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Food For Thought: How Nutrients Affect the Brain

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An overview of nutritional strategies to optimize brain function.

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Food For Thought: How Nutrients Affect the Brain

  1. 1. Food For Thought: HowNutrients Affect The Brain Michael Lara, MD Diplomate, American Board of Psychiatry and Neurology Private Practice Psychiatry and Psychopharmacology Belmont, CA email: mlaramd@yahoo.com Twitter: FlamingBrains Facebook: www.facebook.com/FlamingBrains
  2. 2. Program Overview
  3. 3. Program Overview• Nutrition and Neurotransmitters
  4. 4. Program Overview• Nutrition and Neurotransmitters• Inflammation and Mood
  5. 5. Program Overview• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite
  6. 6. Program Overview• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite• Blood Sugar, Brain and Behavior
  7. 7. Program Overview• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite• Blood Sugar, Brain and Behavior• Optimizing Sleep and Awareness
  8. 8. Nutrients that InfluenceKey Neurotransmitters
  9. 9. Neurotransmitter Function
  10. 10. 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
  11. 11. 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
  12. 12. 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• Psychopharmacology focused on mimicking or altering the effects of neurotransmitters
  13. 13. Amino Acid Building Blocks
  14. 14. Amino Acid Building Blocks• Protein from diet is broken down into amino acids; during starvation muscle protein is broken down
  15. 15. 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
  16. 16. 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
  17. 17. 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
  18. 18. Tryptophan Methionine Phenylalanine Threonine Valine Leucine Isoleucine Lysine Cysteine Tyrosine Glycine Serine Taurine Carnitine Aspartic Acid Glutathione Thyroxine Glutamine Glutamate Asparagine PyroglutamateTryptamine Serotonin Dopamine GABA Melatonin Epinephrine Norepinephrine Essential Amino Acid (must be obtained from diet) Non-essential Amino Acid (made from essential) Neurotransmitter
  19. 19. Serotonin
  20. 20. Serotonin• Neurotransmitter associated with feelings of well- being and happiness
  21. 21. Serotonin• Neurotransmitter associated with feelings of well- being and happiness• Also regulates sleep and appetite
  22. 22. Serotonin• Neurotransmitter associated with feelings of well- being and happiness• Also regulates sleep and appetite• 90% of body’s total serotonin located in gut
  23. 23. 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)
  24. 24. 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)
  25. 25. Dopamine
  26. 26. Dopamine• Dopamine is pleasure and reward neurotransmitter
  27. 27. Dopamine• Dopamine is pleasure and reward neurotransmitter• Synthesized from tyrosine via tyrosine hydroxylase
  28. 28. Dopamine• Dopamine is pleasure and reward neurotransmitter• Synthesized from tyrosine via tyrosine hydroxylase• Dopamine is precursor for norepinephrine and epinephrine
  29. 29. 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
  30. 30. 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
  31. 31. Dopamine Synthesis
  32. 32. Dopamine Synthesis
  33. 33. Dopamine Synthesis
  34. 34. L-Tyrosine
  35. 35. L-Tyrosine• Synthesized from L-phenylalanine; precursor to dopamine
  36. 36. L-Tyrosine• Synthesized from L-phenylalanine; precursor to dopamine• Diet sources include: chicken, turkey, fish, almonds, avocados, cheeses, yogurt, pumpkin seeds
  37. 37. 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
  38. 38. 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
  39. 39. GABA
  40. 40. GABA• Major inhibitory neurotransmitter in CNS
  41. 41. GABA• Major inhibitory neurotransmitter in CNS• Associated with relaxing, anti-anxiety, anticonvulsant effects
  42. 42. GABA• Major inhibitory neurotransmitter in CNS• Associated with relaxing, anti-anxiety, anticonvulsant effects• Synthesized in the brain from glutamate and Vitamin B6
  43. 43. 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
  44. 44. Glutamate
  45. 45. Glutamate• Major excitatory neurotransmitter in CNS
  46. 46. Glutamate• Major excitatory neurotransmitter in CNS• Involved in learning, memory, and neuroplasticity (long-term-potentiation)
  47. 47. 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)
  48. 48. 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
  49. 49. 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
  50. 50. Glutamine
  51. 51. Glutamine• Conditionally essentially amino acid
  52. 52. Glutamine• Conditionally essentially amino acid• Used as source of cellular energy
  53. 53. Glutamine• Conditionally essentially amino acid• Used as source of cellular energy• Produced from glutamate; muscle contains 90% of body’s total glutamine stores
  54. 54. 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
  55. 55. 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
  56. 56. 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
