What’s Eating You? Food, Mood, and Cardiovascular Risk

From Cardiology for the Primary Practitioner, presented by Albany Medical College

Sharon Alger-Mayer, MD, Associate Professor of Medicine, Division of Clinical Nutrition,
Albany Medical College, Albany, NY

Educational Objectives

The goal of this program is to improve management of diet in patients at risk for cardiovascular disease. After hearing and assimilating this program, the clinician will be better able to:

1.   Describe the metabolic effects of leptin, ghrelin, and cortisol.

2.   Assess sleep, stress, diet, and exercise levels before recommending lifestyle modification.

3.   Help patients outline a successful diet and exercise plan.

4.   Discuss the effects of different types of carbohydrates on gene expression in abdominal fat.

5.   Explain cardiovascular benefits of phytochemicals such as resveratrol.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Alger-Mayer and the planning committee reported nothing to disclose.

Acknowledgements

Dr. Alger-Mayer spoke in Troy, NY, at Cardiology for the Primary Care Practitioner, presented November 7, 2009, by Al­bany Medical College. The Audio-Digest Foundation thanks Dr. Alger-Mayer and the Albany Medical College for their co­operation in the production of this program.

Introduction: lifestyle shown to cause >50% of deaths among middle-aged women; 72% of cardiovascular mortality attributed to lifestyle; family history and genetics play role in hunger, satiety cues, and metabolic rate; environmen­tal exposure and diet patterns cause changes in brain and relationship to food

Crosstalk between gastrointestinal (GI) tract, brain, and fat stores: throughout GI tract, chemicals give feedback about eating (eg, what is being eaten, last time food eaten) to brain through bloodstream and vagus nerve to help brain regulate hunger; fat is endocrine organ that can produce and release chemical messages into bloodstream (eg, telling brain about level of fat stores); constant crosstalk occurs throughout day; person with sufficient fat stores and no weight loss  —  after lunch, satiety peptides released by gut and adipose cells suppress chemicals associated with increased appetite (eg, neuropeptide Y, agouti-related peptide); energy-controlling pathway stimulated; satiety hormones increase; metabolism increases (ie, more calories burned off as heat); person with decreasing fat stores and weight loss  —  leptin levels low; 4 to 5 hr before lunch, ghrelin released from stomach stimulates hunger and cravings; appetite-motivating pathway stimulated; satiety hormones suppressed

Low levels of leptin: active in hypothalamus and limbic system (ie, reward system); affect chemicals in brain (eg, do­pamine); magnetic resonance imaging (MRI) studies show increases in areas of brain (eg, nucleus accumbens, cau­date nucleus) that cause greater cravings and higher drive for food, even immediately after feeding; when patients genetically deficient in leptin shown picture of food, cravings stimulated, even when not hungry

Addiction-like behavior: animal studies suggest sugar causes release of endogenous opiates and dopamine similar to addictive drugs; rats given intravenous (IV) sugar bolus had brain changes similar to rats who self-administer ad­dictive drugs; when sugar taken away, withdrawal behavior and decrease in dopamine similar to that seen with ad­dictive drugs; under certain conditions, foods rich in fat and sugar capable of promoting addiction-like behavior and neuronal changes; in certain individuals, diet pattern of restricting food followed by overeating (ie, decreases in leptin followed by increases in dopamine) can lead to addiction-like pattern

Adapting to weight loss and starvation: with weight loss, body receives signal about decrease in fat stores; metabo­lism decreases; enzymes that cause fat storage (eg, lipoprotein lipase) increase; chemicals in brain that stimulate hunger increase; over time, suppression of thyroid axis continues to decrease metabolism; stimulation of limbic re­ward system drives desire to obtain high-calorie, high-fat foods

Stress and cortisol: stress decreases leptin and increases ghrelin (stimulator of hunger and craving); study of 50 women  —  salivary cortisol measured at baseline and repeated after 15 min of relaxation; women told to prepare and present 5-min presentation on controversial topic to group of experts; in some women, cortisol levels remained un­changed after presentation; in other women (“high stress reactors”), cortisol increased significantly in response to stress; women asked to document daily intake of food and daily stresses for 2 wk; in high stress reactors, snacking strongly associated with daily stresses (suggests high cortisol reactivity to stress promotes food intake); abdominal fat  —  men and women with high waist-to-hip ratio had greater cortisol reactivity to stress and poorer coping skills, compared to those with low waist-to-hip ratio; suggested that elevated cortisol in response to stress may contribute to development of abdominal fat; recent research suggests cortisol stimulates preadipocytes to proliferate, differen­tiate into fat cells, and fill with fat; rats fed high-fat, high-sugar diet and exposed to long-term stress had 50% greater increase in visceral fat, compared to animals on same diet alone; over 3 mo, rats developed symptoms of metabolic syndrome; bathing preadipocytes cultured from human visceral and subcutaneous fat in cortisol solution found to have profound effect on gene expression in fat cells (eg, upregulation of genes that cause insulin resistance and stimulate adipogenesis); 11-b hydroxysteroid dehydrogenase type 1  —  enzyme induced by cortisol; amplifies cortisol action by converting inactive cortisone to active cortisol; highly expressed in visceral fat; fat cells may have ability to generate cortisol locally, independent of serum cortisol levels; fat cell recognized as endocrine organ with ability to produce and release chemicals that affect metabolism (eg, leptin, tumor necrosis factor [TNF]-a, interleu­kin [IL]-6, angiotensinogen, and cortisol); increased deposition of visceral fat leads to characteristics of metabolic syndrome

