Vitamins-Minerals Supplements – WHAT DO YOU TAKE?

John Pan, MD

Should You Take?

NIH Consensus Conference No evidence of benefit Most panel members take supplements

What for

Causes of all disease/dysfunction Free radical Inflamation Antioxidant Anti-inflammatory

How do you choose Dosing BID Dissolution USP XXIV, gel-caps

Absorption Amino acid Chelation, Nano technology

Formulation Ingredient source – natural Vit-E – mixed Updated Vitamin, mineral, antioxidant, anti-inflammatory

WHAT

Vitamins Minerals Antioxidants Anti-inflammatory

Vitamins Essential nutrients scurvy-Vit-C; rickets-Vit-D; pellegra-Vit-B3

Normal metabolic function Krebs cycle: B1,2,3,5,6 & Biotin Homocysteine: B6,12 & Folic Acid

Water soluble/Fat soluble Vit-C & B vitamins - Vit-A, D, E & K

RDA/RDI – Recommended Daily Allowance/Reference Daily Intake

Disease prevention – community-gender/age based – healthy population

Biochemical individuality, genetic heritage, health

Vitamin E

Organic source Tocopherols Alpha, beta, gamma Tocotrienols Alpha, beta, gamma Mixed

Vitamin D

Vit-D3 (skin-UVB) – 25(OH)D (liver) – 1,25(OH)2D (kidney) Mechanism of Action VDR – Vit-D Receptor VDREs - Vit-D Response Elements – modulate

gene transcription Function Calcium balance – Cell differentiation – Immunity

– Insulin secretion – Blood pressure regulation

Vitamin D Risk factors Exclusively breast fed infants Dark skin Aging Sunscreen and skin covering clothing Fat malabsorption syndromes IBS Obesity

Measurement 25(OH)D: 20-25nmol/l – 50nmol/l – 80 nmol/l

Toxicity – 100,000 IU? Supplement

Minerals Essential for normal physiologic function Coenzymes, biochemical reactions, alter electrical

currents, open transport channels, muscle contractions, excretory, hormone & immune function

Major & Minor-Trace 5 gms total, daily requirement=100mg + : calcium,

phosphorus, magnesium, potassium, sodium, chloride

Absorption Amino acid chelate Calcium/magnesium : 2/1

Free Radical

Free radical is a cluster of atoms one of which contains an unpaired electron in its outermost shell of electrons Oxygen, nitrogen & sulfur Reactive Oxygen Species (ROS) Sources Ionizing radiation – Air pollutants – Tobacco

smoke – Alcohol - Fried foods - Stress

ROS - Formation

Interaction of ionizing radiation Natural bi-product of cellular respiration Electrons passing “down” the respiratory

chain leak away from the main path and directly reduce oxygen molecule to superoxide anion

Synthesized by enzymes in phagocytic cells – neutrophils & macrophages

ROS - Types

Hydrogen peroxide Hypochlorite ion Hydroxyl radical Most reactive Most damaging Superoxide anion or Singlet Oxygen

ROS - Damage

Cell Membrane Fatty acid side chain

Hydroxyl radical removes a hydrogen atom from one of the carbon atoms

A molecule of water, leaving an unpaired electron React with oxygen forming a singlet oxygen Begin chain reaction until two radical form a

covalent bond linking the two Deformed fatty acid chains – damage cell

membrane function Mitochondria – directly exposed during cellular

respiration

ROS - Damage

Mitochondrial mutation Hydroxyl radical Attacks all deoxyribose > breaks in DNA strand Deaminate nucleotide > Single nucleotide

plymorphisms SNPs Cumulative accelerated degradation of

mitochondrial fucntion Premature aging, cancer, neurodegenrative

diseases

ROS - Benefit

Hydrogen peroxide necessary in synthesis of thyroxine Macrophages & neutrophils Generate singlet oxygen that kills bacteria Neutrophils Generate hydrochlorite ions – antiseptic Chemotherapy & Radiation

