Brain on Fire:An Orthomolecular Approach to

Decreasing Inflammation

Dr. Erin Wiley NDNaturopathic Doctor

C0- Founder & Clinic DirectorIntegrative Health Institute

Why?

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Why?

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© Integrative Health Institute 2010

What we will cover

• Introduction to Inflammation• Brain on Fire: How inflammation effects the brain

and it’s relationship to anxiety and depression• Global view: Reducing Inflammation with

Lifestyle Medicine• An Orthomolecular Approach: Anti-inflammatory

and restorative nutrients and supplements

Inflammation

• North America is suffering from an epidemic of chronic inflammatory disease:– caused by changes in our food

supply, diet, and lifestyle.– can be prevented with diet and

lifestyle modification

Inflammatory Disease

• Heart disease• Diabetes• Arthritis• Cancer• Autoimmune disease• Osteoporosis• Allergies• Alzheimers Disease• Depression

Inflammation• Inflammatory markers are directly

correlated with body fat percentage, waist circumference and insulin insensitivity*

• The populations most at risk include: those with metabolic syndrome and type II diabetes

*Inflammation and Insulin Resistance. Festa et. al, Circulation. 2000;102:42-47.

Inflammation and Obesity

• Approximately 59% of Canadian adults are overweight or obese

• In 1978 only 15% of Canadian children were overweight or obese, in 2007 that number increased to 29%

• By 2040 it is estimated that 70% of adults over 40 will be overweight or obese

Statistics Canada, Canadian Community Health Survey, 2009, 2010.

Why?

• A population trending towards an obesity epidemic is a population suffering from inflammation

• A population suffering from inflammation is physiologically at risk for mental illness

• Epigenetics becomes a factor

Inflammation Simplified

• Appropriate Inflammation: The body attacks foreign bacteria and virus and damaged cells as a method of protection

• Inappropriate chronic inflammation: The immune system attacks and damages it’s own cells - brain damage!

Inflammation and Depression MOA

• Inflammation decreases 5-HTP• Inflammation increases Glutamate• Inflammation causes microglia cells to

release neurotoxic substances that decrease neuroplasticity

• Inflammation lowers the number of astrocytes, decreasing the brains ability to protect itself and recover from neurotoxic damageInflammation, Glutamate, and Glia in Depression: A Literature Review CNS Spectr. 2008;13(6):501-510

Inflammation and Anxiety

• Inflammation causes dopamine levels to rise which can lead to insomnia, and feelings of anxiety and agitation

Anti- Inflammatory Lifestyle

• Global Picture - Treat the source = Treat the lifestyle– Diet– Exercise– Detoxification– Stress Reduction

Diet

• Sugar– There is no doubt about it sugar is

inflammatory– High carbohydrate diet = excess

insulin production– Leading cause of metabolic syndrome

Sugar

The average Canadian consumes 23.1 Kg of sugar per year

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Where is Sugar found in our diet?

• Cereal

• White bread, bagels, buns, pizza crust

• Pasta, fries, white rice

• Sports drinks, pop, juice, coffee (latte)

• Candy, chocolate

• Processed foods

Low Carbohydrate Diet

• Low carbohydrate diets are associated with a reduction in inflammation– Paleo Diet– Ketogenic Diet– General Recommendation: Eat between

3-6 servings of carbohydrates per day– 1/2 your plate full of green and colourful

veggies

Diet - Eat Healthy Fats

• Coconut Oil• Olive Oil• Avoid Hydrogenated or chemically

manufactured fats

Brain Gut Connection

• Eliminate food sensitivities– Most common presentation: gluten, dairy,

soy, eggs, sugar– Characterized by an IgG mediated immune

response– Leading to dysbiosis and in imbalance in

healthy flora that modifies the Th1/Th2 response

• Food sensitivities cause systemic low grade inflammation

Exercise• Research has shown that exercise is an

effective treatment for mild to moderate depression.

• Japan “shinrin-yoku” meaning forest bathing - Dr. Marc Berman Journal of Affective Disorder

• Dr. Mike Evans: 23 1/2 Hours - What is the single most important thing you can do for your health

• Exercise May Beat Mental Activity in Preserving Cognition. Medscape. Oct 24, 2012.

Exercise and InflammationResearch:• Exercise not only decreased the levels of pro-

inflammatory cytokines IL-6, TNF-a, and C-reactive protein but also simultaneously enhanced the concentrations of anti-inflammatory cytokines IL-4, IL-10 and TGF-b when compared with controls

Lakka TA, et. Al. Effect of exercise training on plasma levels of Creactive protein in healthy subjects: the HERITAGE Family Study. Eur Heart J 2005;26:2018–2025.

