Introduction to Integrative Medicine for Mental Health

Louis B. Cady, MD

Founder, CEO Cady Wellness Institute

“There are two objects of medical education: to heal the sick and to advance the science.”

- Dr. Charles H. Mayo, MD

“The glory of medicine is that it is always moving forward, that there is always more to learn.”

- Dr. William J. Mayo

“There are more things in Heaven and Earth than are dreamt of in

your earthly philosophy, Horatio.”

“Hamlet” – by William Shakespeare

A case of depression? Symptoms at presentation:

• 43 year old aerobically fit male – competitive cyclist/ pharmaceutical rep. Drinks protein shakes (whey).

• Mind and emotions:– Depression – Difficulty with memory, attention, – Short attention span– Weakness, fatigue, loss of energy

• Miscellaneous:– Fatigue– Apathy/lethargy – Sleep apnea (previously reviewed) – Difficulty getting out of bed in the a.m. – Recurrent apthous ulcers

TREATMENT

Classic “atypical presentation”• History continued:

– Exhausted/fatigued with multiple vague symptoms for 3 years. Taking naps in car in afternoon while working.

– Intermittently nauseated for last two years. MD ignored him.

• Known attention deficit disorder. Started on lis-dexamfetamine by family physician

• Past history: at 41 yoa – diagnosed with Rocky Mountain Spotted Fever. Treated with Doxycycline– Ulcer dx by GI doc, with + h. pylori.

• Rx: macrodantin + metronidazole.

– “Pins & needles sensation under skin began – May 2009 (Antihistamine tried – didn’t work. )

Diagnostic Interventions and Trial Tx• Sleep study – non revealing• IgE food allergy possibility per dermatologist. Anti-

histamine used. Sxs would stop then come back. • Soreness – consulted pain management doctor.

No help. • Transdermal testosterone tried (low normal T) –

no help. • Cholecystectomy – Sept 2009• Severe constipation Dec 2009 – went days

without bowel movement• Colonoscopy – benign. Possible “small bowel

bacterial overgrowth.” ABX used. • Dx’ed with possible Lyme’s – more ABX.

Other past dx/tx procedures:- CT brain – normal - CT abdomen – normal- HIDA (gallbladder) scan – abnormal

- (Gallbladder subsequently removed)- MRI – lower lumbar – essentially normal but

with slightly bulging disc- MRI – thoracic and cervical – good - Colonoscopy & sigmoidoscopy – benign. - Muscle biopsy – “nerve damage”- Stress EKG and Stress Echocardiogram –

normal.

More symptoms at presentation• dry/brittle skin; puffy wrinkled skin• dark circles under eyes• persistent rash with pins and needles sensations on skin

• “heaviness” in legs; shortness of breath

• exhaustion with minor exertion

• certain foods cause ill feelings• difficulty losing weight• Needs to drink coffee to get going in a.m.

• Tired 1 – 3 hours after eating

• Feels faint or weak.

• Rates self as overweight

Lab review – May 2011– Testosterone 460 {300 – 890}– % Free Testosterone 1.4%(L) {1.6 – 2.9%}– CBC shows ANEMIA

• RBC 3.87 (L) {4.5 – 6.0}HGB 12.8 (L) {14 – 17}

• HEMATOCRIT 37% (L) {42 – 51%}

– TFT’s• TSH 1.13• FTI 4.50 (L)• T4 thyroxine 4.9 (L) {6.1 – 12.2}• T3% uptake 36.4% {32 – 48.4$}

– A.m. cortisol 10.4 {5 – 23}

– Iron 103 {76 – 198}– 25-OH Vitamin D low (outside lab)

Working hypotheses, treatment• Anemia – etiology unclear• Hypoadrenia• Rule out post-viral fatigue syndrome• Subclinical hypothyroidism• Possible symptoms of low testosterone• Possible IgG food sensitivities (dairy?)• Probable candida (by history) • Low Vitamin D• History of depression and ADHD – on treatment• History of Lyme Disease – allegedly treated

Initial treatment planning

• Consider transition to compounded porcine thyroid

• Consider testosterone

• Dairy free diet. (based on history)

• Start Xymogen IgG 2000 DF

• NutraProbiotics – one daily

• Get more labs, including IgG

Interventions and follow-up

• 6/14/2011 – Start NO DAIRY DIET. Baseline medications (incl. Lexapro, T4), continued. Probiotics. Minimize exposure to brewer’s yeast.

