The Secrets of High-Dose Polyphenols · 2018. 8. 13. · The Secrets of High-Dose Polyphenols....
Transcript of The Secrets of High-Dose Polyphenols · 2018. 8. 13. · The Secrets of High-Dose Polyphenols....
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The Secrets of High-Dose Polyphenols
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Polyphenols
• Provide plants with color
• Little known before 1995
• 8,000 known polyphenols
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Classes of Polyphenols
• Flavanoids (green tea)
• Isoflavones (genistein)
• Phenolic acids (curcumin)
• Stilbenoids (resveratrol)
• Tryosol esters (olive oil)
• Proanthocyanins (chocolate)
• Anthocyanins (blueberries)
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Maqui
(Aristotelia chilensis)
Delphinidin
Low bioavailability
Good bioavailability
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Polyphenols
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Gut Health
• Microbial “gardeners”
– How plants fight off microbial invaders
• Prebiotics
– Stimulate friendly bacterial growth
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Other Mechanisms of Action
• Anti-oxidants
– Activation of Nrf2
• Anti-inflammatory
– Inhibition of NF-κB
• Aging-aging
– Activation of AMP kinase
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Major Pathways Activated By Polyphenols
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Polyphenols Are Super-Antioxidants
• Gene transcription factor for expression of SOD and GPX
• Activation by polyphenols
Scapagnini et al Mol Neurobiol 44:192 (2011)
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heme oxygenase 1
ferritin
thioredoxin
GSH transferases
UDP-glucoronosyltransferases
NAD(P)H:quinone oxidoreductase 1
-glutamylcysteine synthetase
GSH-reductase
catalase
biliverdin/bilirubin
CO
Fe
GSH synthesis
regeneration of ubiquinol and tocopherol
regeneration of GSH and dehydroascorbate
multifunctional roles
regeneration of oxidized thioredoxinand dehydroascorbate
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Phase 2 Response Phase 2 ResponseNrf2/keap1/ARE CytoprotectionPhase 2 Response
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OR2
HO
OH
OH
R1
HO
Keap1
Nrf2
antioxidant
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Anti-inflammatory Actions
• Activation of PPAR-γ
• PPAR-γ inhibits NF-κB
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Anti-Aging Actions
• Activation of AMP-kinase
www.zonediet.com
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AMP Kinase: The Enzyme of Life
AMP Kinase
Calorie RestrictionPolyphenols
SIRT1
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Actions of AMP kinase
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How Many Polyphenols Do You Need?
Reduce oxidation 0.5 g/day
Reduce cellular inflammation 1 g/day
Reduce the rate of aging 1.5 g/day
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Potential Sources of Polyphenols
• Vegetables: 0.1% of weight
• Fruits: 0.2% of weight
• Spices : 1% of weight
• Cocoa: 3% of weight
• Refined polyphenol extracts: Up to 40% of weight
www.zonediet.com
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Typical Sources Providing 1 gram of Polyphenols
• 1 kg of vegetables
• 500 g of berries
• 500 ml of extra virgin olive oil
• 12 glasses of red wine or 120 glasses of white wine or 1200 glasses of vodka
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Is There A “Best of the Best” Among Polyphenols?
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Polyphenol Purification
• Whole plant
• Juice
• Powder
• Alcoholic extract
• Chromatographic extract
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Maqui Extracty Toxicity Studies
• Acute (rats and rabbits)
– 84 mg/kg I.P for 10 days
– 1g/kg oral for 7 days
• No toxicity
• Sub-chronic (Pigs)
– 1.4 g/kg per day for 42 days
• No histology changes
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Domestication Of Wild Maqui Berries is a Dirty
Business
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Indiana Jones Without His Bullwhip in Patagonia
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Polyphenols Have To Be Absorbed To Increase Longevity
Zamora-Ros et al J Nutr 143: 1445 (2013)
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Absorption Depends on Water Solubility
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Maq 25 µM
Activation of Nrf2
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IL-6
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IL-1β
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LPS
LPS + Res
LPS + Maq
LPS + Rev
Control
Effects On Cytokines.
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Polyphenol Pharmacokinetics
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Thinking Faster with Purified Cocoa Polyphenol Extracts
• 25% increase in cognitive speed in 3 months
– Mastroiacovo D et al. AJCN 101: 538 (2015)
• Increased activity in hippocampus and improved cognitiion in 3 months
– Brickman et al. Nature Neurosci 17: 1798 (2014)
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Refined Is Sometimes Better Than Natural With Cocoa
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Cadmium Contamination
• Single serving violates CA Prop 65 for cadmium intake per day
• New EFSA standards for cocoa and chocolate products in 2019
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CocoaRx: Coming Soon
• 50 times lower cadmium levels than natural cocoa powder
• 4 times higher polyphenol levels than natural cocoa powder
• Bars, shakes, and desserts as ideal delivery systems for cocoa polyphenol extracts