Advanced Nutritional Strategies for Optimal Health and Performance ...

Advanced Nutritional Strategies forOptimal Health and Performance inWarfighters

Primary Funding• Department of Defense - Combat FeedingProgram, Natick, MA• DARPA (Defense Advanced Research ProjectAgency)• Quercegen Pharma• Gatorade Sports Science Institute• National Institute of Health (NIH)• National Cancer Institute (NCI)• American College of Sports Medicine Foundation

Optimal Health & PerformanceMINDNUTRITIONPHYSICALACTIVITYBODY

Brain/Muscle Food - Best Bets• Carbohydrates – Good bet to delay mental andphysical fatigue• Caffeine – Good bet to delay mental and physicalfatigue• Optimal doses vary widely and side effects can beserious in high doses, especially if combined withother stimulants• Quercetin – Good evidence of a benefiton mental and physical fatigue• Curcumin – Some evidence of faster performancerecovery following muscle damage• Muscadine Extract – Rising fast

Brain/Muscle Food - Long Shots• Tyrosine – Reasonable evidence of benefitson mental function, but not in athletes• Ginseng – limited evidence of a benefit oncognitive function, but not physicalperformance• Ginkgo Biloba – limited evidence on cognitivefunction but not physical performance• Tea Catechins – good indirect evidence of apossible performance benefit, but no data ofa specific benefit on mental or physicalperformance

Brain/Muscle Food - Losers• Amino Acids – mixed evidence, butpreponderance of evidence does not supportbenefit• Choline/DMAE – no good evidence of abenefit• Ephedrine/amphetamine – evidence supportsa performance benefit, but side effects aretoo great.• Omega-3 fatty acids – good evidence for arole in brain development and cognition, butno evidence for improved mental/physicalperformance in adult exercisers.

Quercetin• Flavonol consumption by U.S. adultsis approximately 20-50 mg/day(quercetin 3/4s this amount)• Apples, onions, berries, red grapes,black tea, and other fruits andvegetables are sources of quercetin.One large red apple has ~10 mgquercetin.• Quercetin is readily absorbed withplasma half-lives of 6 to 12 hours.

QuercetinH OOO HO HWorldwide inexpensiveGMP supply is in place.O HOO HFood Additive in Japan;Supplement in US;GRAS in US;FDA-notified GRASin process

Hypothesized Mechanisms of Performance• Central Nervous System• Caffeine-like CNS stimulation• Increase in oxidativemetabolism via increasedmitochondria• Reduced oxidative stress &inflammation• Musclebenefits of Quercetin• Increased oxidativemetabolism via increasedmitochondria• Reduced oxidative stress &inflammation

Quercetin Can Increase MitochondrialNumber and Function in Muscle and Brainin rodents• Ingestion of as little as 12.5 mg/kg in mice and rats(~875mg in humans) of quercetin for 7 daysincreased mitochondrial mass/capacity by 25 - 100%in skeletal MUSCLE, Liver, and BRAIN.• Studies are ongoing in humans in my lab.• Effects are lost after 7 days without Q.

3.53.02.5Fig. 2A. mtDNA Muscle (Top) & Brain*160140120Fig. 2B. Cyt.C Muscle (Top) & Brain**Fold Increase2.01.5% Increase10080601.0400.5200.0 2.52.0*140120**100Fold Increase1.51.0% Increase8060400.5200.0Placebo 12.5mg/kg/Q 25mg/kg/Q0Placebo 12.5mg/kg/Q 25mg/kg/Q

Importance of Mitochondria• Powerhouse of the cell– Oxygen consumption and ATP production– Regulates substrate utilization (fat vscarbohydrate)– Important regulator of cell death(apoptosis) and aging• Most important limiting factor to enduranceexercise performance– Increases VO2max, utilization of fatrelative to carbohydrate, spares muscleand liver glycogen and increases lactatethreshold

Health Effects of MitochondriaLoss/Dysfunction• Exercise intolerance• Metabolic diseases– Obesity– Cardiovascular disease– Diabetes• Neurodegenerative Diseases– Age-related Dementia– Alzheimer’s Disease– Frailty Syndrome– Sarcopenia (Cachexia/Wasting Syndrome)

Quercetin Can Increase VO 2 max andEndurance Exercise Performance inrodents and humans• 7d of Quercetin feeding was associated with– Increased endurance performance during forcetreadmill running and voluntary wheel running insedentary mice– Increased VO2max and endurance cycling in fit,but not highly trained, humans.• Benefits are lost after 7 days without Q.

Maximal Exercise Capacity

Voluntary Wheel Running

Voluntary Wheel Running Apparatus – Testof 24 hr Physical Activity Patterns

Treadmill run timeto fatigueVoluntary Wheelrunning160140160* * ** ** * *150**% Increase1201008060% Increase140130120110**40100200Placebo 12.5mg/kg/Q 25mg/kg/Q90Baseline1 2 3 4 5 6 7 8 9 10 11 12 13 14Treat Admin.PlaceboQuercetin (QU995)Day

Health Sciences Research Center

Health Sciences Research Center

7-day Quercetin (1000mg/d) IncreasedMaximal Aerobic Power (~3.9% in Humans)545250* #* p

7-day Quercetin (1000mg/d) Increased EnduranceCycling Capacity (~13% in Humans)Time to Fatigue (min)14012010080604020* #Baseline Quercetin Placebo* p

Summary of Performance Studies• Quercetin feedings of as little as 12.5mg/kg/d for 7 daysis associated with– ~30% - 100% increases in mitochondrialdensity/capacity in skeletal muscle, brain, and liver ofmice and rats– Increased VO 2 max and endurance capacity (bothrodents and humans)– Faster recovery of performance following exerciseinducedmuscle-damage– Exercise training and Quercetin have synergisticbenefits• Biological mechanisms include pathways in both muscleand brain

Optimal Health & PerformanceMINDNUTRITIONPHYSICALACTIVITYBODY