Transcript Title

R&DA Conference October, 2008
Current work and new lipid strategies to
combat warfighter stress
©Arcadia Biosciences, Inc. CONFIDENTIAL
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PROGRAM GOALS
Contract with US Department of Defense to develop long shelf-life
tomatoes and lettuce using novel molecular breeding technology
TILLING®
DOD Program Goals
– Increase shelf-life by 50-100% with no loss in nutrition, freshness,
color, crispness or taste
– Grown domestically for military procurement
– Available through normal commercial channels
Arcadia - using selective breeding technology to achieve program
goals
– Increasing firmness
– Preventing over-ripening
– Introducing better chilling tolerance
– tomatoes and lettuce treated differently for shipping/storage
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DISTRIBUTION CHALLENGES
• Tomatoes are a soft fruit when ripe and easily subject to damage .
• Tomatoes are repeatedly handled throughout the distribution system.
Fruit suffers losses at very handling point as it softens and loses
firmness
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–
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HAND picked from plants
HAND and machine sorted over packing shed line
HAND packed into boxes
Resorted by HAND after 7 days of ripening
Resorted by HAND at point of delivery
Resorted by HAND at final destination
• Tomatoes suffer from chilling injury when stored below 55°F.
– Most leafy greens, vegetables and fruits are stored below 40°F
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INCREASED FIRMNESS
Increased firmness using by our lead gene candidate
Exp Firmness
25
Firmness (N)
20
15
hom
wt
10
Linear (hom)
Linear (wt)
5
0
0
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10
4
15
20
Days after Light Red
25
30
REDUCED ROT
Using our lead long shelf life candidate (55F)
Harvest at Breaker
Candidate
Control
After 1 month
Candidate
Control
After 4 months
Candidate
Control
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STUDIES IN PROGRESS
• Natick Soldier Center
– Sensory evaluation of greenhouse and field
grown tomatoes 2008
– Temperature storage studies
• Marita Cantwell at UC Davis Post Harvest Physiology
– Firmness
– Ethylene sensitivity
– Shelf life studies
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Enhancing Warfighter Performance
By Stress Reduction Using Novel Dietary
Lipid Strategies
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Arcadia Biosciences, Inc.
Using agricultural biotechnology
to develop plants that improve the
environment and human health
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GLA – An Essential Omega-6
• Evening primrose and borage oil – traditional sources
– Only 10% and 20% GLA
– Supply inconsistent – high price
• GLA Safflower Oil
– > 50% GLA concentration
– Supply consistency
– Cost effective
Warfighter Stress
maximum of inducing factors
In Harm’s Way
No family - new
associations
Physiological
Stress
Climatic factors
Varied sleep patterns
Psychological
Stress
New dietary regimens
Fatigue
Hereditary based Stress
Bodily injury
Essential Fatty Acids - Omega-3 & Omega-6
Discovered 1930’s - Burr & Burr
 Essential
 Essential
 Essential
 Essential
 Essential
 Essential
►
►
►
►
►
►
your body can not make them
you will perish without them
offer vital inflammatory control
providing immense systemic support
proper brain development for infants
many countries now establishing DVs
EFAs - the Omega Oils
Two primary classes - omega-3s and omega-6s
• Omega-3s > fish oil - high public profile
 ALA, EPA, DHA
• Omega-6s > varied and often confusing commentary
 ARA (arachidonic) for infants – excess is bad for adults
 LA (linoleic) good for cholesterol - excess problematic?