  57. 57. 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
  58. 58. The Yin and the Yang of Neurotransmitters Glutamate is the major excitatory neurotransmitter in the CNS Glutamate GABA GABA is the major inhibitoryneurotransmitter in the CNS
  59. 59. Acetylcholine
  60. 60. Acetylcholine• Involved with learning and short-term memory
  61. 61. Acetylcholine• Involved with learning and short-term memory• Synthesized from B vitamin choline and Vitamin B5, pantothenic acid
  62. 62. Acetylcholine• Involved with learning and short-term memory• Synthesized from B vitamin choline and Vitamin B5, pantothenic acid• Dietary sources: eggs and lecithin from soy
  63. 63. Acetylcholine• Involved with learning and short-term memory• Synthesized from B vitamin choline and Vitamin B5, pantothenic acid• Dietary sources: eggs and lecithin from soy• Supplements: phosphatidylcholine and phosphatidylserine
  64. 64. Acetylcholine• Involved with learning and short-term memory• Synthesized from B vitamin choline and Vitamin B5, pantothenic acid• Dietary sources: eggs and lecithin from soy• Supplements: phosphatidylcholine and phosphatidylserine• Damage to cholinergic neurons associated with Alzheimer’s disease
  65. 65. Acetylcholine• Involved with learning and short-term memory• Synthesized from B vitamin choline and Vitamin B5, pantothenic acid• Dietary sources: eggs and lecithin from soy• Supplements: phosphatidylcholine and phosphatidylserine• Damage to cholinergic neurons associated with Alzheimer’s disease• Acetyl-L-carnitine and nicotine stimulate ACh receptors
  66. 66. email: mlaramd@yahoo.com Twitter: MichaelLaraMD
  67. 67. Endogenous Opiates
  68. 68. Endogenous Opiates• Endogenous opiates (endorphins) function as neurotransmitters and are released during exercise, eating, sex, excitement and pain
  69. 69. 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
  70. 70. 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
  71. 71. 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
  72. 72. Inflammation and Mood
  73. 73. Inflammation
  74. 74. Inflammation• Response of vascular tissues to harmful stimuli
  75. 75. Inflammation• Response of vascular tissues to harmful stimuli• Cytokines are key messenger proteins that regulate inflammatory process
  76. 76. 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
  77. 77. 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
  78. 78. 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
  79. 79. Inflammation and Cortisol
  80. 80. Inflammation and Cortisol• Hypothalamic-pituitary-adrenal axis modulates reactions to stress and regulates mood, energy storage, sex, and immune systems
  81. 81. 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
  82. 82. 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
  83. 83. 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
  84. 84. Inflammation and Depression
  85. 85. Inflammation and Depression• Increases in stress-induced inflammatory response in depressed patients
  86. 86. Inflammation and Depression• Increases in stress-induced inflammatory response in depressed patients• Cytokines induce “sickness behavior” characterized by fatigue and depression
  87. 87. 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
  88. 88. 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
  89. 89. 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
  90. 90. Effects of Cortisol on Hippocampus Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001
  91. 91. Effects of Cortisol on Hippocampus Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001
  92. 92. Effects of Cortisol on Hippocampus Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001
  93. 93. Effects of Cortisol on Hippocampus Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001
  94. 94. Effects of Cortisol on Hippocampus Andreasen, Brave New Brain: Conquering Mental Illness in the Era of the Genome, 2001
  95. 95. Telomere Shortening and Mood Disorders
  96. 96. Antidepressants and Inflammation
  97. 97. 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• Anti-inflammatory drugs currently under investigation as antidepressants
  98. 98. Inflammation and Alzheimer’s
  99. 99. Inflammation and Alzheimer’s • Most common form of dementia
  100. 100. Inflammation and Alzheimer’s • Most common form of dementia • Accumulation of b-amyloid plaques and tau proteins (neurofibrillary tangles)
  101. 101. 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
  102. 102. 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
  103. 103. Projected Changes in Prevalence of AD between 2000-2025
  104. 104. Anti-inflammatory Nutrients
  105. 105. Anti-inflammatory Nutrients• Anti-inflammatory foods include fruit and vegetables, fish, walnuts, flax and whole grains
  106. 106. 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
  107. 107. 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
  108. 108. 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
  109. 109. 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)
  110. 110. 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
  111. 111. Anti-Inflammatory Nutrients
