title: Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels.
abstract: 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.
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut 06510, USA. carrie.redlich@yale.edu
authors.forename: C A
authors.initials: CA
authors.lastname: Redlich
authors.forename: W S
authors.initials: WS
authors.lastname: Blaner
authors.forename: A M
authors.initials: AM
authors.lastname: Van Bennekum
authors.forename: J S
authors.initials: JS
authors.lastname: Chung
authors.forename: S L
authors.initials: SL
authors.lastname: Clever
authors.forename: C T
authors.initials: CT
authors.lastname: Holm
authors.forename: M R
authors.initials: MR
authors.lastname: Cullen
mesh_terms: D000368:Aged; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001195:Asbestosis / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D002338:Carotenoids / Q000097:blood*; D004224:Diterpenes; D004311:Double-Blind Method; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000084562:Retinyl Esters; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019207:beta Carotene / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D019207:beta Carotene; D014801:Vitamin A; C014794:retinol palmitate; D002338:Carotenoids