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.

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

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

4. 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.”

5. 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).

6. As of 4/11/2018

7. 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

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

10. 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

11. Ordinary people are
losing their jobs too….

14. Jan. 21, 2018 USA TODAY

16. Unemployment, underemployment are
contemporary problems…

17. Genetic tendencies in ADHD

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

19. 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.

20. What does it “look like”?
A section for kinesthetic and
visual learners…

23. ADHD – not concentrating
Inferior Orbital pre-frontal cortex
Images courtesy of Daniel Amen, MD – Amen Clinics, Inc.,
Newport Beach, CA. Used with permission.

24. ADHD - concentrating

25. ADHD – concentrating, on RX

26. ADD – inattentive, without Rx ADD – inattentive, on Amph
Images courtesy of Daniel Amen, MD – Amen Clinics, Inc., Newport Beach, CA

27. 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

28. 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

30. 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.

31. 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.

33. 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).

34. 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.

35. My Previous Notion of Therapeutic Options

36. 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.

37. MY ADVICE:
•Google.com
•Scholar.google.com
•PubMed.gov

39. • 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.”

40. • “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.”

41. • 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/

42. • 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.”

43. 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.

44. 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.

45. 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

46. 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

47. Should we use this??

48. 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”

49. 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.

50. 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?

51. Polar
head
Fatty
acids
Phosphate
group
Glycerol
backbone
Phospholipid molecule
omega-3
Fatty acids

53. 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?

55. 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

56. 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).

57. 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.

58. 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.

59. 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.

60. Putting it all together with new
technology…
Two illustrative cases

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

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

66. 2C19: PPI’s anti-epilpetics.
Plavix (clopidrogel)
Valium (diazepam)
2D6 - most psych drugs, amphetamine, TCA’s, codeine, etc.

69. 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

70. “Nothing but marijuana makes me
happy” – 14 yoa
• Tired and fatigued
• A little depressed
• Somewhat hostile towards mom
• WANTS WEED!!!!

73. *

75. 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.

76. 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.

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

78. 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)

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

80. 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