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Food For Thought: How Nutrients Affect The Brain, 2013 Edition

Food For Thought: How Nutrients Affect The Brain, 2013 Edition






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    Food For Thought: How Nutrients Affect The Brain, 2013 Edition Food For Thought: How Nutrients Affect The Brain, 2013 Edition Presentation Transcript

    • Food For Thought: How Nutrients Affect The Brain Michael Lara, MD Diplomate, American Board of Psychiatry and Neurology Private Practice Psychiatry and Psychopharmacology San Francisco, CA
    • When diet is wrong, medicine is of no use. When diet is correct, medicine is of no need ~Ayurvedic Proverb
    • Michael Lara, MD mlaramd@gmail.com www.brainwebinar.com Twitter: @MichaelLaraMD For More Information:
    • Program Overview • Nutrition and Neurotransmitters • Inflammation and Mood • Stress-Related Eating and Appetite • Blood Sugar, Brain and Behavior • Optimizing Alertness and Sleep
    • Nutrients that Influence Key Neurotransmitters
    • "Let food be thy medicine and medicine be thy food" ~Hippocrates
    • Neurotransmitter Function • Neurotransmitters are messenger molecules produced by nerve cells to communicate and control almost every function of the body: mood, memory, appetite, and sleep-wake cycle • Many are made from essential amino acids from nutrients (primarily proteins) in our diet • Psychopharmacology focused on mimicking or altering the effects of neurotransmitters
    • Norepinephrine Serotonin Dopamine Alertness Concentration Energy Obsessions Compulsions Memory Pleasure Reward Motivation Attention Appetite Sex Aggression Anxiety Impulsivity Mood Cognition
    • Amino Acid Building Blocks • Protein from diet is broken down into amino acids; during starvation muscle protein is broken down • Amino acids are converted, with the help of cofactors, to neurotransmitters in CNS • Amino acids also are used to make membrane receptors for neurotransmitters • The only source of the essential amino acids is the protein in your diet
    • Tryptophan Methionine Phenylalanine ValineThreonine Leucine Isoleucine Lysine Serotonin Melatonin Cysteine Glutathione Dopamine Tyrosine Epinephrine Norepinephrine Glycine Serine CarnitineTaurine Glutamate Aspartic Acid GABA Glutamine
    • Serotonin • Neurotransmitter associated with feelings of well- being and happiness • Also regulates sleep and appetite • 90% of body’s total serotonin located in gut • Foods with a higher ratio of tryptophan to leucine and phenylalanine increase production of serotonin (bananas, papayas, dates) • Foods with a lower ratio decrease production of serotonin (wheat, rye bread)
    • L-Tryptophan 5-Hydroxy-Tryptophan Serotonin 5-HIAA Monoamine Oxidase
    • Dopamine • Dopamine is pleasure and reward neurotransmitter • Synthesized from tyrosine via tyrosine hydroxylase • Dopamine is precursor for norepinephrine and epinephrine • Low levels associated with ADHD, Parkinson’s, depression, addictions, and introversion • High levels associated with mania, psychosis, and extroversion
    • Tyrosine L-Dopa Dopamine Norepinephrine
    • GABA • Major inhibitory neurotransmitter in CNS • Associated with relaxing, anti-anxiety, anticonvulsant effects • Synthesized in the brain from glutamate and Vitamin B6 • L-theanine, kava, skullcap and valerian are thought to increase GABA peripherally but do NOT cross blood-brain barrier
    • Glutamate • Major excitatory neurotransmitter in CNS • Involved in learning, memory, and neuroplasticity (long-term-potentiation) • Excessive glutamate binds to NMDA receptor and causes neuronal death (excitotoxicity) • Found in cheese, soy sauce, and responsible for umami, one of five basic tastes • Sodium salt is food additive and flavor enhancer: monosodium glutamate, or MSG
    • Glutamine • Conditionally essentially amino acid • Used as source of cellular energy • Produced from glutamate; muscle contains 90% of body’s total glutamine stores • Uses: reduces healing time after operations, decreases muscle breakdown, enhances immunity; increases human growth hormone • Other studies demonstrate stabilizing effect on blood sugar and decreased cravings for alcohol in recovering alcoholics • Dietary sources: beef, chicken fish, eggs, wheat cabbage, beets, spinach, parsley • Doses: 5-15 grams/day
