The document reviews recent findings on the relationship between dietary fats and inflammation, challenging the notion that omega-6 fatty acids are pro-inflammatory while omega-3 fatty acids are wholly anti-inflammatory. Clinical evidence indicates that increased intake of arachidonic acid and linoleic acid does not significantly alter inflammation levels, while omega-3 fatty acids show moderate anti-inflammatory effects in specific contexts. Additionally, it concludes that saturated fats may have pro-inflammatory effects at high doses, and modern margarines can be less inflammatory compared to butter.

1. Fats and inflammation
New twists in old an old tale
Page 1

2. 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
2 www.pronutritionist.net

3. Popular black & white claim among
Paleo & Low Carb ”schools”
TFA
n-3
n-6

4. 1
Claim #1:
Arachidonic acid the driver of
inflammation
Page 4

5. Arachidonic acid & inflammation.
Evidence from clinical trials
• Increasing dietary intake • Roberts et al. 2007 (1.2 g AA/day,
no change inflammation paramaters
of arachidonic acid (AA) except in IL-6, which decreased)
by 2-4 times above • Kakutani et al. 2011 (No change in
normal intake does NOT inflammation parameters at the AA
dose of 0.72 g)
increase inflammation in
humans (randomized • Calder P. Dietary arachidonic acid:
controlled trials lasting harmful, harmless or helpful? Br J
some weeks) Nutr. 2007 Sep;98(3):451-3.
• Calder P. Polyunsaturated fatty
• New mechanisms of anti- acids and inflammatory processes:
inflammatory actions of New twists in an old tale. Biochimie
2009;91:791–795
AA have been invented
(Calder 2009)

6. Point # 1
Human RCT evidence: increased intake of
arachidonic acid does not lead to increased
inflammation (at least in short term).
6

7. 2
Claim #2: High intake of linoleic acid
increases inflammation in humans due
to increased arachidonic acid levels
Page 7

8. Linoleic acid & inflammation. Evidence
from clinical trials
• Johnson & Fritsche. Effect of
• A meta-analysis of 15 Dietary Linoleic Acid on Markers of
clinical studies: When Inflammation in Healthy Persons: A
intake of linoleic acid is Systematic Review of Randomized
Controlled Trials. Journal of the
increased by some 20-50 Academy of Nutrition and Dietetics
g/day, no change can be 2012; 112: 1029-1041
detected in inflammation
markers in blood or
erythrocytes
• The length of the studies:
2-9 weeks

9. Linoleic acid intake & AA response
Evidence from clinical trials
• Rett & Whelan. Increasing dietary
• A meta-analysis of 32 linoleic acid does not increase
clinical studies: When tissue arachidonic acid content in
intake of linoleic acid is adults consuming Western-type
diets: a systematic review. Nutr
changed dramatically (10- Metab (Lond). 2011 Jun 10;8:36.
300 % vs normal), no
significant change can be
detected in arachidonic
levels
• The length of the studies:
some weeks

10. Point # 2
Human RCT evidence:
Increased intake of linoleic acid is NOT linked
• increased inflammation
• increased arahidonic acid levels
10

11. 3
Claim #3: Omega-3 fatty acids are
strongly anti-inflammatory
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12. Omega-3 FA’s & inflammation.
Evidence from clinical trials
• A meta-analysis of 26 • Rangel-Huerta et al. Omega-3 long-
chain polyunsaturated fatty acids
clinical studies supplementation on inflammatory
• Among healthy biomakers: a systematic review of
randomised clinical trials. Br J Nutr.
individuals, no change 2012;107 Suppl 2:S159-70
in inflammation
markers
• In cardiovascular and
renal diseases n-3 fats
decreased moderately
inflammation
• The length of the studies:
2-12 weeks

13. 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
13

14. 4
Claim#4. Saturated fat is more or less
neutral in terms of inflammaton
Page 14

