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)

OBJECTIVE: The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result. METHODS: Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination. RESULTS: Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters. CONCLUSION: Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

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)

OBJECTIVE: The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result. METHODS: Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination. RESULTS: Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters. CONCLUSION: Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels.

The Carotene and Retinol Efficacy Trial (CARET), a randomized, placebo-controlled lung cancer chemoprevention trial of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate, was prematurely terminated when a 46% excess lung cancer mortality was found in subjects on the active arm. Before the CARET intervention ended, 21 men were recruited to participate in a 6-month biomarker study using the same intervention as CARET that determined the effect of this supplementation on lung nutrient levels. Plasma and bronchoalveolar lavage (BAL) cell nutrient levels were measured before and after the intervention. The group in the active arm (n = 10) had plasma carotene level increases of over 10-fold, with a small increase in plasma retinol levels BAL cell levels of beta-carotene in the active group also increased 10-fold, from 4.5 to 46.3 pmol/10(6) cells (P = 0.0008), with no change in BAL cell retinol levels. Surgically obtained lung tissue from three CARET subjects in the active arm showed elevated carotene lung tissue levels but no increase in lung retinol levels compared to a group of surgical controls. Combined with our previous work showing a strong correlation between BAL and lung tissue nutrient levels, these findings suggest that supplementation with beta-carotene and vitamin A results in increased lung tissue as well as BAL cell levels of beta-carotene, with little change in lung retinol.

Maternal serum vitamin A levels are not associated with mother-to-child transmission of HIV-1 in the United States.

HIV-1 transmission from mother to child has been associated with maternal vitamin A status in studies of women living in Africa. This finding has raised the question of whether vitamin A supplementation might help reduce transmission in the United States as well as worldwide. In industrialized nations, however, both the vitamin A nutritional status of HIV-1-infected pregnant women and the association of vitamin A levels with vertical transmission were unknown. Furthermore, vitamin A is teratogenic, and supplements during pregnancy have caused birth defects. To investigate whether maternal serum levels of vitamin A (retinol) and three other micronutrients correlate with vertical transmission of HIV-1 in the United State, we studied 95 HIV-1-infected pregnant women and followed their infants to determine whether transmission occurred. Sera were obtained during the third trimester of pregnancy from 95 HIV-1-infected women living in the New York and Los Angeles metropolitan areas. The two cohorts were established to study vertical transmission of HIV-1 and to reflect the racial, ethnic, and socioeconomic status of HIV-1-infected in women in the United States. We measured serum levels of vitamin A (retinol) and three other micronutrients, vitamin E (alpha-tocopherol), beta-carotene, and lycopene, in the mothers using reverse-phase high-performance liquid chromatography and determined the HIV-1 infection status of their infants using virus cultivation and polymerase chain reaction. Sixteen of the 95 women transmitted HIV-1 to their infants. Statistical analysis of the data indicated that low maternal serum retinol levels during the third trimester of pregnancy were not associated with mother-to-child transmission of HIV-1. None of the women had retinol levels so low as to have clinical symptoms of vitamin A deficiency. The serum levels of alpha-tocopherol, beta-carotene, and lycopene, three micronutrients that act as antioxidants and enhance immune function, were also measured. Statistical analysis of the data revealed no association of the levels of these three micronutrients with vertical transmission of HIV-1. Analysis of the data obtained from 95 women in the United States indicates that vitamin A deficiency is rare, and serum retinol levels are not associated with risk of vertical HIV-1 transmission. In view of the teratogenic effects of vitamin A when taken as a supplement during pregnancy, pregnant HIV-1-infected women living in nations where vitamin A deficiency is not a public health problem should not be advised to take extra vitamin A supplements.