Clinical Use of Supplements inAge Management Medicine

Rebecca R Murray APRN, MS, FNP, CDE

Endocrine Nurse PractitionerInstitute for Hormonal Balance

Orlando, FL

Medical DirectorWard-Murray Healthcare and Consulting LLC

Orlando, FL

“Quality of Life”...What we ALL DESIRE!

• What contributes to “Decreased Quality of Life”-Cardiovascular Disease or Events→ “Cardiac Cripple”-Stroke→ hemiplegia/paralysis-Fractured hip (#1 reason for loss of independence in women)-Cognitive Impairment

• What contributes to “Healthy Aging”- Healthy “vascular endothelium”- Preventing “embolic events”- Strong bones- Maintaining optimal brain health

What prevents us from experiencing optimal

“Quality of Life”?

Myocardial Infarction (Heart Attack)

Cerebral Vascular Accident (Stroke)

Mastectomy Scar: Breast Cancer

Osteoporosis and Bone Fractures

Cognitive Impairment/Alzheimer’s Disease

What is a “Common Denominator”?

Acute verses Chronic Inflammation

Long Term Effects of Chronic Inflammation

Insulin Resistance Syndrome

The most common problem you see in practice!

Ideal: Getting all our nutrients from food

Scientific American Journal

Use of Supplements by age group in 2018

Not all supplements are “created equal”

Factors Affecting Nutrient Optimization

• Ability to absorb and/or utilize nutrients

• Drug-Nutrient Interaction leading to depletion of nutrient

• Greater need for the nutrient

Ability to absorb and/or utilize nutrients• Hydrochloric acid in stomach necessary to absorb Vitamin B12

-Pernicious Anemia-Achlorhydria-Use of Proton Pump Inhibitors

• Gastric Bypass Surgery

• Inflammation/destruction of intestinal villi

• Lack of enzymes→ lack of absorption of fat soluble vitamins

• Genetic mutations→ decreased absorption or receptor defects

• Enzymatic defects in converting vitamins to “usable form”-MTHFR 677 and 1298 genetic mutations

Evidence of Drug-Nutrient Interactions

• The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years

• Unfortunately, nutrient deficiencies seldom present as classically described and, with the exception of the most common micronutrient issues, many health care providers are not knowledgeable about micronutrient deficiency or excess

• This may lead to erroneous attribution of deficiency states to a disease state or the aging process itself and may delay diagnosis

• Drug-induced micronutrient depletion may be the origin of otherwise unexplained symptoms, some of which might influence medication compliancePharmaceutics. 2018 Mar; 10(1): 36

Evidence of Drug-Nutrient Interactions: PPI’s Acid-Suppressing Drugs

Pharmaceutics. 2018 Mar; 10(1): 36

Vitamin B12Vitamin CIronCalciumMagnesiumZincB-Carotene

Medications that decrease CoQ10 levels

In addition to aging and the natural decline in the production of CoQ10:

• Statins

• Beta Blockers

• Central Acting Antihypertensives

• Thiazide Diuretics

Dietary Supplements & CVD: Abstract

-The market of nutritional supplements is expected to expand over 6%/year through 2018 due to growing interest in personal health, aging population, and promising personalized care products.

-The most used dietary supplements are fish oil, multivitamins, Vitamin D, and coenzyme Q10 (CoQ10) in this order, while probioticsis the fastest growing supplement. In the U.S., over 68% of the population use dietary supplements regularly

Dietary Supplements & CVD: Abstract (cont’)

-Vitamin D levels have been associated with the occurrence of coronary artery disease, heart failure, and atrial fibrillation;

- CoQ10 deficiency has been associated with myocardial dysfunction and with statin myopathy;

- Probiotics has been suggested to lower both blood pressure and circulating lipids

1990 Article on Lovastatin and Coenzyme Q10

1990 Article on Lovastatin and Coenzyme Q10• The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-

methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA.

• Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol

• The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy

• Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function.

Statin: Mechanism of Actions

Title: Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

• Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production

• Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment

• After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. Vitamin E group showed no difference.

Caso G, et al. Am J Cardiol. 2007 May 15;99(10):1409-12. Epub 2007 Apr 3

Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.

• Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo

• The intensity of muscle pain was measured as the Pain Severity Score (PSS) and the Pain Interference Score (PIS)

• In the placebo group, PSS and PIS did not change

• Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients

• No differences in liver and muscle enzymes or cholesterol values were found.

Med Sci Monit. 2014 Nov 6;20:2183-8. doi: 10.12659/MSM.890777

“Metabolic Cardiology”

• Research by cardiologist Dr Stephen Sinatra

• “Magnificent Four” for treatment of Congestive Heart Failure (CHF)-Coenzyme Q 10-Magnesium (natural vasodilator depleted by diuretics)-L-Carnitine (amino acid substrate for mitochondrial energy production)-D-Ribose (amino acid substrate for mitochondrial energy production)

• Studies showed improvement in cardiac output

Case Studies

• Two men (ages 62 and 74)

• Both had Dyspnea On Exertion resulting in Shortness of Breath

• Both ended up in ER with Cardiac Catheterization→ EF of 25-30%

• Both were told they needed implantable defibrillator and pacemaker due to high risk of hypoxia to the heart due to low cardiac output (EF)

• Both wanted a second option for a “functional medicine approach”

Case Studies: Treatment Plan

• Coenzyme Q10 100 mg BID: (used ubiquinol form which is the reduced, antioxidant form of coenzyme Q10 as compared to ubiquinone)

• D-Ribose 2,000 mg and L-Carnitine 2,000 mg 5 ml BID(as a “super-saturated” in a solution in 5 ml)

• Magnesium (in an absorbable chelated form) 400 mg BID: (used Malate form but if caused GI urgency, switched to a buffered bisglycinate form)

• Omega-3 fish oils (for anti-inflammatory effect) 2 grams BID

• Multivitamin

• Dietary changes: Avoiding inflammatory fats (fried foods) and foods that cause ROS and AGE’s such as charred meats

Case Studies: Results

• Over 6 months, both gradually increased activity levels without DOE

• Repeat testing showed increase in Cardiac Output to 55-60%

• Both went back to work full-time and enjoy “improved QOL”!!!!

• In the man on Medicare, statement: “Now I can’t get Medicare to approve and pay for an implantable defibrillator and pacemaker”

Inflammation: Basis for many disease processes

• ROS: Reactive Oxygen Species→Oxidative Damage (8 OHdG levels)

• AGEs: Advanced Glycation End-products

• Vascular/Endothelial Dysfunction

• Inflammatory Cytokines and Interleukins

• Atherosclerotic plaques

• Neurodegeneration

How to Reduce Inflammation in the Body

• Identify and eliminate dietary factors-AutoImmune Paleo (AIP) plan eliminates gluten and dairy, etc-Inflammatory Fats-Advanced Glycation End-products (AGE’s contribute to aging)-Food sensitivities-Heavy metals (i.e. Mercury in fish)

• Nutrient supplementation-Antioxidents-Omega 3 oils-Tocotrienols (Vit E fraction from Annatto)

Vitamin E Family

Composition of Vitamin E from plants

Vitamin E: Tocopherols and Tocotrienols

“The recent literature underlines that, given the detrimental effect of low intake and serum levels of tocopherols and tocotrienols on bone, muscle mass, and cognitive function, a change in the lifestyle must be the cornerstone in the prevention of these specific age-related pathologies related to vitamin E-deficient status. The optimum diet therapy in the elderly for avoiding vitamin E deficiency and its negative correlates, such as high inflammation and oxidation, must aim at achieving specific nutritional goals.”

