Fats and inflammation

New twists in old an old tale

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Background

• It has been suggested by some, almost bluntly, that omega-6 fatty acids are proinflammatory and hazardous and omega-3 fatty acids are strongly anti-inflammatory (Michel de Lorgeril 2011 & many advocates of paleo and low carb diet)

• However, Harvard and many other academic nutrition experts have opposed this view: – ”Adequate intakes of both n-6 and n-3 fatty acids are essential for good

health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to ”improve” this ratio would likely increase rates of cardiovascular disease and diabetes.” (Willett 2007)”

• Major advances have been made during latest years

• This slide deck summarizes the key findings that have changed the landscape

www.pronutritionist.net2

n-6n-6n-3n-3

TFATFA

Popular black & white claim among Paleo & Low Carb ”schools”

Claim #1:Arachidonic acid the driver of

inflammation

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Arachidonic acid & inflammation. Evidence from clinical trials

• Increasing dietary intake of arachidonic acid (AA) by 2-4 times above normal intake does NOT increase inflammation in humans (randomized controlled trials lasting some weeks)

• New mechanisms of anti-inflammatory actions of AA have been invented (Calder 2009)

• Roberts et al. 2007 (1.2 g AA/day, no change inflammation paramaters except in IL-6, which decreased)

• Kakutani et al. 2011 (No change in inflammation parameters at the AA dose of 0.72 g)

• Calder P. Dietary arachidonic acid: harmful, harmless or helpful? Br J Nutr. 2007 Sep;98(3):451-3.

• Calder P. Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie 2009;91:791–795

Point # 1

Human RCT evidence: increased intake of arachidonic acid does not lead to increased

inflammation (at least in short term).

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Claim #2: High intake of linoleic acid increases inflammation in humans due

to increased arachidonic acid levels

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Linoleic acid & inflammation. Evidence from clinical trials

• Johnson & Fritsche. Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials.  Journal of the Academy of Nutrition and Dietetics 2012; 112: 1029-1041

• A meta-analysis of 15 clinical studies: When intake of linoleic acid is increased by some 20-50 g/day, no change can be detected in inflammation markers in blood or erythrocytes

• The length of the studies: 2-9 weeks

Linoleic acid intake & AA response Evidence from clinical trials

• Rett & Whelan. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review. Nutr Metab (Lond). 2011 Jun 10;8:36. 

• A meta-analysis of 32 clinical studies: When intake of linoleic acid is changed dramatically (10-300 % vs normal), no significant change can be detected in arachidonic levels

• The length of the studies: some weeks

Point # 2

Human RCT evidence:

Increased intake of linoleic acid is NOT linked • increased inflammation

• increased arahidonic acid levels

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Claim #3: Omega-3 fatty acids are strongly anti-inflammatory

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Omega-3 FA’s & inflammation. Evidence from clinical trials

• Rangel-Huerta et al. Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr. 2012;107 Suppl 2:S159-70

• A meta-analysis of 26 clinical studies

• Among healthy individuals, no change in inflammation markers• In cardiovascular and renal diseases n-3 fats decreased moderately inflammation

• The length of the studies: 2-12 weeks

Point # 3

Human RCT evidence: Marine based omega-3 fatty acids are likely to be modestly anti-inflammatory among healthy humans and

moderately anti-inflammatory in some diseases

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Claim#4. Saturated fat is more or less neutral in terms of inflammaton

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Saturated fat (SFA) & inflammation. Evidence from clinical trials

• In meal and fat challenge studies, high dose SFA increases IL-6, LPS and CRP levels

• In a clinical study SFA increased inflammation markers whereas in another it did not (Bjermo et al. 2012, Petersson et al. 2010)

• Mechanisms: – Increased absorption of LPS– Decreased conversion of ALA to EPA

& increased conversion of LA to γ-LA (eventually increase in AA concentration)

– Decrease in the anti-inflammatory action of HDL (even if the concentration is increased)

• Warensjö et al. Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention. Nutr Metab Cardiovasc Dis. 2008;18(10):683-90

• Harte et al. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care. 2012 ;35(2):375-82

• Masson CJ, Mensink RP Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men.. J Nutr. 2011 May;141(5):816-21.

