Louis B. Cady, MD, FAPA – CEO & Founder – Cady Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute Wellness Institute Adjunct Clinical Lecturer – Indiana University School of Medicine Department of PsychiatryFunctional & Integrative Neuropsychiatry – Evansville,

Indiana

New Concepts in Micronutrients, Antioxidants, Raman Spectroscopy and the “FUD Factor”

H - 2

“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

Disclaimer: Pharmanex supplementation and the

BioPhotonic Scanner are not FDA approved for the diagnosis, treatment, prevention, or cure of

ANY disease or “medical condition.”

They ARE appropriate to support the structure and function of the human body.

Learning objectives• Review basic physiology of nutrition• Science of micronutrients• ONE case study – nutrition and how it may relate

to aging • Clinical importance of antioxidants• Raman Spectroscopy and the Pharmanex

Biophotonic scanner• “The FUD Factor”• Changes in medical practice as a result of these

topics

Human nutritional physiology in one slide• Requirements in diet:

– Macronutrients – provide calories:

• C,H, O atoms:– Carbs (can be made from proteins with gluconeogenisis)– fat – some are essential and cannot be synthesized

» (large amounts of processed vegetable oils skew Omega 6:3 ratio)

• protein – (C, H, O, and N – nitrogen containing essential & non-essential amino acids)

• fiber, water

– Micronutrients:• Minerals – both essential and trace

• Vitamins

• Less well established: antioxidants /phytochemicals

Physiology of micronutrients and deficiency syndromes

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

Minerals

Essential:•Magnesium•Chlorine•Phosphorus•Potassium•sodium

Trace•Iodine (28.5% deficient)•Manganese•Selenium•zinc•Molybdenum•Cobalt•Copper•Chromium•Iron•Nickle

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

Huge reduction in Vit D & Iodine in last 40 years (source: www.vitamindwiki.com)

2X to 3X less Vitamin D 4X less IodineAir conditioning, sunscreen, multi-media Less Iodine in milk (no longer used

on cows)indoor jobs, less cholesterol, more obesity Less Iodine in bread (no longer

used in processing)live in cities - which have less UVB Increased use of Iodine blockers:

Fluoride Chlorine and Bromide (used in flour)

also perchlorate in some fertilizersincreased used of farmed fish (1/4 the Vit D) Less iodine in salt:

1) Use table salt much less 2)No Iodine in salt used in processed foods

3) half of iodized salt does not meet requirements

Swiss have increased iodine in ALL of their salt – from 3.75 mg/kg in 1975 to 20 mg/kg in 1998. Their intake > 2X US.

Magnesium mementos• One of the first minerals to disappear with:

– Processed food– Stress

• Decreased by EtOH, caffeine, sodas, meds

• Considered “anti-stress” mineral– Decreases cortisol (rel to sleep disruption)– Relaxes muscles, prevents cramps (sleep

disruption)– Decreases anxiety; improves sleep

Symptoms of Magnesium Deficiency

PSYCHIATRIC ISSUES:•Difficulty with memory and concentration•Depression, apathy•Emotional lability•Irritability, nervousness, anxiety•InsomniaAutismADHD

Migraine headaches PMS Dysmenorrhea Fibromyalgia Fatigue CONSTIPATION

Health Conditions Associated with Magnesium Deficiency

SELENIUM DEFICIENCY in FASEB:

• “Adaptive dysfunction of selenoproteins from the perspective of the ‘triage’

theory: why modest selenium deficiency may increase risk of diseases of aging.”

Foundation of American Societies for Experimental Biology

McCann, J, Ames BM. FASEB J. 2011 Jun;25(6):1793-814.

“the foot soldier”

LifePak Nano has 200% of RDA of selenium.

Se+

THYROID HORMONE

& 76% the RDA for iodine

“The concomitant evolution between plasma Se decrease over a 9-year period and cognitive decline suggested that optimal Se status is potentially important to maintain neuropsychological functions in aging people.”

“The concomitant evolution between plasma Se decrease over a 9-year period and cognitive decline suggested that optimal Se status is potentially important to maintain neuropsychological functions in aging people.”

Negative downstream effects from selenium deficiency:

“…cancer, heart disease, and immune dysfunction are prospectively associated with modest selenium deficiency…. suggesting that Se deficiency could be a CAUSATIVE factor”

McCann, J, Ames BM. FASEB J. 2011 Jun;25(6):1793-814.

Fast food (low Zn) is bad for you.

