Emerging Science on Novel Mind-Body Nutrition for Health and Performance

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Emerging Science on Novel Mind-Body Nutrition for
Health and Performance
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NCAA National Championship, 2010 USC vs UCLA
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University of South Carolina National
Champions, 2010
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Outline

• Background
• Concept of mind-body nutrition
• Theoretical model/focus for this
• presentation
• Emerging Science Benefits and
• potential biological mechanisms
• Quercetin
• Exercise Performance
• Infection
• Cancer
• Curcumin
• Exercise Performance
• Cancer

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Optimal Health and Performance
MIND
PHYSICAL ACTIVITY
NUTRITION
BODY
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Research Team

• Psychoneuroimmunology Lab
• J. Mark Davis, Ph.D., Director
• Angela Murphy, Ph.D.
• Martin Carmichael, Ph.D.
• Ph.D. Students
• Stephen Chen, M.S.
• Ben Gordon
• David Jung, M.S.
• Sara Omanson
• Jennifer Steiner, M.S.
• Reilly Enos, M.S.
• Sharvari Waghmare
• Ciana Barker
• Research Technicians
• Kei Lam
• Jamie McClellan, M.S.
• MS Students
• Joe Alemany

• Faculty Collaborators
• USC - Exercise Science
• James Carson, Ph.D
• John Baynes, Ph.D.
• Steven Blair, Ph.D.
• Raja Fayad, Ph.D.
• USC Epi/Biostat, CPCP
• James Hebert, Ph.D.
• USC Biology, NCI COBRE, CCCR
• Frank Berger, Ph.D.
• Marj Pena, Ph.D.
• Patricia Wood, M.D.
• Tia Davis
• USC Medicine, NCAM Center
• Prakash Nagarkatti, Ph.D Team
• Clemson
• David Gangemi, Ph.D
• NCI

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Primary Research Support

• NIH/NCI
• R21 CA135377-09-2-0117
• 1R24MD002769-01
• 1RO1 CA121249-01
• Defense Advanced Research Projects Agency (DARPA)
• W911NF-07-1-0140
• Department of Defense , Combat Feeding Program
• W911QY-07-0033
• Department of the Army (USAMRAA)
• W817XWH-09-2-0117
• ACSM Foundation (ACSM)

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Conditions Where BRAIN Fatigue is Primary

• Infection
• Cancer
• Chronic Fatigue Syndrome
• Post-Surgery
• Jet Lag
• Prolonged Mental Concentration
• Frailty Syndrome in the Elderly (??)

Mechanisms are largely unknown, but theoretically
could be improved via nutraceuticals with CNS
stimulatory and anti-inflammatory activity
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Optimal Health and Performance
BRAIN
Quercetin Resveratrol Curcumin Tea
catechins/EGCG Beta-glucan Muscadine extract
Quercetin Curcumin
Energy Immune function Inflammation
BODY
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Hypothesized Mechanisms of Quercetin and Curcumin
Benefits on Health and Performance
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Outline

• Background
• Concept of mind-body nutrition
• Functional foods/nutraceuticals
• Theoretical model/focus for this
• presentation
• Emerging Science Benefits and
• potential biological mechanisms
• Quercetin
• Exercise Performance
• Infection
• Cancer
• Curcumin
• Exercise Performance
• Cancer
• Unresolved Issues/Future Directions

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Quercetin

• Apples, onions, berries, red grapes, black tea,
  and other fruits and vegetables are sources of
  quercetin. One large red apple has 10 mg
  quercetin.
• Quercetin is readily absorbed with reported
  plasma half-lives of 6 to 12 hours.
• Food Additive in Japan, Supplement in US (GRAS)
  FDA-notified GRAS in process

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Quercetin Can Increase Mitochondria in Muscle and
Brain in rodents

• Ingestion of as little as 12.5 mg/kg in mice and
  rats (875mg in humans) of quercetin for 7 days
  can increase mitochondrial biogenesis by in
  skeletal MUSCLE, LIVER, and BRAIN.
• Effects are lost after 7 days without Q.