    • Inflammation and Mood
    • Inflammation • Response of vascular tissues to harmful stimuli • Cytokines are key messenger proteins that regulate inflammatory process • Inflammation may have a role in various disease states including depression and Alzheimer’s disease • Food and eating pattern can be inflammatory • Inflammation and stress can lead to accumulation of visceral fat, which in turn can produce inflammatory cytokines and other hormones that affect appetite
    • Inflammation and Cortisol • Hypothalamic-pituitary-adrenal axis modulates reactions to stress and regulates mood, energy storage, sex, and immune systems • Cortisol increases blood sugar through gluconeogenesis and suppresses immune system • Altered patterns of in cortisol secretion in many conditions associated with stress, including MDD and PTSD • Leads to accumulation of visceral fat
    • Inflammation and Depression • Increases in stress-induced inflammatory response in depressed patients • Cytokines induce “sickness behavior” characterized by fatigue and depression • Exists with other diseases of inflammation: DM II, asthma, CAD • Pro-inflammatory cytokines (IL-1, IL-6,TNF) produce symptoms of depression and anxiety • Cytokines overactive HPA axis
    • Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001 Effects of Cortisol on Hippocampus
    • Telomere Shortening and Mood Disorders Simon NM, Smoller JW, McNamara KL, et al. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol. Psychiatry. 2006;60(5):432–435.
    • Simon NM, Smoller JW, McNamara KL, et al. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol. Psychiatry. 2006;60(5):432–435.
    • Antidepressants and Inflammation • Depression associated with up-regulation of inflammatory response system • Hyperproduction of pro-inflammatory cytokines reversed by antidepressants • Antidepressants decrease gamma interferon and TNF-alpha; and increase anti inflammatory IL-10
    • Inflammation and Alzheimer’s • Most common form of dementia • Accumulation of b-amyloid plaques and tau proteins (neurofibrillary tangles) • Evidence of altered immune status in AD • Long-term use of NSAIDs may protect against AD but not vascular dementia
    • Anti-inflammatory Nutrients • Anti-inflammatory foods include fruit and vegetables, fish, walnuts, flax and whole grains • Anti-inflammatory spices include sage, ginger, chili peppers, black pepper, and curcumin • Green tea may inhibit atherosclerosis and hypercholesterolemia • Red wine contains resveratol which protects tissues inside blood vessels • Moderate consumption of alcohol raises good cholesterol (HDL) • Dark chocolate can reduce blood pressure and elevate mood
    • Meat% %Sweets% Poultry,%Eggs,% Cheese,%Yogurt% Fish%and%Seafood% Fruits,%Vegetables%Grains,%Beans,%Nuts,% Olive%Oil% Physical%AcCvity;%Enjoy%meals%with%others% The Mediterranean Diet
    • Alzheimer’s Disease and Mediterranean Diet Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. Mediterranean diet and risk for Alzheimer's disease. Annals of neurology. 2006;59(6):912–921.
    • Omega-3 Fatty Acids • EFAs are required for normal metabolism but are not synthesized by body • EPA, DHA and ALA • Common sources include breast milk, wild fish, seaweed, algae, and flaxseed • Believed to play key role in maintaining fluidity of cell membranes • May also stabilize blood glucose and thereby reduce hunger
    • Omega-3s and Depression • Several epidemiological studies suggest covariation between fish consumption and rates of depression • 2004 study found that suicide attempt patients had lower blood levels of Omega-3 fatty acids • Lower blood levels of DHA associated with higher suicide rates among U.S. military • 2007 meta-analysis showed that Omega-3s significantly improved depression in both patients with unipolar and bipolar disorder • Health benefits of Omega-3s may be especially important in patients with psychiatric disorder due to high prevalence of smoking and obesity
    • Hibbeln J. Fish consumption and major depression. Lancet. 1998.
