin A, we observe that several associations have been made in different organisms such as insects, birds and mammals. With this, the literature points out that the vitamin A can affect biological rhythms, and some studies explored the possibility of a correlation between vitamin A or carotenoids and biological rhythmicity or chronotype. Such studies have also found that low levels of vitamin A intake are associated with disturbed wake-sleep cycles, whereas supplementation of a natural carotenoid compound, crocetin, improved sleep timing and quality.
When it comes to transcription-translation feedback loops, while more research is needed to determine for sure the role of vitamin A in regulating biological rhythms, some studies have found that DVA or vitamin A supplementation after deficiency can affect the expression of several bioclock genes through nuclear receptors and AR proteins. These are possibly the potential mechanisms underlying the effects of VAD on biological rhythm.
Vitamin A and Changes in Light Signal Reception
The literature demonstrates vitamin A being essential for the normal physiological functioning of the eyes in addition to the VAD being able to affect biological rhythms by influencing the reception of light signals, since they are received by the retina and transmitted to the sarcoplasmic nucleus through a photoentrainment process. The latter, in turn, involves a type of intrinsically photosensitive retinal ganglion cells, whose axons can be sent to the CNS, making such cells a potential photoreceptor to synchronize the biological clock with the environmental daylight cycle. Thus, in cases of vitamin A deficiency, retinoic acid and retinal formation may be impaired.
Clinically, it is important that nutritionists in their dietary prescriptions pay attention to vitamin A levels in order to keep them within the ranges established to meet the daily needs of individuals. Moreover, even though RA is the main active metabolite of vitamin A and VAD is inevitably associated with the abnormal RA signaling pathway, the possibility that there are other factors capable of affecting the functions of the RA and VAD signaling pathways is not ruled out.
Suggested reading: Vitamin A deficiency: what are the consequences?
Vitamin A and biological rhythms
: Guo X, Wang H, Xu J, Hua H. Impacts of vitamin A deficiency on biological rhythms: Insights from the literature. Frontiers in Nutrition. 2022;9. doi:https://doi.org/10.3389/fnut.2022.886244