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Fats and inflammation

         New twists in old an old tale




Page 1
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
Popular black & white claim among
Paleo & Low Carb ”schools”




TFA
                                    n-3
n-6
1

                  Claim #1:
         Arachidonic acid the driver of
                inflammation




Page 4
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)
Point # 1

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




6
2

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




Page 7
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
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
Point # 2
                 Human RCT evidence:
     Increased intake of linoleic acid is NOT linked
                • increased inflammation
           • increased arahidonic acid levels



10
3

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




Page 11
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
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
4

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




Page 14
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.
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
5

          Claim#5: Extra virgin oil is anti-
                  inflammatory




Page 17
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.
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
6
     Claim#6: Margarine is bad for your
       health because it artificial and
        probably contains trans fat




Page 20
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
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
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)

Page 23
My conclusion on fatty acids




                       n-6
           TFA   SFA                          n-3
                       MUFA




24                           www.pronutritionist.net
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
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
Please read the whole papers

          Just follow the yellow links to
                the original papers



Page 27
Follow me

                  http://twitter.com/pronutritionist
             http://www.facebook.com/pronutritionist
                http://www.pronutritionistblog.com

          Reijo Laatikainen, Authorized Nutritionist, MBA,
                              Dietitian




Page 28

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Fats and inflammation

  • 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 Page 11
  • 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) Page 23
  • 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 Page 28