    • Medium Chain Triglycerides • MCTs are medium-chains (6-12 carbons) fatty acids of glycerol • Do not require energy for absorption, utilization, storage • Coconut oil is composed of 66% MCTs • MCTs promote fat oxidation and reduced food intake • MCTs are used in treatment of neurodegenerative disorders; mechanism likely involves induction of ketosis.
    • Stress-Related Eating and Appetite
    • C.M.’s Story December 2010 March 2012 www.brainwebinar.com
    • Cortisol and Appetite • Main hormone associated with chronic stress • Chronic elevated cortisol causes elevated blood glucose, which can lead to type 2 diabetes • Cortisol also increases activity in amygdala, resulting in increased craving for sweet, salty, fatty foods • Cortisol increased by loss of sleep, excessive exercise, psychological stress and restrictive dieting • Excess cortisol associated with stress of restrained eating and body image disturbance • Effects of chronic cortisol elevation may be mitigated by omega-3 supplementation
    • Endogenous Opiates • Endogenous opiates (endorphins) function as neurotransmitters and are released during exercise, eating, sex, excitement and pain • B-endorphin, released by pituitary, is cleavage product from POMC • B-endorphin may have role in mediating runner’s high • Opiate blockers (naltrexone) used for weight reduction, alcohol abuse and for reducing euphoria associated with self-injurious behaviors
    • Regulation of Appetite • Human appetite control systems designed for survival in primitive times • Regulated by lower brain structures (amygdala, hypothalamus), dopamine-driven reward circuits, and higher prefrontal cortex circuits • Automatic, impulsive eating behaviors associated with primitive brain structures may be overcome by higher prefrontal cortex, responsible for decision-making and planning
    • The Starvation Response • Biochemical and physiological changes that reduce metabolism in response to lack of food • During short periods of energy abstinence, body will burn FFA from body fat stores; after prolonged starvation, body will break down lean tissue and muscle • Glucose in diet is used first, then stored glycogen, then breakdown of fats into glycerol + free fatty acids
    • Caloric Restriction • Dietary regimen that restricts total calorie intake by 10-25% • CR shown to reduce BP, fasting glucose, fasting insulin (65%), and c-reactive protein • Believed to activate longevity genes (SIRT1) and reduce oxidative stress • Shown to extend lifespan in many organisms, including primates but human studies are ongoing
    • Intermittent Fasting • Alternating periods of fasting with non-fasting, typically for no longer than 24 hours. • Benefits include improved regulation of blood glucose, reduction of chronic inflammation, enhanced cognition and reduction of body fat while preserving lean body mass. • In a common 18/6 variation, fasting is done from 6:00 pm until noon the next day. Nutritionally balanced meals favoring protein and healthy fats are recommended during eating period from Noon until 6:00 pm. BCAAs and MCTs may be used during the fast to manage hunger. • To optimize health benefits, resistance training is recommended immediately before breaking the fast (i.e. from 11:00-noon)
    • Google Trends “Intermittent Fasting”
    • Resistance Training 1 day/week Heavy Singles Sprint Training 2 days/week; 20/20 Intermittent Fasting 3 days/week Omega-3 Fatty Acids 4 grams/day Leisurely Nature Walks 5 days/week
    • Blood Sugar, Brain and Behavior
    • Glycemic Index • Glycemic index is the measure of how much and how quickly a food will raise blood glucose, which is then lowered by insulin • Glycemic load is the measure of the total effect of a meal on blood glucose • High glycemic index foods include refined grains products, potatoes, and sugary foods • Low GI foods include legumes, fat-free dairy products, some fruits, and barley
    • Supplements for Stabilizing Blood Sugar Stevia Rebaudiana Platago Ovata
    • Dietary Fiber • Fiber is a diverse group of compounds, including lignin and complex carbohydrates, that cannot be digested by human enzymes in the small intestine • Viscous fibers, such as those found in oat products and legumes, can lower serum LDL cholesterol levels and normalize blood glucose and insulin responses • For adults who are 50 years of age and younger, the AI recommendation for total fiber intake is 38 g/day for men and 25 g/day for women. For adults over 50 years of age, the recommendation is 30 g/day for men and 21 g/day for women 1. Chandalia M, Garg A, Lutjohann D, Bergmann von K, Grundy SM, Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. New England Journal of Medicine. 2000;342(19):1392–1398.
