Healthy Eating&

DrinkingAlan Crozier

Institute of Biomedical and Life Sciences

University of GlasgowScotland, UK

Professor of Plant Biochemistry and Human Nutrition

FRUITS AND VEGETABLES CONTAIN:

minerals, fibre, vitamins and phytochemicals

Common C6-C3-C6 Flavonoid Structures

O

OO

OO

OO

OO

O

OH

O

O

OOH

Anthocyanin(berries, grapes, plums etc)

Flavanone(citrus fruit)

Flavan-3-ol (aka catechins)(F & V, red wine, chocolate, green tea)

Flavonol(F & V, red wine, tea)

Flavone(celery, parsley)

Isoflavone(soya)

A C

B12

34105

6

79

1'

2'3'

4'

5'6'

8

O+

OH

Structures of Common Dietary Phenolics

O

OO

HO

HOO

OH

OH

Ellagic acid

Sanguiin H-10(Ellagitannin - hydrolysable tannin)

OHOO

HO

HOOH

O

HOOH

HO

OOH

OH

O

HO

HO OH OH OH

OH

OO

OHO

HO

O

HOOH

HO

OOH

OH

O

O

O

O

O O O

OOH

OH O

OH

HOOH

OH

COOH

Gallic acid

O

OH

OH

OHOHO

HOOH

trans-Resveratrol-3-O-glucoside(Stilbene)

OO

OH

OH

OHHOOC

OH

OH

5-O-Caffeoylquinic acid(chlorogenic acid)(Hydroxycinnmate)

HO

HO

OOH

OH

HO

HO

O

OH

OH

Procyanidin trimer C2

(Condensed tannin)

OH

OH

HO

HO

O

OH

OH

OH

EU

TU

Fruit and Vegetable Consumption in the U.K. (2004)

• Only 14% of men and 27% of women in the U.K. consume five a day

Office of National Statistics, 2004

Healthy Supplements to a 5-a-Day Diet

Red wine - lots of phenolics, 3 glasses per day because of alcohol

Green tea - rich in flavan-3-ol monomers

Cocoa - rich in flavan-3-ol monomers and procyanidins - problem - fats

Fruit juices - varied phenolics - sugar limits intake

Nuts with the skin - contain vitamin E, flavonoids and fats (salt)

Black tea - lots of thearubigins - with or without milk ?

Berries - raspberries, blueberries, blackberries, strawberries etc

UK

UKUKUK UK

Mal

Two-three pieces of chocolate per day !

Theobroma cacao, otherwise known as cocoa

Seeds from the pods are roasted and used to make cocoa and chocolate

Chocolate and cocoa are rich sources of flavan-3-ol monomers (catechins) and polymers (procyanidins)

which are strong antioxidants but also contain unsaturated fats

HO

OH

O

OH

OH

(Š)-Epicatechin

OH

HO

HO

O

OH

HO

OH

O

OH

OH

OH

Proanthocyanidin B2 dimer

OH

OH

HO

HO

O

OH

HO

HO

O

OH

OH

OH

OH

OH

HO

HO

O

OH

OH

OH

Proanthocyanidin C1 trimer

Cocoa and chocolate contain monomeric and polymeric flavan-3-ols

Protective Effects of Flavan-3-ol-Rich Cocoa

Improves vascular health reduced platelet aggregation enhanced vasodilation - reduced blood pressure

Kuna Indians San Blas Island 4 cups cocoa per day with age minimal increase in blood pressure reduced hypertension and other CDVs

Kuna Indians Panama City 6-fold lower cocoa intake with age increased in blood pressure hypertension and other CDVs

Schroeter et al. PNAS 103, 1024-9, 2006Zutphen StudyReduced blood pressure

50% decreased risk of CVD

00

55

1010

1515

2020

2525

3030

milkmilk(20 - 34% cocoa)(20 - 34% cocoa)

darkdark(70 - 85% cocoa(70 - 85% cocoa))

cocoacocoa(100%)(100%)

3535

proc

yani

din

cont

ent

proc

yani

din

cont

ent

(µm

ol/g

)(µ

mol

/g)

Procyanidin Content Different Types of ChocolateProcyanidin Content Different Types of Chocolate

(Roger Corder)

 

Red Wines, Procyanidins and Inhibition of Endothelin-1 Synthesis

Corder et al. Nature, 30 November 2006

 

French 1999 Census - Regional Male Longevity

Corder et al. Nature, 30 November 2006

Population(106)

Men> 75 per 105

Women> 75 per 105

RatioM:W > 75

Men > 75(% diff. nat. av.)

France 58.52 2754 4944 0.56 0Midi-Pyrenees 2.55 3667 5898 0.62 + 33.1

In Midi-Pyrenees, South West France……….

