Food For Thought: How Nutrients Affect The Brain

Michael Lara, MD

Diplomate, American Board of Psychiatry and NeurologyPrivate 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

AlertnessConcentration

Energy

ObsessionsCompulsions

Memory

PleasureReward

Motivation

Attention Appetite

SexAggression

AnxietyImpulsivity

MoodCognition

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 Valine Threonine 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 Training1 day/week

Heavy Singles

Sprint Training2 days/week; 20/20

Intermittent Fasting3 days/week

Omega-3 Fatty Acids4 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. AdultsBRFSS, 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 EvidenceFor Popular Dietary

Supplements

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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: @MichaelLaraMDmlaramd@gmail.com

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