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Integrative Medicine and the Brain

Integrative Medicine and the Brain. Integrative Medicine Curriculum 2014 Marc Engfield MD FRCP Internal Medicine & Acupuncture. Integrative Medicine and the Brain. Integrative Medicine Curriculum 2014 Marc Engfield MD FRCP Internal Medicine & Acupuncture. Objectives.

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Integrative Medicine and the Brain

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  1. Integrative Medicine and the Brain Integrative Medicine Curriculum 2014 Marc Engfield MD FRCP Internal Medicine & Acupuncture

  2. Integrative Medicine and the Brain Integrative Medicine Curriculum 2014 Marc Engfield MD FRCP Internal Medicine & Acupuncture

  3. Objectives • Name three specific CNS disorders that are associated with environmental toxins • Name five foods that are associated with reduced risk of neurodegenerative disease • Be able to describe the role of chronic inflammation in neurologic disorders • Know one evidence-based CAM treatment for anxiety, depression and migraine

  4. Gut-brain axis • Immune hypersensitivity • Microbial neurotoxins • Malabsorption and deficiency • Inflammation and hormone imbalance • Liver stress and free radical stress

  5. Mind-Body is one • Everything is connected Brain-Spine-Nerves Neuro-Immune-Endo Incredible complexity • Are drugs the answer? antidepressants Antipsychotics Sedatives Alzheimer RX • Integrative healing is simple

  6. Food additives • Average UK consumer eats 20 additives per day • Artificial Colours • Synthetic antioxidants BHA, BHT, TBHQ • Preservatives Sorbate, benzoate, sulphite, nitrate, propionate

  7. Additives and ADHD • 297 UK students – 153 3yo and 144 8-9yo • Daily fruit drink with or without artificial colors and sodium benzoate for 6w • Global hyperactivity aggregate worse (p=0.044) • 2x Greater effect on 3yo • PMID: 17825405

  8. Pesticides and Parkinson’s • Oxidative stress in DA-ergicsubstantianigra • 46 case-control and cohort studies worldwide • Overall RR 1.62 (1.4-1.88) • Occupational RR 2.5 (1.5-4.1) • PMID: 22389202

  9. Pesticides • Epidemiologic links to • Several cancers • Childhood diseases • Low sperm counts • Allergy and asthma • Autoimmune disorders • When will we learn?

  10. Genes and Toxins • Apolipoprotein E clears amyloid from the brain • apoE4 allele is the most important risk factor for Alzheimer dementia • Modulates role of dietary toxins on Alzheimer risk 23779114 • Toxins affect each of us differently

  11. Neuroinflammation • Many CNS disorders involve brain inflammation • Inflammation is a body-wide process • Leaky capillaries are part of the process • This can also affect the BBB

  12. Activated microglia • Macrophages in the CNS Infection Tumors Cellular debris • Activated microglia Normally in a resting state Activated by several triggers Produce housekeepers Neurotoxic when chronic

  13. Activated microglia • inflammatory mediators IL-1α, IL-1β, TNFα MMPs and lytic proteases Acute-phase proteins Amyloid precursor protein NO – a neurotoxin • Precedes symptom onset AD, Parkinson’s MS, Huntington’s, ALS Massive in Traumatic Brain Injury Neuropathic pain Macular Degeneration

  14. Hormones • Hormone imbalances are known to affect the CNS • Many subclinical disorders may go undiagnosed • Some are obvious • Some are controversial • Hormones vs neurotransmitters?

  15. Many factors … • Poverty, Social isolation • Light Affects 5HT activity Seasonal affective disorder • Sleep Early and deep REM sleep • Chronic stress Overactive HPA axis High cortisol, CRH Chicken-and-egg question

  16. Principles of treatment • Nourish the brain Real food Selective supplements • Eliminate toxins Food, water, air, EMF, skin • Promote healing Exercise Awareness, meditation Positive emotions • Treat imbalances

  17. Brain food • Cocoa contains flavanols • Expression of proteins for neurogenesis, connectivity • Angiogenesis and bloodflow • Observational studies so far 23810791 • Dark chocolate 70% cacao 1 square per day

  18. Anthocyanins • 16010 pts in Nurses Health Study followed for 18y • Blueberries and strawberries linked to slower cognitive decline by about 2.5y • P=0.014 for trend • PMID: 22535616

  19. Brain food • Vegetables 22836704 • Olive oil polyphenols and fats 23732551 • grapes and berries polyphenols 22836704 • turmeric many curcuminoids23873854 • light to moderate alcohol consumption 19546653 • Walnuts PUFAs and polyphenols 24500933

  20. Many other foods • Many herbs and spices • Goji20157238 • Mulberry 19443193 • Coconut oil and water 21114897 • Mostly animal studies measuring amyloid and memory

  21. Supplementation • B vitamins and folate • Omega-3 fatty acids • Antioxidants • Clean water • Phosphatidylcholine

  22. Exercise • Many benefits Decreased stress Improved blood blow Brain stimulation endorphins • It works 23 RCTs in 907 pts Many flawed methodology Trend to moderate benefit CD004366 2009