  112. 112. Alzheimer’s Disease and Mediterranean Diet
  113. 113. Omega-3 Fatty Acids
  114. 114. Omega-3 Fatty Acids• EFAs are required for normal metabolism but are not synthesized by body
  115. 115. Omega-3 Fatty Acids• EFAs are required for normal metabolism but are not synthesized by body• EPA, DHA and ALA
  116. 116. 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
  117. 117. 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
  118. 118. 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
  119. 119. 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
  120. 120. Antidepressants• SSRIs (fluoxetine, citalopram, sertraline) increase availability of serotonin by blocking reuptake pump• SNRIs (duloxetine, venlafaxine) increase availability of serotonin and norepinephrine• TCAs (amitriptyline, nortriptyline, imipramine, doxepin) increase availability of serotonin, norepinephrine but also activate other receptor subtypes• MAOI (selegiline, tranylcypromine, phenelzine) inhibit enzyme that breaks down serotonin, norepinephrine and dopamine
  121. 121. 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
  122. 122. 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
  123. 123. 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
  124. 124. Stress-Related Eating and Appetite
  125. 125. Cortisol and Appetite
  126. 126. Cortisol and Appetite• Main hormone associated with chronic stress
  127. 127. Cortisol and Appetite• Main hormone associated with chronic stress• Chronic elevated cortisol causes elevated blood glucose, which can lead to type 2 diabetes
  128. 128. 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
  129. 129. 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
  130. 130. 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
  131. 131. 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
  132. 132. Regulation of Appetite
  133. 133. Regulation of Appetite• Human appetite control systems designed for survival in primitive times
  134. 134. 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
  135. 135. 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
  136. 136. The Starvation Response
  137. 137. The Starvation Response• Biochemical and physiological changes that reduce metabolism in response to lack of food
  138. 138. 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
  139. 139. 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
  140. 140. 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
  141. 141. L-tryptophan• Essential amino acid obtained only through diet• Precursor to serotonin and melatonin• Believed to contribute to post-meal drowsiness but mechanism likely involves insulin secretion after high carb meal• Competes with BCAAs and L-tyrosine for passage through blood-brain barrier
  142. 142. Dietary Interventions for Psychiatric Conditions• Elimination diets for ADHD have largely failed to identify a single causative nutrient• Medium carbohydrate diet (Zone Diet) for mood disorders• Ketogenic diet for bipolar disorder• Medium-chain triglycerides for Alzheimer’s (Axona)
  143. 143. Ketogenic Diets• High-fat, adequate-protein, low calorie diet used to treat epilepsy in children• Evidence for efficacy in Parkinson’s, Alzheimer’s, ALS, traumatic brain injury, stroke• In absence of glucose, liver breaks down fat to free fatty acids and ketone bodies• Ketones cross blood-brain barrier and are used as fuel source• 4:1 ratio of fat: protein+carbohydrates
  144. 144. Medium Chain Triglycerides• MCTs are more ketogenic that LCTs, which are more common dietary source of fats• Allows more carbohydrate in diet compared to classic ketogenic diet• Most common source: coconut oil• Used also for weight loss, and by endurance athletes and bodybuilders
  145. 145. Blood Sugar, Brain and Behavior
  146. 146. Hypoglycemia• Defined as fasting blood glucose < 70 mg/dL• May cause impaired judgement, emotional lability, slurred speech, and ataxia• If blood glucose <55 mg/dL, epinephrine is released from adrenal glands, resulting in shakiness and dysphoria; <10 mg/dL may cause coma• Prolonged hypoglycemia can impair cognitive function and motor control
  147. 147. Hyperglycemia• Generally blood glucose > 200 mg/dL• Symptoms include polyuria, blurred vision, arrhythmia, and coma• Prediabetes: Fasting blood glucose 100-125 mg/dL• Skipping meals may increase fasting blood glucose, but insulin response leads to delayed postprandial hypoglycemia
  148. 148. 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• Blood glucose can be stabilized by emphasizing low GI foods, and eating 5 times a day (either small meals, or 3 moderate meals and 2 snacks)
  149. 149. 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
  150. 150. Psyllium and Blood Glucose
  151. 151. Sugar and The Brain
  152. 152. Sugar and The Brain• Brain uses 25% of glucose that is available to body
  153. 153. 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
  154. 154. 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
  155. 155. 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
  156. 156. 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.