Sleep: sleep restriction (<6.5 hr per night) causes increased hunger and impaired glucose tolerance (partially medi­ated by higher levels of cortisol and ghrelin); small study found subjects with sleep deprivation had significant in­creases in snacking of carbohydrates and sweet foods at night (when individual would normally be asleep); laboratory studies show sleep deprivation causes rapid drop in insulin sensitivity, thereby causing predisposition to glucose intolerance; epidemiologic studies show reduced sleep increases risk for diabetes and obesity in adults and children

Initiating lifestyle modification: 5% to 10% weight loss improves manifestations of metabolic syndrome; chal­lenges include working with patient to achieve long-term lifestyle change and ongoing success; 1) understand start­ing point; ask patient for 3-day food record that documents foods eaten and emotions and moods that drive food choices; ask patient to wear step counter for 3 days to obtain baseline assessment of activity; ask for 7-day record of sleep cycle; ask patient about recreational activities and stress relief; 2) discuss lifestyle assessment with patient; patients often feel overwhelmed and challenged by daily life; difficult for patients to invest time and energy into in­tervention; help patient set reasonable goals; therapy should be patient-centered (guide patient through important decisions)

Diet study: reviewed various healthy diets, all comprised of <8% fat, adequate fiber, and low cholesterol, with carbo­hydrates from foods with low glycemic index; primary outcome, weight loss after 2 yr; excluded patients with dia­betes and unstable heart disease; recommended calorie deficit of 750 calories less than amount needed for weight maintenance; patients received strong support (eg, group and individual sessions), given 2-wk meal plans, and asked to document foods and exercise for 90 min/wk; results  —  at 2 yr, no significant difference in change in weight or waist circumference among diet groups; most patients lost weight; most weight loss occurred in first 6 mo; »25% of patients continued to lose weight for 2 yr; at 2 yr, »33% lost 5% of initial body weight, »15% had lost 10% of initial body weight; drop in fasting insulin seen with all diets except diet comprised of 65% carbohydrates (greatest drop seen with high-protein diet); similar decrease in triglycerides and benefit in reducing metabolic syn­drome seen among diet groups; participation in group sessions positive predictor of success; patients who attended 66% of group sessions lost average of 9 kg over 2 yr; modest calorie reduction and healthy diet regardless of mac­ronutrient composition resulted in weight loss and reduction in cardiovascular risk; select diet that patient feels will work for him or her

Effect of type of carbohydrate on gene expression: study  —  one group given oat bread and 210 g of mashed pota­toes each week; other group given rye bread and 210 g of pasta; diets similar in fiber and no difference in fat or pro­tein; rye and pasta group characterized by low postprandial insulin response, compared to high response in oat and potatoes group; study looked at effect on gene expression and abdominal fat in patients with metabolic syndrome; results  —  dietary change in carbohydrate affected expression of genes in abdominal fat; in low glycemic index group, insulin-signaling genes downregulated; upregulation of 62 genes linked to stress response and cytokine-me­diated immunity seen in high glycemic index group; significant effect of diet on gene regulation independent of en­ergy intake and body weight; subsequent study  —  looked at effect of whole grains vs refined grains on cardiovascular risk in patients with metabolic syndrome; patients asked to reduce calories by 500 per day; after 12 wk, despite no difference in weight loss, greater percentage of abdominal fat lost in whole grain group, with 38% reduction in C-reactive protein (magnitude of reduction similar to results achieved with statins)

Exercise: cohort study of patients who maintained ³30-lb weight loss found physical activity (burning 2800 calo­ries/wk by walking [»11,000 steps/day], and performing higher-intensity exercise twice weekly) powerful predictor of success; over 20 wk, patients who performed multiple short bouts of exercise throughout day (compared to sin­gle continuous exercise session) exercised more days, accumulated more minutes of exercise per week, and lost more weight with similar cardiovascular benefits

Supplements 

Rho-iso-a acids: found in hops; high activity on glycogen synthetase kinase pathway; regulates insulin signaling and its association with inflammation; study found adding rho-iso-a acids and acai berry extract to healthy Med­iterranean-style diet (eg, diet high in omega-3 fatty acids, low glycemic index carbohydrates, high quality pro­teins, and fruits and vegetables) for 12 wk reduced cholesterol and triglycerides more than standard group; resolution of metabolic syndrome in phytochemical group, 43% vs 22% in standard group; Framingham 10-yr risk scores dropped by 5.6% in phytochemical group vs 2.9% in standard group; no difference in weight loss be­tween groups; reduction in low-density lipoprotein (LDL), 17% in phytochemical group vs 8.4% in standard group; increase in high-density lipoprotein (HDL), 7% in phytochemical group vs 3% in standard group; drop in triglycerides, 35% in phytochemical group vs 14% in standard group; consumption of phytochemicals in whole foods recommended as part of healthy diet rather than in pill form; diets high in saturated fat have negative effect on protein kinase pathways and may negate beneficial effects of phytochemicals

