1. Brain on
Fire:
An Orthomolecular Approach to
Decreasing Inflammation
Dr. Erin Wiley ND
Naturopathic Doctor
C0- Founder & Clinic Director
Integrative Health Institute
2. Why?
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3. Why?
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5. 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
7. 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.
8. 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.
9. 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
10. 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!
11. 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 damage
Inflammation, Glutamate, and Glia in Depression: A Literature Review CNS Spectr.
2008;13(6):501-510
12. Inflammation and Anxiety
• Inflammation causes dopamine levels to
rise which can lead to insomnia, and
feelings of anxiety and agitation
13. Anti- Inflammatory Lifestyle
• Global Picture - Treat the source = Treat the
lifestyle
– Diet
– Exercise
– Detoxification
– Stress Reduction
14. Diet
• Sugar
– There is no doubt about it sugar is
inflammatory
– High carbohydrate diet = excess insulin
production
– Leading cause of metabolic syndrome
15. Sugar
The average Canadian
consumes 23.1 Kg of
sugar per year
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16. 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
17. 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
19. 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
20. 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.
21. Exercise and Inflammation
Research:
• 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.
22. 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
23. 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
24. Stress Reduction
• Mindfulness Meditation
• Yoga
• Tai Chi
• Qi Gong
• Prayer
25. 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
26. 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.
27. 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.
28. 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.
29. 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?
30. Probiotics
• It is well established
that probiotics
decrease inflammation
• But what about the QuickTime™ and a
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connection?
31. 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 neurotransmitters
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. Epub 2011 Aug 29.
32. Inflammation - Repairing the
Damage
• Top anti-oxidants: • Nrf 2 Activators:
– Alpha Lipoic Acid – Sulforaphane
– N- Acetyl - Cysteine – Curcumin
– Green Tea Extract
33. 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 tissue
Free 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
34. 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
35. 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.
36. Broccoli - Sulforaphane
• Most concentrated in
broccoli seed extract.
Supplementation is
often recommended in
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changes
37. 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
38. Curcumin - from Tumeric
• Can be limited by
absorption
• Look for products that
contain 95% QuickTime™ and a
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curcuminoids or a
supra-critical extract
• Black pepper helps
with absorption
39. Green Tea Extract
• Green tea is associated
with lower levels of
depression in the
elderly
• American Journal of Clinical Nutrition QuickTime™ and a
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40. Glutathione - The Ultimate
Antioxidant
• Glutathione depletion
is a major feature of
most mental health
disorders such as: QuickTime™ and a
schizophrenia, bipolar decompressor
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disorder, and
depression
41. Glutathion is degraded in the
stomach
• Many companies offer
oral supplements. But
don’t be fooled, oral
supplementation will not QuickTime™ and a
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effect circulating levels of are needed to see this picture.
glutathione in the blood
stream
Eur J Clin Pharmacol. 1992;43(6):667-9.The
systemic availability of oral glutathione.
42. Glutathione - by IV
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• Naturopathic Doctors certified in IV Therapy offer
glutathione therapy
43. 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
Low levels of 5-HTP lead to depression, Excessive glutamate leads to depression, Astrocytes repair cellular damage
Cracker test
70-80% of your immune system is located in your GUT, GUT mood connection
More evidence has linked exercise with a positive effect on the brain. A new study finds that older adults who reported being the most physically active had less brain atrophy, higher volumes of gray matter, and less damage to white matter compared with their more sedentary counterparts.Not only was the sample size, at almost 700 participants, much larger than those of other studies looking at the effect of physical activity on the brain, but this study is the first to look in detail at the effect of exercise on white matter, the brain's "wiring," .lead author Alan J. Gow, PhD, senior research fellow, Center for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, United Kingdom, told Medscape Medical News. "That's probably one of the unique aspects of the study, the focus on the wiring, as well as on the volumes and shrinkage of actual gray matter." However, the researchers found no association between social and mentally stimulating leisure activities and these brain changes. The study is published in the October 23 issue of Neurology.
Endocrine-disrupting chemicals (EDCs) are either man-made or naturally occurring chemicals thatinterfere with the body’s ability to regulate its growth, development,metabolism and other functions.EDCs are sometimes referred to as hormone mimics or, for those that behave like estrogen, estrogen mimics. There are hundreds of EDCs inthe environment, in food, and in consumer products. They include components of plastics* and plasticizers (including BPA and phthalates), dioxins, PCBs*, PBBs, pesticides*, heavy metals*, industrial chemicals and fuels, preservatives and fragrances in cosmetics, and many more. Hormones work in your body in very tiny amounts, so even small exposures to EDCs can affectdevelopment and function. Unlike most other toxic substances, low doses of EDCs may be more harmful than higher doses. Higher exposures may overwhelm the endocrine system and cause less response to the chemical. This is a concern because safety testing of chemicals assumes that low doses are not harmful if higher doses do not show effects. Most EDCs have not been thoroughly tested for health effects at very low exposures.
OBJECTIVE: To compare therapeutic effects of eicosapentaenoic acid (EPA), fluoxetine and a combination of them in major depression. METHOD: Sixty outpatients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score >or=15 in the 17-item Hamilton Depression Rating Scale (HDRS) were randomly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine, or their combination for 8 weeks. Double dummy technique was used to double blind the study. Patients were assessed at 2 week intervals. Change in HDRS was the primary outcome measure. RESULTS: Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study, with the last observation carried forward. Treatment, age of onset and baseline HDRS had a significant effect on HDRS at week 8. EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment. Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms. Response rates (>or=50% decrease in baseline HDRS) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups, respectively. 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.
The consumption of cruciferous vegetables has long been associated with a reduced risk in the occurrence of cancer at various sites, including the prostate, lung, breast and colon. This protective effect is attributed to isothiocyanates present in these vegetables, and sulforaphane (SF), present in broccoli, is by far the most extensively studied to uncover the mechanisms behind this chemoprotection. The major mechanism by which SF protects cells was traditionally thought to be through Nrf2-mediated induction of phase 2 detoxification enzymes that elevate cell defense against oxidative damage and promote the removal of carcinogens. However, it is becoming clear that there are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity. Moreover, these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.
It may turn out to be helpful. Turmeric, the yellow spice that colors curry and American yellow mustard, is a potent natural anti-inflammatory agent. Its active constituent, curcumin, has shown promise as an antidepressant in animal models, and curcumin also has been found to enhance nerve growth in the frontal cortex and hippocampal areas of the brain. Researchers in India have suggested performing clinical trials on humans to explore turmeric's efficacy as a novel antidepressant.
Glutathione is critical for one simple reason: It recycles antioxidants. You see, dealing with free radicals is like handing off a hot potato. They get passed around from vitamin C to vitamin E to lipoic acid and then finally to glutathione which cools off the free radicals and recycles other antioxidants. After this happens, the body can 途 e duce � or regenerate another protective glutathione molecule and we are back in business.However, problems occur when we are overwhelmed with too much oxidative stress or too many toxins. Then the glutathione becomes depleted and we can no longer protect ourselves against free radicals, infections, or cancer and we can 稚 get rid of toxins. This leads to further sickness and soon we are in the downward spiral of chronic illness.