• 6/30/11 – better energy. “allergic shiners” gone. (Labs reviewed) – Rx: started DHEA – 50 mg SR; 5HTP – up to

100 mg daily for documented low serotonin. Slight increase in thyroid Rx. Start Nystatin.

Most relevant labs (ordered before appointment):

Other interventions and current status

• Testosterone cypionate – 100mg cc IM q wk.

• Armour thyroid – (needed it for a while), then didn’t • Supplements – in addition to high potency multivitamin

twice daily (including Zinc)…– Adrenal supplementation – 2 twice daily– DHEA 50 mg SR daily – B-12 – liquid– Vitamin C – 2500 mg per day in 4 – 5 divided doses– Vitamin D – 5,000 IU daily – IGF2000 DF (Xymogen) – one scoop periodically.– Calcium and 5HTP– Coenzyme Q10 400 mg per day

• Continue 70 mg lis-dexamfetamine and 20 mg escitalopram

Zinc & Testosterone

• Low Zinc- associated with low testosterone– Tsai, E.C., Boyko, E.J., Leonetti, D.L., & Fujimoto, W.Y. (2000).

Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men. International Journal of Obesity and Related Metabolic Disorders, 24, 485-491.

• Per U.S. Department of Agriculture, 60% of US men between 20 – 49 years of age do not get enough.

• Fast food = low zinc = testicular tissue inflammation = decreased testosterone– El-Sewedy MM et al. J Pharm Pharmacol. 2008 Sept;60 (9):1237-

42.

Inadequate micronutrient intake in men and women in southern Brazil

1,222 adults 22 – 63 years old in Florianópolis1,222 adults 22 – 63 years old in Florianópolis

Inadequate micronutrient intake estimated Inadequate micronutrient intake estimated

Inadequate intake of Vitamins A, C, D, and E (52-100%)Inadequate intake of Vitamins A, C, D, and E (52-100%)

Calcium (87.3%) and iron intake(13.7%) inadequate in womenCalcium (87.3%) and iron intake(13.7%) inadequate in women

25.1% Zinc deficiency in men25.1% Zinc deficiency in men

T vs Cognitive Function

Rosario ER. JAMA. 292(2004):1431-2

T vs Cognitive Function• 400 independently living men, 40-80yo

– 100 in each age decade– MMSE 21-30, average 28– TT: 208-1141ng/dL; Bio-avail T 78-470ng/dL

• HIGHER T = better cognitive performance in OLDEST AGE category

• Men testosterone in lowest quintile – did worse than men in highest quintile

• Highest Bio-available Testosterone more significant than TOTAL Testosterone, age, intelligence level, mood, smoking, and alcohol.

Muller M. Neurology. 64(2005):866-71

T vs Mood in men

• Study: 278 men, >45yo, followed 2 years

• Compared to eugonadal patients, hypogonadal men w/TT <200ng/dL had – 4-fold increase risk of depression– Significantly shorter time to depression

diagnosis

• Depression risk inversely related to TT w/statistical significance <280ng/dL

Shores MM, Arch Gen Psychiatry. 61(2004):162-7

Low Vitamin D linked to depression[Muhlestein JB et al. Am Heart J, 2010; 159(6):1037-43.

(citation from Dr. Shaw)

• 7,358 patients >/= 50 yoa with CV diagnosis and NO HX of depression

• “Vitamin D levels were significantly associated with an increased risk of depression, compared with optimal vitamin D levels.”

• Optimal level: > 50 ng/ml– Normal 31 – 50 ng/ml– Low: 16 – 30 ng/ml; “very low = < 15 ng/ml

8/1/2011 follow-up: strict dairy free diet• “Some days I don’t feel as hot in terms of

energy level. But it has improved. I’m thinking more clearly.”

• Lost 8 lbs (by desire)

• Rode bike in extreme heat on Sunday for 1 hour.

• “I’m able to get out and do things that I feel like doing –working around the house, hanging around my family, and going fishing.”

9/13/2011

• Went out and rode three hours on his bike for first time in years. – “But I came home and crashed.”

