Polyunsaturated Fats and

Serum C-Reactive Protein

Authors: Taulant Muka, Jessica C. Kiefte-de Jong, Albert Hofman,
Abbas Dehghan, Fernando Rivadeneira, and Oscar H. Franco

Presented by: Laurenda Guilford

Background
Rotterdam Study is a Prospective Follow Up study from the Netherlands

which began in 1989. Approx. 20,000 participants involved so far.

Has

lead to over 1,000 papers written

Targets cardiovascular, endocrine, hepatic, neurological, ophthalmic,

psychiatric, dermatological, oncological, and respiratory diseases.

Todays

study comes from data in Rotterdams Genetic and Biomarker Study

results
Blood serum and plasma assessments subsection

4,707 participants in this specific study - Ages 55+

Study Aim: Investigate whether dietary intake of total or individual (n-3,

n-6, n-3:n-6 ratio) PUFAs are associated with increased C-Reactive Protein
(CRP) levels

Background
Inflammation
Purpose a defense and repair mechanism
Triggered by numerous stimuli including: injury, infection,
chronic disease, abnormal proteins, allergens, and chemical
toxins.
Chronic inflammation results in persisting tissue damage,

which are critical components of many chronic human

diseases, including cardiovascular diseases, diabetes and
arthritis

C-Reactive Protein
Acute-phase reactant whose level in blood serum can

increase from 1 g/ml to as much as 1000-fold within

48 h after the onset of inflammation or tissue injury

WOW Look at these

Graphics!

Background
Dietary Guidelines on Fat
Saturated vs PUFAs
Saturated fat should consist of no more than 10% of the

recommended 25 35% of daily total fat intake.

The consumption of MUFAs and PUFAs (including n-3 and n-6

PUFAs) in the diet are encouraged over saturated fats

But some research has shown that a high intake of n6 may lead to exacerbation of inflammation
n-6 forms arachidonic acid- a pro-inflammatory eicosanoid
Increases biomarkers of inflammation, eg: CRP
May lead to disorders such as cardio-metabolic adversities

Background
Important notes about PUFAs in research
n-3 and n-6 PUFAs - Compete for the same enzymes
Intake of plant derived n-6 intake has DOUBLED in

recent decade- but little is known about its effect on

inflammation markers
n-6 inflammatory qualities not thoroughly

researched
Some studies show n-3 and n-6 combo to

CRP

n-6 metabolite (arachidonic acid) is a precursor for a

group of anti-inflammatory mediators as well.

Methods
At Baseline
Assessed dietary intake of PUFAs w/ FFQ (Validated
w/ additional examination of food recall vs. urea labs)
At Baseline AND Follow Up
CRP levels in blood measured w/ highly sensitive

immunoassay testing (Reliability CI of 0.995)

Final Covariates Adjusted for :

Use of Anti-Inflammatory Drugs, Smoking, Education level,

Household Income, Dietary Cholesterol Intake, Physical
Activity, BMI, Current Smoker, DHD (Dutch Healthy Diet)
Quality Index, Prevalent Chronic Disease, N-3 or n-6 PUFAs
in the analyses of n-6 or n-3 PUFAs

Figures Significant Food Sources

Pearson Correlation Coefficients (r) for Correlations Between Dietary Intakes of n-6 and n3 Polyunsaturated Fatty Acids and Their Food Sources, Rotterdam Study, 19891993 a

Food Sourceb

n-6 PUFAs

n-3 PUFAs

Vegetable oils

0.26

0.06

Butter, margarines and

hard frying fats

0.31

0.44

Fish

0.03

0.33

Poultry

0.08

0.12

Red and processed

meats

0.15

0.24

Sweet desserts and

confections

0.14

0.13

Chips

NSc

0.03

Whole grains

0.20

0.15

Total dairy foodd

NS
0.05
Abbreviations: NS, not significant; PUFAs, polyunsaturated fatty acids.
a Overall variance explained by these food items: 22% for n-6 PUFAs; 37% for n-3 PUFAs.
b PUFA intake from all food sources was expressed in g/day.
c Does not significantly contribute to n-3 or n-6 PUFAs (P > 0.05); otherwise, P < 0.05.
d Including cheese.

