Dietary Phenolic Phytochemicals Their antidiabetic role

Dr Lisa Ryan – Functional Food Centre

IntroductionThe prevalence of type 2 diabetes is rising exponentially

Current treatment of the metabolic syndrome & prevention of type 2 diabetes – lifestyle modification

Dietary recommendations emphasise the intake of plant food sources

These foods are a great source of fibre but also of phenolic phytochemicals which may be able to influence glucose metabolism by several mechanisms

Phytochemicals

4

PhytochemicalsNatural plant compounds that provide a variety of health benefits

Fruits and vegetables are known to contain carbohydrates, vitamins and minerals, usually very low in proteins & fat – however also a rich source of phytochemicals

May act as antioxidants or enhance the effects of antioxidants

Simple Colour Classification of Fruits & Veg

�Blue/purple

�Yellow/orange

�Red

�Green

�White/tan/brown

Oxidative Stress & Free Radicals

Free radicals are highly reactive molecules (contain one or more unpaired electron)

Ex. Reactive Oxygen Species (ROS)

They are produced through a no. of different processes

Our bodies have developed different mechanisms to cope

When the body’s natural antioxidant mechanism is overwhelmed = Oxidative Stress

Cellular Targets of Free RadicalsReactive free radicals react with a non radical

Lipid peroxidation occurs in blood vessel walls contributing to the development of atherosclerosis (CHD)

Radicals may attack DNA and cause mutations (cancer)

Free radicals can result in inactivation of enzymes & denaturation of proteins

Increasing evidence suggests that oxidative stress plays a role in both types of DM

PhytochemicalsPotential Role in:

GI/GR – preventing postprandial hyperglycaemia

Insulin signalling

Energy Expenditure

Many different types of phytochemicals

Carotenoids have been extensively studied however relatively little known about polyphenols & other plant extracts

Polyphenols

StilbenesFlavonoids*Phenolic acids

Isoflavones Flavanones Flavonols

Flavones Flavanols Anthocyanins

Flavan-3-ols Proanthocyanidins

FlavonoidsPhenolic phytochemicals; contain aromatic rings

Many occur in nature with a sugar group attached (water soluble)

Phenolics are plant secondary metabolites

Often found in the epidermis of leaves & fruits

Onions, apples, black tea are rich sources

Roles include:Pigmentation

Protect the plant from UV damage

Confer resistance to disease

Health Benefits of Flavonoids

Reduction in CVD risk (consistent)

Reduction in cancer risk (inconsistent)

Reduced diabetes risk (inconsistent)*

Weight management (emerging)

Cognitive function (emerging)

Gut & oral health (emerging)

Polyphenolic Flavonoids in Tea

Caffeine/EGCG and Fat Oxidation

Anthocyanins

Responsible for the red, purple & blue colours of many fruits, veg., cereal grains & flowers

Over 300 structurally distinct anthocyanins have been identified

Diverse range of physiological activities

Potent antioxidant

Physiological effects may be due to antioxidant activity, modulation of cellular biochemical processes or alteration of gene expression

Preventative role in cancer, diabetes, CVD, obesity, inflammation, cognitive decline

Anthocyanins & Functional Foods

Coming soon – The Purple Cow!

Antidiabetic Role of Polyphenols?Polyphenols may influence glucose metabolism by several mechanisms:1) inhibition of CHO digestion and glucose absorption in the intestine2) stimulation of insulin secretion from the pancreatic β–cells3) modulation of glucose release from liver4) activation of insulin receptors and glucose uptake in the insulin-sensitive tissues5) modulation of hepatic glucose output

FFC & Phenolic PhytochemicalResearch

‘undertake leading edge research focussed on tackling obesity, improving glycaemic control and reducing inflammation, thereby

helping to improve the health and well-being of the global population’

Baobab

Polyphenol Content of Extracts

* p < 0.05, denotes significantly greater in polyphenol content as measured by FCR. Values reported as mg Gallic acid equivalents (GAE)/ gram extract