Red wines, mainly for local consumption,made from Tannat grapes – small, lots of seeds,

and, therefore, rich in procyanidins

Traditional methods of wine making, 28 day vinification, so seeds extracted and Madiran wine

contains high levels of procyanidins

Big regional variations in CHD in France. In Midi-Pyrenees, 1999 French census shows 33% more men over 75 years of age

and more than double the number over 90 years of age than the French average

Similar evidence of longevity in Nuoro provinceof Sardinia where procyanidin-rich wines are

produced, mainly for local consumption

“The potential health benefits of tea consumption are well known”

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Young first flush tea (Camellia sinensis) shoots ready for plucking

Green Tea Flavan-3-ol Structures

HO

OH

O

OH

O O

HO OHOH

OH

OH

HO

OH

O

OH

OH

OH

OH

(-)-Epigallocatechin gallate

(-)-Epigallocatechin

HO

OH

O

OH

O O

HO OHOH

(-)-Epicatechin gallate

HO

OH

O

OH

OH

(-)-Epicatechin

HO

OH

O

OH

(+)-Catechin

OH

(+)-Gallocatechin

HO

OH

O

OH

OH

OH

OHOH OH

OH

HO

OH

O

OH

O O

HO OHOH

OH

OH

(+)-Gallocatechin gallate

HO

OH

O

OH

O

OH

OHOOH

OH

OH

HO

Theaflavin

HO

OH

O

O

O

OH

OHOOH

OH

OH

HO

Theaflavin-3-gallate

HO

OH

O

OH

O

O

OHOOH

OH

OH

HO

Theaflavin-3'-gallate

OHHOOH

O

HO

OH

O

O

O

O

OHOOH

OH

OH

HO

Theaflavin-3,3'-digallate

OHHOOH

O

HOOH

OH

O

HOOH

OH

O

OO

OH

OH

OH

OR

Thearubigin

n

Thearubigins are complex polymers of catechins with unknown structure

Principle phenolics in black tea

Compounds Green tea Black teaGallic acid derivatives 128 273Chlorogenic acids 451 215Flavonols 778 570Monomeric catechins 4572 101Theaflavins n.d. 224Thearubigens n.d. 4000+Data expressed as mg/L

Major Phenolic Compounds in Green and Black Tea infusions

Fruit and Vegetable Juices…………….

A convenient supplement to 5-a-day F & V or

a busy lifestyle and less than 5-a-day

Fruit and vegetable drinks may be as effective as consumption of fruit and vegetables in relation to a reduced risk of chronic disease Ruxton et al. Int. J. Food Sci. Nutr. 2006

Kame Project Long-term consumption of fruit and vegetable juices can reduce the incidence of Alzheimer’s disease by 75% Dia et al. Am. J. Medicine 119, 751-9, 2006

Which juices?.....

UK

aUKUKUK UK

Antioxidant Activity of Commercial Fruit JuicesQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.

Juices FRAP (mM Fe++) Welchs purple grape 10 Tesco red grape 3.6 Tesco white grape 1.1 Welchs white grape 1.5 Pomegreat pomegranate/blueberry 6.5 Pomegreat pomegranate/raspberry 6.4 Pomegreat pomegranate 5.4 Tesco grapefruit 4.9 Tropicana premium orange 4.3 Tesco orange 4.4 Copella cloudy apple 9.6 Tesco clear apple 2.2 Tropicana tropical juice 8.2 Ocean Spray cranberry 6.9 Tesco pineapple 2.0 Del Monte tomato 1.4

UK

aUK

Phenolic Compounds in UK Commercial Fruit Juices

Juice Hydroxy-

cinnamates Flavonols Flavan-3-ol monomers

Procyanidins Anthocyanins

Flavanones/ Flavones

Hydroxy-chalcones

Apple, cloudy 163 23 82 445 1.2 n.d. 43 Apple, clear 143 14 56 n.d. n.d. n.d. 47

Cranberry 33 130 36 134 28 n.d. n.d.

Purple grape 162 76 n.d. 434 296 n.d. n.d.

Red grape 33 18 n.d. 10 30 n.d. n.d. White grape 53 n.d. n.d. n.d. n.d. n.d. n.d.

Grapefruit 39 2.1. n.d. n.d. n.d. 242 19

Orange, concentrate n.d. 6.2 n.d. n.d. n.d. 52 22

Orange, pressed n.d. 4.1. n.d. n.d. n.d. 64 21 Tropical fruit 44 2.7. n.d. 11 n.d. 53 4.7. Pineapple 51 n.d. n.d. n.d. n.d. n.d. n.d.

Pomegreat 130 48 n.d. 172 75 n.d. 11

Data express as moles/L. n.d. – not detected;

Combination of Fruit Juices Providing

High Antioxidantsand

Diversity of Phenolic Compounds

Purple grape - flavonols, hydroxycinnmates, procyanidins, anthocyanins

Cranberry - flavonols, procyanidins

Citrus - flavanones

Cloudy apple - hydroxycinnamates, flavan-3-ol monomers, procyanidins, hydroxychalcones

Pomegranate ? - anthocyanins, ellagitannins

To what extent are the various dietary phenolics bioavailable ?

What is bioavailability ?

