CSIRO – Health & Biosecurity

Emerging trends in the global nutraceuticals market: Novel opportunities for the palm oil industry

Mahinda Abeywardena PhD. Senior Principal Scientist & Visiting Professor

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Physiologically Functional Foods

Definition :

‘Specific foods or food components that may deliver specificphysiological and/or health benefits beyond meeting basicnutritional needs’

‘A food with a health claim based on scientific evidence’

Nutraceuticals are often defined as any ‘food or part thereof which provides health benefits including prevention of treatment of disease’(Frost & Sullivan report on Global Nutraceutical Industry)

Functional Foods / Nutraceuticals

Food Pharmaceutical

Sustenance Prevention Treatment

The ‘health & wellbeing’ market consists of two main categories:

• Functional foods and beverages

• Dietary supplements

Other applications include

• Animal feeds / pet foods

• Personal care

Nutraceuticals Market Segmentation

Frost & Sullivan - FICCI

Major Nutraceutical Ingredients

Frost & Sullivan - FICCI

• Regulatory questions• Comply with legal requirements; GMP across supplement industry in particular

• Clean & Green• Responsibly sourced and sustainable ingredients

• An Aging Revolution• Healthy ageing encompasses not only seniors and baby boomers but also

Millennials and middle-age consumers• Key health needs include maintaining mental acuity, blood sugar control,

preserving muscle mass and vigour, weight control and CVD health• Science Rules• Ingredients and products supported by clinical evidence. One of the fast

emerging discipline is personalised nutritional solutions

2017 Market Trends for Nutraceuticals: Key Drivers

Nutraceutical World (2017)

Factors Driving the Nutraceuticals Market

• Growing affluent educated middle class in developing countries

• ‘Older active adults, a fear of all things artificial and more natural solutions for minor ailments will drive the market place’ (Sloan 2015)

• Scientifically validated health benefits of functional foods / supplements aimed at reducing the risk of chronic diseases CVD / diabetes, cognitive health

• Senior citizens and women preferring good digestive health

• Lower R & D and regulatory burdens for ‘pharmaceuticals’ in their ‘nutraceutical’ segment when compared to their prescription and OTC medications

Industry Trends: Vitamin E Market Size Worth Over $2.4bn by 2024

• Vitamin E Market size was over USD 2 billion in 2015, increasing with estimated gains at over 3.5%.

• Increasing healthcare costs resulting in shift in the consumer demand for dietary supplements

• Steady rise in the geriatric population ratio in developed economies (U.S., Europe, Japan)

• Consumers 65 and older accounted for over 35% of U.S. vitamin and health sales in 2015

• Older consumers also provides with opportunities for pursuing for novel applications; memory & cognition, digestive, muscle & bone health etc.,

• Expanding market for animal feed additives - (a key micronutrient in the livestock feed industry) - for improving immunity, health, reproduction and meat quality. Similarly, in the pet industry

• Rising consumer awareness and preference for ‘all things natural’ is facilitating global Vitamin E market growth

(Global Market Insights Inc; 2016)

Palm-based Phytonutrients

Lipid solubleVitamin E (rich in tocotrienols, T3)Carotenes (both α and β-carotenes)T3/Carotene/CoQ10 mixtures

Water soluble• Polyphenols (oil palm phenolics)

• Palm oil is the largest natural source of tocotrienols• Palm vitamin E; 30% tocopherols and 70% tocotrienols• Palm carotene is rich in α-carotene (30-40%)• Palm phenolics (a novel mix of natural phenolics)

Palm Antioxidants and Vascular Function

• Endothelial dysfunction important initial step in development of atherosclerosis

• Abdominal obesity, T2DM, increased glucose, blood pressure, cholesterol, inflammation → Endothelial dysfunction

• Palm tocotrienols & carotenoids promote blood vessel health and function (non-human models); effects uncertain in humans

