Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

Abstract

Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.

Potential Benefits of Black Chokeberry (Aronia melanocarpa) Fruits and Their Constituents in Improving Human Health

“…This has been supported by several pilot studies and a meta-analysis for Aronia berries, which showed that regular consumption of Aronia juice can reduce the incidence of urinary tract infection and the use of antibiotics of elderly residents of nursing homes [50] and decrease blood pressure and total cholesterol levels to show potential cardioprotective effects [60][61][62][63][64][65]. In addition, Aronia berries were found to show immunomodulating activity [55,56,59], and they exhibited synergistic effects with elderberries for their inhibitory potency against β-coronavirus-1 (HCoV-OC43) [53].…”

“…The results showed that consumption of Aronia berries decreased LINE-1 methylation levels and the arachidonic acid/eicosapentaenoic acid ratio. Cardiovascular disease is associated with alterations in DNA methylation and PUFA profile, and thus this clinical trial indicates some potential cardioprotective effects of the habitual consumption of Aronia juice [60].…”

Chokeberry (A. melanocarpa (Michx.) Elliott)—A Natural Product for Metabolic Disorders?

“…A study from 2021 assessed the effect of chokeberry juice consumption on the metalation of long interspersed nucleotide element 1 (LINE-1) in peripherial blood leukocytes in women with cardiovascular risk factors, including those who were overweight and dyslipidemic [150]. LINE-1 is considered to be an important factor in assessing the global methylation of the genome in the body.…”

“…Among the polyphenols influencing DNA methylation are catechin, epicatechin, (−)-epigallocatechin-3-O-gallate (EGCG), quercetin, and genistein [154,155]. Stojković et al (2021) showed a decrease in LINE-1 methylation after 4 weeks of consuming chokeberry juice in women, and thus, as the authors emphasized, chokeberry may have had a cardioprotective effect [150].…”

Immunomodulatory Effects of Aronia Juice Polyphenols—Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments

“…In recent years, plant polyphenols have been associated with various beneficial effects on human health because of their antidiabetic, cardiovascular [ 4 ], neuroprotective and antihypertensive [ 5 ] actions. Some evidence of their protective and therapeutic effects on diseases that are closely connected to immune response such as inflammatory diseases, allergic occurrences, or autoimmune diseases has been reported [ 6 ].…”