4/10/2015 1 INTEGRATIVE MEDICINE EVALUATION AND TREATMENT OF COMMON PEDIATRIC DISORDERS Anna Esparham, MD, FAAP and Joy Weydert, MD, FAAP University of Kansas—Departments of Pediatrics and Integrative Medicine DISCLOSURE • We have no relevant financial relationships with the manufacturers(s) of any commercial products(s) and/or provider of commercial services discussed in this CME activity • We do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation. WHAT IS INTEGRATIVE MEDICINE? Personalized medical therapy and treatment of chronic disease that embraces conventional and complementary therapies. Integrative medicine reaffirms the importance of the therapeutic relationship, a focus on the whole person, lifestyle, biochemical (metabolic) individuality and environmental influences. Specific emphasis on “Food as Medicine” and “Developing Resilience”
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4/10/2015
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INTEGRATIVE MEDICINE EVALUATION ANDTREATMENT OF COMMON PEDIATRIC DISORDERS
Anna Esparham, MD, FAAPandJoy Weydert, MD, FAAP
University of Kansas—Departments of Pediatrics and Integrative Medicine
DISCLOSURE
• We have no relevant financial relationships with the manufacturers(s) of any commercial products(s) and/or provider of commercial services discussed in this CME activity
• We do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.
WHAT IS INTEGRATIVE MEDICINE?
Personalized medical therapy and treatment of chronic disease that embraces conventional and complementary therapies.
Integrative medicine reaffirms the importance of the therapeutic relationship, a focus on the whole person, lifestyle, biochemical (metabolic) individuality and environmental influences.
Specific emphasis on “Food as Medicine” and “Developing Resilience”
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WHAT DO THESE HAVE IN COMMON?
Eczema
PCOS
Migraines
ADHD
Frequently seen in pediatrics Increasing incidence Often not improved with
conventional interventions/medications despite your best efforts
They share similar underlying pathophysiologythat contributes to their manifestations
USUAL SEQUENCE OF EVENTS
Conventional medical treatments are prescribed to manage the symptoms that present
When symptom management fails, we do more investigations and try different medications
When that doesn’t work, we refer to sub-specialists
When that doesn’t work we send them to psychiatrist/psychologist
TODAY’S OBJECTIVES
Understand the shared underlying mechanisms that contribute to common pediatric disorders
Appreciate the role that healthy nutrition and nutritional supplements play in the treatment of these disorders
Learn of other evidence-based integrative medicine therapies used in these disorders
FA Patterns in Atopic Dermatitis Low Gamma-Linolenic Acid Levels1,2
Found in evening primrose oil/borage oil Omega-3 Fatty Acids may reduce risk3
1. Simon D et al. Adv Ther. 2014. doi: 10.1007/s12325-014-0093-02. Foolad N. et al. JAMA Dermatol. 2013; 149(3): 350-53. Saadeh D et al. Nutrients. 2013; 5(9): 3399-3423
ATOPIC DERMATITIS: DIETARY ASSESSMENT
Zinc—Necessary for Skin Healing Zinc levels lower in children with AD than controls1,
1. Kim J et al. Acta dermato-venereologica. 2014; 94(5): 558-622. Toyran M et al. J Investig Allergol Clin Immunolog. 2012; 22:341-443. David TJ et al. Br J Dermatol. 1990; 122: 485-4894. David TJ et al. Br J Dermatol 198; 111: 597-601
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ZINC FOOD SOURCES
Zinc Food sources from: www.whfoods.com
Serum Zinc Levels:
Dietary Adequacy: Is the patient meeting 100% of their needs?
ATOPIC DERMATITIS: DIETARY ASSESSMENT
Vitamin D—ideal 25 OH-D level of 50-80 ng/ml Vitamin D deficiency increases the risk of sensitization to food
allergens and the severity of atopic dermatitis
Children given 4000 IU daily for 21 days Significant in cathelicidin levels Reduced colonization of skin pathogens.
