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Natural Treatments for ADHD - April 11, 2018

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This presentation will be delivered April 11, 2018 on recorded webinar for the Autism Global Conference. It was my pleasure to prepare and present this lecture (in webinar form), outlining a coherent philosophy of finding biological underpinnings that can cause or contribute to, or exacerbate, mental dysfunction. In the case of this presentation, the question is "How much of ADHD symptomatology is caused by a lack of a good medication, or, rather, lack of a coherent strategy for finding and fixing underlying biological abnormalities?"

Those biological abnormalities in this presentation include MTHFR polymorphisms, COMT polymorphisms, elemental deficiencies (lithium, magnesium, zinc, iron, and copper), essential fatty acid deficiencies, the confound of high fructose corn syrup, and many others.

Rational strategies for nutraceutical intervention are reviewed.

Published in: Health & Medicine
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Natural Treatments for ADHD - April 11, 2018

  1. 1. Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute Adjunct Clinical Lecturer – Indiana University School of Medicine Department of Psychiatry Functional & Integrative Neuropsychiatry – Evansville, Indiana The Natural Treatment of ADHD: New Hope and New Directions For: The Autism Global Summit – April 11, 2018
  2. 2. Prevalence: how much, and “why so much”?
  3. 3. Increased methylphenidate usage for attention deficit disorder in the 1990’s. Safer DJ et al. Pediatrics. 1996 Dec; 98(6 Pt 1):1084-8} • 2.5 X increase in MPH tx between 1990 and 1995 – 2.8% (1.5 million) US youths aged 5-18 received this medication in mid-1995 • “The increase in methylphenidate…appears largely related to – an increased duration of treatment; – More girls, adolescents and inattentive youths on the medication – And a recent improved public image of medication treatment.”
  4. 4. For both groups of people hearing this presentation -- • Parents/patients with straight ADD/ADHD – Medications are not necessarily evil – Holistic “bio-med” interventions are more desirable. – Some interventions that patients with autism receive (and all functional testing) may ALL be relevant in terms of remediating biological symptoms exacerbating ADHD. • Parents/patients with ASD & ADD/ADHD – Select the most disabling set of symptoms and try to start stabilizing them first. – Medications should be used with CAUTION and, unless absolutely necessary, not for “chemical restraint.” – EVERY biomedical intervention and diagnostic modality should be considered. (Resources: every other presentation at this Summit).
  5. 5. As of 4/11/2018
  6. 6. The recent literature • Prenatal exposure to substances resulted in more mental health symptoms assoc. with ADHD and ASD, compared to controls. – Sandtorv LB et al. Subst Abuse. 2018 Mar 22;12:1178221818765773. doi: 10.1177/1178221818765773. eCollection 2018. • Use of augmented reality smartglasses – the Empowered Brain system – a behavioral and social communication aid for child, adolescents, and young aduts with ASD and high ADHD symptoms. The study showed initial evidence of the potential of this system to “reduce ADHD related symptoms… with ASD.” – Vahabzadeh A et al. JMIR Ment Health. 2018 Mar 24;5(2):e25. doi: 10.2196/mental.9631 • Children with both ASD and ADHD have an increased risk of anxiety and mood disorders. Physicians who care for children with ASD should be aware of the coexistence of these treatable conditions. – Gordon-Lipken E et al. Pediatrics. 2018 Apr;141(4). pii: e20171377. doi: 10.1542/peds.2017-1377
  7. 7. www.billfoster.com - Reviving American Manufacturing, accessed 1 27 2014www.billfoster.com - Reviving American Manufacturing, accessed 1 27 2014
  8. 8. http://www.scdigest.com/assets/newsViews/08-06-12-2.php accessed 01 27 2014http://www.scdigest.com/assets/newsViews/08-06-12-2.php accessed 01 27 2014
  9. 9. Ordinary people are losing their jobs too….
  10. 10. Jan. 21, 2018 USA TODAY
  11. 11. Unemployment, underemployment are contemporary problems…
  12. 12. Genetic tendencies in ADHD
  13. 13. Faraone SV et al. Biol Psychiatry 2005 June 1;57(11):1313- 1323. Graphic from CNS Spectr. 2007;12:4 (Suppl 6): 6- 7
  14. 14. Genetic etiologies • Genes most commonly associated with ADHD involve dopamine. – Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention- deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1313-1323. • PET studies show excess DAT in presynaptic neuron (15% higher than in controls) – Spencer TJ, Biederman J, Ciccone PE, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry. 2006;163(3):387-395.
  15. 15. What does it “look like”? A section for kinesthetic and visual learners…
  16. 16. ADHD – not concentrating Inferior Orbital pre-frontal cortex Images courtesy of Daniel Amen, MD – Amen Clinics, Inc., Newport Beach, CA. Used with permission.
