Effects of Replacing Saturated Fatty Acids with Walnuts or Vegetable Oils on Central Blood Pressure, Arterial Stiffnecuss Indices, Lipids, Lipoproteins, and the Gut Microbiome in Adults at Risk for Cardiovaslar Disease

Open Access
- Author:
- Tindall, Alyssa
- Graduate Program:
- Nutritional Sciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 12, 2019
- Committee Members:
- Penny Margaret Kris-Etherton, Dissertation Advisor/Co-Advisor
Penny Margaret Kris-Etherton, Committee Chair/Co-Chair
Laura E Murray-Kolb, Committee Member
Gregory C Shearer, Committee Member
David Nathan Proctor, Outside Member - Keywords:
- Walnuts
Microbiome
Bioactives
Cardiovascular Disease
Hypertension
PUFA - Abstract:
- The purpose of this dissertation was to investigate the effects of walnut consumption on traditional and emerging cardiovascular disease (CVD) risk factors and the contributions of α linolenic acid (ALA) versus bioactives in adults at risk for CVD. The specific study objectives were (1) to determine whether the individual or combined effect of the bioactives and ALA content of walnuts play a critical role in CVD risk reduction to better understand the underlying mechanisms and (2) to understand how differing fatty acid and bioactive profiles may modulate the gut microbial community. In a randomized, three-period, crossover, controlled-feeding study, participants were fed isocaloric, weight maintenance diets for six weeks each following a two-week Western-style run-in diet. The three study diets included the walnut diet [(WD; 7% saturated fatty acids (SFA), 9% monounsaturated fatty acids (MUFA), 16% polyunsaturated fatty acids (PUFA), 2.7% (ALA)] that provided whole walnuts (57-99 g/day), the walnut fatty acid matched diet (WFMD; 7% SFA, 9% MUFA, 16% PUFA, 2.6% ALA) that had the same fatty acid profile as the WD (but devoid of walnuts), and the oleic acid replaces ALA diet (ORAD; 7% SFA, 12% MUFA, 14% PUFA) that substituted the ALA content of walnuts in the WD with oleic acid and was otherwise macronutrient matched to the other two diets. The run-in diet was formulated to represent a Western-style diet (12% SFA, 12% MUFA, 7% PUFA). In the first study, we examined the effects of the three study diets on central and peripheral blood pressure, markers of vascular health, and lipids and lipoproteins in 45 participants. After six weeks, central diastolic blood pressure decreased on the WD (-1.78±1.0 mmHg) from baseline (P=0.02) compared to the ORAD (0.15±0.7 mmHg, P=0.04). The WD lowered bMAP (-1.44 ± 0.7 mmHg, P=0.04) and cMAP (-1.72 ± 0.8 mmHg, P=0.02) compared to baseline, but there were no differences between the diets. TC was lowered following the WD (-15.8 ± 3.2 mg/dL), WFMD (-14.6 ± 2.9 mg/dL), and ORAD (-11.2 ± 2.7 mg/dL) from baseline (P for all <0.0001). Similarly, LDL-C decreased after the WD (-13.4 ± 2.9 mg/dL), WFMD (-11.1 ± 2.3 mg/dL), and ORAD (-9.2 ± 2.3 mg/dL) from baseline (P for all <0.0001) and HDL-C was also reduced from baseline following the WD, WFMD, and ORAD (-1.8 ± 0.8 mg/dL, -2.1 ± 0.9, -1.1 ± 0.7, respectively, P for all <0.0001). Non-HDL-C was reduced following the WD, WFMD, and ORAD (-14.0 ± 2.9 mg/dL, P<0.006; -12.5 ± 2.5, P<0.0009; -11.0 ± 2.2, P<0.03, respectively). There were not significant differences between diets for lipoprotein endpoints. There were no significant differences in measures of arterial stiffness. In the second study we investigated the effects of the study diets on the gut microbiome through 16S rRNA sequencing. Our results demonstrate enrichment of eubiotic bacteria, including butyrate producers such as Roseburia [Relative abundance (RA)=4.2%, LDA=4.2, P=0.0008], Eubacterium eligensgroup (RA=1.4%, LDA=3.6, P=0.05) and Butyricicoccus (RA=0.3%, LDA=3.3, P=0.01) following the WD and Roseburia (RA=3.6%, LDA=3.8, P=0.02), Eubacterium eligensgroup (RA=1.5%, LDA=3.4, P=0.02) after the WFMD. Our data also showed enrichment of Gordonibacter (RA=0.04%, LDA=3.2, P=0.03), a gut bacteria involved in the metabolism of a walnut-bioactive, i.e., ellagitannins, was uniquely enriched following the WD. We also observed correlations between gut bacteria and CVD risk factors after the WD; Eubacterium eligens was associated with brachial MAP (R=-0.50; P=0.0009), central diastolic BP (-0.52; 0.0006), and central MAP (-0.47, 0.002), Lachnospiraceae was associated with brachial MAP (R=-0.37, P=0.02), central diastolic BP (-0.32; 0.04), central MAP (-0.35; 0.02), TC (-0.35; 0.03), non-HDL-C (-0.37; 0.02), and Leuconostocaceae was associated with brachial MAP (R=0.34; P=0.03) and central MAP (0.34; 0.03). Overall, these data indicate that the fatty acid profile of walnuts lowers CVD risk and there may be additional benefits to consuming whole walnuts beyond their fatty acid profile on novel and established cardiovascular risk factors. We investigated the contributions ALA versus bioactives in walnuts and report evidence of reductions in central systolic blood pressure and favorable changes in the gut microbiome that may be protective against CVD. Together, these two studies provide information to add to the existing knowledge of the underlying mechanisms of walnut consumption associated with cardiovascular benefits.