The Impact of Diet on Cognition

Transcription

1 The Impact of Diet on Cognition The Shape of Things to Come The Economist, Dec Dr Alex Richardson Senior Research Fellow, University of Oxford Founder Director, Food and Behaviour Research The Modern, Western-Type Diet Childhood behavioural and learning difficulties the Overlap Dyslexia Modern, junk food diets are seriously damaging our physical health leading to increased rates of: Obesity Type-II Diabetes Diet also affects our Heart Disease brains and behaviour Cancer Allergies / Immune Disorders Dyspraxia ADHD Autistic Spectrum These diagnoses are descriptions they are not explanations. Difficulties are dimensional, affecting > 20% of UK school children Psychological / Psychiatric Disorders Bipolar Disorder Schizophrenia Depression Anxiety Disorders Diagnoses are descriptive based on behaviour, not etiology Conditions are dimensional i.e. continuous with normal function Comorbidity is high, adding to heterogeneity within each The role of Nutrition? Appropriate nutrition is essential for: The growth and development of brains and bodies Building, maintaining, fuelling and repairing every cell in every part of the brain and body At least 39 essential nutrients must be provided by our food These include vitamins and minerals, essential amino acids, and omega 3 and omega 6 fatty acids Many of these are lacking from modern diets Individual differences affect dietary requirements Specific nutrients may be needed in unusually high quantities There may be allergies or intolerances to certain foods 1

2 Ratio of Rate of Disciplinary Incidents Supplementation/Baseline Nutrition and Antisocial Behaviour (Gesch et al, 2002 Brit. J. Psychiat.) Gesch et al 2002: RESULTS All Disciplinary Incidents - Intent to treat (ITT) = Randomised controlled trial of dietary treatment 231 young offenders imprisoned at a highsecurity unit in the UK took part Each received either a multivitamin + fatty acid supplement, or a matched placebo Could diet help to reduce violence and cut crime? Bef ore Supplementation During Supplementation Activ e Placebo offences: Active vs Placebo: % (p 0.027) Activ e Placebo Error bars drawn at two standard errors to indicate the 95% confidence interv al Supplementation for at least 2 weeks: Active vs Placebo: -34.0% And for violent offences only: -37.0% The unbalanced diet Many nutritional features of modern western diets are both evolutionarily novel and pathological High Glycaemic Load Altered Fatty Acid Composition Altered Macronutrient Composition Reduced Micronutrient Density Acid-Alkaline Balance Sodium-Potassium Ratio Dietary Fibre Sugar Fat Vitamins, Minerals etc Fibre `Cordain et al. Origins and evolution of the western diet: health implications for the 21 st century. Am J Clin Ntr 2005, 81: The Human Brain is 60% FAT and it matters what kind Is the Changing Fat Content of our Diets Changing our Minds? The absolute essentiality of Omega-3 DHA (and Omega-6 AA) for brain development Professor Michael Crawford, Imperial College School of Medicine, London Founder, Institute of Brain Chemistry and Human Nutrition, London 1970s: gave warning to W.H.O. and governments: Brain Disorders will be next 2

3 Professor Michael Crawford, Imperial College, A.J.Richardson, Food And Behaviour London Research 2010 Why Might Omega-3 be Important for Child Behaviour and Learning? Theoretical Rationale? Long-chain omega-3 play critical roles in brain development, brain structure & brain function Evidence of Association? Epidemiological studies Clinical and experimental studies Evidence of Causality? Randomised Controlled Trials Importance of Omega-3 fats for brain development and function (1) Theoretical Rationale Omega-3 were only recognised as essential nutrients in the 1960s The long-chain omega-3 (EPA and DHA) are critical for normal structure and function of the brain and nervous system Dietary shifts following industrialisation vegetable oils, seafood intakes have reduced tissue levels of long-chain omega-3 Changes in Dietary Fat Intake Omega-6 / Omega-3 Ratio Dramatic Increase EFA content of breastmilk of US women Ailhaud G, Guesnet P. Obes Rev Feb;5(1):