Possible Routes for Consumed Dietary Phenolics in HumansPossible Routes for Consumed Dietary Phenolics in Humans

Dietary phenolics

Tissues

Small intestine LIVER

Colon

bilebile

Kidney

General

circulation

Urine

Faeces

Ileostomybag

The fate of strawberry phenolics in humans with a colonThe fate of strawberry phenolics in humans with a colon

Human volunteers ingested 200 g of strawberries withparacetamol and lactulose

Plasma and urine collected at several time points over a 24 h period

All samples analysed by HPLC-PDA-MS2 to determinethe fate of anthocyanins

The fate of strawberry anthocyanins in humansThe fate of strawberry anthocyanins in humanswith a colon - with and without creamwith a colon - with and without cream

Pelargonidin-3-Glucuronide In Plasma After Ingestion of 200 g of Strawberries

50

100

150

200

250

300

0 5 10 15 20 25Time (h)

nmol

/L

With 100 mL double cream

Without cream

Supplement Cmax (nmole/L) Tmax (h ) T1/2 (h) AUC (nmole/L/h)

Strawberries without cream 274 ± 24 1.1 ± 0.4a 2.1 ± 0.7 856 ± 42

Strawberries with cream 227 ± 35 2.4 ± 0.5b 2.8 ± 1.1 895 ± 112

HO

HO

O+

O

OHOH

O

OHOHHO

Cyanidin-3-glucoside

HO

HO

O+

O

OH

O

OHOH

COOHHO

Pelargonidin-3-glucuronide

OH

HO

HO

O+

O

OH

O

OHOHHO

Pelargonidin-3-glucoside

OH

LPH

LPH

HO

HO

O+

OH

OH

PelargonidinLPH

LPH

HO

HO

O+

O

OH

O

OHOH

COOHHO

Pelargonidin-3-glucuronide

Lumen of smallintestine

Wall of small intestine(enterocyte)

Portal vein

HO

HO

O+

O

OH

O

OHOH

COOHHO

Pelargonidin-3-glucuronide

Urine

CBG

To the large intestine

Absorption and Metabolism of Strawberry and Blackberry AnthocyaninsAbsorption and Metabolism of Strawberry and Blackberry Anthocyanins

(1% of intake)

OH

HOOC Protocatechuic acid

OH

OH

HOOC

Vanillic acid

OCH3

OH

HOOC

Syringic acid

OCH3

OCH3

Cyanidin-3-O-rutinoside

HO

HO

O+

OH

O

OH

O

O

HOHO

OH

O

OHHO

HO

HO

HO

O+

OH

O

OH

OHO

HOOH

HOCyanidin-3-glucoside

HO

HO

O+

OH

OH

OH

Cyanidin

Rhamnose

3 4

3 4

Glucose

Liver

Liver

Colon

Colon

Colon

Colonic degradation of anthocyanins

(Aura et al., Eur J Nutr 44, 133-142, 2005)

Flavonol Glycosides

O

OHOHHOOH

O

HO

HO

O

OH

OHO

Quercetin-4'-glucoside Quercetin-3-rutinoside

O

O

HOHO

OH

HO

HO

O

OH

OO

OH

O

OHHOHO

200 g fried onions - 257 moles 300 mL tomato juice- 176 moles

A

0

200

400

600

800

0 1 2 3 4 5 6Time (h)

Con

c. n

mol

es/L

Quercetin-3'-sulphate

Quercetin-3-glucuronide

B

25

50

75

100

125

0 1 2 3 4 5 6

Time (h)

Con

c. n

mol

es/L

0

Quercetin glucuronide sulphate

Isorhamnetin-3-glucuronide

Quercetin diglucuronide

Quercetin-4-Glucoside Metabolites In Plasma

Flavonol Glycosides

O

OHOHHOOH

O

HO

HO

O

OH

OHO

Quercetin-4'-glucoside Quercetin-3-rutinoside

O

O

HOHO

OH

HO

HO

O

OH

OO

OH

O

OHHOHO

200 g fried onions - 257 moles 300 mL tomato juice- 176 moles

0

2

4

6

8

10

12

14

16

0 1 2 3 4 5 6 7 8

Time (h)

Con

cent

ratio

n (n

mol

es/L

)

Quercetin-3-glucuronide

Isorhamnetin-3-glucuronide

Quercetin-3-Rutinoside Metabolites In Plasma

OH

OCH3HOOC

OHHOOC

OH

OHHOOC

OO

HOHO OH

OOH

OHOH

CH3

HO

HO

O

OH

OO

OH

O

HO

HO

O

OH

OHOH

Quercetin

Rutin

3-Methoxy-4-hydroxyphenylacetic acid

3,4-Dihydroxyphenylacetic acid*

3-Hydroxyphenylacetic acid

ring fission

Fate of Rutin In The Large Intestine

Possible Routes for Consumed Dietary Phenolics in HumansPossible Routes for Consumed Dietary Phenolics in Humans

Dietary phenolics

Tissues

Small intestine LIVER

Colon

bilebile

Kidney

General

circulation

Urine

Faeces

Ileostomybag

• Eat five 80 g portions of different fruits and vegetables per day

• Variety rather than excess appears to be the key to a health diet

• As well as the F&V, drink fruit juices, cocoa, tea and, in moderation, coffee and red wine, and eat a little dark chocolate and some nuts

• Supplements, such as quercetin antioxidant tablets, increase the possibility of excessive intakes. Would you or could you eat 1+ kg of onions per day ?

Meanwhile