AUTHOR=McEneny Jane , Henry Sarah-Louise , Woodside Jayne , Moir Susan , Rudd Amelia , Vaughan Nick , Thies Frank 

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

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.954593

DOI=10.3389/fnut.2022.954593

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><p>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, HDL<sub>2</sub> and HDL<sub>3</sub>. These changes were also associated with a decrease in serum amyloid A (SAA), potentially enhancing their anti-atherogenic properties.</p></sec><sec><title>Objective</title><p>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.</p></sec><sec><title>Design</title><p>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, &lt;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). HDL<sub>2</sub> and HDL<sub>3</sub> 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.</p></sec><sec><title>Results</title><p>Lycopene in serum and HDL significantly increased following consumption of both the high tomato diet and lycopene supplement (<italic>p</italic>  ≤  0.001 for both). Lycopene, either as a tomato-rich food or a supplement, enhanced both serum- and HDL<sub>3</sub>-PON-1 activities (<italic>p</italic>  ≤  0.001 and <italic>p</italic> = 0.036, respectively), while significantly reducing HDL<sub>3</sub>-SAA-related inflammation (<italic>p</italic> = 0.001). Lycopene supplement also significantly increased HDL<sub>3</sub>-LCAT activity (<italic>p</italic> = 0.05), and reduced the activity of both HDL<sub>2</sub>- and HDL<sub>3</sub>-CETP (<italic>p</italic> = 0.005 and <italic>p</italic> = 0.002, respectively). These changes were not associated with changes in the subclasses distribution for all lipoprotein fractions or the size of lipoprotein subclasses.</p></sec><sec><title>Conclusion</title><p>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 HDL<sub>3</sub>-associated SAA, confirming that SAA may represent a sensitive inflammatory biomarker to dietary change.</p></sec><sec><title>Clinical Trial Register</title><p>(<ext-link ext-link-type="uri" xlink:href="https://www.isrctn.com" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.isrctn.com</ext-link>), ISRCTN34203810.</p></sec>