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Functional Medicine Management of Chronic Fatigue

Presented by:Emily Gutierrez, DNP, C-PNP, PMHS, IFM-CPApril 25th, 2020

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Who Am I?

v DNP Johns Hopkinsv C-PNP University of Texas at Austin v Institute of Functional Medicine

Certified Practitionerv Co-Owner of Neuronutrition

Associates (pediatric functional medicine)

v Co-Author of The Parents Roadmap to Autism: A Functional Medicine Approach

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Reports suggest that one-fifth of primary care visits involve fatigue as a symptom.

Reference: Rosenthal, et al., 2008

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Objectives for thinking about fatigue functionally:

• Fatigue in the functional medicine model• Antecedents, triggers, and mediators • Metabolic imbalances • Oxidative stressors• Gut dysbiosis • Toxicity • Case studies

* Bonus materials on COVID19 at the end of the presentation

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What is fatigue?Subjective: Diagnosis of Exclusion There are no magic bullets for fatigue, everyone has their own individual variation and experience.

Central = our perceived effort (neurologic); Lack of motivation, initiation, sustained effortPeripheral= ATP depletion; running out of metabolic energy

Dx: Systemic Exertion Intolerance Disease Dx: Chronic Fatigue Syndrome Dx: Myalgic EncephalomyelitisDx: Orthostatic Hypotension (POTS, autonomic dysfunction)

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Functional medicine is the medicine of “why”?David Hasse, MD

• There is no single pill for an ill.

• Diagnosis should be the beginning of your examination, not the end.

• One condition has many causes and one cause has many conditions.

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Complexity

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RED FLAG RULE OUTS FOR CHRONIC FATIGUE

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PSYCHIATRIC RED FLAG RULE OUTS FOR CHRONIC FATIGUE

Institute of Functional Medicine, 2019

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Antecedents

• Geneticpredisposition• Beliefsystem(“Ionlyneed4hoursofsleep”,“Ihavetostayupallnightandfinishthis”)• Nutrientinsufficiency• Caloricexcess• Sedentarylifestyle• Allergenexposure

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Triggers

• Travel,vector/tickexposures• Sleepdeprivation• Sedentarylifestyle• CVriskfactors• GIriskfactors• EBV/ViralInfections• StrepInfections• Menomentorrhagia anemia•Weightloss• Bloodinstool• Cognitivedecline,paraesthesias,• Ataxia(heavymetalexposures)

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Mediators

• Sleep• Diet • Belief system • Support system• Continued toxic exposures

(smoking, vaping, air pollution, etc)• Stress

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“The time to relax is when you don’t have time for it.”

Sydney J. Harris

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• Snoring • Apnea• Collar Size (Men >17, Women >16)• Daytime Sleepiness • Hypertension

R/O Sleep Apnea

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Top 10 Sleep Hygiene Musts

1.Do not drink caffeine after 2PM; if you are sensitive to caffeine, not until after 12PM.

2.Avoid alcohol 3 hours before bed. 3.Complete aerobic exercise 3 hours before bed. 4. Avoid anxiety-provoking activities close to bedtime (watching news, paying bills, charting). 5. As much as possible, go to sleep and wake up at the same time each day.6. Turn down the light in the bathroom and in rooms you are in 15 minutes before going to bed.

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Top 10 Sleep Hygiene Musts Cont.7. Make sure your sleeping area is the correct temperature range (not too hot or too cold).8. Consider replacing your pillows with hypoallergenic pillows. Drooling children beware for mold. 9. Avoid sleeping near electromagnetic fields. Try to have your head at least 8 feet away from electromagnetic fields, if possible. Possible sources of electromagnetic fields include: electrical outlets, clock radios, stereos, cell phones, computers and monitors. Consider moving these devices or moving your bed or your position in the bed. 10. Don’t stay in bed more than 20-30 minutes trying to fall asleep. Leave your bedroom and go to a relaxing room other than the bedroom and read or do a relaxation technique (e.g., meditation)

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Supplements for Sleep • Melatonin – 1-5 mg to fall asleep and/or 5-20 mg time released melatonin to

stay asleep

• 5-HTP – 100-200 mg 1 hour before bedtime (increases serotonin, increasing melatonin)

• Taurine – 500-2000 mg 1 hour before bedtime

• Magnesium – 200-400 mg is a typical dose (glycinate, threonate).

• To decrease nighttime cortisol or stress consider using ashwaganda, phosphorylated serine, L-theanine, GABA, or lemon balm.

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Phosphatidylserine- Think “Serine Soothes”

• Known to lower cortisol

• Improves mood

• Helps with ADHD

• 150-200mg/day in children (4-12 years)

• 600-800mg/day in adults Reference: Kingsley 2006 & Starks 2008

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Culprits in dysbiosis and inflammatory gut stress

• Allergic stress IgE Allergies IgG Allergies • Dysbiosis (leading to endotoxemia)- bacteria,

fungal, parasitic, viral• Insufficiency dysbiosis- HCL, enzymes beneficial

flora, healing foods

Leads to: maldigestion, malabsorption, malnutrition, immune stress

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Metabolic Endotoxemia

Increased intestinal permeability (leaky gut); particles, such as bacteria, waste, and antigens, (like undigested food proteins) end up in the bloodstream where they are not supposed to be. Gram negative bacteria high in lipopolysaccharides (LPS) are especially toxic.

Lipopolysaccharides (LPS) are large complex molecules found in gram-negative bacteria. LPS are endotoxins and when absorbed they can cause a very strong overreaction of the immune system.

When a patient is in this cycle, LPS are pouring from the gut lumen into the bloodstream, causing inflammation, and making autoimmunity (and other symptoms such as fatigue and depression) worse.