• Fast food = high energy density = low essential micronutrient density, ESPECIALLY ZINC

• Antioxidant processes are dependent on Zinc• Fast food = severe decrease in antioxidant

vitamins and zinc, correlating with inflammation in testicular tissue – with underdevelopment of testicular tissue and decreased testosterone levels

Special needs - Zinc

• Low Zinc- associated with low testosterone– Per USDA, 60% of US men between 20 – 49

years of age do not get enough.– N.B.: Do not supplement with > 50 mg daily (can

interfere with Cu+ metabolism)• 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

Louis B. Cady, MD – CEO & Founder – Cady Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute Wellness Institute Adjunct Asst. Prof of Psychiatry – Indiana University School of Medicine Department of

PsychiatryChild, Adolescent, Adult, Functional Neuropsychiatry –

Evansville, Indiana

Hormones, Cognitive Dysfunction & Depression in Older Adults

AMMG Fall Conference – Nov. 2, 2012 – General Session Curriculum 2:00 – 2:45 pm Las Vegas, NV - USA

T vs Cognitive Function

Rosario ER. Age-related testosterone depletion and the development of Alzhiemer disease. 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 with lowest 1/5 T = worse than men with highest 1/5 T

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

Muller M, et al. Neurology. 2005 Mar;64(5): 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

T vs. Heart Disease

• Men with CAD have significantly LOWER levels of androgens than normal controls.– English, KM et al. Men with coronary artery disease have lower

levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000 June; 21(11):890-4.

• “There is early evidence from non-randomized studies that physiological testosterone replacement is extremely safe and may reduce cardiovascular mortality.”– Hackett G. Testosterone and the heart. Int J Clin Pract. 2012

July;66(7):648-55.

Low T in aging male: The case of the Phrustrated Pharmacist (8/3/2014)

• 73 yo MWM retired (2009) R.Ph. “burned out.” Essentially sitting home depressed. Not going anywhere.

• Presenting Rx:– Fluoxetine – 40 mg – Seroquel 50 mg XR for sleep (??)– Hydralazine, amlodipine, Zocor, Meformin, ASA

• ROS: decrease in libido. Profound fatigue.

Mental Status Examination: • Depression:

– Sad/depressed/down in the dumps

– Lack of/loss of interest in things.

– Trouble concentrating

– Insomnia/trouble sleeping at times.

– Decreased energy

– Guilty/worthless – which is irrational – he has nothing to feel guilty about it. (6 total symptoms; 5 = required)

• Other sxs:– Weakness, hopeless, feeling life is not worth living, sleeping too

much, loss of libido, and full diagnostic criteria met for generalized anxiety disorder

Relevant markers• Thyroid functions

– TSH 0.43 {0.34 – 5.61}– Free T4 1.34 {0.587-1.64}– Free T3 2.8 {2.0 – 4.4}– Reverse T3 32.1 (H) {9.2 - 24.1}

• Sex hormone– LH 8.7 (H) {1.24 – 8.62}

– Total testosterone 199 (L) {348 – 1197}

– Free Testosterone 3.6 (L) {6.6 – 18.1}

– PSA 0.24 {0.0 – 4.0]– Estradiol 13.6 {7.6 – 42.6}

• Coenzyme Q10 0.75 {0.37-2.20}

• BPS 24,000 {>50,000}

Interventions – 8/14/2013

• Testosterone IM– 200 mg ASAP, then 100 mg every 4 days until

levels better.• DHEA – 25 mg timed release• Liothyronine, timed release• LifePak Nano (200% Selenium; 100% Zinc RDA)• (continued fluoxetine)

The Phrustrated Pharmacist: What happened?

• 11/26/2013 – (3 ½ months later)– Going to all grandchildren’s soccer games

– Out mowing his yard and mulching leaves

– Depressive symptoms ELIMINATED.

– Appetite has gone up; but clothes fitting better.

– Plenty of energy.

• 1/16/2014– “I’ve been doing good – I’m doing everything. I walk the dog

every day. I go to the soccer games.”

– Has gone to get OSA checked.

– Has lost so much weight (60 lbs) he’s using clothes pins on pajamas.

What happened to labs (1/6/2014)?

