R&D Forum 1 - Vitafoods Europe · Is more better? Improved bioavailability of Omega-3 for improved health Speaker: Prof. Philip C. Calder, Professor of Nutritional Immunology, Human

R&D Forum 1Marine Ingredients

Is more better? Improved bioavailability of Omega-3 for improved health

Speaker:

Prof. Philip C. Calder, Professor of Nutritional Immunology, Human Development & Health Academic Unit, Faculty of Medicine, University of Southampton, UK

NIHR Southampton

Biomedical Research Centre in nutrition

The NIHR Southampton Biomedical Research Centre in nutrition is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospital Southampton NHS

Foundation Trust and the University of Southampton

Improved bioavailability of omega-3

for improved health

Philip C. Calder

University of Southampton

Southampton

UK

([email protected])

Vitafoods, Geneva, May 2018

EPA and DHA

Eicosapentaenoic acid (EPA) 20:5w-3

Docosahexaenoic acid (DHA) 22:6w-3

H3C COOH

H3C

COOH

Prospective US study of w-3 fatty acid intake and coronary heart disease outcomes:

The Nurse’s Health Study

Hu et al. (2002) J. Am. Med. Assoc. 287, 1815-1821

Total CHD (P < 0.001)

Fatal CHD (P = 0.01)

Non-fatal MI (P = 0.003)

1.0

0.8

0.6

0.4

0.2

0

Lowest Highest

Quintile of EPA + DHA intake from diet

Prospective US study of w-3 fatty acid status

and sudden death:

The Physician’s Health Study

1

0.8

0.6

0.4

0.2

01 2 3 4

Rela

tive r

isk o

f su

dd

en

death

Quartile of whole blood EPA + DHA

Adjusted for age & smoking

Also adjusted for BMI, diabetes,

hypertension, hypercholesterolemia,

alcohol, exercise & family history of

MI

Albert et al. (2002) New Engl. J. Med. 346, 1113-1118

CVD : Classic and emerging risk factors

CLASSIC:AgeSexFamily history (genetics)

Smoking

High alcohol consumptionHigh blood pressureDiabetesObesityLack of physical activity

High serum (LDL) cholesterol

EMERGING:High serum triglyceridesElevated post-prandial lipaemiaEndothelial dysfunctionTendency towards thrombosisInflammation

Elevated plasma homocysteine

Poor antioxidant status

CVD : Classic and emerging risk factors

CLASSIC:AgeSexFamily history (genetics)

Smoking

High alcohol consumptionHigh blood pressureDiabetesObesityLack of physical activity

High serum (LDL) cholesterol

EMERGING:High serum triglyceridesElevated post-prandial lipaemiaEndothelial dysfunctionTendency towards thrombosisInflammation

Elevated plasma homocysteine

Poor antioxidant status

= Improved by omega-3 fatty acids

Omega-3 index = EPA+DHA in red blood cells

Omega-3 fatty acids

Receptors Membrane composition

FluidityRaft assembly Substrates for

eicosanoids,

resolvins etc.

Signals

Cell & tissue

responsesAltered

(patho)physiology

Improved

Health/Decreased

disease risk/

Better clinical

outcome

CE

LL

ME

MB

RA

NE

Having more omega-3s in the blood, in

cells and in tissues is associated with

better health

Overview of whole body fatty acid metabolism

GUT

Digestion & absorption

Fatty acids in lipoproteins;Non-esterified fatty acid

(Transport pools)

LIVER

Fatty acidmetabolism

ADIPOSE

Fatty acid storage

CELLS ANDTISSUES

Fatty acids in cell membranes(Functional

pools)

DIET

(Mainly as TAG)

• Many different compartments

• Many chemical forms in those compartments

• Within one compartment (e.g. blood) there will be

many pools (e.g. red cells, white cells, platelets,

TGs, PLs, CEs, NEFAs …)