4 DHA [mmol per whole brain] Long-chain Omega-3 (and Omega-6) Fats are Essential for Healthy Brain Development Synthesis of Long-chain from Shorter-chain Polyunsaturated Fatty Acids (PUFA) Shorterchain PUFA omega-6 LA (Linoleic) 18:2 GLA 18:3 omega-3 ALA (A-linolenic) 18:3 SDA 18:4 DGLA 20:3 * 20:4 97% of the Omega-3 in the Brain is DHA Longchain PUFA AA (Arachidonic) 20:4 * Adrenic 22:4 DPA(n-6) 22:5 EPA 20:5 * DPA(n-3) 22:5 DHA 22:6 Functional Fats : Conversion of Omega-3 and Omega-6 to Regulatory Substances Endocannabinoids (2-AG, Anandamide) DGLA AA EPA Resolvins DHA Endocannabinoids (Synaptamide) Docosanoids (neuroprotectins) Why we need Omega-3 LC-PUFA (1) 1. For the normal structure of cell membranes DHA (and omega-6 AA) increase membrane fluidity, essential for optimal cell signalling 6-10% of the brain should be DHA DHA is particularly concentrated at synapses, where chemical signals between cells are exchanged Omega-6 Pro-inflammatory Pro-coagulant Omega-3 Anti-inflammatory Dopamine, serotonin and other brain signalling chemicals are influenced by omega-3 status A.J.Richardson, Food Anti-coagulant And Behaviour Research 2014 Why we need Omega-3 LC-PUFA (2) 1. For the normal structure of cell membranes Omega-3 (and omega-6) increase membrane fluidity, essential for optimal cell signalling 2. Brain development Omega-3 and Omega-6 LC-PUFA make up around 20% of dry brain mass, and affect brain growth and connectivity DHA and AA are preferentially transferred via the placenta, and are found in breastmilk (so are important in infant formula) DHA accumulation in brain in early life 10 5 Weeks of pregnancy Months after birth Martinez,

5 WISC Verbal IQ at age 8 Synapes in Hippocampal Neurons Maternal Omega-3 DHA deficiency impairs synapse development Adequate DHA Deficient in DHA Omega-3 and Vision Omega-3 fatty acids from fish oils are absolutely essential to the visual system 30-50% of the retina should be made of the omega-3 DHA At the earliest stages of visual processing, DHA deficiency can reduce retinal signalling to 1/1000 normal levels. Omega-3 deficiency is associated with poor night vision and other problems with visual, spatial and attentional processing. 30 µm Cao et al. J. Neurochem Hee Yong Kim, NIH, 2014 Why we need Omega-3 LC-PUFA (3) 1. The structure of all cell membranes Omega-3 (and omega-6) increase membrane fluidity, essential for optimal cell signalling 2. Brain development Omega-3 and Omega-6 LC-PUFA make up around 20% of dry brain mass, and affect brain growth and connectivity DHA and AA are preferentially transferred via the placenta, and are found in breastmilk (so are important in infant formula) 3. Maintenance of optimal brain function throughout life Cell signalling depends on membrane fluidity Omega-3 and omega-6 LC-PUFA and their derivatives influence almost all brain signalling systems They also profoundly affect hormonal balance, blood flow and immune system function (2) Evidence of Association Epidemiological and Experimental Studies Maternal Seafood Intake During Pregnancy and Child Developmental Outcomes Evidence from the ALSPAC Children of the 90s study Hibbeln et al, The Lancet, 2007 Do the Benefits of Consuming Fish and Seafood in Pregnancy outweigh the Potential Risks? Child s Verbal Intelligence (IQ) at 8 years Hibbeln et al, The Lancet, 17 Feb 2007 r = 0.97 r 2 = 0.95 F=27.2 p<0.02. Mother s Omega-3 intake from seafood at 32 weeks of pregnancy 102 (energy %)

6 Fine motor control at 42 months of age Child s Fine Motor Control at 3.5 years Hibbeln et al, The Lancet, 17 Feb 2007 r = 0.99 r2 = 0.98 t= 393 p< Mother s Omega-3 intake from seafood at 32 weeks of pregnancy (energy %) Evidence for fatty acid abnormalities in ADHD, Autism, Dyslexia and related conditions Blood biochemical studies Relative deficiencies of long-chain omega-3 (EPA/DHA) Elevated omega-6/omega-3 ratio especially AA/EPA (an index of inflammatory tendencies) Increased oxidative stress / lipid peroxidation Enzyme abnormalities consistent with increased loss of omega-3 / omega-6 fatty acids DHA Enhances Frontal Functioning in Boys Design Healthy boys age 8-10 (n=33) Randomised into 3 groups 400 mg DHA, 1,200 mg DHA, placebo 8 weeks duration fmri at baseline and 8 weeks during CPT Results McNamara et al, (2010) Am J Clin Nutr. greater DLPFC activation from 0-8 weeks in omega-3 groups vs controls higher blood omega-3, higher middle + inferior frontal activation, faster reaction times UK - General School Population The DHA Oxford Learning And Behaviour (DOLAB) Study Montgomery P, Burton JR, Sewell RP, Spreckelson TF & Richardson AJ. PLoS One, 2013, June 24 Low blood Long Chain Omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior DOLAB Study Screening stage Healthy children aged 7-9 years from mainstream schools, selected for below-average reading at age 7 Measuring Blood Fatty Acids Fingerstick lancet device Innovative method of collecting blood samples Ethically acceptable Objective measure of fatty acids superior to subjective reports of food intake Filter paper to collect blood - for analysis of fatty acid composition Blood Analyses for the DOLAB Study carried out by DSM Nutritional Lipids 6