  157. 157. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI ≥30, or about 30 lbs. overweight for 5’4” person) 1990 2000 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%Source: Behavioral Risk Factor Surveillance System, CDC.
  158. 158. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI ≥30, or about 30 lbs. overweight for 5’4” person) 1990 2000 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%Source: Behavioral Risk Factor Surveillance System, CDC.
  159. 159. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI ≥30, or about 30 lbs. overweight for 5’4” person) 1990 2000 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%Source: Behavioral Risk Factor Surveillance System, CDC.
  160. 160. 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
  161. 161. 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
  162. 162. 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
  163. 163. Optimizing Sleep and Awareness
  164. 164. What is ADHD?• Neurobehavioral disorder beginning in childhood that results in: Inattention • • Impulsivity • Hyperactivity• Causes dysfunction in at least two different areas: • Peer or family relationships • Work or school • Home• Symptoms are not accounted for by another medical or psychiatric condition
  165. 165. Nutrients for Improving Attention• SAMe• B-vitamins• Omega-3 Fatty Acids• L-tyrosine• DMAE
  166. 166. B-Vitamins and ADHD• B-vitamins are co-factors in the synthesis of monoamines • Most evidence for B-6 (pyridoxine) deficiency, but B-9 (folate) and B-12 deficiencies have been documented• High-stress states deplete body’s stores of B-vitamins• Antidepressants and stimulant medications are known to deplete B-vitamins• Key ingredient in many OTC formulations for ADHD treatment • Focus Factor, Synaptol• Recommend High-Potency, Hypoallergenic B-Complex with meals every morning
  167. 167. An Overview of Anxiety Disorders• Generalized Anxiety Disorder• Panic Disorder• Post Traumatic Stress Disorder• Obsessive-Compulsive Disorder
  168. 168. Dietary Supplements for Anxiety Disorders• L-theanine• Kava kava• Valerian• Passion flower• GABA• 5-HTP
  169. 169. 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
  170. 170. Valerian• Decreases sleep latency and improves sleep quality• Decreases GABA breakdown• Suggested doese is 450-600 mg taken 2 hours before bedtime
  171. 171. 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
  172. 172. 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
  173. 173. Nutrients for Cognitive Impairment• Omega-3 fatty acids• Ginko biloba• Phosphatidylcholine and phosphatidylserine• B-vitamins• Medium Chain Triglycerides (Axona)
  174. 174. 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
  175. 175. Phosphatidylcholine and Serine• PC is a major component of cell membranes• PC supplementation believed to slow down age-related (oxidative damage) and enhance learning and memory• FDA: “PS may reduce the risk of dementia in the elderly”• PS may reduce exercise-induced stress by blunting response to cortisol
  176. 176. 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
  177. 177. Chocolate Red Wine Green Tea
  178. 178. 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
  179. 179. 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
  180. 180. Summary
  181. 181. Summary• Nutrition and Neurotransmitters
  182. 182. Summary• Nutrition and Neurotransmitters• Inflammation and Mood
  183. 183. Summary• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite
  184. 184. Summary• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite• Blood Sugar, Brain and Behavior
  185. 185. Summary• Nutrition and Neurotransmitters• Inflammation and Mood• Stress-Related Eating and Appetite• Blood Sugar, Brain and Behavior• Optimizing Sleep and Awareness

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