13-Oct-15

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“Anti- Inflammation” a dietary approach

Robert GibsonProfessor of Functional Food,

University of Adelaide

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The five cardinal signs of inflammation

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Where inflammation is uncontrolled or excessive or continues unabated

tissue damage and metabolic changes occur

Diseases or conditions that involve inflammation

CAUSATIVEAsthmaAllergic diseasesAtopic diseasesPsoriasisType-2 diabetesAtherosclerosisObesity Fatty liver diseaseNeurodegenerative diseases

ASSOCIATIVE

Rheumatoid arthritisCrohn’s diseaseUlcerative colitisMultiple sclerosisAcute cardiovascular eventsResponse to surgeryMajor injury and trauma Sepsis

Lupus

Type-1 diabetes

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However, the clinical manifestations of inflammation are not always visible

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Why?

• Many hypotheses

• The most popular – change in lifestyle

• What does this mean?

– Increase in pollutants

– Change in diet

• Biggest change in diet – massive increase

in omega 6 polyunsaturates

• My primary focus: The fats in our diet

– Do they explain the rise in chronic diseases?

Apparent Consumption of LA-rich

Vegetable Oils in the U.S. (1909-99)

4.6 fold increase in the apparent consumption

of LA-rich vegetable oils since the early 1900’s

Similar trend in Australia

0

10

20

30

1909-

19

1920-

29

1930-

39

1940-

49

1950-

59

1960-

69

1970-

79

1980-

89

1990-

99

Why is this increase in LA important?

OMEGA 6

LALinoleic Acid

EPA, 20:5Eicosapentaenoic

Acid

DHA, 22:6Docosahexaenoic

Acid

AA, 20:4Arachidonic

Acid

OMEGA 3

ALAa-Linolenic

Acid

PUFAPlant oils

LCPUFAAnimal and fish

Dietary AA/DHA

Transported to every cell via

plasma lipoproteins

Incorporated into membrane

phospholipids↑DHA↓AA

Absorbed in gut

Free Fatty Acids

(FFA or NEFA)

CyclooxygenasesLipoxygenases

ProstaglandinsLeukotrienes

MaresinsProtectinsResolvins

Action on target cells

Fatty acids can give rise to

potent inflammatory regulators

ARA in various

membrane phospholipids

Free ARA2-series PGs

2-series TXs

15-HPETE

15-HETE

Lipoxin A4

12-HPETE

12-HETE

5-HPETE

5-HETE

4-series LTs

2-AG AEA

COX pathway

12

-LO

X p

ath

wa

y

CYT P450 pathway

5-, 8-, 9-, 11-, 12-,

15-, 19-, 20-HETE

EETs

DHETs

20-carboxy-ARA

20-hydroxy-PGs

The omega 6 arachidonic acid gives rise to many inflammatory mediators

ARA in various

membrane phospholipids

Free ARA2-series PGs

2-series TXs

15-HPETE

15-HETE

Lipoxin A4

12-HPETE

12-HETE

5-HPETE

5-HETE

4-series LTs

2-AG AEA

COX pathway

12

-LO

X p

ath

wa

y

CYT P450 pathway

5-, 8-, 9-, 11-, 12-,

15-, 19-, 20-HETE

EETs

DHETs

20-carboxy-ARA

20-hydroxy-PGs

w-3 fatty acids

The omega 3 fatty acids down regulate this process

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Example: rheumatoid arthritis

Effect of omega 3 fatty acids

Presenting the work of Prof Les Cleland and his colleagues (Proudman, James) at the Royal Adelaide Hospital

The Adelaide RA ‘treat to target’ trial

• A pragmatic trial in early stage RA

• Examined low (0.4g) vs high (5.5g) dose omega 3 (EPA+DHA, ~1:1) for 1 year

• Primary outcome: Dosage of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) prescribed according to symptoms

Omega 3 clinical trial - Rationale

• Benefits of fish oil have biological plausibility

• Omega 3 EPA and DHA can inhibit production of the pro-inflammatory compounds (PGE2, and LTB4, and the peptide mediators TNFα and IL1β) derived from AA

• These actions encompass the same molecular targets as NSAIDs (COX) and TNF blockers

• Furthermore EPA and DHA can be metabolised to the E and D resolvins that have been shown to resolve experimentally induced inflammation

Treatment regimen

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Effect of omega 3 on progression to lefunomide (potent anti-inflammatory drug)

Percent achieving remissionEffect of omega 3 fish oil

Conclusions

Fish oil intakes at pharmaceutical levels (>5g

EPA+DHA/d) can be used in conjunction with front

line therapy to

• Reduce intake of anti-inflammatory drugs

• Increase remission rates

These data confirm the potent anti-

inflammatory effects of omega 3 fatty acids

Need an omega 3 supplement?