Supplementation with 1,000 IU daily increased 25 OH-D levels, reduced AD severity, and reduced serum cytokine levels Normalization of Th-1 and Th-2 interleukin serum patterns
Baek, et al. J Pediatr. 2014;165(4):849-854.Hata. Allergy Clin Immunol. 2008;122(4):829-831Di Filippo, et al. Int Arch Allergy Immunol. 2015;166(2):91-96.
1. Liepa et al. Nutrition in Clinical Practice. 2008; 23(1): 63-712. Mavropoulos JC et al. Nutr Metab. 2005;2: 35
PCOS: VITAMIN D
Vitamin D =
Secosteroid
Not just a mediator of “calcium
homeostasis”
Immunomodulatory
Antimicrobial Antiproliferative
Mediator in Chronic Disease
Metabolism & Glucose Homeostasis1
•Upregulates insulin gene transcription
•Improves insulin secretion and glucose tolerance
•Activates PPAR-δ – a transcription factor implicated in regulation of fatty acid metabolism
1. N El-Fakhri et al. Hormone Research in Paediatrics. 2014
PCOS: DIETARY ASSESSMENT
Vitamin D Low blood levels of serum 25 (OH)D Intervention studies improved androgen profiles, blood
pressure, glucose metabolism and menstrual frequency
Treatment: Follow US Endocrine Society Guidelines Maintain Vit D levels between 40-60 ng/ml
Pal L et al. Gynecol Endocrinol. 2012;28:965-968Wehr E et al. J Endocrinol Invest 201;34: 757-763
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PCOS: DIETARY ASSESSMENT
Omega 3 Fatty Acids Imbalance of n-6/n-3 fatty acids results in
inflammation 8-week supplementation with 720 mg EPA & 480
mg DHA/day improved insulin resistance, lipid profiles, and adiponectin levels in overweight PCOS patients
Treatment: 1-2 grams of Omega-3 fatty acids daily with meal
Rafraf M et al. J AM Coll Nutr. 2012;31:361-368
PCOS: DIETARY ASSESSMENT
Chromium picolinate Increases insulin sensitivity and decreases fasting blood
glucose compared to metformin in clomiphene citrate-resistant patients1
Treatment: 200-1000 mcg daily2
1. Amooee S. et al. Iran J Reprod Med. 2013; 11(8): 611-18
2. Chromium. Natural Medicines Comprehensive Database. Nov 2014.
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ACUPUNCTURE/ACUPRESSURE
PCOS: INTEGRATIVE MEDICINE TREATMENT
Supplement with Vitamin D, O-3, Zinc (if copper is high), Chromium picolinate
Lifestyle Modification 5-10% weight loss
[Moran LJ et al. Cochrane Database Syst Rev 2011;7:CD007506]
D-Chiro-Inositol or Myo-Inositol Improves menstrual cycle regularity, Acne score, endocrine and insulin
resistance profiles in young overweight PCOS patients [Formuso C et al. Minerva Ginecol 2015 Feb 11 [Epub ahead of print]
N-acetylcysteine or liposomal glutathione NAC improved pregnancy and ovulation rates compared to placebo
[Thakker D et al. Obstet Gynecol Int 2015; 817849]
PCOS: INTEGRATIVE MEDICINE TREATMENT
Acupuncture/TCM Improved ovulation frequency in acupuncture group compared to
physical therapy [Johansson J et al. Am J physiol Endocrin Metab. 2013; 304(9):E934-43]
Mindfulness Mindfulness based stress management program revealed significant
reductions in stress, depression, anxiety symptoms and salivary cortisol in women with PCOS
[Stefanki C et al. Stress. 2015; 18(1): 57-66]
Yoga A holistic 12-week yoga program improved AMH, LH, testosterone
levels, hirsutism, and regulated menstrual frequency [Nidhi R et al. J Altern Complement Med. 2013; 19(2):153-60]
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MIGRAINE/HEADACHES