    • Psyllium and Blood Glucose Anderson JW, Allgood LD, Turner J, Oeltgen PR, Daggy BP. Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia. The American Journal of Clinical Nutrition. 1999;70(4):466–473
    • Sugar and The Brain • Brain uses 25% of glucose that is available to body • If blood glucose falls too low, mood can become impatient, irritable, and aggressive • Self-control requires adequate glucose in the brain • Sugar, fat, and salt activate reward circuits in the brain that override prefrontal circuits that govern higher cognitive function such as self-control
    • Insulin Resistance and Prediabetes • Prediabetes is a condition in which blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes • The U.S. Department of Health and Human Services estimates that about one in four U.S. adults aged 20 years or older—or 57 million people—had prediabetes in 2007 • Studies have shown that most people with prediabetes develop type 2 diabetes within 10 years, unless they lose 5 to 7 percent of their body weight—about 10 to 15 pounds for someone who weighs 200 pounds—by making changes in their diet and level of physical activity.
    • Source: Behavioral Risk Factor Surveillance System, CDC. 2000 Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI ≥30, or about 30 lbs. overweight for 5’4” person) 2010 1990 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
    • Appetite Suppressants • Psychostimulants: increase DA and NE • Phentermine: primarily increases NE, but also increases 5-HT and DA • Sibutramine: NE and 5-HT reuptake inhibitor • Bupropion/naltrexone • Orlistat: reduces absorption of fats from GI tract • Natural appetite suppressants
    • Naltrexone • Opioid receptor antagonist used in treatment of alcohol dependence • Believed to reduce dopaminergic activity in reward centers of brain • Used to treat self-injurious behaviors, impulse control disorders (trichotillomania, kleptomania, compulsive gambling) • May reduce reward associated with over-eating and is key component in weight loss drug Contrave
    • Branched Chain Amino Acids • Leucine, isoleucine, and valine are essential amino acids • Used medically to treat ALS, hepatic encephalopathy, and tardive dyskinesia • Used by athletes to improve exercise performance and reduce muscle breakdown during intense exercise • May also blunt the release of insulin and may therefore reduce appetite associated with caloric restriction • Recommended doses: 5-20 grams/day in divided doses
    • Optimizing Alertness and Sleep
    • Nutrients for Improving Mood and Cognition • Amino acid precursors for neurotransmitter synthesis • Folate pathways in cofactor synthesis • Enhance blood flow • Antioxidants
    • SAMe • Donor of methyl groups in many essential biologic reactions, including the synthesis of neurotransmitters • Efficacy equal to FDA approved antidepressants • Expensive; may induce mania; GI upset; insomnia • Doses range from 200-1,600 mg/day in divided doses
    • Folic Acid • Folate deficiency associated with increased risk of depression • In patients who suffer from depression, 7 out of 10 may have a specific genetic factor that limits their ability to convert folate from diet to L-methylfolate • At risk populations for low folate levels: MTHFR polymorphism, diabetes, hypothyroidism, excessive EtOH and smokers • Drugs that deplete folate include: oral contraceptives, antiepileptic drugs, metformin, methotrexate, niacin • L-methylfolate (medical food product) crosses blood brain barrier to assist in synthesis of neurotransmitters
    • L-Tyrosine • Synthesized from L-phenylalanine; precursor to dopamine • Diet sources include: chicken, turkey, fish, almonds, avocados, cheeses, yogurt, pumpkin seeds • A number of studies have found tyrosine to be useful during conditions of stress, cold, sleep deprivation, and improvements in cognitive and physical performance • Dosing: 1-6 grams/day in divided doses
