Limited appearance of apocarotenoids is observed in plasma after consumption of tomato juices: a randomized human clinical trial

Abstract

Background: Nonvitamin A apocarotenoids occur in foods. Some function as retinoic acid receptor antagonists in vitro, though it is unclear if apocarotenoids are absorbed or accumulate to levels needed to elicit biological function.

Objective: The aim of this study was to quantify carotenoids and apocarotenoids (β-apo-8'-, -10'-, -12'-, and -14'-carotenal, apo-6'-, -8'-, -10'-, -12'-, and -14'-lycopenal, retinal, acycloretinal, β-apo-13-carotenone, and apo-13-lycopenone) in human plasma after controlled consumption of carotenoid-rich tomato juices.

Design: Healthy subjects (n = 35) consumed a low-carotenoid diet for 2 wk, then consumed 360 mL of high-β-carotene tomato juice (30.4 mg of β-carotene, 34.5 μg total β-apocarotenoids/d), high-lycopene tomato juice (42.5 mg of lycopene, 119.2 μg total apolycopenoids/d), or a carotenoid-free control (cucumber juice) per day for 4 wk. Plasma was sampled at baseline (after washout) and after 2 and 4 wk, and analyzed for carotenoids and apocarotenoids using high-pressure liquid chromatography (HPLC) and HPLC-tandem mass spectrometry, respectively. The methods used to analyze the apocarotenoids had limits of detection of ∼ 100 pmol/L.

Results: Apocarotenoids are present in tomato juices at 0.1-0.5% of the parent carotenoids. Plasma lycopene and β-carotene increased (P < 0.001) after consuming high-lycopene and β-carotene tomato juices, respectively, while retinol remained unchanged. β-Apo-13-carotenone was found in the blood of all subjects at every visit, although elevated (P < 0.001) after consuming β-carotene tomato juice for 4 wk (1.01 ± 0.27 nmol/L) compared with both baseline (0.37 ± 0.17 nmol/L) and control (0.46 ± 0.11 nmol/L). Apo-6'-lycopenal was detected or quantifiable in 29 subjects, while β-apo-10'- and 12'-carotenal were detected in 6 and 2 subjects, respectively. No other apolycopenoids or apocarotenoids were detected.

Conclusions: β-Apo-13-carotenone was the only apocarotenoid that was quantifiable in all subjects, and was elevated in those consuming high-β-carotene tomato juice. Levels were similar to previous reports of all-trans-retinoic acid. Other apocarotenoids are either poorly absorbed or rapidly metabolized or cleared, and so are absent or limited in blood. β-Apo-13-carotenone may form from vitamin A and its presence warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02550483.

FIGURE 1

HPLC-MS/MS chromatograms of apocarotenoid and apolycopenoid standards. Colors represent different MS/MS transitions and peaks are annotated in Table 2.

FIGURE 2

Subject selection CONSORT flow diagram.

FIGURE 3

Linear regression of plasma β-carotene concentrations (n = 35) vs. plasma β-apo-13-carotenone concentrations (n = 35) from all visits (n = 3). Green squares are subjects on control, orange circles are those on high-β-carotene tomato juice, and red triangles are those on high-lycopene tomato juice, P < 0.001.