15. Saturated fat (SFA) & inflammation.
Evidence from clinical trials
• In meal and fat challenge • Warensjö et al. Effects of saturated and
studies, high dose SFA unsaturated fatty acids on estimated
increases IL-6, LPS and CRP desaturase activities during a controlled
levels dietary intervention. Nutr Metab
• Cardiovasc Dis. 2008;18(10):683-90
In a clinical study SFA increased
• Harte et al. High fat intake leads to
inflammation markers whereas
acute postprandial exposure to
in another it did not (Bjermo et al.
2012, Petersson et al. 2010)
circulating endotoxin in type 2 diabetic
subjects. Diabetes Care. 2012 ;
• Mechanisms: 35(2):375-82
– Increased absorption of LPS
• Masson CJ, Mensink RP Exchanging
– Decreased conversion of ALA to
saturated fatty acids for (n-6)
EPA & increased conversion of LA
to γ-LA (eventually increase in AA polyunsaturated fatty acids in a mixed
concentration) meal may decrease postprandial lipemia
– Decrease in the anti-inflammatory and markers of inflammation and
action of HDL (even if the endothelial activity in overweight men.. J
concentration is increased) Nutr. 2011 May;141(5):816-21.

16. 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
16

17. 5
Claim#5: Extra virgin oil is anti-
inflammatory
Page 17

18. Olive oil & inflammation. Evidence
from clinical trials
• In two clinical trials among • Fito et al. Anti-inflammatory effect of
men with atherosclerosis, virgin olive oil in stable coronary disease
patients: a randomized, crossover,
extra virgin olive oil was controlled trial. Eur J Clin Nutr. 2008
anti-infllammatory Apr;62(4):570-4
• Widemer et al. Beneficial effects of
• Refined olive oil is neutral polyphenol-rich olive oil in patients with
early atherosclerosis.Eur J Nutr. 2012
in terms of inflammation
Aug 8.
according to a single meal
study and a clinical trial • 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.

19. 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
19

20. 6
Claim#6: Margarine is bad for your
health because it artificial and
probably contains trans fat
Page 20

21. Margarin & inflammation. Evidence
from clinical trials
• In a recent single meal • Masson CJ, Mensink RP Exchanging
test, margarine was anti- saturated fatty acids for (n-6)
polyunsaturated fatty acids in a mixed
inflammatory whereas meal may decrease postprandial lipemia
butter induced and markers of inflammation and
endothelial activity in overweight men.. J
inflammatory response Nutr. 2011 May;141(5):816-21.
• In a clinical study (12 • Bjermo et al. Effects of n−6 PUFAs
compared with SFAs on liver fat,
weeks) margarine as the lipoproteins, and inflammation in
2nd vehicle of omega-6 fats abdominal obesity: a randomized
controlled trial. American Journal of
induced anti-inflammatory Clinical Nutrition Am J Clin Nutr. First
properties vs butter published April 4, 2012, doi: 10.3945/
ajcn.111.030114

22. Point # 6
If anything, modern margarines that are devoid
of trans fat, are modestly anti-inflammatory. At
least when compared to butter based
regimens.
22

23. 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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24. My conclusion on fatty acids
n-6
TFA SFA n-3
MUFA
24 www.pronutritionist.net

25. My conclusion on edible fats. A whole
less dramatic
Margarine
BMI Butter Refined >30 %
>40 Fish oil Weight
/cream canola oil
&T2D loss
Extra virgin
Refined olive oil Olive Oil
Massive obesity if far more inflammatory than
changes in dietary fats
Massive weight loss leads to dramatic
decrease in inflammation markers in severe
obesity

26. 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.
26

27. Please read the whole papers
Just follow the yellow links to
the original papers
Page 27

28. Follow me
http://twitter.com/pronutritionist
http://www.facebook.com/pronutritionist
http://www.pronutritionistblog.com
Reijo Laatikainen, Authorized Nutritionist, MBA,
Dietitian
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