  17. 17. ADHD - concentrating
  18. 18. ADHD – concentrating, on RX
  19. 19. ADD – inattentive, without Rx ADD – inattentive, on Amph Images courtesy of Daniel Amen, MD – Amen Clinics, Inc., Newport Beach, CA
  20. 20. Integrated: how to avoid over-reliance on meds • Holistic evaluation, treatment, and supplementation! • Smart prescribing! • School: – Excellent working relationships with school – Good teaching • HOME: – Diminish “electronic screens” effect – Good home discipline – Good sleep/wake schedules – Good diet AND NUTRITION – Adequate exercise • Parent training: parenting, stress tips
  21. 21. What the peer-reviewed literature says • Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. • Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. • Videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D2 occupancy indicating sub- sensitivity of dopamine reward mechanisms. Weinstein A, et al. Neurosci Biobehav Res. April 2017
  22. 22. Death by video game • 2005 – S. Korean, addicted to StarCraft – lost job, girlfriend. Spent all money at an internet. 14-18 hours at a time. – One day, went 50 hours nonstop, collapsed, and died from exhaustion and dehydration. • 2015 – Taiwan man – dead from cardiac failure after a three-day online gaming binge. • 2007 – 15 year old boy shot both parents over his video game (Halo 3) being confiscated • 17 year old Philippine teen murdered his 68 year old GM for interrupting his game in an internet café.
  23. 23. New diagnostic codes and treatment facilities • ICD-10 Diagnostic codes: – Y93.C1 – keyboard playing video games – Y93.C2 – video games including cell phones, communication devices (tablets) and other interactive devices. • Treatment facilities – McLean Hospital in Belmont MA has set up Computer Addiction Services. – Chinese Government operates several clinics to treat those suffering from overuse of online games, chatting, and web surfing. “Electrical shock treatments” used.
  24. 24. Di Chiara, G et al. Neuropharmacology, 47(1), Supl 1, 2004:227-241 • Addictive drugs increase extracellular dopamine in nucleus accumbens. • Brain imaging studies: have demonstrated correlation between psychostimulant induced increase of extracellular CA and self-reported measures of liking and “high”(euphoria).
  25. 25. Emergence of diagnoses of game playing pathology • “Internet gaming disorder” – Now listed in DSM5 research appendix as a “condition for further study.” • “GAMING DISORDER” – World Health Organization, 2018 – Applies on online and offline gaming.
  26. 26. My Previous Notion of Therapeutic Options
  27. 27. Do stimulant drugs work in children with ASD and ADHD? • Meta-analysis of four cross-over studies, with 113 children ages 5 – 13 (83% boys) • “We found that short-term use of methylphenidate might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication, although the low quality of evidence means that we cannot be certain of the true magnitude of any effect. There was no evidence that methylphenidate has a negative impact on the core symptoms of ASD, or that it improves social interaction, stereotypical behaviours, or overall ASD.” – Sturman N et al. Methylphenidate of children and adolescents with autism spectrum disorder. Cochrane Database Syst Rev. 2017 Nov 21;11:CD011144. doi: 10.1002/14651858.CD011144.pub2.
  28. 28. MY ADVICE: •Google.com •Scholar.google.com •PubMed.gov
  29. 29. • The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects • “…but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.” • The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects • “…but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.”
  30. 30. • “We argue that a change in the ratio of n-6/n-3, especially during early life, may induce developmental changes in brain connectivity, synaptogenesis, cognition and behavior that are directly related to ASD.” • “We argue that a change in the ratio of n-6/n-3, especially during early life, may induce developmental changes in brain connectivity, synaptogenesis, cognition and behavior that are directly related to ASD.”
  31. 31. • Western diet: omega 3 fatty acid deficiency and increased fructose intake. • “Both promote brain insulin resistance and increase the vulnerability to cognitive dysfunction.” • “Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function.” • Western diet: omega 3 fatty acid deficiency and increased fructose intake. • “Both promote brain insulin resistance and increase the vulnerability to cognitive dysfunction.” • “Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775234/
  32. 32. • In Adults with ADHD: • DECREASED DHA, AA, and DHGLA • “We could demonstrate that a lack of polyunsaturated FAs in blood serum of subjects with ADHD persists into adulthood. Furthermore, we could show that adult ADHD symptomatology positively correlates with elevated levels of saturated stearic and monounsaturated FAs.HGLA were lower than controls.” • In Adults with ADHD: • DECREASED DHA, AA, and DHGLA • “We could demonstrate that a lack of polyunsaturated FAs in blood serum of subjects with ADHD persists into adulthood. Furthermore, we could show that adult ADHD symptomatology positively correlates with elevated levels of saturated stearic and monounsaturated FAs.HGLA were lower than controls.”