Relationship Between Dietary Intake of Polyunsaturated Fatty Acids (in Quartiles) and Serum CReactive Protein Level in the First and Third Rounds of the Rotterdam Study, 19891997

m C-reactive protein (CRP) concentration according to quart

of dietary intake of polyunsaturated fatty acids (PUFAs)
TOTAL
PUFA
INTAKE

N-6 PUFA
INTAKE

Men
Women Taulant Muka et al. Am. J. Epidemiol. 2015;181:846-856
The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins
Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:
journals.permissions@oup.com.

um C-reactive protein (CRP) concentration according to quart

of dietary intake of polyunsaturated fatty acids (PUFAs)
n-3 PUFA
INTAKE

n-3:n-6
PUFA
INTAKE

Men
Women -

Taulant Muka et al. Am. J. Epidemiol. 2015;181:846-856

The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins
Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:
journals.permissions@oup.com.

Interpretation of Results
After adjustment for age, gender, and all covariates.there

was an inverse association seen between Total PUFA and n6 PUFAs and CRP levels.
Many studies showing that n-3 PUFAs lower inflammatory

markers were done in Japan.

HIGH fish intake=HIGH long chain n-3 PUFA intake (EPA/DHA).
39% of this study participants did not eat any fish!

The association between n-3 PUFAs and higher CRP may be

due to the n-3s coming from butter, not fish.

No significance was found with all covariates adjusted fora clue as

to need for more research and clarity as to effects of type and
sources of dietary n-6/n-3

Interpretation of Results
-linoleic acid (ALA) n-3 is found in vegetable

oils, meats, and margarines.

Its conversion to EPA/DHA is limited in humans

which may explain the contradictory n-3 results

seen in this study!

High n-3:n-6 ratio was related to higher serum

CRP in females, but not in males

This may be due to a womans ability to synthesize

more EPA and DHA from ALA (-linoleic acid)

A Closer Look at the Study Design

Limitations

Advantages

Dietary fat intake only

assessed at baseline
FFQs can be limited by errors
Could not investigate specific
n-3 PUFAs
Could not investigate serum
levels of fatty acids
Did not assess OTHER
inflammatory markers
Physical activity was only
measured in the third round
All subjects included
NO exclusions????

Large Population Group

Prospective Design
1st prospective to use CRP @

2 times
Adjustment for broad range
of confounding variables
Highly detailed statistical
analysis

Conclusions
High intakes of PUFAs Mainly n-6 are associated

with lowered CRP levels

This may diminish chronic systemic inflammation

This study may provide support to the

continuance of current recommendations about n6 PUFAs

This study may suggest the substitution of

seafood derived n-3 for plant derived n-3 to

increase anti-inflammatory effects

Conclusions
Implications for our Field
When giving advice on the health benefits of

foods with n-3 PUFAs, recognize the source of

the n-3 may play a part in anti-inflammatory
control
Also, recognize that n-6 may also be beneficial

for their anti-inflammatory benefits. Studies

are unclear at this point.

References
1. Dietary Guidelines for Anericans 2010 - DietaryGuidelines2010.pdf.
http://health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf. Accessed
October 25, 2015.
2. Muka T, Jong JCK, Hofman A, Dehghan A, Rivadeneira F, Franco OH. Polyunsaturated
Fatty Acids and Serum C-Reactive Protein The Rotterdam Study. Am J Epidemiol.
2015;181(11):846-856. doi:10.1093/aje/kwv021.

3. Nutrition Counseling & How to Eat Healthy. Sun Health Wellbeing.

http://www.sunhealthwellbeing.org/nutrition-counseling/. Accessed October 26, 2015.
4. Steyers CM, Miller FJ. Endothelial Dysfunction in Chronic Inflammatory Diseases.
International Journal of Molecular Sciences. 2014;15(7):11324-11349.
doi:10.3390/ijms150711324.
5. Which is safer? Olive Oil or Butter at Fresh.co.nz. http://fresh.co.nz/which-issafer-olive-oil-or-butter/. Accessed October 26, 2015.

Graded Assignment Proof