7 The Omega-3 Index In adults, % EPA+DHA in red blood cells is a well-validated index of cardiovascular disease risk Omega-3 index (EPA + DHA) 12% 8% 4% 0% Low risk High risk Mean for UK children 2.46% Children s reported fish consumption? Parents reported that: Almost 9 / 10 of these children ate fish less than twice a week.* 9% did not eat fish at all * UK Dietary guidelines = 2 portions of fish a week DHA and Reading ability* (n = 493) Children with higher blood DHA were better readers (rho= 0.114, p < 0.01) DHA and Working Memory* (n = 493) Children with higher blood DHA had better working memory (rho=.141 p < 0.002) *British Ability Scales (BAS) II, Word Reading NB: This association held when controlling for relevant demographic factors such as age, sex and socioeconomic status *British Ability Scales (BAS) II, Digit Span Forward) NB: This association held when controlling for relevant demographic factors such as age, sex and socioeconomic status DHA and ADHD-type Symptoms (n=402)* Higher blood DHA status was associated with fewer attention and behaviour problems (parent-rated) Oppositional (rho = -.16, p < 0.001) Hyperactivity (rho = -.12, p < 0.012) Anxiety (rho = -.12, p < 0.018) Psychosomatic (rho = -.15, p < 0.002) Global Restless-Impulsive (rho = -.11, p < 0.032) Global Emotional Lability (rho = -.17, p < 0.001) Global Total Index (rho = -.14, p < 0.007) DSM-IV Hyperactive-Impulsive (rho = -.13, p < 0.007) *Conners Parent Rating scales (CPRS-L) Blood DHA and Children s Sleep Montgomery et al (2014) J. Sleep Research, March 8 th Children with lower blood DHA had more sleep problems (rho= -0.11, p < 0.05) 7

8 Reading / Spelling gain (months) Mean +/- 1SE (3) Evidence of Causality Randomised Controlled Trials Dysfunctions of Body and Mind that Omega-3 from Fish and Seafood can help to prevent or ameliorate Cardiovascular Disease Heart Disease and Stroke Inflammatory / Auto-immune Disorders e.g. Rheumatoid Arthritis Visual Problems Retinopathies of Prematurity, Diabetes, Old Age Disorders of Behaviour, Learning and Mood? Depression and other mental health problems ADHD / Dyspraxia / Dyslexia etc ADHD symptoms Treatment effect sizes 0-3 months Richardson and Puri (2002) Prog. Neuropsychopharm. Biol. Psychiat. 26:233-9 Psychosomatic Sub-scales (Mean change / Baseline SD) 0.72 ADHD symptoms Treatment effect sizes 0-3 months Richardson and Puri (2002) Prog. Neuropsychopharm. Biol. Psychiat. 26:233-9 DSM Inattention Global scales (Mean change / Baseline SD) 0.61 Cognitive Problems 0.60 DSM Total 0.58 Anxiety 0.54 Restless-Impulsive 0.54 Hyperactivity 0.41 Conners' Total 0.50 Perfectionism 0.24 Emotional Lability 0.34 Opposition Social Problems HUFA (n=15) Placebo (n=14) DSM Hyperactivity Conners' Index HUFA (n=15) Placebo (n=14) THE OXFORD-DURHAM STUDY: A randomised controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Richardson AJ & Montgomery P. Pediatrics, 2005, 115: underachieving children aged 5-12 years from mainstream schools All showed specific difficulties in motor coordination (DSM-IV DCD) 40% were behind expected achievement in reading and spelling Over 30% scored in the clinical range for ADHD-type symptoms (>2SD above population means) Reading and Spelling Richardson AJ & Montgomery P. Pediatrics, 2005, 115: Active treatment Compared with expected progress for normal children, gains were > 3 x normal rate for reading, > 2 x for spelling Placebo Gains were 1 x normal rate for reading, < 0.5 x for spelling Group Differences Reading p < Spelling p < Improvements in Literacy Skills Reading Age Gain 0-3m Spelling Age Gain 0-3m Active (N=55) Placebo (N=57) 8