  33. 33. Reduced Levels of Omega-3 Fatty Acids are Associated with ADHD Antalis et al., Prostaglandins Leukot Essent Fatty Acids, 2006. 75(4-5): p. 299-308.
  34. 34. This summary demonstrates that a deficiency in brain PUFAs will lead to cognitive deficits, while supplementation of PUFAs can rehabilitate cognitive deficits, as manifested in attention deficit hyperactivity disorder, stress/anxiety, and aging. This summary demonstrates that a deficiency in brain PUFAs will lead to cognitive deficits, while supplementation of PUFAs can rehabilitate cognitive deficits, as manifested in attention deficit hyperactivity disorder, stress/anxiety, and aging.
  35. 35. PUFA’s as cognitive enhancers • Low dose PUFA supplementation study • French community dwellers aged 70 or over reporting subjective memory complaints; NOT DEMENTED. • PUFA – 800 mg DHA / 225 mg EPA • Less cognitive decline over 36 months. Hooper C et al. Cognitive changes with omega-3 polyunsaturated fatty acids in non-demented older adults with low omega-3 index. J Nutr Health Aging. 2017; 21(9):968- 993
  36. 36. PUFA + Methylphenidate (Ritalin) • 40 children with ADHD in study, 2014. – 82.5% boys, 17.5% girls • Two groups: – MPH + PUFA – MPH + placebo • Response to treatment (reduction of at least 25% of signs) – MPH + Placebo 60% – MPH + PUFA 90% Moghaddam MF et al. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD” a double-blinded randomized clinical trial. Electron Physician. 2017 May25;9(5):4412-4418
  37. 37. Should we use this??
  38. 38. Further elongation problems: lack of nutrients • REQUIRED for delta-6 desaturase: – Magnesium – Zinc – B vitamins • FAD (B2) • Niacin (B3) • P-5-P (B6) – C – insulin “chiropractic” “psychiatric”
  39. 39. Extra slide of online viewing • Key principles of essential fatty acid supplementation are: – Do not use large doses of a generic omega 6 or omega 3 fish oil and presume that you are going to get adequate amounts of EPA and DHA out the bottom of the pathways. – The only two sources of fish oil high in PUFA’s that we get are from eating fish or taking fish oil. Period. If we don’t eat fish, we should probably be on fish oil. – We DO have the ability to synthesize the critical PUFA’s, including EPA and DHA, from precursors, but in order to do so, we must have adequate amounts of the critical trace minerals.
  40. 40. Vayarin® – a new prescription “medical food” – the theory behind development • Lipids are important for brain health • Abnormal lipid balances are associated with ADHD. • Lipid levels (in blood and brain) might be affected by different parameters (e.g., diet, metabolism) • Therefore, why not put more of the good lipids into the brain?
  41. 41. Polar head Fatty acids Phosphate group Glycerol backbone Phospholipid molecule omega-3 Fatty acids
  42. 42. Vaisman, N. et al., Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2009: p. 952-959. What’s the best way to get Omega 3 into mouse brain?
  43. 43. NOTE: The essential elements portion of this test include: •Elemental lithium •Iron •Magnesium •Zinc •copper NOTE: The essential elements portion of this test include: •Elemental lithium •Iron •Magnesium •Zinc •copper
  44. 44. IRON - Most common of all nutrient deficiencies in U.S. school-aged children Murray & Pizzorno. Encyclopedia of Natural medicine. Rocklin, CA: Prima Publishing; 1998. • Deficiency associated with: markedly decreased attentiveness, narrower attention span, decreased persistence, and lowered activity level – all of which respond positively to supplementation. • Kidd. ADHD in Children: Rationale for Its Integrative Management. Alt Med Review 2000; 5(5):402-427. • 30% improvement in Conners ADHD Rating Scale following iron supplementation [(Ferrocal), 5 mg/kg/day for 30 days] in one uncontrolled Israeli study of boys. • Sever et al. Iron treatment in children with attention deficit hyperactivity disorder. A preliminary report. Neuropyshcobiology 1997;35:178-180. 0 5 10 15 20 25 30 35 40 45 serum ferritin Conners before after Significant increase in serum ferritin levels (from 25.9 +/- 9.2 to 44.6 +/- 18 ng/ml) and a significant decrease on the parents' Connors Rating Scale scores (from 17.6 +/- 4.5 to 12.7 +/- 5.4).