  23. Animal-Assisted Therapy • Social behaviour in autism • Counselling in PTSD • Oppositional defiant children • Depression Maintains activity Reduces isolation Companionship Dogs, cats, birds, horses Swimming with dolphins

  24. Emotional healing • EMDR Eye Movement Desensitization and Reprocessing R-L gaze, clapping, sounds Interrupts cortical blocks traumatic memories are ‘processed’ • First-line for PTSD Meta-analysis of 38 RCTs Br J Psychiatr 2007;190:97 • Many other emerging tools

  25. Thyroid • Hypothyroidism and CNS fatigue, weight, appetite Depression, anxiety, cognition Cold, menses, constipation, hair • Is TSH reliable? T4 vs T3 – deiodinase enzymes endocrine disruptors Halides interfere with iodine Emerging research J ClinEndocrinolMetab 94:1623 • Always consider the thyroid

  26. Testosterone • T deficiency is common Depression, anxiety Insomnia, decreased appetite poor memory, concentration Energy, libido, hair growth • T is an antidepressant 7 RCTs of 364 pts z score 4.04 (p<0.0001) – 4 SDs !!! J PsychiatrPract 2009;15:289 • Hormones affect the brain

  27. Sex Hormones • Testosterone, Estrogen and progesterone • Neuroprotective • Regulate amyloid clearance • Low levels associated with AD • RCTs suggest benefit of supplementation

  28. Melatonin • Made by the pineal gland at night and inhibited by retinal light • Receptors in the brain AND throughout the body • RCTs in insomnia and jet lag, cancer and HTN • Excitotoxic damage after brain injury in melatonin-deficient mice

  29. Bioidentical Hormones • Conjugated EQUINE estrogens ≠ estradiol • Medroxyprogesterone acetate ≠ progesterone • Non-patentable • Compounding pharmacies • No evidence of safety but VERY popular with women

  30. Depression • Comorbidity with CVD blood flow platelet function chronic stress Seen in 17-27% of CV patients • Omega-3 appears effective Several small trials Still inconclusive Anti-inflammatory?

  31. Depression and Mortality • 2053 pts in the ACCORD trial of DM2 • Baseline PHQ9 score followed for 48m • All-cause mortality RR 2.24 in probable depression • No link to cardiovascular health • PMID: 22619083

  32. Causes of Depression • Monoamine deficiency? 5HT, NE, E, DA Standard theory Insufficient explanation • Hippocampus Smaller on MRI studies More hyperintense lesions Why? • BDNF Brain-derived neurotrophic factor 3x lower in depressed patients

  33. St John’s wort • Hypericumperforatum Used for centuries – ‘brain tonic’ • Many possible mechanisms Flavonoids, hypericins, hyperfolins Xanthons, biflavonoids Standardized to 0.3% hypericin • Equivalent to SSRIs in 13 RCTs 47% less risk withdrawal from SE PMID: 19028540

  34. Exercise • 32 trials of 1858 pts with major depressive disorder • SMD -0.67 (0.90-0.43) moderate benefit overall • SMD -0.39 in long-term trials • Equivalent to CBT • PMID: 22786489

  35. EEG Biofeedback • Measure brainwaves α, β, δ, θ, SMR Correlate with function • ‘play the game’ Rewards changes in EEG Learn to control your mind • Growing body of EBM Epilepsy, ADHD many RCTs Anxiety, PTSD Peak performance

  36. Snake oil Richest known source of omega-3 20% EPA vs 18% in salmon Traditional Chinese remedy for joint pain Brought to US by Chinese railroad workers Ridiculed by patent medicine salesmen …but it’s making a comeback

  37. Anxiety disorders • Very difficult to treat with drugs • Many different types • Lavender oil 3 trials 23808618 • Passionflower two positive trials 17253512 • Valerian one negative trial 17054208

  38. Migraine headache • Vascular inflammation NYD • Classic vs common Defined by presence of aura Misdiagnosis? • RX serotonin and triptans • Other potential causes Food, environmental allergies Hormone changes MSK sources of pain Stress-CRH link

  39. Natural headache remedies • Canadian Headache Society guidelines for prophylaxis • Strong recommendations Butterbur Riboflavin Coenzyme Q10 Magnesium 22683887

  40. Guided imagery • 60 pts with chronic tension-type headache • Guided imagery vs recall happy memory vs individual RX 3/wk for 3w • Reduced HA intensity, duration and frequency (p<0.05 for all) • PMID: 21985338

  41. Drinking more water • 102 pts with >5 headaches per month who drink <2L/d • Lifestyle advice with water (1.5L/d) or advice only for 3m • Migraine-Specific QOL improved • Perceived benefit in 47% vs 25% of patients • PMID: 22113647

  42. Whatever you do will be insignificant, but it is very important that you do it. M K Gandhi

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