Fruit and Vegetables and Colon Cancer Prevention

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Fruit and Vegetables and Colon Cancer
Prevention Can we design an anti-colon cancer
diet? Garry Duthie Molecular Nutrition Group
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Colon cancer second most common cancer in UK
Cancer Research UK
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Fruit and vegetable consumption reduces colon
cancer risk
years
80 of epidemiological studies indicate
protective effect 5 or more servings fruit/day -
40 decreased risk of adenomas 4 or more servings
legumes/day - 33 decreased risk of
adenomas Recommendation may increase to 9
servings/day!
Michels et al, Cancer Research 2006, 66, 3942
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Little change in fruit and vegetable intake in
Scotland
Review of the SDAP Progress and Impacts 1996-2005
5-a-day difficult to achieve Therefore
9-a-day improbable May need more specific
recommendations Are some plant-based foods better
than others ?
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How to give better dietary advice?
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Phytochemicals may protect against colon cancer?
In vitro studies suggests potential anticancer
activity Eg antioxidant activity, DNA repair
activity, anti-inflammatory activity,
induction of phase II enzymes, pro-apoptotic etc.
Sites of potential action of phytochemicals
Carcinogen exposure
Initiation
Promotion
Tumour growth
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Aspirin protects against colon cancer!
Subjects from Helen McDonald, UoA
Consuming fruit and vegetables increases serum
concentrations of salicylic acid
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Spices are very rich in salicylic acid
Country Colon cancer UK
39.2 India
4.7
Currently comparing salicylate intakes and
urinary concentrations
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Curry function test
Salicylic Acid (nmol/l)
Salicyluric Acid (mmol/mmol creatinine)
160
7
Curry started
urine
140
6
120
5
plasma
100
4
80
3
60
2
40
1
20
0
0
930
1015
1100
1210
1245
1325
1405
1625
1745
time
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Fruit and veg contain many other aspirin-like
phenolics
However, before designing anticancer diet we need
to consider
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Improved food composition databases for phenolics
Rowett Salicylic Acid Food Composition Database
Little data for other phenolics
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Factors that effect phenolic content of foods?
Species, Variety, Growing Conditions, Ripeness,
Processing , Storage
cinnamic acids (esterified)
80
cinnamic acids (free)
70
benzoic acids (esterified)
benzoic acids (free)
60
50
mg 100g-1 (wet weight)
40
30
20
10
0
pear
grape
apple
orange
banana
raspberry
strawberry
blackcurrant
gooseberry
Locally Produced and Commonly Consumed Fruits
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Importance of bioavailability and metabolism
Uptake from GI tract Metabolism in
cells Metabolite formation by bugs Bioactivity of
metabolites
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Absorption and excretion
Study Design
Absorption Plasma Metabolites (free)
n 4 fasted 16 hours
age 32 6 years weight 74 11 kg
strawberry consumption 675 g
Concentration (?g cm-1)
Cinnamic Acids
caffeic acid
sinapic acid
Time (hours)
ferulic acid
p-coumaric acid
Excretion Urine Metabolites (free conjugated)
Benzoic Acids
gentisic
salicylic
syringic
Recovery
vanillic acid
p-hydroxybenzoic acid
protocatechuic acid
gallic acid
Volunteer
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Metabolites in colon
Volunteer
Benzoates
Systemic
Dietary phenolics
Metabolites
colon cancer
Cinnamates
Colon
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Need to validate anticancer diet!

• Need improved biomarkers
• Intervene in high risk individuals?

Remove polyps
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Key messages phytochemicals and colon cancer

• We are addressing
• Mechanisms of action of phytochemicals
• Improving dietary phytochemical databases
• Effects of variety, growing conditions, storage,
  processing
• Bioavailability and metabolism

Improved dietary and/or functional food
recommendations
Prevention