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Pharmaceutical Treatments for Parasites

• E. Histolytica—Flagyl: 750 mg TID x 10 days with Iodoquinol: 650 mg x 20 days

• Cryptosporidium—Alinia: 500 mg BID x 14 days• Giardiasis—Alinia: 500 mg BID or Flagyl: 250 mg TID x 7 days• Blastocystis hominis—Flagyl: 750 mg TID x 10 days or Alinia: 500 mg BID x

3 days• Strongyloidiasis—Ivermectin: 200 mg/kg/day plus broad spectrum

antibiotics x 14 days• Trichuris trichiura – Flagyl: 500 mg TID x 7–10 days or albendazole: 400

mg single dose• Tapeworm—Praziquantel: 20 mg/kg 4–6 x per day for 21 days• Balantidium coli—Tetracycline: 500 mg TID x 10 days Reference: IFM, 2019

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Botanical Treatment Options for Parasites

Treatment time is typically 4–12 weeks

• Oregano (Origanum vulgare)—encapsulated oil: 200 mg TID• Thyme (Thymus vulgaris)—standardized to contain thymol: 100–

200 mg TID• Goldenseal (Hydrastis canadensis)—standardized to contain

berberine: 200–400 mg TID• Artemesia/Chinese Wormwood (Artemesia annua): 1–3 grams TID

Reference: IFM, 2019

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Signs in adults: Dysbiosis, fatigue, brain fog, skin changes, frequent vulvar yeast infections

Signs in children= craving for starchy carbohydrate and sugary foods; frequent yeast infections (diaper dermatitis), stimming, sleep disturbances (fatigue), white coated tongue, other skin rashes (typically red, itchy, in folds of skin, or little circular flat lesions)

*Warning with culturing yeast in stool

Candida/Fungal Overgrowth

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Pharmaceutical Options for Yeast Overgrowth

Duration of treatment ranges from 6-12 weeks, sometimes longer depending on severity of pathology.

• Amphotericin B (Fungilin, Fungizone, etc.) oral compound-250mg BID for <40#, 250mg TID for >40#

• Fluconazole (Diflucan)—50-200 mg daily/weekly, consider loading dose• Ketoconazole (Nizoral)• Lamisil (Terbinafine)• Nystatin—500,000-3,000,000 units/daily TID

*Monitor liver enzymes every six weeks with RX meds*Reference: IFM, 2019

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Botanical Treatments for Yeast Overgrowth

Duration of treatment is typically 3-12 months- supplement therapy typically takes 3x as long as RX therapy.

• Garlic (Allium sativum)—standardized to 5000 mcg allicin potential TID• Goldenseal (Hydrastis canadensis)—standardized to contain berberine 200-

400 mg TID• Oregano (Origanum vulgare) encapsulated oil— 200 mg TID• Thyme (Thymus vulgaris) standardized to thymol—100-200 mg TID

*In general, recommendations are to use botanicals in combinations*

Reference: IFM, 2019

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Bovine Immunoglobulins- RX Enteragam

Enteragam is a serum derived bovine immunoglobulin/protein isolate packaged as a prescription medical food.

Maciej, 2017, demonstrated immunoglobulin therapeutic benefit. They studied a sample of 16 of athletes, and after administration of bovine colostrum for three weeks, intestinal permeability was significantly restored (by measuring zonulinconcentrations in the stool and lactulose/mannitol ratio in the urine) (Maciej, et al).

FDA approved for ages 6 months and older

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Immunoglobulins have been shown to improve IBS symptoms in children down to 6 months. The mechanism of action is binding microbial components (such as yeast, dysbiotic bacteria, and food antigens), helping the GI tract achieve homeostatic balance, improving tight junction protein expression, and nutrient and water absorption.

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Signs of Mitochondrial Dysfunction • poor growth • poor muscle tone • fatigue• activity or exercise intolerance • difficulty chewing or swallowing food• exhibits abnormal movement• developmental delay or regression• language and social impairment• neuropsychiatric symptoms (ADHD, depression, anxiety)• seizures • headaches• Immune system dysfunction (gut, endocrine)

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Mitochondrial stressors

• Excessive calories• Excessive fructose (HFCS)• Excessive alcohol• Lipotoxicity• Inflammation (TNFa)• Chronic or acute hypoxia• Environmental toxins• Micronutrient deficiencies

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Intermittent Fasting:

Current evidence suggests that the benefits to mitochondria of overnight fasting begin at 14 hours for women and 16 for men

• 12 to 16-hour overnight fast, daily (from dinner to breakfast, every day)• 16 to 18-hour fast weekly or monthly (from dinner to lunch, 1-2x per week or

month)• 24-hour fast weekly or monthly • 5:2 program: normal diet for five days, then 25% of “normal” (e.g., 500-600

calories) for two days

Increasing BDNF and Mitochondrial Biogenesis

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PGC- 1a (PPAR-y co-activator 1a)

• Our master regulator of energy homeostasis and mitochondrial biogenesis

• Expressed in mitochondrial rich tissues (heart, skeletal muscle, brown adipose tissue)

• Activated after exercise, fasting, and cold exposure (also T3 and adiponectin)

• Helps switch metabolic activity towards oxidative phosphorylation and antioxidant protection

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Neurotransmitters of Fatigue

• Tryptophan- is released from the brain with mental and physical fatigue

• Competes with branch chain amino receptors• Inflammation triggers tryptophan to covert into

Kynurenic acid and then into quinolinic acid- leading to pathology

• Resulting in excessive glutamate in the brain, excitotoxicity (neural injury), fatigue

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