• The content of EPA and DHA varies in different

compartments and pools

EPA content of samples from healthy humans

EP

A a

s %

of

tota

l fa

tty a

cid

s

DHA content of samples from healthy humans

DH

A a

s %

of to

tal fa

tty a

cid

s

0

2

4

6

8

10

12

14

Pla

sma

TG

Pla

sma

PL

Pla

sma

CE

Pla

sma

NEF

A

RB

C

Pla

tele

ts

Ne

utr

op

hils

Lym

ph

ocy

tes

Cer

eb

ral c

ort

ex

Re

tin

a

Car

dia

c m

usc

le

Ske

leta

l mu

scle

Live

r

Co

lon

ic m

uco

sa

Ad

ipo

se t

issu

e

Spe

rm

EPA and DHA content of samples from healthy humans

EP

A o

r D

HA

as %

of to

tal fa

tty a

cid

s

0

2

4

6

8

10

12

14

Pla

sma

TG

Pla

sma

PL

Pla

sma

CE

Pla

sma

NEF

A

RB

C

Pla

tele

ts

Ne

utr

op

hils

Lym

ph

ocy

tes

Ce

reb

ral c

ort

ex

Re

tin

a

Car

dia

c m

usc

le

Ske

leta

l mu

scle

Live

r

Co

lon

ic m

uco

sa

Ad

ipo

se t

issu

e

Spe

rm

EPA and DHA



eicosanoids,

resolvins etc.

Signals

Cell & tissue

responsesAltered

(patho)physiology

Improved

Health/Decreased

disease risk/

Better clinical

outcome

CE

LL

ME

MB

RA

NE

Mechanisms

• Increased intake of EPA and DHA (to increase levels in

different body compartments) should improve development,

function, health and well-being

• First lets look at pattern of incorporation of EPA and DHA –

we know there are dose and time dependent effects

Study design

• 5 group, parallel design, stratified by age and gender

• Control

• “1 portion oily fish” per week (2.8 g EPA+DHA on ONE day = 2.8 g/week)

• “2 portions oily fish” per week (2.8 g EPA+DHA on TWO days = 5.6 g/week)

• “2 portions oily fish” per week (taken daily – 5.6 g/week as 0.8 g/day)

• “4 portions oily fish” per week (2.8 g EPA+DHA on FOUR days = 11.2 g/week)

• 210 subjects (105 at each centre)

Randomisation (stratified by age and gender)

Control

(Ctrl)

(n=42)

1 portion per week

(1P)

(n=42)

2 portions per week

(2P)

(n=42)

4 portions per week

(4P)

(n=42)

Fasting bloods at 0, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months

Buccal wash at 0, 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months

Adipose tissue biopsy at 0, 6 months, 12 months

Fatty acid composition analysis

Recruitment

healthy men and women, aged 20-80 years (n=210)

2 portions per week

continuous (2P-D)

(n=42)

Analysed the fatty acid composition of:

• plasma PC, TAG, CE and NEFA

• platelets

• erythrocytes

• mononuclear cells

• buccal cells

• adipose tissue

From all subjects at

9 time points

From all subjects at

three time points

Dose and time dependent enrichment

in EPA and DHA in all pools

We described in detail the time course and dose

dependence of intake of EPA and DHA into nine

pools in humans studied over one year

Omega-3 fatty acids



eicosanoids,

resolvins etc.

Signals

Cell & tissue

responsesAltered

(patho)physiology

Improved

Health/Decreased

disease risk/

Better clinical

outcome

CE

LL

ME

MB

RA

NE

Omega-3 fatty acids



eicosanoids,

resolvins etc.

Signals

Cell & tissue

responsesAltered

(patho)physiology

Improved

Health/Decreased

disease risk/

Better clinical

outcome

CE

LL

ME

MB

RA

NE

Does chemical form make a difference?

• 72 healthy subjects

• Chronic intervention

• 3.3 g/day EPA+DHA for 2 weeks

• Oils as rTG, FFA, EE, fish oil,

cod liver oil

• Corn oil as placebo

• Total plasma

• Chronic study

• 24 healthy subjects

• 3 arm cross over

• Placebo vs. fish oil vs. krill oil

• 4 weeks separated by 8 week washout

• 600 mg EPA+DHA/day

• Plasma and erythrocytes

EPA DPA DHA

Placebo

FO

KO

*

Total plasma lipid: change in %

EPA DPA DHA

Placebo

FO

KO

Erythrocytes: change in %*

*

Summary of 12 studies published 1990-2015; duration 3 days to 6

months (most ~4 weeks), variable doses, variable EPA:DHA

Chemical form Where assayed? Finding

EE, TG Plasma PL EE = TG

EE, TG Total serum and serum PL EE = TG

EE, TG Plasma PL and CE PL: EE = TG;

CE: TG > EE

TG, krill oil Total plasma TG = krill oil

rTG, EE, FFA, FO, CLO Total serum tTG > fish oil = CLO = FFA > EE

rTG, EE, krill oil Plasma PL and RBC PL: rTG = EE = krill oil

RBC: tTG > EE

rTG, EE RBC rTG > EE

TG, krill oil Total plasma TG = krill oil

TG, krill oil Total plasma and RBC krill oil > TG

FFA, EE Total plasma FFA > EE (low fat diet)

TG, rTG, EE, krill oil Whole blood rTG > EE > TG > krill oil

(but different doses given)

TG, EE, krill oil Total plasma and RBC TG = EE = krill oil

Summary chronic studies

1. EPA and DHA are incorporated in a dose, time and pool dependent fashion

from ALL formulations

2. With regard to incorporation of EPA and DHA into the plasma some studies

report:

TG > EE and TG > FFA > EE

But some studies report no difference between TG and EE

3. Differences between findings might be due to the exact pool being studied,

background fat intake, sample size, dose, exact mix of EPA vs DHA, other

factors

Pl.

