Effects of long-term intake of retinol on selected clinical and laboratory indexes

Cartmel, Brenda; Moon, Thomas E.; Levine, Norman

doi:10.1093/ajcn/69.5.937

Cited by 30 publications

(23 citation statements)

References 26 publications

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“…Cartmel et al (1999) suggested from their results that moderate concentrations of vitamin A may have an adverse effect on the LDL/HDL ratio: the LDL/HDL ratio increased slightly from 3.071.08 to 3.371.18 (NS) in the retinol group and from 3.171.17 to 3.271.14 (NS) in the placebo group in conjunction with a relative lowering of HDL and a relative increase in LDL in the retinol compared to the placebo group. Lowering of HDL and an increase in LDL has also been reported with use of some synthetic retinoids (Vahlquist et al, 1985;Marsden, 1986;Tangrea et al, 1993); such a change in LDL/HDL ratio increases risk of ischemic heart disease.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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Background: The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk ¼ 1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. Design: We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. Intervention: In the asbestos-exposed pilot (N ¼ 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N ¼ 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. Results: Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (Po0.0003) and serum triglycerides (Po0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n ¼ 863) as compared to the placebo group (n ¼ 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. Conclusion: The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2005

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“…Kushi et al (63) found that supplemental vitamin A was not associated with a lower risk of dying from coronary disease. Cartmel et al (64) evaluated the adverse effects of long-term systemic retinol intake. The median follow-up time was 3.8 yr.…”

Section: Carotenoids and Cardiovascular Disease (Cvd)mentioning

confidence: 99%

“…After 49 mon of follow-up, triacylglycerol was 11% higher, cholesterol was 3% higher, and HDL was 1% lower in the retinal group than in the placebo group. Because a 1% increase in cholesterol concentration has been reported to be associated with a 2% increase in coronary heart disease (64), the interpretation of the effects of long-term ingestion of 7,576 RE vitamin A/d should be approached cautiously. Further studies are needed to confirm this finding.…”

Section: Carotenoids and Cardiovascular Disease (Cvd)mentioning

confidence: 99%

Nutritional and potential disease prevention properties of carotenoids

Basu

Vecchio²,

Flider³

et al. 2001

J Americ Oil Chem Soc

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Epidemiological studies have shown that people who consume diets with a high content of vegetables have a reduced risk of degenerative diseases such as specific cancers, cardiovascular disease, age-related macular degenerative disease (AMD), and cataracts. There is no convincing evidence that the protective role of vegetables against cancer and cardiovascular disease is due to carotenoids. However, there is a strong possibility that lutein and zeaxanthin present in food materials may prevent AMD and cataract formation. Increased use of cooked tomato products also has been shown to reduce prostate cancer risk as a result of increased bioavailability of cis-lycopene. One of the most important biochemical mechanisms underlying the cancer-preventive activity of carotenoids is the stimulation of intercellular gap junction communications. β-Carotene, canthaxanthin, and lutein are efficient inducers of intercellular gap junction communication, whereas α-carotene and lycopene are less active.Paper no. J9851 in JAOCS 78, 665-675 (July 2001).

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“…In one large Phase III trial of orally administered retinol (25,000 IU/day for up to 5 years) in 2,297 randomized participants with evidence of moderate to severe actinic keratosis, the vitamin A intervention was associated with minimal toxicity (i.e., mild elevation of serum lipids) and a 32% reduction in the risk of squamous cell carcinoma (1,4). Having previously shown that vitamin A doses as high as 300,000 IU/day were well tolerated for up to 1 year in patients with advanced cancers, we were interested in evaluating the safety and efficacy of retinyl palmitate doses in the intermediate range of 25,000 -75,000 IU/day in the treatment of patients with sun-damaged skin (5).…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin

Alberts

Ranger‐Moore

Einspahr³

et al. 2004

Clinical Cancer Research

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Purpose: Previously, we reported the results of a Phase III, placebo-controlled trial in 2,297 randomized participants with moderately severe actinic keratoses wherein 25,000 IU/ day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50,000 or 75,000 IU/day would be both safe and more efficacious in skin cancer chemoprevention.Experimental Design: One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25,000, 50,000, or 75,000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sundamaged skin.Results: There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25,000 IU/day, 50,000 IU/day, and 75,000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22,600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25,000 and 50,000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor ␣, retinoic acid receptor ␤, and retinoid X receptor ␣ at the 50,000 IU/day vitamin A dose.Conclusions: The vitamin A doses of 50,000 and 75,000 IU/day for 1 year proved safe and equally more efficacious than the 25,000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.

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Effects of long-term intake of retinol on selected clinical and laboratory indexes

Cited by 30 publications

References 26 publications

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

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

Nutritional and potential disease prevention properties of carotenoids

Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin

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