• Brachial artery flow mediated dilation (FMD) accepted technique to quantify endothelial function

• Reduced FMD associated with increased future CVD events (Ras et al., 2013)

T3 and Vasculature:Human studies

Carotino

• Compare effects of 8 weeks supplementation with either palm-tocotrienols (Carotino-T380) or palm-carotenes (Carotino-CC60) compared to placebo on endothelial function in participants at risk of impaired vascular function

Primary aim

• Other markers of endothelial function; inflammatory markers; glucose, insulin, insulin resistance; arterial stiffness

Secondary outcomes

• Supplementation with either palm-tocotrienols (T380) or palm-carotenes (CC60) will result in greater improvements in vascular function, cardiovascular disease risk profile compared to a non-active placebo

Hypothesis

Study Design:

δ-T3, α-T3, γ-T3 and α -tocopherol concentration at 0, 4 and 8 weeks after treatment

P la c e b o T R F -8 0 C C -6 00 .0 0

0 .0 2

0 .0 4

0 .0 6

0 .0 8

δ-t

oco

trie

no

ls (µ

g/m

l)

W e e k 0

W e e k 4

W e e k 8

*

*

P la c e b o T R F -8 0 C C -6 00 .0 0

0 .0 5

0 .1 0

0 .1 5

0 .2 0

0 .2 5

α-t

oco

trie

no

ls (µ

g/m

l)

W e e k 0

W e e k 4

W e e k 8

**

P la c e b o T R F -8 0 C C -6 00 .0 0

0 .0 5

0 .1 0

0 .1 5

0 .2 0

γ-to

cotr

ien

ols

(µ

g/m

l)

W e e k 0

W e e k 4

W e e k 8*

*

P la c e b o T R F -8 0 C C -6 00

5

1 0

1 5

2 0

α-t

oco

ph

ero

l (µ

g/m

l)

W e e k 0

W e e k 4

W e e k 8

* *

Values are mean ± SE. *, significantly different from baseline and from placebo treatment.TRF-80 (420mg/day tocotrienol + 132mg/day tocopherol), CC-60 (21mg/day carotenes) or placebo (palm olein) supplements for 8 weeks.

α-carotene and β-carotene concentration at 0, 4 and 8 weeks after treatment

Values are mean ± SE. *, significantly differe nt from baseline and from placebo treatment. TRF-80 (420mg/day tocotrienol + 132mg/day tocopherol), CC-60 (21mg/day carotenes) or placebo (palm olein) supplements for 8 weeks.

Palm antioxidants and Vascular Function

Study outcomes:

• Daily supplementation with palm-tocotrienols increased plasma tocotrienols levels

• Daily supplementation with palm-carotenes increased plasma carotene levels

• Palm tocotrienols had no effects, superior or detrimental, on vascular function

• Palm carotenes had no effects, superior or detrimental, on vascular function

• No evidence of adverse drug-interactions (with medications)

Nutraceuticals: Emerging global markets

Brain health• Cognitive health is a thriving niche, particularly since it has applications throughout all

life stages and areas of the world• Dietary supplements positioned around memory or mood/relaxation claims is US$2.7

billion in retail sales (Euromonitor 2016)

Diabetes & complications• The diabetes drugs market, valued as a USD 30.95 billion market in 2016, is expected

become a USD 44.53 billion market by 2021, at a CAGR of about 7.5%. (Mordor Intelligence 2016)

• Great opportunity to develop efficacious anti-diabetic nutraceuticals and anti-glycation agents to combat secondary complications of diabetes

Polyphenols Market and Forecast

• Exceeded US$700 in 2015 and predicted to reach $1,127 by 2024. Major ingredients include grape seed, green tea and apple

• Key drivers are favourable ‘food safety’ regulations and increasing consumer awareness of health benefits

• Health & wellness applications include CVD, blood pressure, diabetes, eye disease, skin damage & repair, cancer etc.