• Working full time as pharmaceutical representative. No longer napping.

• Lyme disease diagnosed based on new labs. Treatment started.

9/13/2012 – one year later

• Vigorous. Working around the house.

• No limit to activities (or distance for his rides)

• Career going well

• Biking going well

• Enjoying life.

The treatment – quick review (some had been tapered one year later)

• Testosterone cypionate – 100mg cc IM q wk.

• Porcine thyroid – (needed it for a while), then didn’t • Supplements – in addition to high potency multivitamin

twice daily (including Zinc)…– Adrenal supplementation – 2 twice daily– DHEA 50 mg SR daily – B-12 – liquid– Vitamin C – 2500 mg per day in 4 – 5 divided doses– Vitamin D – 5,000 IU daily – IGF2000 DF (Xymogen) – one scoop periodically.– Calcium and 5HTP– Coenzyme Q10 400 mg per day

• Continue 70 mg lis-dexamfetamine and 20 mg escitalopram

BODY

MIND

ACTIONS

The Story of Alan• 2/24/2010 – “ADHD hampers his ability to focus and

comprehend information. He becomes overwhelmed. Lacks confidence in reading. Teacher believes he is capable.”

• Past history: “a busy child. “Couldn’t keep him in a chair.” • ADHD dx in kindergarten. Multiple Rx since, incl. Abilify

• At presentation:– 20 mg amphetamine salts XR in a.m., 3 mg guanfacine ER in a.m.,

5 mg aripiprazole at 4 pm.

– “Heart is racing” for two months.

– Hx of stimulant rebound and having to push the dose– Stools like tar since starting on Abilify.

• Rating scales:– DSM-IV 9/8 before meds; DSM-IV 9/4 ON meds

Treatment summary and new developments

• Medications adjusted. Stimulant lowered and L-tyrosine started with it (increased to 1 gram twice daily ).– Changed to Concerta + Ritalin (a.m.), Intuniv,

Risperdal, and Depakote (250 mg 3x/day)

• 11/9/10 and 12/6/10 – “meltdowns” at school. States “I am going to KILL you,” when he is upset. Kicking the table at school and not looking at the teacher.

• OAT test and IgG Food Allergy panel ordered.

December 7, 2 010

Organic acid testing – 12/23/2010

Pertains to energy production, Kreb cycle, B vitamins, CoQ10, Mg

Interventions

• 1/5/2011:– School insisting he is “autistic” (meltdowns)

– At appointment told to remove wheat, peanuts, and milk from diet

– Started on CoQ10, high potency balanced B-complex, alpha lipoic acid, Vit C & Vit E

• 2/8/2011 – Alan - “for the first time I think the medicine is getting right.” (no changes made to Rx). Barlean’s Lemon Zest oil added.

Winding up of case• 4/1/2010 – five weeks of “awesome behavior” at school

with “no blow-ups whatsoever.” – “The school authorities are amazed.” – Won STUDENT OF THE WEEK (!!)

• 5/31/2011 – concluded school year; no blow-ups.

• 8/30/11 – some blowups, but not the “explosive kind like he had last year.”

• 12/21/11- scored “distinguished” in math and “proficient” in reading. (continues supplements and diet)

• 2/17/2012 – “Tired.” RX: lower Concerta from 54 to 36 mg

• Having more meltdowns at school. New labs ordered.

IgG results – 3/29/2012

- Started on Nystatin, compounded, liquid – up to 50,000 IU three times daily. Also Probiotic. - ELIMINATE MILK & WHEAT

Progress!

Repeat IgG testing 06/28/2012

Original IgG 3/9/2012

Organic acid test – 6 26 2012

• Arabinose c/w candida• All B-vitamin markers improved• Coenzyme Q10 high normal • HVA, VMA, 5HIAA – all increased.• Vit C low but c/w water solubility and a.m. spec.

Alan – conclusion 7/31/2012• Concluded school year well.

• “Was more interactive and playing on the playground.”

• Went up on state testing 17 points in reading. At grade level in math.

• Playing outside more, riding his bicycle.

• Vitamin C increased to 500 mg twice daily

• Start on Curcumin/turmeric for inflammation

• STABLE. See back 9/30/2012.

Do we really need all those supplements and vitamins???

