Vitamin A Abstracts 4


Cutaneous lesions associated with a deficiency in vitamin A in man
            (Frazier and Ch'uan-K'uei, 1931) Download
In addition to the classic signs of keratomalacia, the majority of these patients manifested certain cutaneous lesions of such uniform character as to suggest their being of more than coincidental signifi-cance. This assumption was given further support by the fact that they  ...

The status of retinoids in women suffering from hyper- and hypothyroidism: interrelationship between vitamin A, beta-carotene and thyroid hormones.
            (Goswami and Choudhury, 1999) Download
Retinoid status with reference to beta-carotene and retinol has been studied in women suffering from hyper- and hypothyroid conditions. The interrelationship between the retinoids and triiodothyronine and thyroxine hormones has been established from the cases mentioned after estimation of the respective compounds from the blood serum. It has been found that there is an increase in beta-carotene and retinol in the hypothyroid and a decrease of the same in the hyperthyroid conditions respectively.

Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011).
(Joo et al., 2015) Download
The association of high vitamin A intake and low bone mineral density (BMD) is still controversial. To determine the association of dietary vitamin A intake and serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481 subjects (2907 men and 3574 women) aged ≥50 years from the Korean National Health and Nutrition Examination Survey (2008-2011) were divided into groups according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50-75, >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean dietary vitamin A intakes were 737 and 600 μg RE (Retinol Equivalents) in men and women, respectively. Total hip and femoral neck BMD in men and lumbar spine BMD in women were both positively correlated with dietary vitamin A intake in subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L, both the top (mean 1353 μg RE) and bottom (mean 218 μg RE) tertiles of dietary vitamin A intake had lower BMD than the middle group (mean 577 μg RE). In this population, BMD was the highest among men and women with serum 25(OH)D = 50-75 nmol/L and that there were no differences in BMD by vitamin A intake in these vitamin D adequate groups. This cross-sectional study indicates that vitamin A intake does not affect bone mineral density as long as the serum 25(OH)D concentration is maintained in the moderate level of 50-75 nmol/L.

Short-term vitamin A supplementation does not affect bone turnover in men.
            (Kawahara et al., 2002) Download          
Limited data in humans and animals indicate that excess vitamin A stimulates bone resorption and inhibits bone formation, effects that over time might lead to bone loss and fracture. Thus, it is possible that vitamin A supplementation is a currently unrecognized risk factor for the development of osteoporosis. To further evaluate this possibility, a prospective, randomized, single-blind study of vitamin A supplementation was conducted in 80 healthy men age 18-58 y. One half received 7576 microg (25,000 IU) of retinol palmitate daily with their evening meal; the others took a placebo. Blood was collected from fasting subjects and serum prepared at baseline and after 2, 4 and 6 wk of supplementation. Serum bone specific alkaline phosphatase (BSAP) and N-Telopeptide of type 1 collagen (NTx) were measured at all time points. Serum osteocalcin (Oc) was measured at baseline and after 6 wk of supplementation. BSAP, NTx and Oc did not differ between the supplemented and placebo-treated groups over the course of the study. In conclusion, short-term vitamin A supplementation at this dosage in healthy men does not alter serum markers of skeletal turnover. Thus, it is unlikely that short-term administration of vitamin A would contribute to the development of osteoporosis. Whether long-term vitamin A supplementation might have adverse skeletal effects remains to be determined.

Vitamin a is a negative regulator of osteoblast mineralization.
            (Lind et al., 2013) Download
An excessive intake of vitamin A has been associated with an increased risk of fractures in humans. In animals, a high vitamin A intake leads to a reduction of long bone diameter and spontaneous fractures. Studies in rodents indicate that the bone thinning is due to increased periosteal bone resorption and reduced radial growth. Whether the latter is a consequence of direct effects on bone or indirect effects on appetite and general growth is unknown. In this study we therefore used pair-feeding and dynamic histomorphometry to investigate the direct effect of a high intake of vitamin A on bone formation in rats. Although there were no differences in body weight or femur length compared to controls, there was an approximately halved bone formation and mineral apposition rate at the femur diaphysis of rats fed vitamin A. To try to clarify the mechanism(s) behind this reduction, we treated primary human osteoblasts and a murine preosteoblastic cell line (MC3T3-E1) with the active metabolite of vitamin A; retinoic acid (RA), a retinoic acid receptor (RAR) antagonist (AGN194310), and a Cyp26 inhibitor (R115866) which blocks endogenous RA catabolism. We found that RA, via RARs, suppressed in vitro mineralization. This was independent of a negative effect on osteoblast proliferation. Alkaline phosphatase and bone gamma carboxyglutamate protein (Bglap, Osteocalcin) were drastically reduced in RA treated cells and RA also reduced the protein levels of Runx2 and Osterix, key transcription factors for progression to a mature osteoblast. Normal osteoblast differentiation involved up regulation of Cyp26b1, the major enzyme responsible for RA degradation, suggesting that a drop in RA signaling is required for osteogenesis analogous to what has been found for chondrogenesis. In addition, RA decreased Phex, an osteoblast/osteocyte protein necessary for mineralization. Taken together, our data indicate that vitamin A is a negative regulator of osteoblast mineralization.

