A randomized controlled trial of the effects of a prudent diet on cardiovascular risk factors, gene expression, and DNA methylation - the Diet and Genetic Intervention (DIGEST) Pilot study

Abstract

Background: Risk of cardiovascular disease (CVD) can be increased by single-nucleotide polymorphisms (SNPs) in the 9p21 region of the genome. However, observational studies have shown that the deleterious effect of 9p21 SNPs on CVD might be offset by consuming a diet rich in fresh fruits and vegetables. This association may be driven by diet-influenced modifications in epigenetic and gene expression profiles. In this pilot study, we aimed to: i. test the feasibility of provision of a 'Prudent' and 'Western' diet outside of a specialized clinic, ii. assess the impact of each diet on cardiovascular risk factors. Methods: A single centre, parallel two-arm, pilot randomized controlled trial (RCT) with food provision was conducted in a university teaching hospital outpatient clinic (McMaster university, Hamilton, ON, Canada). The aim was to recruit 80 participants, which allowed for a 10 % dropout. The actual study consisted of 84 apparently healthy participants (69 % women, 18 to 77 years) at low cardiovascular risk. Participants were randomly assigned to follow one of two weight-maintaining diets: 'Prudent' or 'Western' for 2-weeks. The Prudent diet provided <7 % of energy as saturated fat, a polyunsaturated: saturated fat ratio of 1.0, and increased fibre, fruits and vegetables. The Western diet was high in processed foods and sugar, with a moderate quantity of fruit and vegetables. All food was provided. Feasibility outcomes included time to recruitment and retention of participants, successful provision of foods, along with adherence to and palatability of the assigned diets. Secondary outcomes were changes in total cholesterol, low density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) to obtain variance and estimates of effect sizes to inform the sample size calculation for a definitive trial.

Metabolic Trajectories Following Contrasting Prudent and Western Diets from Food Provisions: Robust Biomarkers of Short-Term Changes in Habitual Diet

“…Major changes in self-reported dietary patterns among DIGEST participants were evident after 207 2 weeks as summarized in Table 1. Although there were no significant changes in BMI or average 208 caloric intake between the two treatment arms, greater palatability and satiety was previously 209 reported for participants assigned to a Prudent diet [25]. As expected, the Prudent diet group (W-P) 210 had higher intake of dietary fiber (total, insoluble, soluble), major electrolytes (K, Mg) fruit and/or 211 vegetable, vitamins, poly:sat, protein, and sugar or total carbohydrates, whereas the P-W group had 212 higher intake of fat (total, saturated, and trans), sodium and cholesterol.…”

“…Since all DIGEST participants had poor Prudent diet eating habits at baseline (Table 1), we hypothesized that assigning a Prudent diet (W-P) from food provisions would likely induce a more pronounced metabolic phenotype change than a Western diet (P-W); indeed, several top-ranked metabolites (q < 0.05, FDR) measured in plasma and urine were largely positively associated with a Prudent diet as shown in volcano plots ( Figure S5). Unlike controlled feeding studies within a laboratory setting, DIGEST participants were provided cooking suggestions with meal plans by a dietician that still allowed for flexibility in food preparations [25]. In this study, short-term dietary changes were found to impact the intake of 20 specific nutrient categories from self-reported diet records ( Table 2; Table S1; Figure S4).…”

“…5 of 20 randomized to a Prudent diet (referred to as W-P). Overall, participants reported excellent 169 adherence to all provided food items [25].…”

“…Herein, metabolic phenotyping of matching blood and urine specimens were analyzed from 76 healthy participants from the Diet and Gene Intervention (DIGEST) pilot study, which was a 77 randomized controlled trial to explore the short-term effects of a Prudent diet on CVD risk factors 78 where individuals were provided all foods to prepare at home [25]. A modest reduction in systolic 79 and diastolic blood pressure and total cholesterol was reported for participants following a Prudent 80 diet for two weeks as compared to a Western diet; however, dietary adherence relied on participant 81 self-reporting and food preparation methods were not standardized likely contributing to 82 variability in treatment responses [25]. In this work, we sought to identify specific metabolic 83 trajectories in plasma and urine that function as responsive biomarkers reflecting short-term 84 changes in habitual diet, that were measured in free-living individuals outside of a dedicated 85 metabolic ward or hospital stay.…”

“…A global epidemic of obesity and chronic non-communicable diseases threaten to reduce life 46 expectancy and impose a severe burden on public health [1,2]. Diet and lifestyle are two key modifiable determinants of human health of particular importance for risk of cardiovascular 4 of 20 The DIGEST study was a two-arm parallel dietary intervention involving healthy/non-141 smoking participants recruited from the local community as described elsewhere [25].…”