* * *

Bioavailability vs Bioaccessibility

OH

OH

?Intestine

Bioaccessibility

Bioavailability

inflammation

triglyceridesglycaemia

Inte

stin

al

bo

rder Blood

Bioaccessibility of Baobab

Polyphenols

Baobab 1 Baobab 2 Baobab 3 Baobab 4 Baobab 5 Baobab 6

Baseline 23.3 ± 0.6 21.2 ± 0.5 27.7 ± 0.2 26.5 ± 0.2 24.0 ± 0.3 28.2 ± 0.3

Gastric 63.0 ± 0.6* 62.0 ± 0.6* 61.6 ± 0.7* 63.5 ± 0.5* 60.5 ± 0.5* 63.2 ± 0.6*

Duodenal 76.9 ± 1.3* 76.4 ± 0.9* 76.0 ± 0.7* 77.3 ± 0.9* 71.8 ± 0.7* 75.9 ± 0.5*

* p < 0.05, denotes significant increase from the FCR values prior to in vitro

digestion. Values reported as mg Gallic acid equivalents (GAE)/ gram extract

Phytochemicals & Blood Glucose Response

What is the Glycemic Index

A ranking of food carbohydrates –based on the incremental area under the blood glucose curve

Comparing equal amounts of carbohydrate: reference food = glucose or white bread

Plasma glucose response to ingestionof 50 g CHO

-20

0

20

40

60

80

100

120

140

160

0 50 100 150 200 250 300

Minutes after meal

mg

/dl

Glucose Lentils

Kidney beans Potato

Bread Oatmeal

Rice

(Krezowski et al., 1987)

In vitro digestion

Food Sample

Oral phase

Gastric phase

Ileal phase

Salivary amylase

Pepsin

Pancreatic amylase

Baobab extract in white bread

mg/g

sugar

rele

ase

Green Tea Extract in White Bread

mg/g

sugar

rele

ase

Extracts in White Bread

FFC & Beetroot Juice

Rich in polyphenols & nitrates

Betalains

Water-soluble pigments, replace anthocyanins in most plants of the order Caryophyllales (also found in some fungi)

Less well used in food processing than anthocyanins& carotenoids

These pigments are stable between pH 3-7, suitable for use in low acid food

Two main types, betacyanins & betaxanthins

Beetroot juice has been shown to contain high levels of polyphenols, betalains, as well as other bioactive phytochemicals

DesignIn a randomised, cross-over design, 20 healthy adults (8 male / 12 female) consumed one of three test beverages each containing 50g of available CHO (following on from pilot study)

The meals consisted of 225 mL of beetroot juice (Beetroot), 225 mL of a matched control beverage (Control), or 225 mL glucose as a positive control

On each test day postprandial finger prick blood samples were taken at baseline (-5, 0) 5, 15, 30, 45, 60, 90, 120 and 150 minutes to measure both blood glucose (5 µL) and plasma insulin (300 µL)

Food frequency questionnaires were analysed using the phenol explorer database (Neveu et al., 2010) to estimate habitual polyphenol intake

Glucose (segmental area under the curve)

0.00

20.00

40.00

60.00

80.00

100.00

120.00

140.00

160.00

180.00

200.00

0-30 0-45 0-60 0-90 0-150

Time (minutes)

sAU

C G

luco

se

MCON

BEET

GLUC

Glucose (area under the curve)

3.00

3.50

4.00

4.50

5.00

5.50

6.00

6.50

7.00

7.50

0 5 15 30 45 60 90 120 150

Time (minutes)

Blo

od

Glu

co

se (

mm

ol/

L)

MCON

BEET

GLUC

Insulin (segmental area under the curve)

200.00

700.00

1200.00

1700.00

2200.00

2700.00

0-30 0-45 0-60 0-90 0-150

Time (minutes)

Insu

lin

sA

UC

MCON

BEET

GLUC

Insulin (area under the curve)

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

90.00

0 5 15 30 45 60 90 120 150

Time (minutes)

Insu

lin

(µ

IU/m

L)

MCON

BEET

GLUC

ResultsSegmental area under curve analysis revealed a significantly lower postprandial glycaemic response at 0-30 minutes and a significantly lower insulin response at 0-30, 0-45, 0-60 for the beetroot juice drink compared to the control (P < 0.05)

This suggests an effect of beetroot phytochemicals or nitrate on insulin secretion, insulin receptor sensitivity or insulin utilisation

β-glucan

In vitro digestion of flatbreads with HMW barley β-glucan

0

50

100

150

200

250

300

350

400

0 20 40 60 80 100 120 140

Digestion time (min)

Glu

cose rele

ase (m

g/g

sam

ple

)

0% beta glucan 4% beta glucan8% beta glucan

Thondre et al., Food Research International (2010)

0

50

100

150

200

250

300

350

400

0 50 100 150

Digestion Time (min)