Davis, Am J Physiol. 2008
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Citrate Synthase mRNA soleus
Cytochrome C mRNA Soleus
Citrate Synthase mRNA Soleus




Citrate Synthase mRNA Brain
Cytochrome C mRNA Brain



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mtDNA Muscle (Top) Brain
Cyt C Conc. Muscle (Top) Brain






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Importance of Mitochondria

• Powerhouse of the cell
• Oxygen consumption and ATP production
• Regulates substrate utilization (fat vs
  carbohydrate)
• Most important limiting factor to endurance
  exercise performance
• Increases VO2max, utilization of fat relative to
  carbohydrate, spares muscle and liver glycogen
  and increases lactate threshold

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Health Performance Effects of Mitochondria
Loss/Dysfunction

• Exercise intolerance
• Metabolic diseases
• Obesity
• Cardiovascular disease
• Diabetes
• Neurodegenerative Diseases
• Age-related Dementia
• Alzheimers Disease
• Frailty Syndrome

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Quercetin Can Increase VO2max and Endurance
Performance in Mice and humans

• 7d of Quercetin feeding was associated with
• Increased endurance performance during force
  treadmill running and voluntary wheel running in
  sedentary mice
• Increased VO2max and endurance cycling capacity
  in young healthy, but untrained, humans.

Davis, Am J Physiol. 2008
Davis, Int J Sports Med Exerc Metab. 2010.
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Maximal Endurance Capacity
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Voluntary Wheel Running
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Voluntary Wheel Running Apparatus Test of 24 hr
Physical Activity Patterns
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Treadmill run time to fatigue
Voluntary Wheel running












Treat Admin.
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Human Performance Studies
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7-day Quercetin (1000mg/d) Increased Maximal
Aerobic Power (3.9 in Humans)
plt0.05 vs. Baseline plt0.05 vs. Placebo

n 12 men women
Placebo
Quercetin
Baseline
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7-day Quercetin (1000mg/d) Increased Endurance
Cycling Capacity (13 in Humans)
plt0.05 vs. Baseline
plt0.05 vs. Baseline plt0.05 vs. Placebo

n 12 men womens
Placebo
Baseline
Quercetin
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fMRI study of the effects of quercetin and
caffeine on brain activation during exercise in a
fatigued state
Quercetin
Caffeine
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EXPERIMENTAL SESSIONS
Placebo Session
Caffeine Quercetin Session
Quercetin Session
Caffeine Session
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Global Effects of Quercetin and Caffeine
Caffeine gt Placebo Quercetin gt Placebo
Caffeine Red Quercetin Green Overlap
Yellow
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Region of Interest Results Primary Motor Cortex
p0.0033
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Region of Interest Results Anterior Ventral
Premotor Cortex
p0.0045
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Our Previous fMRI Research identified the aPMv as
a primary site of fatigue during exercise

• Ipsilateral Anterior Ventral Premotor Cortex
  (aPMv)
• exercise-induced supraspinal fatigue
• (Davis et al. revision under review, Am J
  Physiol.)

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Conclusion

• Both Q and C increased widespread cortical
  activity during a simple motor task in a fatigued
  state
• While there was some overlap, differences were
  found between for Quercetin and Caffeine
• Quercetin - greater activation in aPMv and
  primary motor cortex
• Caffeine decreased activation in ventral
  striatum
• First fMRI evidence of an acute effect of
  quercetin on the brain as compared with caffeine
  during exercise a fatigued state

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Effects of quercetin on respiratory influenza
(H1N1) infection in mice at rest and following
periods of stressful exercise
Good in vitro evidence to support a role of
quercetin on immune function and resistance to
Infection. However, there is no data on Influenza
infection, which is the most serious of common
respiratory infections in humans
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Quercetin-Immune Effects

• Quercetin possesses antioxidant, free radical
  scavenging, and anti-inflammatory properties that
  may influence immune system competence and
  resistance to microbes, although most data come
  from in vitro and animal experiments.
• Such experiments suggest that quercetin increases
  neutrophil chemotaxis and respiratory burst
  activity, macrophage phagocytosis, NK cell lytic
  activity, and mitogen-induced lymphocyte
  proliferation, and macrophage anti-viral function
  (Alvarez et al., 2006 Exon et al., 1998).