Hypervitaminosis A and fractures.
            (Lips, 2003) Download
The toxicity of certain foods that contain high amounts of vitamin A has been recognized for centuries. Chronic vitamin A toxicity, caused by a high intake of vitamin A (25,000 to 50,000 IU per day or more) over a long period, is characterized by bone and joint pain, anorexia, nau- sea and vomiting, and weight loss. Benign intra- cranial hypertension and hepatosplenomegaly may ensue. The study by Michaëlsson and colleagues suggests that vitamin A supplementation and fortification of food with vitamin A may be harmful in Western countries, where the life expectancy is high and the prevalence of osteoporosis is increasing.

Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies.
            (Michaëlsson et al., 2014) Download
BACKGROUND:  A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting. OBJECTIVE:  The objective was to determine whether α-tocopherol intake or serum concentrations are associated with fracture risk in older women and men. DESIGN:  Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used. RESULTS:  During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of α-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). α-Tocopherol-containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of α-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1-4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum α-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48). CONCLUSION:  Low intakes and low serum concentrations of α-tocopherol are associated with an increased rate of fracture in elderly women and men.

The acute and chronic toxic effects of vitamin A.
            (Penniston and Tanumihardjo, 2006) Download
The acute and chronic effects of vitamin A toxicity are well documented in the literature. Emerging evidence suggests that subtoxicity without clinical signs of toxicity may be a growing concern, because intake from preformed sources of vitamin A often exceeds the recommended dietary allowances (RDA) for adults, especially in developed countries. Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA. Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are nonsensitive indicators in this range of liver vitamin A reserves. The metabolism in well-nourished persons of preformed vitamin A, provided by either liver or supplements, has been studied by several research groups. To control vitamin A deficiency, large therapeutic doses are administered in developing countries to women and children, who often are undernourished. Nevertheless, little attention has been given to the short-term kinetics (ie, after absorption but before storage) of a large dose of vitamin A or to the short- and long-term effects of such a dose given to lactating women on serum and breast-milk concentrations of retinol and its metabolites. Moreover, appropriate dosing regimens have not been systematically evaluated to ascertain the quantitative improvement in vitamin A status of the women and children who receive these supplements. The known acute and chronic effects of vitamin A toxicity have been reported previously. However, further research is needed to ascertain the areas of the world in which subclinical toxicity exists and to evaluate its effects on overall health and well-being.



Frazier, Chester N and Hu Ch’uan-K’uei (1931), ‘Cutaneous lesions associated with a deficiency in vitamin A in man’, Archives of Internal Medicine, 48 (3), 507-14. PubMed:
Goswami, UC and S Choudhury (1999), ‘The status of retinoids in women suffering from hyper- and hypothyroidism: interrelationship between vitamin A, beta-carotene and thyroid hormones.’, Int J Vitam Nutr Res, 69 (2), 132-35. PubMed: 10218151
Joo, NS, et al. (2015), ‘Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011).’, Nutrients, 7 (3), 1716-27. PubMed: 25763530
Kawahara, TN, et al. (2002), ‘Short-term vitamin A supplementation does not affect bone turnover in men.’, J Nutr, 132 (6), 1169-72. PubMed: 12042428
Lind, T, et al. (2013), ‘Vitamin a is a negative regulator of osteoblast mineralization.’, PLoS One, 8 (12), e82388. PubMed: 24340023
Lips, P (2003), ‘Hypervitaminosis A and fractures.’, N Engl J Med, 348 (4), 347-49. PubMed: 12540650
Michaëlsson, K, et al. (2014), ‘Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies.’, Am J Clin Nutr, 99 (1), 107-14. PubMed: 24225359
Penniston, KL and SA Tanumihardjo (2006), ‘The acute and chronic toxic effects of vitamin A.’, Am J Clin Nutr, 83 (2), 191-201. PubMed: 16469975