Migraine attacks are result of inflammationat level of trigeminovascularconnections1
Mitochondrial dysfunction2
Hormonal Imbalance/Menstrual Disorders3
Dysfunctional stress response4
Diet & Nutrition5
Majority are myofascial May not have “body
awareness” of muscle tension/stress
History often reveals multiple traumas Physical, emotional,
repeated illnesses These affect body
mechanics and nerve function
PE often reveals myofascial restrictions or trigger points
1. Akerman S et al. Nat Rev Neurosc. 2011; 12(10): 570-842. Yorns WR & Hardison HH. Seminars in Ped Neurol. 2013;20(3): 188-933. Hassan S et al. Pain. 2014. doi: 10.1016/j.pain.2014.08.0274. Parashar R et al. Int J Womens Health. 2014 24;6: 921-55. Finkel A et al. Current Pain Headache Reports. 2013; 17(11): 373
Common Signs/Symptoms of Deficiency:Beefy red tongue, seborrheic dermatitis, cheilosis, and sore throat
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MIGRAINE REPLETION
Vitamin B2: Riboflavin 200-400 mg/day for migraine prophylaxis1
Riboflavin is in a B-complex [Colombo B. Neurological Sciences. 2014; 35(1): 141-144]
MIGRAINE:INTEGRATIVE MEDICINE TREATMENT
Elimination Trial, Whole Foods & Anti-Inflammatory Diet to reduce inflammation
Magnesium over the course of 16 weeks reduced migraine frequency and severity
in children [Wang F, et al Headache 2003; 43:601-10]
Co-enzyme Q10 safely reduced migraine frequency and associated disability in children
who were found on screening to have low clinical co-enzyme Q-10 values.
[Hershey AD, et al Headache 2007 47: 73-80 ]
Riboflavin (B-2) Riboflavin may be effective in migraine, with a more favourable
response in boys and in individuals with severe migraine. [Condo M.J Headache Pain 2009; 10: 361–365]
MIGRAINE:INTEGRATIVE MEDICINE TREATMENT
Butterbur root extract at least a 50% reduction in migraine attacks in 77% of children
aged 6-17. [Pothmann R. Headache 2005 Mar; 45(3):196-203]
Mind-Body techniques Breathing/relaxation training, biofeedback and cognitive-behavioural
therapy, stress management [Trautmann E. Cephalalgia. 2006 Dec;26(12):1411-1426]
CD-ROM program on home computers for 4 weeks had significant improvements in headache activity above and beyond those in the control group.
[Connelly M, Rapoff M, et al J Pediatr Psychol 2006;31(7):737-747]
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MIGRAINE:INTEGRATIVE MEDICINE TREATMENT
Diet/Sleep/Hydration/Regular meals Lifestyle factors are often primary in initiating and maintaining
headache syndromes in children [Grazzi L. Neurol Sci 2004;25(Suppl 3):S223-225]
Music Therapy music therapy was superior to placebo over 12 weeks as well
as 6 months later [Oelkers-Ax R, et al Eur J Pain. 2008 Apr;12(3):301-13.]
MIGRAINE:INTEGRATIVE MEDICINE TREATMENT
Acupuncture/Acupressure DBRPCT in 43 children with migraine or tension-type headache
found a significant improvement in headache-free days for children receiving “true” acupuncture with low level laser.
[Gottschling S, et al Pain 2008 Jul 15;137(2):405-12.]
MIGRAINE:INTEGRATIVE MEDICINE TREATMENT
Manual therapies OMT, cranio-sacral, myofascial release, massage “Hands on” helps where meds fall short Initially start with practitioner, but teach self-therapy
[Bronfort G. J Manipulative Physiol Ther. 2001;24:457-466]
Physical therapy/Yoga Therapies to improve posture Therapies for core strengthening
[Hainsworth KR. Pain Manag Nurs. 2014;15(2):490-498.]
