A randomized trial finds lycopene supplements boost HDL PON-1 antioxidant activity and lower CETP activity in HDL2 and HDL3 without changing particle size (Front Nutr 2022)

Original title: 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

Front Nutr · 1 January 2022 · 6

McEneny J, Henry SL, Woodside J, Moir S, Rudd A, Vaughan N, Thies F

In a randomized controlled trial of 225 disease-free, moderately overweight adults aged 40-65 years assigned to a control diet, a lycopene-rich diet, or the control diet plus a lycopene supplement, both the lycopene-rich diet and the supplement significantly raised serum and HDL lycopene concentrations (P <= 0.001 for both) and enhanced serum and HDL3 paraoxonase-1 activity (P <= 0.001 and P = 0.036, respectively), while significantly reducing HDL3 serum amyloid A-related inflammation (P = 0.001). The lycopene supplement also significantly increased HDL3 lecithin-cholesterol acyltransferase activity (P = 0.05) and reduced the activity of both HDL2 and HDL3 cholesteryl ester transfer protein (CETP) (P = 0.005 and P = 0.002, respectively). These functional changes occurred without altering lipoprotein subclass distribution or particle size.

Original abstract

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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.