Iodine, selenium, and iron

“Pending strong evidence …from randomized trials, it appears prudent for all adults to take vitamin supplements.” Fletcher & Fairfield, JAMA 2002

Ames & Micronutrient Triage - deconstructed

1. Inadequate dietary intakes of vitamins/minerals are widespread. [United States & Brazil are not exceptions!]

– Excessive consumption of energy-rich, micronutrient-poor, refined food

1. Deficiencies in many micronutrients cause DNA damage in cultured or living human cells.

2. Proposal: DNA damage and late onset disease are consequences of a triage allocation based on micronutrient scarcity.

– Natural selection favors short-term survival at expense of long-term health.

Ames B. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17589-94. Epub 2006 Nov 13.

Ames & Micronutrient Triage - deconstructed

4. If proposal is correct, “micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact.”

5. “A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life.”

Ames B. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17589-94. Epub 2006 Nov 13.

North America 85%

South America 76%

Asia 76%

Africa 74%

Europe 72%

Australia 55%

% Mineral depletion from the soil during the past 100 years, by continent

Source: UN Earth Summit Report 1992

• “Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase.”

– Zimmermann MB, Kohle J. Thyroid. 2002 Oct;12 (10):867-78

– Subclinical hypothyroidism assoc. with Fe deficiency.

– Nekrasova TSA, 2013 Kloin Med (Mosk).2013; 91 (9):29-33.

– Fe deficiency associated with Thyroid microsomal antibody levels.

– Wang YP et al. J Formos Med Assoc. 2014 Mar;113(3):155-60.

– Fe salts + T4 worked best. – Ravanbod M et al. Am J Med. 2013

May;126(5):420-4.

Consider IRON deficiency

136 citations search on “iron deficiency hypothyroidism” as of 8/27/2017

Must have selenium to make Liothyronine (T3)

Se+

THYROID HORMONE

Must have Iodine & Iron to make thyroid hormone

Must have iodine to make T4!

Source: Office of Dietary Supplements, NIH accessed 8/11/2013http://ods.od.nih.gov/factsheets/Iodine-QuickFacts/

Louis B. Cady, MD

CONCLUSIONS: Only few studies have been performed and enrolled populations from south/southeast region of Brazil. The actual Identification and background information: [Iodine Deficiency Disorder] prevalence analysis is complex because it was detected bias due influence of individual studies and very high heterogeneity. IDD might still be high in some areas but this remained unknown even after this meta-analysis evaluation. The generation of a national program for analysis of iodine status in all regions is urgently required.

CONCLUSIONS: Only few studies have been performed and enrolled populations from south/southeast region of Brazil. The actual Identification and background information: [Iodine Deficiency Disorder] prevalence analysis is complex because it was detected bias due influence of individual studies and very high heterogeneity. IDD might still be high in some areas but this remained unknown even after this meta-analysis evaluation. The generation of a national program for analysis of iodine status in all regions is urgently required.

Sources/locations of iodine deficiency:

• Chlorinated or fluorinated drinking water• Not using iodized salt• Consumption of NaCL in processed foods

• Consumption of soy & “goitrogens” - cabbage, broccoli, cauliflower and Brussels sprouts

• Being pregnant• People living with iodine deficient soils &

eating local foodsLouis B. Cady, MD

24 citations as of September 4, 2017

• “Low selenium status is associated with increased risk of thyroid disease. Increased selenium intake may reduce the risk in areas of low selenium intake.”– Wu Q et al. Low population selenium status is associated with increased

prevalence of thyroid disease. J Clin Endocrinol Metab. 2015 Nov;100 (11):4037-47.

• “We demonstrated …the beneficial effects obtained by selenomethionine treatment on patients affected by subclinical hypothyroidism.”– Nordio M. Combined treatment with myo-inositol and selenium ensures

euthryoidism in subclinical hypothyroidism patients with autoimmune thyroiditis. J Thyroid Res. 2013;2013:424163

From Chet Holmes - Grow Your Business 10X web presentation

Perhaps the ability not only to acquire the confidence of the patient, but to deserve it, to see what the patient desires and needs, comes through the sixth sense we call intuition, which in turn comes from wide experience and deep sympathy for and devotion to the patient, giving to the possessor remarkable ability to achieve results.

...William J. Mayo, 1935