  45. 45. Iron & ADHD – 2018 data • Meta-analysis to compare ADHD symptoms and iron levels/iron deficiency (ID) – 17 articles met search criteria. • “Peripheral serum ferritin levels were significantly lower in ADHD children, but with no significant difference in iron or transferrin levels. (!!!) • “Our results suggest that ADHD is associated with lower serum ferritin levels and ID.” Tseng PT et al. Peripheral iron levels in children with attention-deficit hyperactivity disorder: a systematic review and meta-analysis. Sci Rep. 2018, Jan 15;8(1):788.
  46. 46. Zinc link --- and friends • Psychiatr Pol 1994 May-Jun;28(3):345-53 [Deficiency of certain trace elements in children with hyperactivity] [Article in Polish]Kozielec T, Starobrat-Hermelin B, Kotkowiak L. Zakladu Medycyny Rodzinnej Pomorskiej Akademii Medycznej. • The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group--healthy children from Szczecin. The highest deficit was noted in hair. • Our results show that it is necessary to supplement trace elements in children with hyperactivity.
  47. 47. Magnes Res 1997 Jun;10(2):143-8 Kozielec T, Starobrat-Hermelin B.,, 1997, cont. • 116 children with ADHD • Magnesium deficiency was found in 95 per cent of those examined: – most frequently in hair (77.6 per cent) – in red blood cells (58.6 per cent) – and in blood serum (33.6 per cent) • CONCLUSIONS: magnesium deficiency in children with ADHD occurs more frequently than in healthy children. Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility.
  48. 48. Putting it all together with new technology… Two illustrative cases
  49. 49. The adorable rager – parents concerned; interested in natural treatment • 7 years of age • Generally sweet • Unpredictable rages • Assaultive • Intermittently totally unmanageable
  50. 50. Google: L-methylfolate: a vitamin for your monoamines. Stahl
  51. 51. 2C19: PPI’s anti-epilpetics. Plavix (clopidrogel) Valium (diazepam) 2D6 - most psych drugs, amphetamine, TCA’s, codeine, etc.
  52. 52. THEREFORE: informed treatment decisions • Diet – eliminate dairy and wheat • L-Methylfolate support to bypass MTHFR • Vayarin for membrane stabilization • 5HTP to supply more raw material for serotonin synthesis • Lithium – 10 drops = 0.5 mg
  53. 53. “Nothing but marijuana makes me happy” – 14 yoa • Tired and fatigued • A little depressed • Somewhat hostile towards mom • WANTS WEED!!!!
  54. 54. *
  55. 55. Treatment decisions • Enlyte – (L-methylfolate plus methylate B-vitamins and trace iron) • Based on other labs: – Selenium and magnesium – Low dose thyroid (T3) • Ultra low dose Bupropion if needed to be started in 2 – 3 weeks. • New insight – rhodiola rosea as COMT inhibitor. – Blum K et al. Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: A hypothesis. Medical Hypotheses 2007, vol 69, issue 5 pages 1054-1060.
  56. 56. Treatment of side effects: • Folic acid appears to stimulate appetite in ADHD children treated with MPH • Randomized, double blind clinical trial with 70 outpatients, ages 6 – 1 2 years. – Group 1 – 1 mg/kg MPH plus 5 mg folic acid/day – Group 2 – 1 mg/kg MPH plus placebo. • “Appetite was significantly improved in group 1” Riahi F et al. Effects of folic acid on appetite in children with attention deficit hyperactivity disorder treated with methylphenidate: a randomized double-blind clinical trial. Iran J Med Sci. 2018 Jan;43(1):9-17.
  57. 57. “Don’t think ‘either/or.’ Think ‘both/and.’” - Dan Burrus
  58. 58. Summary – WHAT YOU CAN DO • Get rid of/stop playing video games. Beware computer/internet addiction • Get functional medicine testing: – IgG Food Allergies, organic acid testing, hair analysis, pharmacogenomics (esp. MTHFR and COMT). Conventional (but sophisticated) labs, e.g. RBC Mg, RBC Zn, etc. B12 AND Methylmalonic acid. • Avoid over-reliance on medication • Holistic: – Address ANY MTHFR deficiencies. – Fish oil (good quality EPA/DHA), replace elemental deficiencies (magnesium, zinc, copper, iron), & replenish gut microbiota with probiotics – Consider low dose lithium, rhodiola (if indicated) – Consider precursor loading therapy (l-phenylalanine, l-tyrosine, 5- dydroxytrptophan)
  59. 59. “There are things known and there are things unknown, and in between are the doors.” - Jim Morrison
  60. 60. Contact information: Louis B. Cady, M.D. www.cadywellness.com Office: 812-429-0772 E-mail: lcady@cadywellness.com 4727 Rosebud Lane – Suite F Interstate Office Park Newburgh, IN 47630 (USA) Link to all slides from this presentation: www.slideshare.net/lcadymd

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