• Supply of raw material is an issue. Technological advancements in the extraction / purification of polyphenols from fruit, vegetable, plants and herbs is predicted to boost the market demand

• Highest demand for polyphenols is seen from the functional beverage sector

Market Research Report (2016: ID 978-1-68038-127-6)

• Phenolics (2.4%)• Vitamins• Fruit acids• Fruit sugars

Oil Palm Phenolics (OPP)PP

Liquid milling waste:45 MMT (Malaysia)>100 MMT (globally)

Holding Tank

Centrifugalsystem

Lower aqueous phase containing nutraceuticals

Holding Tank

Series of membrane systems

POMW

Plate heat exchangers for cooling

Upper oil phase

Pelletedsolids

Antioxidant rich filtrate

Palm oil mill

Recovery of water soluble polyphenols (Oil Palm Phenolics: OPP)

Oil Palm Phenolics: Pre-clinical SubstantiationTest Extracts

conductance / resistance vessels

anti-arrhythmic activity

prebiotic / histology

Active compounds IP

Vascular function

Cardiac function

Gut health

Blood pressure dietary feeding and BP

PP

?

Progress review meeting 2013

N=1037 rats:17 experiments

Caecal Bulk

• OPP increases caecal contents

F u ll C a e c u m

0 .0

0 .5

1 .0

g/1

00

g b

od

yw

eig

ht

a

a

D ig e s ta

0 .0

0 .5

1 .0

g/1

00

g b

od

yw

eig

ht

a b

a cb d

c d

T is s u e

0 .0

0 .5

1 .0

g/1

00

g b

od

yw

eig

ht

+ O P P in d ie t

C o n tro l (A IN )

+ O P P in d r in k

+ G T in d r in k

a

a

n=6 per group. Common superscripts indicate significance at p<0.05 (ANOVA, Tukeys). OPP at 50 mg GAE/day. GT, Green tea.

Faecal Moisture

• OPP increases faecal moisture• Darker coloured faeces

% m

ois

ture

0

1 0

2 0

3 0

4 0

5 0 C on tro l (A IN )

Ju ice 5 0 G A E

Ju ice 7 5 G A E

OPP at 50 or 75 mg GAE/day

Control OPP

• OPP suppresses water absorption in gut lumen?

Gut Motility and Contractility

Glass bead inserted 3 cm into colon, time measured for expulsion (minutes). * indicates significance at p<0.05 (ANOVA, Tukeys).

C o lo n ic m o t i l it y t e s t

0

5 0

1 0 0

1 5 0

Min

ute

s*

*C o n tro l

O P P d r in k

3 0 % H A M S

lower times mean faster colonic transit (laxation).

Gut Contractility

• Faster transit of pellet in distal colon with OPP • Correlates with increased colonic contractility• Better laxation (anti-constipation)?

C o n t ra c t ility o f D is t a l C o lo n

-1 0 -9 -8 -7 -6

0

2 0

4 0

6 0

L o g [A n g io te n s in I] (M )

Co

ntr

acti

lity

(mm

/g)

* *

H A M S

O P P D r in k

C o n t r o l

In vitro gut contractility apparatus

Digesta Analysis (short chain fatty acids)

SCFA - Concentration

• OPP increases concentration of SCFA in caecal and colonic digesta(pre-biotic effect)

n=10 animals per group. Common superscripts indicate significance at p<0.05 (ANOVA, Tukeys). Total SCFA is the sum of all SCFA measured.

0

2 0

4 0

6 0

8 0

1 0 0

SC

FA

µm

ol/g

A ce t ic P ro p io n ic B u ty r ic T o ta l

b

a

a b

a ba

Ju ic e (5 0 G A E )

b

b

a

a b

C o n t r o l

Ju ic e (7 5 G A E )

OPP-Beneficial Microbial Effects• Digesta microbial DNA was extracted from OPP feeding studies.

