1. Raj Patel, M.D. Chronic Fatigue Key To Successful Treatment Raj Patel, MD Medical Options for Wellness Los Altos, CA 650-964-6700 www.DrRajPatel.net

2. Raj Patel, M.D. Chronic Fatigue vs CFIDS CFIDS: Centers for Disease Control and Prevention (CDC) uses the following criteria: Having severe chronic fatigue of six months or longer duration with other known medical conditions excluded by clinical diagnosis, and Concurrently having four or more of the following symptoms: substantial impairment in short-term memory or concentration, sore throat, tender lymph nodes, muscle pain, multi-joint pain without swelling or redness, headaches of a new type, pattern or severity, unrefreshing sleep, and post-exertional malaise lasting more than 24 hours.  CFIDS is vaguely defined with no consistently conclusive test  Level of testing to rule out other diagnoses can vary dramatically based on the knowledge and expertise of the clinician

3. Raj Patel, M.D. Chronic Fatigue & Other Similar Illnesses  Examples: Fibromyalgia Chronic Fatigue Chronic Lyme Disease Autism ADHD  These illnesses lack hard objective diagnostic tests  Diagnosis is made based on signs and symptoms which can and do greatly overlap  These illnesses are syndomes rather than a single disease entity. Therefore, each illness is a “mixed bag” with different underlying contributing factors playing a role in each individual.

4. Raj Patel, M.D. Chronic Fatigue & Other Similar Illnesses (con’t)  All of these illnesses are frequently associated with methylation cycle impairments and chronic viral &/or bacterial infections  These two factors in turn lead to a number of disturbances that we frequently associate with these conditions: Neurotransmitter Imbalances Hormonal Imbalances Food Intolerances Heavy Metals * Lifestyle and emotional factors play a big role in determining how active these infections become

5. Raj Patel, M.D. Useful Testing in Evaluating Chronic Fatigue*  RNase-L activity (Viral Immune Pathology)  Urine Amino Acid Analysis (Doctor’s Data)  SAM/SAH/Homocysteine (Vitamin Diagnostic)  Urinary neopterin/biopterin (Philippe Auguste Labs)  Lyme & Coinfection Panel (IgenX)  TSH, total & free T4, total & free T3  CBC and Chemistry Panel  24 hour salivary cortisol  Urinary neurotransmitter profile  Electrodermal testing  Testing for HHV6, EBV, CMV, XMRV, etc.  Mental status and psychological screening * Other testing may be necessary based on the individual’s symptoms

6. Raj Patel, M.D. Methylation Cycle  Definition: Methylation involves transfer of methyl group  Methylation plays a role in: Neurotransmitter synthesis and breakdown Renal disease Cardiovascular disease Cancer Heavy metal detoxification Anti-viral immune modulation

7. Raj Patel, M.D. Methionine Synthase Homocysteine SAH SAM 5 MTHF 5,10 MTHF MSR B12ZnMg Cystathione Cysteine Glutathione Homocysteine Taurine CBS P5P Methylation Cycle MTHR

8. Raj Patel, M.D. Methylation Cycle (con’t) Methylation Impairments result from:  Single Nucleotide Polymorphisms (SNPs): Can impair methylation Commonly found in the general population SNPs involving MTHFR C677T have a 47% incidence among Caucasians Ulrich CM. et al. Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):659-68  Heavy metals at low levels can suppress key enzymes involved in methylation  Viruses can impair methylation cycle enzymes

9. Raj Patel, M.D. Methylation Cycle (con’t)  Testing to assess methylation: genomic testing urine/serum amino acid analysis  Nutritional Support to open/bypass areas of impairment: Methyl B12 / Cyano B12 TMG (or DMG) Folic/Folinic acid P5P/B6 Reduced Glutathione

10. Raj Patel, M.D. Chronic Fatigue Take Home Message: Identifying the underlying factors playing a role in a particular individual’s illness is critical to determining what treatment to prescribe, and thereby achieving a successful outcome.