Glu

co

se

re

leas

ed

(m

g/g

sa

mp

le)

0% beta glucan 4% beta glucan 8% beta glucan

In vitro digestion of flatbreads with LMW barley β-glucan

Thondre & Henry, Int J Food Sci Nutr (2011)

In vivo study using β-Glucan

Randomised cross-over design

Unleavened flat breads with β-Glucan

Healthy subjects

-5 0 15 30 45 60 90 120

Glucose Analysis

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 15 30 45 60 90 120

Time (minutes)

De

lta g

luc

ose

(m

mo

l/l)

Glucose 0 g beta glucan

4 g beta glucan 8 g beta glucan

Thondre & Henry, Nutr Research, 2009

Glycemic response to flatbreads with HMW barley β-Glucan

GI of flatbreads with HMW barley β-Glucan

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

0 4 8

Amount of beta glucan (g)

Gly

cem

ic I

nd

ex

Thondre & Henry, Nutr Research, (2009)

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 15 30 45 60 90 120

Time (min)

Delta g

lucose (m

mol/l)

Glucose 0 g beta glucan

4 g beta glucan 8 g beta glucan

Glycemic response to flatbreads with LMW barley β-Glucan

Thondre & Henry, Int J Food Sci Nutr (2011)

0

10

20

30

40

50

60

70

0 4 8

Amount of beta glucan (g)

Gly

ce

mic

In

de

x

GI of flatbreads with LMW barley β-glucan

Thondre & Henry, Int J Food Sci Nutr (2011)

Polyphenol content of β-Glucan extracts

Thondre et al., Food Chemistry (2011)

0

200

400

600

800

1000

1200

1400

75% BG 25% BG 30% BG

70% Acetone 70% Methanol 70% Ethanol Acidified Methanol

Po

lyp

he

no

l c

on

ten

t ( µµ µµ

g/g

sa

mp

le)

75% BG – LMW; 25 and 30% BG - HMW

Comparison of β-Glucans with other antioxidants

0

10

20

30

40

50

60

70

80

90

100

GA FA Trolox AA BB BFRF

Antioxidant source

Inh

ibit

ion

(%

)

Thondre et al., Food Chemistry (2011)

HMW Beta glucan

0

100

200

300

400

500

600

Cra

nber

ryA

pple

Red

gra

pe

Straw

berry

BF

RF

BB

Bro

ccol

iS

pinac

hP

each

Oni

on

Red

pep

perB

anan

aO

range

Pea

r

Gra

pefru

itP

inea

pple

Car

rot

Glu

cag

elC

abba

ge

Co

rnR

ice

Whea

tPo

tato

Lettu

ce

Oat

sC

eler

yC

ucu

mbe

r

Source

Fre

e p

hen

olics (

mg

GA

E/1

00g

sam

ple

)

Thondre et al., Food Chemistry (2011)

Comparison of β-Glucans with common sources of polyphenols

HMW beta glucan

Influence of polyphenols on in vitro starch digestibility of porridge oats

y = -0.7455x + 1946.1

R2 = 0.8762

1400

1450

1500

1550

1600

1650

1700

1750

1800

1850

0 100 200 300 400 500 600 700

Rapidly digested starch (mg/g sugars released)

Po

lyp

he

no

l co

nte

nt

(ug/g

GA

E)

0

200

400

600

800

1000

1200

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Sample no.

Su

ga

rs r

ele

as

ed

(m

g/C

HO

in

sa

mp

le)

0 min gastric 20 min 60 min 120 min 180 min

0

200

400

600

800

1000

1200

1400

1600

1800

2000

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Oats porridges

Po

lyp

he

no

l co

nte

nt

(ug

/g G

AE

)

Thondre et al, 2011, Proceedings of the Nutrition Society, 70 (OCE4), E138

Future Work

Currently investigating the effect of adding different plant extracts and pure polyphenols to different food systems with a particular focus on

Insulin signalling

Energy Expenditure

Satiety

SummaryPhenolic Phytochemicals as functional ingredients represent an exciting & developing area of nutrition

Foods that can attenuate the postprandial glycaemic response may help to control BMI, blood glucose control and ultimately protect against the development of Diabetes …

Antidiabetic PhenolicPhytochemicals……..

….Enjoy!

Thank you for your kind attention.

lisaryan@brookes.ac.uk

http://www.shs.brookes.ac.uk/research/functional-food

: +44 1865 483199