FFA

rTG

TG

Capsules

given

Healthy

volunteers

n=100

Randomised

to capsule type

EE

Baseline Week 1 Week 2 Week 4 Week 8 Week 12

20 ml blood collected at each visit. Plasma, mononuclear cells and RBCs were isolated.

Blood sample collection

Chronic study:

Annette West, Graham Burdge &

Philip Calder

Capsule forms used:

• TAG

• Re-esterified TG

• EE

• FFA

• Placebo (palm oil)

All capsules contained 1.1 g EPA + 0.4 g

DHA

We found no difference between

TG, re-esterified TG, EE and FFA

New study:

Annette West and Philip Calder (unpublished)

• In situ emulsification of EE (as used by Qin et al)

• N = 80 healthy subjects

• 4 groups

• SMEDS EPA-EE vs EPA-EE

• SMEDS DHA-EE vs DHA-EE

• Total EPA+DHA matched across all groups (1.3 g per day)

• EPA and DHA tracked in plasma for 24 hours after single dosing

without a meal

• EPA and DHA tracked in plasma, white blood cells and red blood

cells for 12 weeks with repeated daily dosing prior to breakfast

Plasma EPA and DHA after single dosing

SMEDS EPA-EE

vs

EPA-EE

SMEDS DHA-EE

vs

DHA-EE

Plasma EPA and DHA after repeated daily dosing

SMEDS EPA-EE

Vs

EPA-EE

SMEDS DHA-EE

Vs

DHA-EE

Red blood cell EPA+DHA (Omega-3 Index) after repeated daily dosing

SMEDS EPA-EE vs EPA-EE SMEDS DHA-EE vs DHA-EE

Omega-3 Index = EPA + DHA as a

% of all fatty acids in red cell

phospholipids

The higher omega-3 status achieved with the in situ emulsification

procedure is biologically and clinically significant

Summary

• The omega-3s EPA and DHA act on cells to alter their behaviour in away that

optimises cellular responsiveness

• Epidemiological studies and RCTs show that higher intake of omega-3s is

linked with improved health

• We now know quite alot about how blood and blood cells, and to a lesser

extent tissues, respond to different amounts of omega-3s

• Over a period of days to weeks to months, EPA and DHA are incorporated in a

dose, time and pool dependent fashion from ALL formulations

• With regard to long term incorporation of EPA and DHA into the plasma and

RBC, some studies report differences among formulations (TG > FFA > EE) but

not all studies (including ours) show such differences

• Some, but not all, studies show improved incorporation of EPA and DHA from

krill oil which provides some of the omega-3 in phospholipid form

• Pre-emulsification and in situ emulsification may offer advantages to promote

EPA and DHA incorporation – so far only tested in one not yet published

chronic study

The potential and applications of seaweed: Highly nutritious, sustainable and incredibly cleverSpeaker:

Dr. Craig Rose, Founder and Managing Director, Seaweed&Co, UK

The Potential & Applications of Seaweed: Highly Nutritious, Sustainable

& Incredibly Clever!Dr Craig Rose / [email protected] / +447779 004 374

CONTENTS

•What is Seaweed

•What it can do

•Our PureSeaTM, and why

•Summary of benefits

WHAT IS SEAWEEDAlgae

Macro-algae(seaweeds)

Micro-algae

650 UK species10,000 globally

None are toxic, but supply & source is essential

e.g. spirulina and chlorella

WHAT IS SEAWEED….Perceptions

WHAT IS SEAWEED….Sustainable

• Requires no…• Fresh water• Fertiliser• Land

WHAT IS SEAWEED….Surely there is loads

WHAT IS SEAWEED….Where it comes from

• Harvested from the wild• Small/artisan scale

• Large/commercial scale

WHAT IS SEAWEED….Where it comes from

• Cultivated and harvested• Large scale cultivation for multiple industries

• Small scale, emerging technologies

PURESEATM GOODNESSNaturally innovative ingredients

Organic Hebridean Ascophyllum Seaweed

Naturally Oak Smoked Organic Scottish Seaweed

Micro-encapsulated Hebridean Seaweed Powder

SEAWEED IS HIGHLY NUTRITIOUS

Minerals are key, with other nutrition being antioxidants, phenols, essential fatty acids, all the amino acids and vitamin groups

SEAWEED IS HIGHLY NUTRITIOUS

SEAWEED IS RICH IN IODINE• A natural source of iodine• UK is vastly iodine insufficient

(worse than South Sudan!)