Resveratrol: use of products containing polyphenols (eg, grapes, wine) shown to reduce cardiovascular risk; benefit of wine greater than that of other alcoholic beverages; resveratrol found in skins of grapes; other active polyphe­nol found in grape seeds; reduces BP, improves endothelial function, decreases platelet aggregation, and activates proteins that prevent cell death in bacteria; incubation of endothelial cells that line vasculature with flavenoid-rich red wine shown to upregulate nitric oxide (NO) synthetase and protein expression for NO, resulting in 3-fold increase in NO in endothelial cells

Cocoa: beneficial effect on BP, insulin resistance, and platelet function; proposed mechanisms include activation of NO and antioxidant and anti-inflammatory effects; consumption of 75 g of dark chocolate for 3 wk shown to im­prove HDL cholesterol by »14% and decrease LDL oxidation in healthy subjects; in hypertensive patients, 100 g over 2 wk showed beneficial effects on some markers; meta-analysis of randomized controlled trials of 173 sub­jects showed dark chocolate reduced systolic and diastolic BP after 2 wk; effects on BP appear to require less in­take than other changes; beneficial effects most likely due to increased bioavailabity of NO; polyphenols stimulate NO synthetase, increase vascular arginase (helps to prevent breakdown of NO), and decrease white blood cell adhesion and migration (early signs of atherosclerosis inhibited by polyphenols); milk chocolate and white chocolate do not have same beneficial effects; alkalinization of dark chocolate reduces flavenoids; in non­diabetic patients, chocolate consumption associated with dose-dependent decrease in cardiac mortality after first myocardial infarction

Stress reduction: exercise  —  can reduce stress, anxiety, and depression; raises dopamine and may reduce cravings for foods high in fat and sugar; in animals, shown protective against stress-induced anxiety and depression; attenu­ates stress-induced changes in serotonin and noradrenaline; breathing technique  —  take deep breath and hold for 4 sec, then exhale; breathe from abdomen; within 1 min, parasympathetic tone increases; heart rate, BP, and salivary cortisol decrease

Implementing plan: select specific behavior to change; set reasonable goals (eg, walk for 10 min/day) and increase gradually; plan should be clear and specific; performing physical activity with friend or partner increases likelihood of success; online community support helpful; rewarding successful lifestyle changes helpful; track changes often enough to make benefits clear to patient, but not so often patients feel discouraged

Questions and answers: caffeine  —  shown to reduce insulin resistance; amounts variable; both green tea and coffee beneficial; coding for weight-related comorbidities  —  code for high BP, type 2 diabetes, hyperlipidemia, or meta­bolic syndrome; vitamin D  —  affects immune system; data suggest it may affect glycolysis; according to guidelines, serum level >30 ng/mL sufficient; treat deficiency aggressively (eg, 50,000 IU/wk of ergocalciferol; if parathyroid hormone elevated, consider twice weekly dosing); 1000 to 2000 IU/day of vitamin D₃ (inexpensive, over-the-coun­ter form) more effective at raising serum levels than vitamin D₂ (ergocalciferol); start patients on vitamin D₃ when starting high-dose prescription supplementation

Suggested Reading

Bosch JA et al: A general enhancement of autonomic and cortisol responses during social evaluative threat. Psychosom Med 71:877, 2009; Covas MI et al: Wine and oxidative stress: Up-to-date evidence of the effects of moderate wine con­sumption on oxidative damage in humans. Atherosclerosis  2009 Jul 8 [Epub ahead of print]; Dietrich MO et al: Feeding signals and brain circuitry. Eur J Neurosci 30:1688, 2009; Grassi D et al: Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 81:611, 2005; Handjieva-Darlenska T et al: The effect of high-fat diet on plasma ghrelin and leptin levels in rats. J Physiol Biochem 65:157, 2009; Kallio P et al: Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Am J Clin Nutr 85:1417, 2007; Malone M et al: The lifestyle challenge program: a multidisciplinary approach to weight management. Ann Pharmacother 39:2015, 2005; Patel SR: Reduced sleep as an obesity risk factor. Obes Rev 10 Suppl 2:61, 2009; Sacks FM et al: Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 360:859, 2009; Stofkova A et al: Activation of hypothalamic NPY, AgRP, MC4R, AND IL-6 mRNA levels in young Lewis rats with early-life diet-induced obesity. Endocr Regul 43:99, 2009; Takahashi S et al: Differential effect of resveratrol on nitric oxide production in endothelial f-2 cells. Biol Pharm Bull 32:1840, 2009.