Exercise• 20-30 minutes per day• 3-5 days a week• From Walking, Yoga, to Strength

Training• Running for Anxiety• Challenge your intensity• Follow Your Exercise Progression -

Accountability

Detoxification

• Neurotoxic and Hormone Disrupting Chemicals can be found in our environment:– Pesticides, solvents, BPA, Phthalates

• Signs of hormone disruption:– Sensitivity to parfume, alcohol, coffee– Reactions to drugs and medication– Allergies and sensitivities

Stress Reduction

• Mindfulness Meditation• Yoga• Tai Chi• Qi Gong• Prayer

An Orthomolecular Approach

• Fish Oil: EPA and DHA– Omega 3 fatty acids are anti-

inflammatory– DHA structural component of the brain– EPA the primary anti-inflammatory

omega 3 fatty acid in the brain– When omega 3 fatty acid levels are low

in the brain increased neuro-inflammation occurs

EPA Versus Fluoxetine For Major Depressive Disorder• Aust N Z J Psychiatry. 2008 Mar;42(3):192-8.• Comparison of therapeutic effects of omega-3

fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder.

• 60 patients randomly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine, or their combination for 8 weeks.

Results

• EPA +  fluoxetine combination was significantly better than fluoxetine or EPA alone

• Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms.

• CONCLUSIONS: In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder. EPA + fluoxetine combination was superior to either of them alone.

Meta-analysis Fish Oil For Depression

• Meta-analysis showed significant antidepressant efficacy of omega-3’s

• However a call for more research is needed due to publication bias and heterogeneity. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

Fish Oil• Key points:

– Therapeutic dose for inflammation: greater than 2 grams (2000mg/day) of EPA

– Therapeutic dose for improved mood: No less than 1000mg of EPA per day. Ratio: significantly more EPA than DHA (6:1)

– Outstanding safety profile!!!!– Can we get enough from diet?– What about flax oil?

Probiotics

• It is well established that probiotics decrease inflammation

• But what about the brain GUT connection?

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Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the

vagus nerve.

• In mice: Lactobacillus Rhamnosus reduced inflammatory markers, lowered corticosteroid hormone release, and elevated GABA

• A direct effect on neurotransmittersProc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. Epub 2011 Aug 29.

Inflammation - Repairing the Damage

• Top anti-oxidants:– Alpha Lipoic Acid– N- Acetyl -

Cysteine

• Nrf 2 Activators:– Sulforaphane– Curcumin– Green Tea Extract

Alpha Lipoic Acid

• Suggested MOA:– Improves insulin sensitivity, increases

tryptophan in the brain and promotes serotonin synthesis

Med Hypotheses. 2000 Dec;55(6):510-2.Alpha lipoic acid: a novel treatment for depression.

– Powerful anti-oxidant prevents and repairs damage

– Specifically protects neuronal tissueFree Radic Biol Med. 1997;22(1-2):359-78. Neuroprotection by the metabolic antioxidant alpha-lipoic

acid. – Induction of Glutathione synthesis

• Orally or by IV administration

N-Acetyl Cysteine• Suggested MOA:

– Powerful anti-oxidant: repairs damaged brain tissue

– Boosts the bodies primary anti-oxidant Glutathione

– N-acetyl cysteine is neuroprotective in a variety of neurodegenerative disease models

Nrf2 Activation - Activating the Genes that make

antioxidants• The body can produce it’s own antioxidants and detoxification enzymes internally– Nrf2 is the genetic pathway that regulates the

production of antioxidants such as glutathione and superoxide dismutase (SOD).

– Regulates the production of detoxification enzymes

– Down regulates signaling factors that promote inflammation.

Broccoli - Sulforaphane• Most

concentrated in broccoli seed extract. Supplementation is often recommended in addition to dietary changes

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Curcumin and Mental Health

• “Curcumin demonstrates neuroprotective action in Alzheimer's disease, tardive dyskinesia, major depression, epilepsy, and other related neurodegenerative disorders. The mechanism of its neuroprotective action is not completely understood. However, it has been hypothesized to act majorly through its anti-inflammatory and antioxidant properties.”

Indian J Pharm Sci. 2010 Mar-Apr; 72(2): 149 154. Overview of Curcumin in Neurological Disorders

Curcumin - from Tumeric• Can be limited by

absorption• Look for products

that contain 95% curcuminoids or a supra-critical extract

• Black pepper helps with absorption

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Green Tea Extract

• Green tea is associated with lower levels of depression in the elderly

• American Journal of Clinical Nutrition

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Glutathione - The Ultimate Antioxidant

• Glutathione depletion is a major feature of most mental health disorders such as: schizophrenia, bipolar disorder, and depression

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Glutathion is degraded in the stomach

• Many companies offer oral supplements. But don’t be fooled, oral supplementation will not effect circulating levels of glutathione in the blood stream

Eur J Clin Pharmacol. 1992;43(6):667-9.The systemic availability of oral glutathione.

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Glutathione - by IV

• Naturopathic Doctors certified in IV Therapy offer glutathione therapy

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Opportunity

• An Integrative Approach– Address the root cause, support optimal

body composition and prevent metabolic syndrome

– Synergy: Diet, Exercise, Stress Reduction– Anti-inflammatory Supplements: Fish Oil

and Probiotics– Talk to your Naturopathic Doctor about

antioxidants ALA, NAC, Nrf2 Activators, and Glutathione

© Integrative Health Institute 2010

Integrative Health InstituteDr. Erin Wiley ND

Integrative Health Institute46 Sherbourne St, 2nd Floor

T: 416 260 6038www.integrativehealthinstitute.ca