• GLA – a vital metabolic omega-6 fatty acid
GLA + EPA = Synergy
Simplified EFA Pathway
• n-6 and n-3 paths > parallel
• Eicosanoids – signaling
molecules effecting
inflammation - immunity
• EPA and DGLA metabolites
both act as inflammatory
mediators
COX/LOX also metabolize ARA to
pro-inflammatory eicosanoids
Most ARA from animal product consumption
Parallel Pathways – Complimentary Efficacy
Benefits of either GLA or EPA are quite similar
Both offer dietary support for a host of similar conditions
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Inflammatory Control
Stress – Neurological Disorders
Arthritis – Joint Pain
Immune System Support
Skin diseases - rashes
Compulsive disorders, ADHD, cognitive functions
Cardiovascular Disease
 Substantial clinical science supporting both GLA and EPA
Inflammatory Control is Critical
Uncontrolled inflammation - implicated in many diseases
 Autoimmune disorders
 Neurological disorders
 Asthma – respiratory distress
 Eczema, dermatitis, psoriasis
 Cardiovascular disease
 Diabetes and Metabolic Syndrome
 Rheumatoid arthritis
Shubert R, et al, 2007, Influence of low-dose polyunsaturated fatty acids supplementation on
the inflammatory response of healthy adults, Nutrition Oct;23(10):724-30
EFAs in stress management
 GLA shown to improve task performance under stress
– Reduces blood pressure and heart rate responses to stress
– Data suggests diet can alter stress reactivity in man1
 EFA supplementation linked to reduced depression
– Meta-analysis by Appleton et al2 2006 – Am. J of Clinical Nutrition
– Depression – response to low-grade systemic inflammation
– Supports: bipolar disorders, schizophrenia, mental acuity
 GLA + EPA reduces antisocial behavior
– Study of 231 incarcerated young men shows a 26 -37% decline3
– Study recently replicated in the NL – 34% decline
- Inflammatory Control Abbott Nutrition – Ross Labs
• OxepaTM Medical Food
• 4.0g/L GLA + 4.6g/L EPA daily
• Inflammatory modulation for ICU patients
with respiratory distress syndrome
• As published in the Journal of Critical Care Med.
– GLA + EPA reduced term of ICU confinement from
17.5 to 12.8 days ( > 25% reduction)
• Ross cited references
Gadek JE et al. Crit Care Med 1999;27(8):1409-1420.
Singer P et al. Crit Care Med 2006;34(4):1033-1038.
Pontes-Arruda A et al. Crit Care Med 2006;34(9):2325-2333.
Murray MJ et al. Am J Physiol1995;269:H2090-H2099.
Horrobin DF. Rev Contemp Pharmacotherapy 1990;1:1-45.
Pacht ER et al. Crit Care Med 2003;31(2):491-500.
Inflammatory Sports Injuries
• Pharma Nord - ActiveComplex
• GLA plus EPA/DHA formulated with
complimentary vitamins/minerals
• Used for 10 yrs. by Danish Olympic
teams for treatment of inflammatory,
over-use injuries
• Systemic and cellular balance of
inflammatory versus anti-inflammatory
eicosanoids
GLA/EPA and Joint Pain
• Clinicals show GLA + EPA tested on RA reduced:
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pain
swelling
inflammation
morning stiffness
• Dozens of positive clinical results
• Reduces or eliminates need for NSAID medication
• 1988, Belch JJ study – 450mg GLA + 240mg EPA
 80% GLA+EPA - stopped or major reduction in NSAIDs
 71% with just GLA
 33% for placebo group
Belch JJ,et al. Effects of altering dietary essential fatty acids on requirements for non-steroidal antiinflammatory drugs in patients with rheumatoid arthritis: a double-blind placebo-controlled study.
Ann Rheum Dis 1988;47:96-104.
Reduced NSAID Usage
100
90
80
Percentage of
patients on full
NSAID dosage
70
60
50
40
30
20
10
0
0
3
6
9
12
Months of GLA/EPA supplementation
Belch JJ et al. Annals Rheum Dis 1988 47: 96-104
COX Inhibitors
• Aspirin, naproxen and other non-selective inhibitors act
on all COX enzymes (not just COX2)
• Inhibits important GLA/DGLA metabolite > PGE1
• PGE1 protects stomach lining – hence bleeding
with excess aspirin, naproxen, NSAIDs.