• Thyroid functions– TSH 0.47 {0.34 – 5.61}– Free T4 0.67 {0.587-1.64}– Free T3 3.8 {2.0 – 4.4}– Reverse T3 14.5 {9.2 - 24.1}

• Hormones (Rx of 80 mg T twice weekly)– Total testosterone 582 {348 – 1197}– Free Testosterone 12.0 {6.6 – 18.1}– DHEA-Sulfate 378 (“H”) {30.9 – 295.6”; OPTIMAL

RANGE – per Cenegenics is about 500

Biophotonic scans:

• 24,000 - 8/27/2013

• 40,000 - 9/27/2013• 43,000 - 11/26/2013 (this is without a

lot of LifePak Nano and none in the last two weeks. He is eating more fruits and vegetables.)

• 43,000- 1/16/2014 on one pack

Final follow-up of Frustrated Fpharmasist – 4/15/2014

• Animated and alert. • Got hired to tutor pharmacology at local

community college. • Playing in handbell choir again.

– “I’m not very good – they let me play the half notes and whole notes with the great big bells.”

• Quipped about a customer he recalled who came in ask (in past) and asked for “methyl-testosteroney.”

• On CPAP for six weeks. Doing well.

Teaching points• No change in antidepressants required to

ELIMINATE depression.• LifePak Nano used to support the structure &

function of the body.• Appropriate allopathic care given.• Predictable results occurred. • BUT WHAT ABOUT THE LAST 20 YEARS?• This way of thinking works in ALL specialties.

SHIFT: Vitamins

• They are essential nutrients (except Vit D)

• Deficiencies result in classic/obvious diseases:– Goiter, scurvy, osteoporosis, pernicious anemia,

impaired immune function, disorders of cell metabolism, some forms of cancer, premature aging, poor psychological health (including eating disorders)

• Shils et al. (2005). Modern Nutrition in Health and Disease. Lippincott Williams and Wilkins. ISBN 0-7817-4133-5.

• Irritability• Apathy• Personality changes• Depression • Memory loss• Dementia• Hallucinations• Violent behavior• Anxiety

Symptoms of B12 Deficiency

• Diminished sense of touch and pain

• Clumsiness• Weakness• Pernicious anemia• Chronic fatigue• Tremors• GI problems

Mental Physical

The Effects of high dose B vitamins on stress at work

• “Occupational stress is increasing in Western societies.”

• 3 month, double blind, placebo control, randomized study

• Measured: Personality, work demands, mood, anxiety, and strain

• After variances in personality and work demands were

controlled, the vitamin B complex treated group reported significantly lower personal strain and a reduction in confusion and depressed/dejected mood after 12 weeks.

Strough C et al. The effect of 90 day administration of a high dose vitamin B-coplex on work stress. Hum Psychopharmacol. 2011 Sept 8. doi 10.1002/hup.1229 (Swinburne University of Techbnology – Hawhorn, Victoria, Australia.)

“Homocysteine lowering by B-Vitamins slows the rate of accelerated brain atrophy in MCI”…

Smith AD, Smith SM, de Jager CA, Whitbread P, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012244

CONCLUSIONS: “The accelerated rate of brain atrophy in elderly with MCI can be slowed by treatment with homocysteine-lowering B-vitamins.”

OK. It slows shrinkage. But are they sharper? [deJager CA et al. Int J Geriatr Psychiatry. 2012 June;27(6):592-600]

“B-vitamins appear to slow cognitive and clinical decline in people with MCI.”

Oxidative stress in the body – where does it come from?

Generation of free radicals in electron transport chain

http://www.nature.com/nm/journal/v11/n6/fig_tab/nm0605-598_F1.htmlAging; mitochondrial DNA damage

What causes oxidative stress?

• Environmental Toxins– Heavy metals – Pesticides/herbicides– Preservatives– PCB’s, Dioxins, Phthalates

• Toxins produced in (or injected into) the body– Yeast and bacteria– Products of cellular metabolism– Dental amalgams/vaccines (Hb)

• Emotional Stress– Anxiety/Tension– Fear– Anger

What are some consequences of oxidative stress?

• Depressed immune system• Increased inflammation (&pain)• DNA damage• cancer• Behavioral deterioration• Impaired cognitive function• Decreased memory

15,318 US adults in 3rd National Health and Nutrition Examination Follow-up study. (Different lifestyles and health risk factors were accounted for in the study)

“serum alpha-carotene concentrations were inversely associated with risk of death from all causes, CVD, cancer, and all other causes[sic].”

• Study population:– N=1,389; age range {59-71 yoa}– 9 year study

• Relative risks:– all cause mortality at 2.94X in men in lowest

quintile (95% CI, P=0.03)– cancer 1.72X in men (95% CI, P=0.01

• “Total plasma carotenoids levels were independently associated with mortality risk in men.”