Antioxidants - Endogenous Endogenous Super Oxide Desmutase – SOD

Converts 2 superoxide anion and 2 hydrogen molecules to 1 Oxygen and 1 hydrogen peroxide

Glutathione peroxidase Converts 2 GSH & 1 hydrogen peroxide to

1 GSSG & 2 water

Catalase Converts 2 hydrogen peroxides into 2

molecules of water and 1 oxygen

Antioxidants - Exogenous Vitamin-A – Retinol – 900mcg/700mcg Quench singlet oxygen Toxicity – Liver & Teratogenic Preformed (animal) & Carotenoids (veg)

Vitamin-C – Ascorbate Electron donor > ascorbyl radical Oral dose – plasma concentration – sigmoidal Saturated at 400mg/day – entire absorbed dose

excreted above 500mg/day Vitamin-E – Tocopherols & Tocotrienols Alpha, beta, gama & delta Peroxyl radical scavenger Lipid domain of the body – cell membrane - LDL

Antioxidants - Exogenous Zinc Protects membranes against oxidative damage Forms Cu/Zn-SOD

Copper Cu/Zn-SOD & ceruloplasmin

Manganese Scavenge hydroxyl and superoxide radicals MnSOD – principle mitochondrial oxidant defense

Selenium Glutathione peroxidase

Antioxidants - Exogenous

Flavonoids Proanthcyanidins Quercitin

Citrus bioflavenoids – Rutin Green tea polyphenols

EGCG

Antioxidants - Exogenous

Carotenoids Beta-carotene & alpha-carotene Lycopene

Zeaxathin Lutein

Antioxidant - Exogenous

Co Q-10 Protect against lipid peroxidation in cell

membrane Inhibits oxidation of LDL-cholesterol Alpha Lipoic Acid Scavenge all ROS

Biomarkers Antioxidant Nutrients

Carotenoids – Beta-carotene Dietary-reliablel – Plasma-HPLC - Tissues – Fat &

Skin Vitamin-E – alpha tocopherol Dietary-supplement – Plasma-HPLC – Tissue –

adipose Vitamin-C Dietary-multivariable – Plasma-HPLC

Selenium Dietary-soil dependent – Plasma-AAS – Toe nail

Biomarkers Oxidative Stress

Lipid Oxidation Thiobarbiturate acid-reactive substance

TBARS Breath hydrocarbons – Pentane & Ethane LDL resistance to oxidation DNA Oxidation 8-OHdG – HPLC & ELISA - Lymphocyte

Biomarker Oxidative Stress

Protein Oxidation Protein carbonyls – colorimetric & ELISA Neurodegenerative diseases Overall capacity Oxygen radical absorbance capacity

ORAC Total peroxyl radical-trapping antioxidant

potential TRAP

Other Complexities

Interactions Vit-E protects Vit-A, increasing storage Vit-C regenerates the tocopheroxyl radical

and restores Vit-E’s antioxidative functions Antioxidant to Pro-oxidant Beta-carotene in absence of Vit-C & E Vit-C in presence of iron Hydrogen peroxide with ferrous iron

Essential Fatty Acids

Balancing Omega-3 & Omega-6 Omega-3 Fatty Acids Fish oil Flax seed oil Omega-6 Fatty Acids Animal fats Plant: borage, sunflower, safflower

Omega-3

EPA & DHA Dose – 600 mg Fish oil Krill oil ALA Flax seed oil

Botanicals Boswellia serrata Boswellic acid 1,200 mg, bid-tid – blocks

lipoxygenase

Tumeric-Curcumin Ginger – 500-1,000 mg/day/powder, 5g fresh

Ashwaganda Capsaicin cream – 0.25%-0.75%

How do you choose Dosing BID Dissolution USP XXIV, gel-caps

Absorption Amino acid Chelation, Nano technology

Formulation Ingredient source – natural Vit-E – mixed Updated Vitamin, mineral, antioxidant, anti-inflammatory