• Quantitative Real-Time PCR assays were used to examine changes in numbers of selected bacterial groups and species with key roles in bowel health.

• Species significantly increased are detailed below. Effects are considered beneficial changes and may be linked with fermentation of fibres.

In vitro Fermentation

Carbohydrates in OPP

Total Sugar Total Starch Total Fibreg/100g Total

8.9 0.7 4.1 13.7

OPP preparation contains two distinct ‘bioactive families’• Cardio-vascular actions• Fermentable substrates for gut microbes

Pe

rce

nt

0

2 0

4 0

6 0

8 0

1 0 0

S t a r c h

S u g a r

F ib r e

O P P (2 2 K G A E )

Values are expressed as mean ± SEM for n=7 batches.

Gut health outcomes: Summary

Sugar Starch Fibreg/100g Total

8.9 0.7 4.1 13.7

% m

ois

ture

0

1 0

2 0

3 0

4 0

5 0 C o n tro l (A IN )

Ju ic e 5 0 G A E

Ju ic e 7 5 G A E

Faecal moisture

0

1 0 0

2 0 0

3 0 0

4 0 0

5 0 0

SCFA

µm

ol

A c e t ic P r o p io n ic B u t y r ic T o t a l

a b

b

a

a bba

a b

b

a

SCFA

Carbohydrate Histology Microbiology

D is t a l C o lo n

-1 0 -9 -8 -7 -6

0

2 0

4 0

6 0

L o g [A n g io t e n s in I] (M )

Co

ntr

acti

lity

(mm

/g)

* *

Goblet cell staining in rat distal colon

Periodic Acid Schiffs/Alcian Blue

Alcian blue/nuclear fast red

Contractility

OPP contains fermentable substrates for gut microbes

Pe

rce

nt

0

2 0

4 0

6 0

8 0

1 0 0

F ib re

S u g a r

S ta rc h

OPP induced beneficial changes (RT-PCR) on key microbes responsible for maintaining GI health

Motility

0

5 0

1 0 0

1 5 0

2 0 0

Exp

uls

ion

(M

inu

tes)

**

C o n tro l

O P P d r in k

H A M S

lower times = faster colonic transit (laxation)

Effects of SCFA: acetate, propionate and butyrate

• Increase mucus thickness• Improve integrity of intestinal barrier• Lowered visceral pain sensitivity• Butyrate is energy source for colonocytes • Butyrate has anti-cancer effect • Reduces digesta pH - pathogens and absorption of toxic

metabolites• Modulate colonic muscular activity and improve splanchic

blood flow• Promote water and electrolyte uptake• Modulate gut immune response: anti-inflammatory and anti-

allergic effects

Fibre, microbes and the gut

competitionexclusion

IgA production

Promotion ofTregs Inflammasome activation

IL-18 productionEpithelial integrity

Tissue repairStimulation ofMucous production

Inhibition of inflammation/Altered cell recruitment

FiberIndigestiblestarch Commensal

bacteria

IL-18

FoxP3

Acetate (~ 40 mM)

Butyrate (~20 mM)

Propionate (20 mM) Thorburn et al., Immunity (2014) 40: 833

Tan et al., (2017) Ann. Rev. Immunol

Dietary metabolites affect signalling and influence immune, metabolic, and nervous systems

Protective bacteria Non-protective bacteria

Summary

• OPP has shown potential to improve bowel health. The fibres found to be present in OPP may be the primary cause of the fermentation-related benefits

• There is a growing global interest and demand for prebiotic fibres (dietary fibres which induce changes in the gut microbiota that lead to a health benefit)

• An opportunity exists to developing novel prebiotics and stool bulking agents from OPP

CSIRO – HEALTH & BIOSECURITY

Thank youDr Mahinda AbeywardenaSenior Principal Research Scientist & Visiting Professort +61 8 8303 8889E mahinda.abeywardena@csiro.auw www.csiro.au