Epidemiology of Vascular Aging (EVA)

Vitamin/mineral supplementation & cancer, cardiovascular, and all-cause mortality (EPIC-Heidelberg) Li K, Kaaks R., et al. Eur J Nutri July 2011

• Purpose: evaluate vitamin/mineral supplementation with CA, CV dz, and mortality

• Methods:– 23,943 healthy participants, followed x 11 years– Baseline and “new-use” supplementation noted

• Results: 513 CA deaths, 264 CV deaths– “No MVI supplement had any significant effect”

– Baseline users of antioxidant supplements had significantly reduced risk of cancer [HR 0.52] and all cause mortality [0.58]

• “sick user” phenomenon discussed.

Lipid peroxidation, antioxidant status & survival in institutionalized elderly

• Plasma MDA predicted mortality independently of all other variables.

• B-carotene and alpha tocopherol were independently associated with survival. Huerta JM et al. Free Radical Research

2006, vol 40, no 6. pp 571-578.

Antioxidant assessment

Reference:www.cadywellness.com/cadywhitepaper2008.pdf

Reference:www.cadywellness.com/cadywhitepaper2008.pdf

Center for Biomedical Optics – Dixon Laser Institute, University of Utah

• Werner Gellermann, Ph.D. – Research Professor

• Colleague – Igor Ermakov, Ph.D., et al.

• Technologies – “Novel Raman Spectroscopy and Raman Imaging.”

• Funding:– National Institutes of Health– State of Utah– Spectrotek, LLC

“A method and apparatus are provided for the determination of levels of carotenoids and similar chemical compounds in biological tissue such

as living skin.”

(c) 2013 Louis B. Cady, M.D. - all rights reserved

Dissolved carotenoids in stratum corneum

27 days

Scientific Validation: Peer-reviewed by the medical & research communities

• Society of Investigative Dermatology, May 25, 2000.

– Non-Invasive Raman Spectroscopic Detection of Carotenoids in Human Skin.

• Arch Biochem Biophys. 2010 Dec 1;504(1):40-9. Epub 2010 Aug 1.

– Validation model for Raman based skin carotenoid detection

• J Eur Acad Dermatol Ven. 2011 Aug;25(8):945-9.

– Skin carotenoid levels in adult patients with psoriasis.

“RS accurately measures total carotenoids in human skin with less intra-individual variability than measurement of

serum carotenoids by HPLC analysis. RS technology is a valid and reliable noninvasive method to rapidly assess carotenoid nutritional status in humans.” (J Am. Coll Nutr 2009)

“RSS spectroscopy is a reliable method for non-invasive measurement of B-carotene levels in skin, and may be used as an important biomarker of antioxidant status in nutritional and health studies in humans.”

Ramirez-Velez, et al. Non-invasive assessment of β-carotene levels in the skin of Colombian adults. Endocrinol Nutr. 2012 April

• “The totality of the evidence supports the use of skin carotenoid status as an objective biomarker of fruits/vegetable intake…”

• “..skin carotenoids may effectively serve as an integrated biomarker of health…”

• “The totality of the evidence supports the use of skin carotenoid status as an objective biomarker of fruits/vegetable intake…”

• “..skin carotenoids may effectively serve as an integrated biomarker of health…”

• “Thus, this biomarker holds promise as both a health biomarker and an objective indicator of fruits & vegetables intake….”

• “Thus, this biomarker holds promise as both a health biomarker and an objective indicator of fruits & vegetables intake….”

BTW – what does that “SCS” actually mean in REAL LAB MEASUREMENTS?• Y = 12703 * X + 5891.7

– Where Y is the SCS, and X is the carotenoid concentration in MICROgrams/ml, viz:

• 25,000 = 12703X + 5891.7• 25,000 – 5891.7 = 12703 * X• 19,108.3 = 12703 * X• 19,108.3 /12703 = X• X = 1.50 MICROgrams /ml

• Rule of thumb: 1,000 on SCS = .06 ug carotenoid/ml blood serum

• (e.g., SCS of 71,000 = 4.26 ug carotenoid/ml)

Source: NuSkin/Pharmanex

vitaminsvitamins

mineralsminerals

Omega-3 Omega-3

fatty acidsfatty acids

Phytonutrients

Phytonutrients

Antioxidants

Antioxidants

(bone health)

(bone health)

LifePak Nano - % RDA in 2 packets• B12 - 1,000% (as 60 MICROgrams

cyanocobalamin)• B6 - 500%• Folic acid/folate - 150%

• Magnesium 76% (as 300 Mg amino acid chelate)

• Zinc 100% (15 mg as zinc chelate)

• Selenium 200% (L-selenomethionine & NaSeO3)

• Iodine 76%

• Chromium 166%

• Vitamin C 834%

• Vitamin A 300% (83% as Beta carotene and plant

extracts)

HOMOCYSTEINE lowering

Do YOU Need Fish Oil?