9 Behaviour: ADHD-type symptoms Richardson AJ & Montgomery P. Pediatrics, 2005, 115: Reduction in ADHD-related Symptoms Omega-3 from fish oils are effective in reducing ADHD symptoms DSM Combined-type DSM Hyperactivity DSM Inattention Conners Global Index CG Emotional Lability CG Restless-Impulsive Conners Index Social Problems Perfectionism Anxiety Hyperactivity Cognitive Problems Opposition Placebo (N=52) Active (N=50) Treatment Effect Size (Mean change 0-3m / Pooled Baseline SD) Bloch and Qawasmi 2011, JAACAP The DHA Oxford Learning And Behaviour (DOLAB) Study What About the General School Population? Richardson AJ,, Burton JR, Sewell RP, Spreckelson TF & Montgomery P (2012) PLoS One,7(9):e43909, Sep 6. Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7-9 Years: A Randomized, Controlled Trial (The DOLAB Study) DOLAB Study Basic Design Randomised Controlled Trial: Population: 360 healthy, normal children aged 7-9 years Normal ability, but reading < 20 th 33 rd centile Treatment: * Algal DHA (600mg/day) or placebo for 16 weeks: Primary outcomes: Reading Behaviour (ADHD-type symptoms) Working Memory Secondary outcomes: Sleep Blood fatty acids *DSM Nutritional Lipids Reading Richardson et al (2012) PLoS One,7(9):e43909 Epub Sep 6. 9

10 % Increase in Reading Age Richardson et al (2012) PLoS One,7(9):e43909 Epub Sep 6. ADHD Symptoms (1) Richardson et al (2012) PLoS One,7(9):e43909 Epub Sep 6. Lowest 33% of readers Lowest 20% of readers Lowest 10% of readers % Reading Age Increase for DHA over placebo ADHD Symptoms (2) Richardson et al (2012) PLoS One,7(9):e43909 Epub Sep 6. Effect of DHA on Sleep Montgomery et al (2014) J. Sleep Research, March 8 th 40% of children (n=188) had clinical-level sleep problems according to parent ratings (Child Health Sleep Questionnaire, CHSQ) In these children, DHA supplementation (600mg/day for 16 weeks) significantly improved their sleep (CHSQ Total Sleep Disturbance Scores) Actigraphy - Gives an Objective Measure of Sleep MicroMini-Motionlogger, Ambulatory Monitoring Inc. Watch-sized device Worn on non-dominant hand or ankle Used for 5 days for better measurement Complemented by parents report sleep diary. Children receiving DHA vs Placebo gained 58 minutes more Sleep Montgomery et al (2014) J. Sleep Research, March 8 th 10

11 Learning is easier when your brain is well fed and well rested! Dietary need for Omega-3 (EPA/DHA) NB: Shorter-chain omega-3 (ALA) from plant sources do not have similar health benefits International scientific organisations recommend: General population (cardiovascular health): > 500mg /day EPA+DHA 1 Depression or other mental health conditions: > 1000mg / day EPA+DHA Most developed countries, typical intakes < 150mg/day (less for children) 1 ISSFAL Statements 2004, 2009; UK JHCI 2005, 15 other International authorities APA Freeman et al 2006, Hibbeln & Davis 2009 More Good Reasons to Eat Fish and Seafood Other key nutrients in fish and seafood are very important for brain function, such as Selenium Iodine Zinc Vitamin D B Vitamins Nutrition in disorders of behaviour, learning and mood other issues 1. Blood sugar regulation problems? 2. Micronutrient deficiencies or imbalances? 3. Anti-nutrients and toxicity issues? 4. Food allergies or intolerances? 5. Enzymes / gut flora 6. Leaky gut problems / malabsorption? SUMMARY Long-chain Omega-3 (EPA and DHA) are essential for brain development and function - but dietary intakes are very low in most developed countries Blood DHA% directly relates to behaviour and learning in children with ADHD and in the general population Dietary supplementation with Omega-3 LC-PUFA can improve behaviour and learning in children with ADHD and related conditions in healthy but underperforming children from the general school population Further Information For details of this and related research see Food And Behaviour Research and the book They are what you feed them 11