Diet & Cellular Stress Review PDF

Diet & Cellular Stress Cohort studies – subjects who don’t have the outcome at baseline are followed for when & if outcome occurs Case series – case reports comparing patients w/ the same tx. Case control – pts with a disease or outcome of interest vs. pts w/out disease or outcome Single point in ti...

Diet & Cellular Stress Cohort studies – subjects who don’t have the outcome at baseline are followed for when & if outcome occurs Case series – case reports comparing patients w/ the same tx. Case control – pts with a disease or outcome of interest vs. pts w/out disease or outcome Single point in time data collection Health Efficacy - ability to make this body feel good in healthy ways Addiction - ability to make this body feel good in unhealthy ways Intakes are invariably healthy & unhealthy – healthy vs. unhealthy Everyone has a routine hierarchy of healthier & less healthy foods Addictive eating has global (ecological) impact – is supported by a food industry that profits from addictive eating Experimental dilemma – difficulty in ensuring nutritional adherence – people do not eat ‘on command’ Endothelial Cell Stress - Marin et al., 2011 Endothelial cell stress is linked to atherosclerosis & endothelial cell dysfunction (1) [atherosclerosis – ‘hardening of arteries & blood vessels’] Cell stress leads to a wearing down of cell barriers; maintenance of intact endothelial cell barriers is crucial for healthy vascular structure & function. Athero-protective effects occur through the release of substances that promote anticoagulation, inhibit inflammation & induce vasodilation (2). Atherosclerosis is so common a condition that it is the leading cause of death in the US and Canada. A sticky substance called plaque builds up inside the arteries and blocks them. About half of North Americans between ages 45 and 84 years have atherosclerosis but don’t know it. Atherosclerosis develops slowly as cholesterol, fat, blood cells and other substances in your blood form plaque. When the plaque builds up, it causes the arteries to narrow. This reduces the supply of oxygen-rich blood to tissues of vital organs in the body. [Starving yourself of O2] Ornish (1998) conducted a study where low fat diet & comprehensive lifestyle resulted in regressions of plaque formation Our bodies have the capacity to self heal & remove plaque Endothelial Micro-particles (EMPs) Within blood plasma, they reflect pathologies as quantities increase under disease conditions Experimental interest has focused on EMPs as a surrogate measure of endothelial injuries (4). The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of blood vessels EMPs are extensively involved in atherosclerosis (5). EMP Concentrations: Increases in plasma EMP levels reflect cell injuries due to cytokine release & oxidative stress [Cytokines - proteins made by immune & non-immune cells that affect the immune system. Some cytokines stimulate the immune system and others slow it down] High EMP levels are associated with: coronary syndromes, peripheral arterial disease, diabetes mellitus & metabolic syndrome EMPs indicate vascular dysfunction (7) as EMPs play roles in vascular injury, inflammation & thrombosis (blood clots) Endothelial Progenitor Cells or EPCs EPCs contribute to maintaining the endothelium by replacing injured endothelial cells (10). EPCs are reduced in patients with cardiovascular disease (11), diabetes mellitus & coronary risk factors Atherosclerosis appears to be caused by the loss of endothelialrepair capacities, i.e. too few EPCs (12) EPCs Apoptotic EMPs contribute to tissue repair mechanisms by stimulating the generation of EPCs(13) Interactions between EMPs & EPCs are influential Diet influences EMP - EPC interactions The high prevalence of CVD attributable to lifestyle, revolves around sedentariness & diets high in saturated fats and sugars but low in fatty acids-fruit-vegetables-fiber (14) Marin et al: Assessed Population 20 subjects (mean age 65 y; 10 M, 10 F) assessed for medical hx, physical exam & clinical chemistry analysis. Subjects maintained regular PA / lifestyle & ‘diarized’ events potentially affecting outcomes (eg, smoking-alcohol-food). N = 6 high BP, N = 2 hyperlipidemia, N = 3 diabetes mellitus. No problem alcohol intake or smoking or family hx of CVD. Context This study focused on dietary fat intake & release of EMPs vs. EPCs Particle Comparisons EPCs Mediterranean Diet More High Carbohydrate but Low Fatty Acid Diet (CHO-ALA) Less Saturated Fatty Acid Diet (SFA) Less Comparison of CHO-ALA vs. SFA Particles CHO-ALA SFA EPCs More Less EMPs Less More EMPs Less More More Cholesterol - Triglycerides Comparisons Medit Diet - less Total Cholesterol & less LDL Cholesterol Results: Mediterranean Diet (MD) vs. Saturated Fat Acid Diet (SFA) vs. Low Fat High Carbohydrate Diet with Supplements (CHO - ALA) MedDiet associated with lower levels of microparticles & activated/apoptotic EMPs & a higher levels of EPCs than SFA or CHO-ALA CHO-ALA associated with lower plasma microparticles, & activated apoptotic EMPs than SFA diet Findings suggest decreases in endothelial damage & endothelial dysfunction & improved regenerative capacity with MedDiet, (richer in virgin olive oil than the compared diets) a Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women C.Mason et al Obesity | VOLUME 21 | NUMBER 12 | DECEMBER 2013 Negative Findings Were Not So Negative Baseline Measures: Telomere length inversely associated with age & positively associated with Maximum Oxygen Uptake (p = 0.03) Telomere length not associated with baseline BMI or % body fat Follow up Measures (at 12 months) : Change in telomere length was inversely correlated with baseline telomere length (p =.0001, r = - 0.47) [if telomeres were longer at baseline, there was less change during trial] No significant difference in telomere length detected in any intervention group vs. controls; magnitude of Wt. Loss not associated with telomere length (12 months) Interventions Nutrition + Exercise - Nutrition vs. Exercise - 12-month RCT testing caloric restriction &/or exercise on circulating hormones & other outcomes - therefore 4 groups 1. 2. 3. 4. Controls - no intervention….did telomeres get shorter? Caloric restriction alone Exercise alone Caloric restriction + Exercise Dietary Intervention - Goals - 1,200-2,000 kcal day, < 30% daily calories from fat 10% weight loss Aerobics Intervention - Goals - 45 min of moderate to vigorous AE (4 [METs]) - exercise intensity @ target heart rate of 7085% observed maximum, 5 days/ week * Note the Diet + Exercise group’s results were much closer to significance than diet alone or exercise alone Discussion - 1 Main mechanisms by which obesity shortens telomeres & increase risk of diseases are oxidative stress (which increases telomere erosion) & inflammation (which deteriorates leukocytes) An extensive/expensive 12 mo. program was not associated with significant change in telomere length although positive weight loss was achieved Mean wt. changes were - 2.4% (P = 0.03) in the exercise group, - 8.5% (P < 0.001) in the diet group, and - 10.8% (P < 0.001) in the diet & exercise group, compared to - 0.8% among controls; Are these enough for TL change? The diet & exercise group did best re: Wt. Loss & TL change Discussion - 2 Despite large sample size, study may be underpowered for determining telomere length effects in relation to wt. loss & AE - a larger sample may be required - this study can be used for estimating future RCT sample size requirements Puterman et al. in AE study had 68 subjects sub-divided into 34 vs. 34. 12 mos. of intervention may have been too brief for TL effects to occur. Puterman et al. did only 24 weeks (6 months) of intervention Population may have been too elderly - postmenopausal women (50-75 yrs) Ornish et al. study had male subjects at equivalent ages. Study Power Power - is study planned & executed to detect statistically significant differences? Effect size - the basic quantitative difference between-groups, or within-groups on a specific measure in a specific study The larger the Effect Size in a study, the smaller the Sample Size needed to detect statistically significant differences The smaller the Effect Size in a study, the larger the Sample Size needed to detect statistically significant differences Diet vs. Mindfulness in BP Reduction in Atrial Fibrillation DASH DIET [Dietary Approach to Stop Hypertension] - limited saturated fat intake increased fruit / vegetable consumption reduced sodium increased potassium Bananas, oranges, cantaloupe, honeydew, apricots, grapefruit (dried fruits), spinach, broccoli, potatoes, mushrooms, peas, zucchini, Orange juice, Tomato juice, Apricot juice, Grapefruit juice Milk & Yogurt & Fish (eg. Halibut, Cod) Beans - Lima, Pinto, Kidney, Soybeans, Lentils ★ ★ Discussion - Pirbaglou (2019) Mindfulness-Based vs. Diet-Based Risk Reduction (MBRR - DBRR), Both improved systolic blood pressure (SBP) in AF patients. Significant within-group reductions in SBP, during waking & sleeping from baseline to 16-week follow-up (24 hr ambulatory BP monitoring) No between-group differences found: MBRR & DBRR are = in reducing SBP Significant within-group reductions in SBP during waking & sleeping indicate each approach (MBRR & DBRR) reduces SBP Diet & Cellular Stress - Key Points 1. Dietary choices impact the body at cellular levels - e.g EMPs - EPCs 2. People, generally, have difficulty following a preferred or prescribed diet 3. This adherence difficulty carries through to single-arm & multi-arm clinical trials – because adherence is uncertain - objective measures of ‘healthy eating’ adherence are optimal 4. Existing evidence linking telomere length with diet intake (alone) is not as strong as evidence for comprehensive lifestyle intervention or AE or mindfulness meditation