5X reduction

“You don’t need vitamins: (a) you can get’em in your food; (b)they just make expensive urine.”“I don’t believe in antioxidants.” – from an MD!!

The “FUD Factor”

“Fear, Uncertainty & Doubt” – a well-known term to Mac Fanboys

% of US Resident >/= 2 years of age who are deficient

• Vitamin A 34% deficient• Vitamin C 25% deficient• Vitamin D 70% deficient• Vitamin E 60% deficient• Calcium 38% deficient• Magnesium 45% deficient

“Without enrichment and/or fortification and supplementation, many Americans did not achieve the recommended [bare minimum] micronutrient intake levels…”

[Fulgoni, V, et al. J Nutr. 2011 Oct]

The GREAT news about a BAD study

Conclusions: “In older women, several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk; this association is strongest with supplemental iron.”

Not so fast!• 18 year duration; 38,000 “older” white

women in Iowa

• Supplements: MVI’s, A, D, E, Beta-carotene, B –vitamins, iron, calcium, copper, magnesium selenium, and zinc.

• The real results:– Early results showed women who used C, D,

E, and Calcium had significantly lower rates of death

– Iron supplementation was highly correlated to death rates (but these results were mixed in)

A real hatchet job on MVI’s• Study measured “who dies over 18 years?”

– Average age at start – 61 yoa– Average age at end of study 82 yoa– Average mortality for ALL women in 2003, during

the time of the study, was 80 years of age.

• Conclusion: Over 50% of the women in the Iowa study lived longer than the average life expectancy.

Mursu, Harnack et al – Dietary supplements and mortality rate in older women…. Arch Intern Med 2011 Oct 10;171(18):1625-33.

More hatcheting – poor controls• Hormones (Premarin/provera)

– 13.5% of supplement users– 7.2% of non-supplement users

• No explanation as to why so many women were taking iron.

• Excess levels of vitamin A in some MVI brands

• No evaluation of the quality or potency of the supplements

Mursu, Harnack et al – Dietary supplements and mortality rate in older women…. Arch Intern Med 2011 Oct 10;171(18):1625-33.

Nearly 2X as many!!

44 million inpatients, 460 sites, 2000-2010 = 20% of all US inpatient episodes (1.6% were on ONS during the inpatient episode.)

44 million inpatients, 460 sites, 2000-2010 = 20% of all US inpatient episodes (1.6% were on ONS during the inpatient episode.)

>/= 18 years. No terminal patients, tube feedings.>/= 18 years. No terminal patients, tube feedings.

RESULTS for “ONS”:•2.3 day shorter length of stay•Decreased cost of $4,734 / episode•2.3% reduced probability of early readmission.

RESULTS for “ONS”:•2.3 day shorter length of stay•Decreased cost of $4,734 / episode•2.3% reduced probability of early readmission.

CONCLUSIONS: “Use of ONS decreases length of stay, episode cost, and 30 day readmission risk in the inpatient population.”

CONCLUSIONS: “Use of ONS decreases length of stay, episode cost, and 30 day readmission risk in the inpatient population.”

Tomas J, et al. Am J Manag Care. 2013;19(2):121-128

http://cadywellness.com/do-vitamins-work-two-recent-studies-say-no-should-you-believe-them

Crash course on “how to lie on your studies”

• Bad control group– Example: recent “testosterone & mortality” study

• Misattribution of causality• Not reporting all of the data and discussing it in a

balanced fashion in your abstract– (most people just read the abstracts).

• Using inadequate doses of studied Rx• Using toxic or noxious doses of Rx• Use contaminated, impure test Rx• Confusing “sick user” phenomenon

A personal close

How do you want to age (practice medicine)?

TR 90 – a look back

October 28, 2013 January 28, 2014Jan 29, 2014

“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 remarkableability to achieve results.”

- William J Mayo, M.D., 1935