• Clinical trial

• Allows EU Approved Health Claims:o Normal Growth in Childreno Normal Energy Yielding Metabolismo Normal Cognitive Functiono Normal Functioning of the Nervous Systemo The Maintenance of Normal Skino Normal Production of Thyroid Hormones and Normal Thyroid Function

SEAWEED IS NATURALLY RICH IN IODINE

• Natural iodine source versus artificial source

• Natural iodine from seaweed is retained longer in the body with slower release

• Clinical trials on-going in supplements and pizzas

SEAWEED & FAT ABSORPTION• Newcastle University study

• On whole seaweed and extracts (alginates)

• Investigating lipase activity – responsible for fat digestion

Differing alginate sources & fractions, & their impact on inhibiting lipasei.e. the more inhibition, the less fat is digested and so the less absorbed

SEAWEED & FAT ABSORPTION

• Comparison of seaweed homogenate and drug Orlistat. • When polyphenols were removed (pellet), the production of glycerol was higher than when present,

therefore indicating polyphenols have an impact of the breakdown of fats, and thus production of glycerol (i.e. reduced polyphenols = more glycerol = more fat digestion)

• Can conclude polyphenols limit fat digestion and subsequent absorption as well as seaweed derived polysaccharides

SEAWEED & BLOOD SUGAR MANAGEMENT

A: Hebridean Ascophyllum: 0.5% B: Hebridean Ascophyllum: 2%

Control BreadBread + Seaweed

Impacts of polyphenols on blood sugar management

SEAWEED & BLOOD SUGAR MANAGEMENT

0 30 60 65 90 120 150 180

PolyphenolConcentration(m

gPE)

Time(mins)

Micro-encapsulatedSeaweed&Co.OrganicAscophyllumSeaweed

StandardSeaweed&Co.OrganicAscophyllumSeaweed

Gastric(Stomach)Phase SmallIntesinal Phase

Micro-encapsulated Hebridean Seaweed Powder

WHY PURESEATM

• Sustainably wild harvested from the pristine seas around the Scottish Outer Hebrides

• Scalable to the 10,000s tonnes per year

• Specialist harvesting vessels & Patent Pending processing

• Exclusive harvesting rights from the Crown Estate

• Monitored, & award winning, for sustainability & environmental good practice

QUALITY & TRACEABILITY

• World-class traceability system

• Uniquely “DNA Authenticated SeaweedTM

”

• Transparent traceability with online system detailing:

• Location and dates of harvest

• Maps of harvest site

• Photographs

• Technical documentation

• Names of harvesters

SEAWEED FOR SMOOTHIES

SEAWEED FOR SPORTS

SEAWEED FOR CAPSULES/BLENDS

SEAWEED SUMMARY

Functional Benefits

• Broad nutrition

• Iodine & Health Claims

• Weight & Blood Sugar Management

Key Messages

The Potential & Applications of Seaweed: Highly Nutritious, Sustainable

& Incredibly Clever!Dr Craig Rose / [email protected] / +447779 004 374

ADDITIONAL INFORMATION

SUPERIOR SEAWEED

New Other

ORAC analysis of antioxidant activity Polyphenols

Potential applications of astaxanthin in sports nutrition

Speakers:

Dr. Andy Sparks, Senior Lecturer in Exercise Physiology, Department of Sport and Physical Activity, Edge Hill University, UK

Danny Brown, PhD Student and Graduate Teaching Assistant, Department of Sport and Physical Activity, Edge Hill University, UK

Dr Andy Sparks and Danny BrownSport Nutrition and Performance Research Group,

Department of Sport and Physical Activity, Edge Hill University, Ormskirk, Lancashire, UK

Potential Applications of Astaxanthin in Sports Nutrition

[email protected] | [email protected] www.edgehill.ac.uk

• What is astaxanthin, and why might it be of interest to exercise physiologists and sports nutrition?

• What evidence do we have so far?

• Current and future directions of sport and exercise research on astaxanthin.

www.edgehill.ac.uk

Outline

www.edgehill.ac.uk

A simplistic view of antioxidants

So why are antioxidants important?