Point # 4

If anything, SFA is modestly pro-inflammatory as a part of commonly consumed diet.

At the doses of > 50 grams/meal is likely to be pro-inflammatory

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Claim#5: Extra virgin oil is anti-inflammatory

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Olive oil & inflammation. Evidence from clinical trials

• In two clinical trials among men with atherosclerosis, extra virgin olive oil was anti-infllammatory

• Refined olive oil is neutral in terms of inflammation according to a single meal study and a clinical trial

• Fito et al. Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: a randomized, crossover, controlled trial. Eur J Clin Nutr. 2008 Apr;62(4):570-4

• Widemer et al. Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.Eur J Nutr. 2012 Aug 8.

• Tholstrup et al..Dietary cocoa butter or refined olive oil does not alter postprandial hsCRP and IL-6 concentrations in healthy wome. Lipids. 2011 Apr;46(4):365-70.

Point # 5

Extra virgin olive oil seems to be anti-inflammatory among men with atherosclerosis

(due to polyphenols?)

Refined olive oil (MUFA) seems to be neutral in terms of inflammation

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Claim#6: Margarine is bad for your health because it artificial and

probably contains trans fat

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Margarin & inflammation. Evidence from clinical trials

• In a recent single meal test, margarine was anti-inflammatory whereas butter induced inflammatory response

• In a clinical study (12 weeks) margarine as the 2nd vehicle of omega-6 fats induced anti-inflammatory properties vs butter

• Masson CJ, Mensink RP Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men.. J Nutr. 2011 May;141(5):816-21.

• Bjermo et al. Effects of n−6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. American Journal of Clinical Nutrition Am J Clin Nutr. First published April 4, 2012, doi: 10.3945/ ajcn.111.030114

Point # 6

If anything, modern margarines that are devoid of trans fat, are modestly anti-inflammatory. At

least when compared to butter based regimens.

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Conclusions• Omega-3 fatty are somewhat more proinflammatory than previously

described / thought

• Arachidonic acid poses some anti-inflammatory effects that has not been acknowledged previously

• Saturated fat increases AA levels and decreases EPA levels which may be especially harmful in the absence of omega-3 fatty acids

• Saturated fat increases absorption of LPS from the gut. LPS is an endotoxin and prone to cause wide spread inflammation in artery walls, liver and adipose tissue

• Some argue that high intake linoleic leads to an increase in cancer incidence. According to a large meta-analysis of clinical fat replacement studies and prospective studies this is not the case. (Zock & Katan 1998)

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My conclusion on fatty acids

www.pronutritionist.net24

n-6n-6

n-3n-3SFASFA

MUFAMUFA

TFATFA

My conclusion on edible fats. A whole less dramatic

Refined canola oilRefined

canola oil Fish oilFish oilButter /creamButter /cream

Refined olive oilRefined olive oil Extra virginOlive Oil

Extra virginOlive Oil

BMI >40

&T2D

BMI >40

&T2D

>30 %Weight

loss

>30 %Weight

loss

Massive obesity if far more inflammatory than changes in dietary fats

Massive weight loss leads to dramatic decrease in inflammation markers in severe

obesity

MargarineMargarine

Top 3 readings

• Calder Philip. Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie 2009;91:791–795

• Johnson & Fritsche. Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials.  Journal of the Academy of Nutrition and Dietetics 2012; 112: 1029-1041

• Rett & Whelan. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review. Nutr Metab (Lond). 2011 Jun 10;8:36. 

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Please read the whole papers

Just follow the yellow links to the original papers

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Reijo Laatikainen, Authorized Nutritionist, MBA,Dietitian

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