In this presentation, given at UNIP (Campus Paraiso - Sao Paulo, SP Brazo) for the 2019 Congresso de Saude Mental (Conference on Mental Health), Dr. Cady reviewed the prevalence, inheritability, and social ramifications of ADHD (TADH in Brazil). He specifically reviewed multiple holistic interventions, including limiting "electric screen time,"good quality diet with adequate amounts of essential fatty acids and critically important trace elements, and the use of pharmacogenomic testing as well as functional, integrative medicine testing, all to better characterize logical and reeasonmable points for holistic intervention. This presentation was simultaneously translated into Portugue for the attendees, but unfortunately the slides were not available in translated form. For further information in Brazil on this topic, or to order a video/audio recording of the conference (in Portuguese),contact Luiz Dias of Laboratorio Great Plains in Brazil.

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
Laboratorio Great Plains – April 13, 2019
Sao Paulo, Brazil

4. Prevalence: how much, and “why
so much”?

5. 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.”

6. ADHD Prevalence in Brazilian children
• 1,013 students aged 12 – 14 years at 64
state schools tested using a screening
instrument.
– 5.8% met diagnostic criteria for ADHD
– ”affected youths are at high risk for impairment
and dysfunction in multiple domains.”
• Rhode LA et al. ( Drs. Zimmermann, Schmitz, Martins, and
Tamontina were residents in Child & Adolescent Psychiatry at
Federal University of Rio Gramnde do Sul, Brazil.) Journal of
the American Academy of Child & Adolescent Psychiatry June
1999, volume 38, issue 6, pages 716-722.

7. ADHD and Mental Health Status in
Brazilian school-age children
• Objectives: assess prevalence, mental health
status, and risk factors.
• Methods: children aged 5 – 13 years in public
elementary school.
• Prevalence rate was 5.1% (95% confidence
interval)
• Diagnosis influenced by: maternal educational
status, income class, and prenatal tobacco
exposure.
Arruda MA, et al. J Atten Disord. 2015 Jan;19(1):11-7. doi: 10.1177/1087054712446811.

8. “ADHD is undertreated in Brazil”
Mattos P et al. Revista Brasileira Psiquiatria. Sao Paulo, Dec. 2012
• Letter to the editor:
• Conservative analysis of prevalence – 0.9%
– 5.3% of youths and 2.5% of adults worldwide are more
common estimates.
• Number of doses of methylphenidate sold:
– 2009: 1,413,460 boxes of methylphenidate
-represents 32,986,110 pills
– 2010: 1,674,372 boxes of methylphenidate -
represents 40,585,870 pills
FULL TEXT of the article http://www.scielo.br/scielo.php?
script=sci_arttext&pid=S1516-44462012000400023&lng=en&nrm=iso&tlng=en

9. “ADHD is undertreated in Brazil”
Mattos P et al. Revista Brasileira Psiquiatria. Sao Paulo, Dec. 2012, cont.
• 924,732 Braziledos would be estimated to be
affected, using the 0.9% prevalence.
• Calculation: number of likely cases divided by
number of pills required for continuous treatment.
• Conclusions:
– Only 16.2% in 2008, and 19.9% in 2010 who would be
appropriately treated got it.
• Also noted: 30% of ADHD patients do not
respond to stimulants…

10. For both groups of people hearing
this presentation --
• Clinicians treating 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.
• Clinicians treating patients with
autism spectrum disorder &
ADD/ADHD
– Select the most disabling set of
symptoms & 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 Congresso).

11. 3090 citations – ADHD/Autism
3/3/2019

12. 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

13. www.billfoster.com - Reviving American Manufacturing, accessed 1 27 2014www.billfoster.com - Reviving American Manufacturing, accessed 1 27 2014

14. Forbes Magazine –
Feb 19, 2016

15. 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

16. Ordinary people are
losing their jobs too….

19. Jan. 21, 2018 USA TODAY

21. 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.

22. Genetic tendencies in ADHD

23. Faraone SV et al. Biol Psychiatry 2005 June 1;57(11):1313-
1323.
Graphic from CNS Spectr. 2007;12:4 (Suppl 6): 6- 7

24. 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

25. 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

27. 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.

28. 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.

30. 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).

31. 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.

32. My Previous Notion of Therapeutic Options

33. 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.

34. www.pubmed.gov
www.google.com
www.scholar.google.com

35. • 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.”

36. • “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.”

37. • 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/

38. • 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.”

39. 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.

40. 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.

41. 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

42. 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

43. HOW TO DO IT
• 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.

45. 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

46. 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).

47. 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 (iron deficiency).”
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.

48. 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.

49. Della Lucia CM et al. Nutrients. 2016 May 14;8(5).

50. Della Lucia CM et al. Nutrients. 2016 May 14;8(5).
Methods and results
• 99 children 2-6 years; 42.6% male.
• 2 preschools – one with UltraRice® (UR®) and
one with polished (unfortified) Rice.
• The fortified rice improved: level of Zinc, Thiamine,
Folic acid, mean corpuscular hemoglobin, mean
corpuscular hemoglobin concentration.
• Inadequacies of thiamine, folic acid and IRON
were lower among the test preschool.

51. Assessment of magnesium levels in children with
attention deficit hyperactivity disorder (ADHD)
• 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.
Kozielec T, Starobrat-Hermelin B. Magnes Res 1997 Jun;10(2):143-8

53. The effects of magnesium physiological supplementation
on hyperactivity in children with ADHD. Positive
response to magnesium oral loading test.
• Examined:
– Treatment group: 50 hyperactive children, ages 7-12
years, per DSM IV criteria for ADHD.
– Control group- 25 children
– Treated group – 25 children 200 mg Magnesium per
day.
• Results:
– “an increase in magnesium contents in hair and a
significant decrease of hyperactivity of those examined
has been achieved, compared to their clinical state
before supplementation.”
Starobrat-Hermelin BN, et al. Magnesium Research. 1997 Jun;10(2):149-56

54. Putting it all together with new
technology…
One illustrative cases

55. The adorable rager – parents
concerned; interested in natural
treatment
• 7 years of age
• Generally sweet
• Unpredictable rages
• Assaultive
• Intermittently totally unmanageable

58. Google: L-methylfolate: a vitamin for your monoamines. Stahl

62. 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

63. Crocus sativus (saffron) vs. methylphenidate in
treatment of children with ADHD
• 6 week randomized
double-blind study, n=
54 (children 6 – 17
years), with DSM5
diagnosis of ADHD.
• RX:
– 20 – 30 mg per day
methylphenidate
– 20 – 30 mg saffron
capsules.
“Short term therapy with
saffron capsule showed the
same efficacy compared with
methylphenidate.”
Baziar S et al. J Child Adolescent Psychopharmacology. 2019 Feb 11.

64. 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.

65. “Don’t think ‘either/or.’
Think ‘both/and.’ ”
- Dan Burrus

66. 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. Ferritin.
• 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); saffron
– Consider precursor loading therapy (l-phenylalanine, l-tyrosine, 5-
dydroxytrptophan)

67. “There are things
known and there are
things unknown, and
in between are the
doors.”
- Jim Morrison

68. 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