Vitamin research over past 30 years

Bone Loss: Inflammation & Oxidative Stress

Non-Alcoholic Fatty Liver Disease (NAFLD)

• Commonly associated with obesity and Metabolic Synrome

• 21st century epidemic in liver disease

• Affects upward of 30-40% of adults in the US

• 20% transition Non-Alcoholic SteatoHepatitis (NASH)

• Complications: Liver fibrosis, cirrhosis, and liver cancer

Vitamin E: Tocopherols and Tocotrienols

BACKGROUND: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but α-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's diseaseRESULTS: Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of γ-tocopherol, β-tocotrienol, and total tocotrienolsCONCLUSIONS: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults

Vitamin E: Tocopherols and Tocotrienols

Case Studies

Case Study: Nancy• Chinese female referred for ↑ ↑ LFT’s

• Dx with NASH by liver biopsy

• No treatment→monitor→organ donation list

• Present History: normal BS, elevated trigs,low HDL, under Tx for HTN, overweight

• Family Hx: Mom severe T2DM on dialysis

• New labs: 2 hr IGTT showed: nl BS, ↑↑ insulin

• Developed a “Nutritional Plan”

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Case Study: Nancy (con’t)

• Low Glycemic Diet

• Multivitamin

• Omega-3 Fish Oils 2 grams a day

• Milk Thistle (standardized 80% silymarin) 400-600 mg daily

• N-acetylcysteine 1,800 mg BID

• Alpha Lipoic Acid 300 mg BID

• Results:

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• 62 newly retired female (Fam Hx of CA)

• 20 year history of Type 2 Diabetes

• Increasing insulin → increased weight gain

• HTN (3 antihypertensive meds)

• Elevated Trigs and Low HDL (statin for hyperlipidemia)

• Elevated liver function tests (NASH)

• Diabetic Peripheral Neuropathy (pain meds NSAIDs, opiates)

• Stage 3 Renal Failure

• Extreme fatigue

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Case Study: Pat

Case Study: Pat (con’t)• Low Glycemic Diet • Detox Program • Omega 3 Fish Oils 2 grams a day

• Co-enzyme Q 10 100 mg BID

• Alpha Lipoic Acid 300 mg BID

• Milk thistle 300 mg BID

• N-Acetylcysteine 1,800 mg BID• Methylation support (L-5-MTHF 5 mg, B-Complex)

• Magnesium Bisglycinate chelate 400 mg BID

• Vitamin D 10,000 iu QD (to start, follow levels)

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• Lost 30 pounds

• Insulin requirements 300 units→ 25 units

• No further hypoglycemic episodes

• Hgb A1c 10.8 → 6.8

• Kidney functions tests normalized

• Liver function tests normalized

• No further peripheral neuropathic pain

• B/P 120/78 with only ACE inhibitor

• More energy to play with grandchildren

Case Study: Pat 1 Year Follow-up

Case Study: Alice

• 54 year old female self-referred to my office’s

• 55 year old sister diagnosed with breast cancer

• She had gone to her PCP and asked “How can I prevent breast cancer?”

• Answer: “Have a yearly mammogram.”

• Her answer: “That’s what my sister did.”

• Both sisters agreed to genetic testing for Single Nucleotide Polymorphisms (SNPs)

• Both had the same genetic risks

Enzymes and Estrogen Metabolism

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Case Study: Alice• To increase her estrogen metabolites in favor of the “protective 2OH E1”

-Diindolylmethane 100 mg BID

• To provide increased “methyl donors” for the COMT enzyme:-L-5-MTHF (L-5-MethylTetraHydroFolate) activated folate(bypassing her genetic mutation MTHFR 677 and 1298)

• For glutathione support due to genetic mutation in herGlutathione S Transferase which helps to neutralize the toxic Quinoneswhich causes DNA damage (inflammation level measured by 8OHdG)-N-acetyl cysteine 1,800 mg BID-Glutathione (best Liposomal form for enhanced absorption)

• Results: