Safety of High-Dose Vitamin A

Abstract

The paper reports on the efficacy and side effects of high-dose vitamin A, administered as adjuvant treatment for resected stage I lung cancer in a randomized clinical trial. After a median follow-up of 28 months, 283 patients were evaluable: 138 allocated to treatment with retinol palmitate (300,000 IU daily for at least 12 months) and 145 to standard observation. The clinical results available to date do well justify a continuation of the study. Skin dryness and desquamation were the most frequent symptoms, affecting 60% of all treated patients. Other symptoms such as dyspepsia, headache, nosebleeds and mild hair loss occurred in less than 10% of patients, and were self-terminating. Only in 4 patients (3%) was the treatment interrupted because of symptoms potentially related to vitamin A administration. As for laboratory tests, Γ-GT levels were abnormally elevated in 69% of treated patients vs. 39% of controls at 24 months (mean 149 vs. 58 IU/1; p < 0.05). Serum triglyceride concentrations over 150mg/dl were seen in 74% of treated patients vs. 43% of controls at 12 months (mean 283 vs. 179mg/dl; p < 0.05). There were no other laboratory signs of toxicity attributable to vitamin A. In our experience, high-dose retinoyl palmitate administration was a well-tolerated and safe treatment. The long-term impact on lipid metabolism still remains to be determined.

Vitamin A Intake Is Inversely Related with Adiposity in Healthy Young Adults

“…Furthermore, retinoic acid, which has been related to certain antioxidant properties (42), stimulates the expression not only of UCP1, but also of related uncoupling proteins, such as UCP2 (41) and UCP3 (43), and affects other aspects of white and brown adipose tissue development and function (44). The relationship between vitamin A intake and serum total cholesterol can be explained by a substantial body of evidence that synthetic retinoids and high doses of vitamin A alter lipid metabolism by increasing cholesterol (45)(46)(47).…”

Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET)

“…There is a substantial body of evidence that synthetic retinoids and high dose vitamin A alter lipid metabolism by increasing cholesterol and/or triglycerides Pastorino et al, 1991;Tangrea et al, 1993) and that such changes increase cardiovascular disease risk (Grundy, 1986;Betteridge & Morrell, 1998). Although the differences between the vitamin A/beta-carotene and placebo arms were relatively modest and the triglyceride differential was clearly nonprogressive (Omenn et al, 1994a), evidence from combined cohort studies shows that even a small change in the population mean cholesterol concentration has a substantial effect on coronary heart disease.…”

“…Data for high dose vitamin A (300 000 IU per day) show a similar effect on both triglycerides and cholesterol (Murray et al, 1983;Infante et al, 1991;Pastorino et al, 1991). However, data for moderate dose vitamin A are scant.…”

Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET)

“…Why either b-carotene and/or retinol would cause increased cardiovascular mortality in this population is unclear, but of serious concern, especially considering the magnitude of the effect and the widespread use of these dietary supplements [4,5]. Based on (1) the knowledge that retinoids can cause significant increases in triglyceride and LDL cholesterol levels and reductions in HDL cholesterol levels at routinely used pharmacologic and chemopreventive doses [6 -11], (2) case reports of similar lipid changes following acute high doses of vitamin A [12,13], and (3) the well known strong association between reduced plasma HDL cholesterol levels and increased risk of ischemic heart disease [14], it was hypothesized that long-term supplementation with the CARET doses of vitamin A (retinyl palmitate) and b-carotene might similarly raise triglyceride levels and lower HDL cholesterol levels. This effect would provide a possible explanation for the excess cardiovascular mortality seen in subjects on the active intervention.…”