Age-Related Changes of Vitamin A Status

Abstract

Ageing is an independent risk factor for the development of cardiovascular disease. The ageing process is known to be associated with increased oxidative stress and an increased risk for cardiovascular and other diseases, such as cancer. To delay this process, therapeutic strategies involving the use of naturally occurring antioxidants, such as vitamin A, have gained considerable interest. Therefore, we wanted to investigate in a model of mammalian ageing whether changes in tissue and plasma levels of vitamin A occur with increasing age. This would constitute a prime rationale for its dietary supplementation. Experiments were performed in three different age groups (4-6 months old, 19 months old, 32-35 months old) of F1 (F344 x BN) healthy male rats that were fed a normal diet without any additional supplementation. Vitamin A and carotenoids in plasma and major organs were measured by reverse-phase high-performance liquid chromatography. In 3-year-old rats, vitamin A levels were found to be decreased in plasma (P < 0.0001) as compared with young and middle-aged animals. However, they were markedly increased in the main storage organ (ie, the liver) (P < 0.01-0.0001), and also in the aortic vessel wall. They were undetectable in the heart, irrespective of age. Increased tissue levels of vitamin A, especially in the vasculature, may be part of an age-associated self-regulatory process of adaptation, possibly as a counter-regulation against oxidative tissue damage. Based upon the assumption that in elderly humans, as in our animal model, a similar demand-regulated mechanism may work independently of additional dietary vitamin A supplementation, one may question the strategy of large clinical interventional trials using vitamin A or its derivatives beyond normal dietary intake.

Significance of Vitamin A (Retinol) in Ageing

“…This report provided liver vitamin A concentrations by age groups but without any comments on the age-associated changes. Re-examination of these data has clearly shown that the hepatic concentrations of vitamin A are increased with increasing age (Table 1), agreeing the experimental results [4]. Plasma (or serum) retinol, because of its easy accessibility, is the most commonly used biochemical index for the vitamin status in humans.…”

“…Since the hepatic store of the vitamin appears to be appreciably high in association with ageing, the possibility of vitamin A toxicity in old age cannot be ignored. It is also noteworthy that in parallel with an age-associated increase in hepatic storage of vitamin A, a progressive increase in the level of this vitamin has been found to occur with ageing of the aortic vascular wall in rats [4]. This age-related changes of vitamin A status is also accompanied by increased productions of a variety of reactive oxygen species in vascular wall [16].…”

“…Using male normal rats of different ages, plasma levels of retinol have been reported to be significantly decreased, while its hepatic concentrations are increased in 32 -35 months old compared with those of the 4-19 months old rats [4]. An evaluation of the hepatic store of vitamin A in humans is difficult since the only way to obtain such data is from liver samples collected during autopsy.…”

Vitamin A enrichment: Caution with encapsulation strategies used for food applications

“…Among these, the markers involved in the status and functions of vitamin A have been the subject of considerable interest and debate . Indeed, alterations in retinoid metabolism which occur with senescence, particularly low plasma retinol concentrations have been reported in rats and humans (Borel et al, 1998;Haller, Weggemans, Lammi-Keefe, & Ferry, 1996;van der Loo et al, 2004). Furthermore, a decrease in the signaling pathway of vitamin A (decrease of RAR nuclear expression) has also been reported in rats (Pallet et al, 1997), and in humans (Feart et al, 2005).…”

Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells

“…Alterations in retinoid metabolism and thyroid dysfunction occur with senescence. Age-related alterations in vitamin A metabolism, particularly plasma retinol (ROH) concentration have been reported in rats and humans (11,12). Vitamin A deficiency has also been identified in elderly subjects (13).…”