• Cell damage is linked to states of chronic inflammation, a symptom of many diseases

• In populations with poor nutritional intake, exogenous sources of antioxidants can be limited

www.edgehill.ac.uk

In sedentary individuals this

situation is exacerbated

Inflammation

T2DM

Neuro-degenerative

diseases

Autoimmune diseases

CV Disease

GI Diseases

www.edgehill.ac.uk

The activity/exercise setting

Bene

ficia

lE

ffect

Null-

negative

Effect

Magnitude of exercise stress

Sedentary

Lifestyle Strenuous

Exercise /

Overtraining

Oxidative stress = too low

Regular Exercise

Oxidative stress = too high

↓ ROS

↑ AO

↑ AO enzyme activity

↓ oxidative damage

↑ rate of ox. damage repair

↑ ROS

↓ AO

↓ AO enzyme activity

↑ oxidative damage

↓ rate of ox. damage repair

Astaxanthin’s antioxidant properties

• Has been reported to possess a greater antioxidant function than other phytochemicals

• Suggested to be 10 times more effective than β-carotene and 100 times greater than vitamin E.

www.edgehill.ac.uk

[Miki, 1991. Pure Appl. Chem., 63(1): 141-146]

Can scavenge ROS on

the surface and inside

the phospholipid

membrane of cells

[Shah, et al., 2016. Frontiers in Plant Science, 7: 531]

www.edgehill.ac.uk

Studies to date have suggested a role for astaxanthin in: • Increased fat metabolism during exercise

• Improved exercise performance

www.edgehill.ac.uk

So why is this of interest to athletes and exercise scientists?

[van Loon et al., 2001. J Physiol. 1; 536(Pt 1): 295–304.]

www.edgehill.ac.uk

www.edgehill.ac.uk

Evidence from Mice Exercise Models

• 3-5 weeks of astaxanthin supplementation

• ↑ fat oxidative capacity

• ↓ glycogen depletion

• ↑ endurance exercise performance

[Aoi et al., 2008. Biochem Biophys Res

Comm. 366(4):892-897]

Control Astaxanthin

Non-esterified fatty acids (mEq.L-1) 0.94 ± 0.05 1.05 ± 0.05

Muscle glycogen (mg.g-1 tissue) 2.3 ± 0.1 2.7 ± 0.1*

Plasma lactate (mM) 4.3 ± 0.3 3.5 ± 0.2*

www.edgehill.ac.uk






[Ikeuchi et al., 2006. Biol Pharm Bull.,

29(10): 2106-211]

www.edgehill.ac.uk





[Aoi et al. 2008]


www.edgehill.ac.uk





[Ikeuchi et al., 2006; Aoi et al., 2008, 2018;

Aoi et al., 2018]


www.edgehill.ac.uk

• 4 weeks of astaxanthin supplementation

• Equivocal data reported

[Earnest et al.. 2011. Int J Spo Med.,

32(11):882-888; Res et al. 2013]

Evidence from Human Exercise

Models

www.edgehill.ac.uk



[Res et al. 2013. Med Sci Sports Exerc.,

45(6):1158-1165]


Models

www.edgehill.ac.uk


32(11):882-888]




Models

www.edgehill.ac.uk



• Further research necessary


Models

www.edgehill.ac.uk


32(11):882-888; Res et al. 2013]




• Further research necessary






Models


www.edgehill.ac.uk

• There needs to be more carefully controlled, large sample sized human studies

• Careful consideration of the participant demographic

• Exercise protocol sensitivity

• Athletes prefer independently batch tested supplements

www.edgehill.ac.uk

Future Directions

Acknowledgements: Research funded by grants from AstaReal AB,

Nacka, Sweden and the Faculty of Arts and

Sciences GTA scheme. Images by

@Cadence_Images / cadenceimages.com

[email protected]

@sparks_andy

www.researchgate.net/profile/Andy_Sparks

[email protected]

www.researchgate.net/profile/Daniel_Brown75

Thank you for your attention

@dannybrown93

Supplementary Slides

www.edgehill.ac.uk

Key considerations of human exercise

experimental models

www.edgehill.ac.uk

[Shanks et al., 2009. Pilos Ethics Humanit Med 4:2]

• Bioavailability between models

is not always the same

• Regulating dietary intake is

easier in an animal model

• Human exercise performance

trials have more variability





[Liu et al. 2014; Aoi et al. 2018]


www.edgehill.ac.uk

R&D Forum 1Marine Ingredients

Documents

R&D Forum 1 - Vitafoods Europe · Is more better? Improved bioavailability of Omega-3 for improved health Speaker: Prof. Philip C. Calder, Professor of Nutritional Immunology, Human