• NSAID side effects – resulting from
COX1
20:3
PGE1
non-selective COX inhibition:
DGLA
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Stomach bleeding
High blood pressure
Headaches
Extra platelet aggregation
Fluid retention
15-HETrE
LOX1
D5
EPA inhibits D5
20:4
arachidonic acid
ARA
4-series LT’s
ltb4
5 LOX
COX2
proinflammatory
2-series
prostanoids
EFAs and Skin Health
 Warfighters develop skin irritations – multiple sources
• Climatic factors (hot dry air)
• Chemicals or pollutants as factors
• Stress factors
• Inherent disease – eczema, psoriasis
Reduced Eczema Symptoms by
GLA Supplementation
Severity of
symptoms
9
8
7
6
5
4
3
2
1
0
Itching
Inflammation
Oozing
Vesicle
formation
0
4
8
12
Weeks of supplementation
Adapted from Adreassi, M. et al. Journal of International Medical Research,
1997 Vol. 25, pp 266-274
GLA/EPA for Respiratory Relief
 Clinically proven to combat asthma
 Mitigates bronchial tube inflammation
 Further testing needed for field extremes
GLA/EPA for asthma treatment
 Efficas – GLA/750mg + EPA/500mg as
a medical food
 Specific ratio – maximum inhibition of
inflammatory leukotrienes
 GLA and EPA working in concert to
minimize ARA conversion to inflammatory
leukotriene LTB4
 Surette ME, Stull D, Lindemann J, The impact of a medical food containing
gammalinolenic and eicosapentaenoic acid on asthma management and quality of
life of adult asthma patients. Curr Med Res Opin. 2008 Feb;24(2):559-67
 Department of Chemistry and Biochemistry, University of Moncton, Moncton, NB,
Canada [email protected]
Other benefits of GLA/EPA for both
military & civilian populations
• Conditions aggravated by inflammation
 Osteoporosis
 Cardiovascular health
 Women’s health
 General skin function
 Decreased prospects of sepsis
Directions Forward
 Establish a scientific basis to understand
benefits of dietary uses of controlled
GLA/EPA ratios in the military context
 Develop palatable uses in food systems
 Incorporate dietary antioxidants (Quercetin)
to augment and enhance the control of
inflammatory reactions under stress
Thank You
Ken Ardisson
[email protected]
©Arcadia Biosciences, Inc. CONFIDENTIAL
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Selected References
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Mills DE, et al, 1989, Dietary fatty acid supplementation alters stress reactivity and
performance in man. J Hum Hypertension Apr;3(2):111-6
Appleton KM, Hayward RC, Gunnell D, et al. Effects of n–3 long-chain
polyunsaturated fatty acids on depressed mood: systematic review of published trials.
Am J Clin Nutr 2006;84:1308–16.
Gesch B, et al, Influence of supplementary vitamins, minerals and EFAs on the
antisocial behavior of young adult prisoners. Brit J Psych, 2002 July;181:22-8
Arnold L et al. Gamma-linolenic acid for attention-deficit hyperactivity disorder:
placebo-controlled comparison to d-amphetamine. Biol Psychiatry 1989;25:222-228.
Joshi K, Lad S, Kale M,et al, Supplementation with flax oil and vitamin C improves the
outcome of Attention Deficit Hyperactivity Disorder (ADHD).Prostaglandins Leukot
Essent Fatty Acids. 2006 Jan;74(1):17-21. Epub 2005 Nov 28.
Maida ME, et al, Cytosolic prostaglandin E2 synthase (cPGES) expression is
decreased in discrete cortical regions in pyschiatric disease. Brain Res 2006,
1103:164-172
Lakhan SE, Vieira KF, Nutritional therapies for mental disorders Nutrition Journal
2008 7:2
Schachter HM, et al, Effects of Omega-3 Fatty Acids on Mental Health. Evidence
Report/Technology Assessment AHRQ Pub. No. 05-E022-1 Rockville, MD: Agency
for Healthcare Research and Quality. July, 2005