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HEADACHE TRIGGER POINTS
HEADACHE TRIGGER POINTS
ADHD
Affects11% children ages 4-17 yo1
Increasing in prevalence
Etiology Genetics Nutritional status Oxidative stress Neurotransmitter/endocrine dysregulation Neurologic abnormalities (fronto-striatal and basal
ganglia network) Physical & emotional trauma Environmental toxicity Modern Media
1. Centers for Disease Control and Prevention (2013): Attention-Deficit/Hyperactivity Disorder. Available online: http://www.cdc.gov/ncbddd/adhd/data.html
2. Esparham et al. Children. 2014
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INTEGRATIVE RX FOR ADHD
Dietary therapies Micronutrients Probiotics/Gut Microbiome Neurofeedback Biologic-based Therapies Mind-Body Therapies HBOT Pet therapy Music therapy
Harrington J and Allen K. Pediatrics in Review. 2014, 35(2): 62-78
Children are vulnerable to environmental toxins Organochlorines: DDT, PCBs Organophosphates: pesticides Plastics: BPA & Phthalates Lead
Gilbert SG et al. J Intellect Dev Disabil. 2010; 35, 121-128Aguiar A et al. Environ Health Perspect 2010; 118:1646-1653Sagiv SK et al. Am J Epidemiool. 2010; 171:593-601
TAKE A GOOD ENVIRONMENTAL EXPOSUREHISTORY BESIDES JUST LEAD
Ask patient’s family and family’s parents Do you use weed-killers? Pesticides/insecticides or have an exterminator? Live near farms that spray? Well water? Use of plastics in microwave? Use of fragrances, lotions, makeup that contain BPA, phthalates,
parabens?
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WHY DIETARY THERAPY?
Greater prevalence of GI symptoms among children with ADHD1
Hypothesis: gut-brain axis dysfunction in neuropsychiatric disorders 90% neurotransmitter synthesis in gut2
~66-75% immune system in gut3
1. McKeown C et al. Pediatrics. 2013 Nov; 132(5): e1210-5.2. Gershon MD. Hosp Pract. 1999;34(7)31-23. Weiner HL et al. Immunol. Rev. 201, 241(1): 241-59
HOW-TO: ELIMINATION DIET
Removal of most common food allergies or sensitivities: dairy, gluten/wheat, corn, soy, eggs, citrus, tree nuts, peanuts,
and shellfish
Usually 21-96 day elimination trial and then reintroduce one food every 3-7 days
Have families note any health/physiologic changes in addition to behavioral symptoms during food challenge
ELIMINATION DIET ADHDINCA study:
Impact of Nutrition in Children with
ADHD
1st phase: Open label for individual nutrition guidance
5 Weeks
Elimination diet group or control
group
100 enrolled and randomized with 83
completing first phase and 32 eligible
for second phase
2nd Phase: Double-blind crossover
study
2 weeks
Each group assigned to three foods that
induce low IgG levels or three that induce
high IgG levels
IgE food allergies also consideredPelsser, L.M et al. Lancet 2011, 377, 494–503.
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ELIMINATION DIET: RESULTS
32 (64%) of 50 children showed significant improvement in ADHD symptoms
64% relapsed after food challenge Food IgG panel did not predict deleterious behavior
IgE allergens same in both group-> meaning there may be a food sensitivity component that was not detected by IgG
ELIMINATION DIET:RISK OF NUTRIENT INSUFFICIENCIES
Restricted Diet may result in: Weight Loss Potential insufficiencies: Protein, Vitamin D, Calcium, folate,
Iron
Strategy to avoid complications Utilize and Review Diet Diaries (e.g. written or Mobile Apps) to
review caloric intake Consult Dietitian Supplementation with laboratory guidance during elimination
diet
Dosman C et al. Pediatrics in Review. 2013; 34(10):336-41
Sugar dysregulates neurotransmission, similar to drug addiction
Majority of studies done1,2
Comparing sugar to placebo of aspartame or saccharin.