    • St. John’s Wort • Effective for mild-moderate depression • Response rate 64% v. 59% for TCAs • MOA: the inhibition of cytokines; decrease in 5-HT receptor density • Suggested dose: 900-1,800 in divided doses
    • Ginko Biloba • Long history of use for treatment of cognitive deficits in AD and vascular dementia • May also improve learning capacity • Year long study with 309 patients suggest that ginko may stabilize and improve cognitive performance in demented patients • Suggested doses: 120-240 mg/day
    • N-acetylcysteine • Amino acid derivative used as medication and as nutritional supplement • Precursor of antioxidant glutathione • May be useful for OCD, trichotillomania, impulse control disorder, alcohol- and cocaine-related disorders, and schizophrenia • Believed to counteract glutamate hyperactivity via NMDA receptor • For impulse control disorders, dose 600 mg 3-4x/day
    • Cocoa • Derived from tree theobroma cacao • Rich in flavonoids which protect against coronary heart disease • Health benefits: antioxidant, lowers blood pressure, inhibits platelet aggregation, and reduces inflammation • Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance
    • Chocolate Red Wine Green Tea Nurk E, Refsum H, Drevon CA, et al. Intake of flavonoid-rich wine, tea, and chocolate by elderly men and women is associated with better cognitive test performance. The Journal of Nutrition. 2009;139(1):120
    • “Even a soul submerged in sleep is hard at work and helps make something of the world.” ~Heraclitus
    • Sleep and Mood • American adults average 6.5 h sleep, less than most other countries. Optimal functioning reportedly requires 8 ± 0.5 hours • Sleep maintenance through the night may be disturbed by major depression. Generalized and anticipatory anxiety is especially identified with trouble initiating sleep. • Chronic insomnia increases the risk for depression 5 times, the risk for panic disorder 20 times • Patients with major depressive disorder tend to go into REM (dream) sleep shortly after sleep onset,skipping the earlier stages of sleep
    • Kava Kava • Controlled, double-blind studies suggest it may be helpful for mild anxiety • Works by conversion to kavapyrones: central muscle relaxants and anticonvulsants • Involved with GABA receptor binding and NE uptake inhibition • Suggested dose: 60-120 mg/day
    • Valerian • Decreases sleep latency and improves sleep quality • Decreases GABA breakdown • Suggested doese is 450-600 mg taken 2 hours before bedtime
    • Melatonin • Hormone derived from serotonin • Effective for people with insomnia caused by circadian rhythm disturbances • Interacts with suprachiasmatic nucleus • Resets circadian pacemaker and attenuates an alerting process • Ambient light inhibits production of endogenous MT • Recommended doses 0.25-3.0 mg/day
    • Magnesium • Functions include relaxation and contraction of muscles and production and transport of cellular energy • Assists with cellular glucose utilization to improve insulin resistance • Deficiency results in hyperexcitability, muscle weakness, and sleepiness • Deficiency common with EtOH abuse, some medications (lasix, HCTZ), malabsorption syndromes • Found in green, leafy vegetables, spinach, and unrefined grains • Magnesium sulfate, chloride, or lactate have better bioavailability than magnesium oxide • RDA is up to 420 mg/day
    • Snake Oil? Scientific Evidence For Popular Dietary Supplements informationisbeautiful.net Worth It Line
    • "The wise man should consider that health is the greatest of human blessings. Let food be your medicine." ~Hippocrates
    • Food For Thought: How Nutrients Affect The Brain For More Information: twitter: @MichaelLaraMD mlaramd@gmail.com www.brainwebinar.com