Standard fish oils

Standard fish oilsFatty acid profile (%)

A B C

Total Saturates 33 33 34Total Monunsaturates

26 26 26

Total n-6 3 3 3EPA 21 20 20DHA 14 14 14

I recommend at least 600mg/d of marine omega 3sThat’s four 500mg or two 1000mg capsules/day

High Concentrate fish oil

High concentration fish oilsFatty acid profile (%)

A B C

Total Saturates 9 8 7Total Monunsaturates

8 16 12

Total n-6 4 5 5EPA 46 38 41DHA 25 29 31

Need to read the label – some capsules claim they contain more but they are just BIGGER

First rule for controlling inflammation?

• DON’T FUEL THE FIRE

• Reduce the intake of omega 6 fats

• Choose cooking oils and spreads that are low in omega 6 fatty acids

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Why is decreasing in LA important?

OMEGA 6

LALinoleic Acid

EPA, 20:5Eicosapentaenoic

Acid

DHA, 22:6Docosahexaenoic

Acid

AA, 20:4Arachidonic

Acid

OMEGA 3

ALAa-Linolenic

Acid

PUFAPlant oils

LCPUFAAnimal and fish

How much PUFA do we need

and what proportion of LA and ALA?

0

2

4

6

8

10

24

68

1012

1416 2

4

6

8

10

12

DH

A

en% LA

en% ALA

DHA production highest when total level of PUFA is low and the ratio of LA to ALA is also low

So what do these experiments tell us?

• Amazingly , the total amount of polyunsaturated fats needs to be low – no more that 2%

• This goes against everything we thought we knew about dietary fats

• It’s the balance of omega 6 and omega 3 in the basic fats in our diets that is important –2:1 is ideal

What does this mean for the fats and oils we

eat? How can we achieve this radical

departure from conventional wisdom?

• Reducing the level of polyunsaturates in oils means they have to be replaced with something

• The best option is to replace polyunsaturateswith monounsaturates which are neutral –they don’t give rise to inflammatory molecules

PUFA content of common cooking oilsSaturates Monounsat

uratesPolysomega 6

Polys omega 3

Sunflower 11 39 60 0

Canola 8 62 20 10

Rice bran 20 50 29 1

Olive oil 14 76 10 0

Butter 64 33 2 1

Macadamia 10 88 2 0

Coconut 86 6 2 0

Flaxseed 10 30 10 50

Oils in GREEN are low in LA (omega 6)

Oils to avoid: High Polyunsaturated (omega 6)

Also avoid cheap “vegetable oil “ blendsComposition, origin and age uncertain

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Macadamia:The best oil?

• Very high mono-

unsaturates

• The lowest level of

omega 6

polyunsaturates

• Most stable for

cooking

• For salads just add

10% of Flax oil

OLIVE OIL: Very good

• High in monounsaturates

• Still has about 10%

omega 6 poly’s

• But rich in poly-phenols

(anti-oxidants) – highest

in EXTRA VIRGIN (EV) –

first pressing oil

• Other olive oils less

healthy as they are lower

in polyphenols and

higher in oxidised free

fatty acids

A good oil blend for cooking

+

EV OLIVE OIL

OR

Another good oil blend

+

COCONUT OILEV OLIVE OIL

The best for salads

+

9 parts1part

EV OLIVE OIL

Final thoughts about oils

• Vegetable oil isn’t like wine – older is NOT

better. All oils and fats oxidise over time

• Eat young! Check the use-by date

• Flavour is hugely important – life is too

short to eat ‘poor’ food

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The best spread?

• Low in total PUFA

• Good omega 6 to omega

3 ratio

Eat butter not low-fat spreads,

says heart specialist . The

belief that higher total

cholesterol levels raise the

risk of heart disease is

misguided, an expert has

claimed.

What about blended margarines?

• All relatively high in

omega 6

• Often vegetable oil

blended with olive oil

• Sometimes a butter-

based blend (better)

• Best to avoid

Dietary oil recommendations

Choose oils that are:

• High in monousaturated fats

• Low in omega 6 fats (linoleic acid)

• Low in total polyunsaturates

• Contains some omega 3 fats (alpha linoleic acid)

• I don’t worry too much about Saturates

Why?“Current evidence does not clearly support CVD guidelines that encourage high consumption of PUFA

and low consumption of total saturated fats”CONTROVERSIAL

My choice

For Cooking:

• Macadamia, Olive, or a butter/olive blend

For salads

• Olive or Macadamia with added (10%) Flax oil

(Eat lots of vegetables high in anti-oxidants)

Summary (1)

• Inflammation underlies many common conditions and diseases

• We need to stop ‘feeding’ the inflammatory cascade by reducing the level of pro-inflammatory omega 6 fats

• We also need to favour diets that are rich in foods that contain anti-oxidants including polyphenols

• Human inflammatory cells can convert omega 6 fatty acids to inflammatory molecules – need to reduce

• Omega-3 fatty acids are readily incorporated into inflammatory cells and alter cell signalling, gene expression to reduce inflammatory molecules

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Summary (2)

• Omega-3 fatty acids have a proven role in controlling inflammation in patients with frank inflammatory conditions

• Correcting the balance of omega 6 to omega-3 fatty acids in cooking oils and spreads may impede development of chronic low grade inflammation associated with many chronic diseases

Eat well – eat healthy