Lycopene-rich diets modulate HDL functionality and associated inflammatory markers without affecting lipoprotein size and distribution in moderately overweight, disease-free, middle-aged adults: A randomized controlled trial

Background: The consumption of lycopene-rich foods may lower cardiovascular disease (CVD) risk. Lycopene circulates in the blood bound to lipoproteins, including high-density lipoproteins (HDLs). Preliminary data from our group showed that increased consumption of tomato-based food or lycopene supplement in middle-aged subjects led to functional changes to HDL's sub-fractions, HDL₂ and HDL₃. These changes were also associated with a decrease in serum amyloid A (SAA), potentially enhancing their anti-atherogenic properties.

Objective: We carried out a comprehensive randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods or lycopene supplements affects HDL functionality and associated inflammatory markers, and lipoprotein subfractions size and distribution.

Design: Volunteers (225, aged 40-65 years) were randomly assigned to one of three dietary intervention groups and asked to consume a control diet (low in tomato-based foods, <10 mg lycopene/week), a lycopene-rich diet (224-350 mg lycopene/week), or the control diet with a lycopene supplement (70 mg lycopene/week). HDL₂ and HDL₃ were isolated by ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum. Systemic and HDL-associated inflammation was assessed by measuring SAA concentrations. HDL functionality was determined by monitoring paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin cholesterol acyltransferase (LCAT) activities. The lipoprotein subfractions profile was assessed by NMR.

Results: Lycopene in serum and HDL significantly increased following consumption of both the high tomato diet and lycopene supplement (p ≤ 0.001 for both). Lycopene, either as a tomato-rich food or a supplement, enhanced both serum- and HDL₃-PON-1 activities (p ≤ 0.001 and p = 0.036, respectively), while significantly reducing HDL₃-SAA-related inflammation (p = 0.001). Lycopene supplement also significantly increased HDL₃-LCAT activity (p = 0.05), and reduced the activity of both HDL₂- and HDL₃-CETP (p = 0.005 and p = 0.002, respectively). These changes were not associated with changes in the subclasses distribution for all lipoprotein fractions or the size of lipoprotein subclasses.

Conclusion: Our results showed that dietary lycopene can significantly enhance HDL functionality, without associated changes in particle size and distribution, by modulating the activity of HDL-associated enzymes. Concomitantly, dietary lycopene significantly decreased serum- and HDL₃-associated SAA, confirming that SAA may represent a sensitive inflammatory biomarker to dietary change.

Clinical trial register: (https://www.isrctn.com), ISRCTN34203810.