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Quercetin Reduces Susceptibility to Influenza
Infection at Rest and Following Exercise Stress
(n15-20/group)
Davis, et al. Am J Physiol. 2008





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Effect of Quercetin on Susceptibility to
Infection (Mortality) Following Exercise Stress
(n15-20/group)
Davis, et al. Am J Physiol. 2008





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Summary of Infection Studies in Humans

• Nieman et al. Med Sci Sports Exerc. 2007 (
  URTI)
• Davis, et al., Am J Physiol. 2008 (
  influenza)
• Henson et al. Int J Sports Med, 2008 (
  URTI)
• Heinz et al. Pharmacol Res. 2010 ( all
  subjects , middle age to older fit adults in
  UTRI)

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Quercetins effects on intestinal polyp
multiplicity and inflammatory macrophage number
in the ApcMin/ mouse
Quercetin and Colon Cancer
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Cancer (ApcMin/ mouse model of colorectal
cancer)
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Polyps
Colon Polyp
Polyp
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Polyp Number and Size
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Outline

• Background
• Concept of mind-body nutrition
• Functional foods/nutraceuticals
• Theoretical model/focus for this
• presentation
• Emerging Science Benefits and
• potential biological mechanisms
• Quercetin
• Exercise Performance
• Infection
• Cancer
• Curcumin
• Exercise Performance
• Cancer
• Unresolved Issues/Future Directions

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Curcumin Effects on Performance Recovery After
Exercise-induced Muscle Damage
Curcumin is the most bioactive (anti-inflammatory)
component is Turmeric (in the Indian spice,
currie)
Davis, et al., Am J Physiol. 2006
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Inflammatory Challenge Exercise-induced Muscle
Damage Model in Mice

• Male CD-1 mice ran uphill or downhill at 22m/min
  at a grade of 14 or -14 for a total of 150
  min.
• Downhill (eccentrically-biased) running results
  in microscopic damage in muscle, inflammation,
  delayed muscle soreness, and functional deficits
• Uphill (concentrically-biased) running requires
  more energy and fatigue occurs earlier, but
  produces little or no muscle damage. Control
  treatment for downhill running.

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Delayed Recovery of Treadmill Running Performance
Following Downhill Running
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Delayed Recovery of Voluntary Wheel Running
Performance Following Downhill Running

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Curcumin Reduces Inflammation following Muscle
Injury

• While inflammation is a necessary part of injury
  and healing, it is often exaggerated and leads to
  further injury and delayed recovery of function.
  

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Effect of Curcumin on Performance Recovery
following Muscle-Damaging Exercise
Uphill/Downhill Run
Acclimation to Treadmill or Wheel
Recovery of Performance
Curcumin Feeding
1 2 3 4 5 6
7 8 Experimental
Days
-1 -2 -3 Preliminary Days
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Curcumin improves recovery of treadmill endurance
capacity following downhill running




48 h
72 h
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Curcumin also improves recovery of voluntary
wheel running performance following downhill
running




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Curcumin and Cancer
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Curcumin and Cancer

• The Indian spice, turmeric, that contains
  curcumin (Curcuma Ionga), has previously been
  studied for its chemopreventive potential.
• It has a diverse range of molecular targets
  including transcription factors, growth factors
  and their receptors, cytokines, enzymes and genes
  regulating cell proliferation and apoptosis.

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Curcumin Reduces inflammation in Cancer

• Potential mechanisms for its effect on
  tumorigenesis are known to involve the inhibition
  of cell signaling pathways involving NF?B and
  inflammation.
• Inflammation has been linked to various steps
  involved in tumorigenesis, including cellular
  transformation, promotion, survival,
  proliferation, invasion, angiogenesis, and
  metastasis.

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Cancer (ApcMin/ mouse model of colorectal
cancer)
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Curcumin reduces total polyp number in the
APCMin/ mouse
N10/group P lt 0.001

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Polyp Number and Size Distribution
Plt0.05 for curcumin versus placebo