No evaluation of chronic sugar consumption
1. Wender EH & Solanto MV .Pediatrics. 1991, 88:960-66.2. Wolraich ML et al. JAMA . 1995; 4: 1617-21
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WHOLE FOODS = HEALTH
MAKE IT SIMPLE:
Healthy fat
Healthy protein
Complex carbs at every meal
ADHD:DIETARY ASSESSMENT
Iron Low ferritin and abnormal iron indices
Sleep disturbance in children with ADHD1
Intake in ADHD is lower on medication2
Brain iron is lower in striata and thalamus of children with ADHD3
1. Cortese et al. Eur child adolesc psychiatry 20092. Abou-Khadra MK et al. BMC Pediatr 20133. Adisetiyo V et al. Radiology. 2014
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IRON THERAPY
Serum ferritin <50 ng/mL with sleep disturbance + adhd/autism:
Children six years and older: Elemental iron 45-65 mg (1-2 times daily)
Children six years and younger: 3-6 mg/kg/day of elemental iron Max 150 mg elemental iron per day
Take with Vitamin C to enhance absorption
ADHD:DIETARY ASSESSMENT
Zinc Systematic Review1:
3 out of 80 trials met inclusion criteria Conclusion:
Zinc combined with methylphenidate improved total ADHD score2
Zinc alone decreased hyperactivity and impulsivity, but no effect on inattention3
Zinc did not have any effect on ADHD symptoms, but were able to lower amphetamine medication.4
1. Ghanizadeh A & Berk M. Eur J Clinic Nutrition. 2013; 67(1):122-42. Akhondzadeh S, Mohammadi MR, Khademi M. BMC Psychiatry 2004; 4:9.3. Bilici M et al. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 181–1904. Arnold LE et al. J Child Adolesc Psychopharmacol 2011; 21: 1–19.
ADHD:DIETARY ASSESSMENT
Healthy Fats Several RCT differ in conclusions1,2,3,4
Due to different doses and combinations of PUFA mixes (ALA/LA/EPA/DHA/GLA)
Varying placebos with nutritional properties
Meta-analysis5
Omega-3’s are 40% as effective as methylphenidate
1. Gustafsson, P.A. et al.. Acta Paediatr. 2010, 99, 1540–1549. 2. . Milte, C.M. et al. Nutrition 2012, 28, 670–677. 3. Widenhorn-Muller, K. et l. Prostaglandins Leukot. Essent. Fatty Acids 2014, 91, 49–60. 4. Stevens, L.; et al. Lipids 2003, 38, 1007–1021. 5.Bloch, M.H.; Qawasami, A.. J. Am. Acad. Child Adolesc. Psychiatry 2011, 50, 991–1000.
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FAT FOR THE BRAIN
If not getting enough of fatty acids in diet: suggest dietary changes and supplementation with
balanced omega oil: 3/6/9 plus Phospholipids
(phosphatidylcholine/phosphatidylserine)
EEG-BASED BIOFEEDBACK (NEUROFEEDBACK)
The American Academy of Pediatrics (AAP) recently declared “biofeedback” to be an evidence-based child and adolescent psychosocial intervention with “level 1, best support”.
“Biofeedback” is used to refer to feedback interventions to train either the brain (ie, NF) or the body (traditionally referred to as biofeedback).
Neurofeedback: EEG-based form of biofeedback emphasizes:Positive reinforcement and operant conditioningRetrains abnormal brain wave states back to its normal state
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ADHD: BRAINWAVE VARIANTS
Elevated Theta/Beta Ratio Assessment of responders vs non-responders Dysregulation of slow cortical potentials
Gevensleben H et al. Brain Topogr. 2013
ADHD NEUROFEEDBACK:RESEARCH REVIEW
Meta-Analysis 2012-2014: 3 out of 12 studies included
1. NF significantly improves ADHD total score on parent scale(-0.49)
2. NF improves both inattention and hyperactivity/impulsivity dimensions on parent scale (-0.46 and -0.34)
3. NF improves inattention on teacher scale (-0.30)
Micoulaud-Franchi JA et al. frontiers in human neuroscience. Nov 2014, 8: 1-7