ATVB In Focus

Nutrition and Atherosclerosis

Series Editor: Margo Denke
Previous Brief Reviews in this Series:
• Isganaitis E, Lustig RH. Fast food, central nervous system insulin resistance, and obesity. 2005;25:2451–2462.
• Levine JA, Vander Weg MW, Hill JO, Klesges RC. Non-exercise activity thermogenesis: the crouching tiger hidden
dragon of societal weight gain. 2006;26:729 –736.

Dietary Factors That Promote or Retard Inflammation

Arpita Basu, Sridevi Devaraj, Ishwarlal Jialal

Abstract—Inflammation plays a pivotal role in all stages of atherosclerosis. Cardiovascular risk factors and metabolic
syndrome are typified by low-grade inflammation. Intervention trials convincingly demonstrate that weight loss reduces
biomarkers of inflammation, such as C-reactive protein (CRP) and interleukin (IL)-6. Limited studies have shown that
certain dietary factors; oleic acid, ␣-linolenic acid, and antioxidants RRR-␣-alpha tocopherol, reduce biomarkers of
inflammation. Most of the studies with fish oil supplementation have shown null effects, and conflicting results have
been reported with saturated and trans fatty acids, cholesterol, and soy intake. Much further research is needed to define
the role of individual dietary factors on the biomarkers of inflammation and the mechanism of the anti-inflammatory
effects of weight loss. (Arterioscler Thromb Vasc Biol. 2006;26:995-1001.)
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Key Words: C-reactive protein 䡲 diet 䡲 inflammation 䡲 macronutrients 䡲 micronutrients 䡲 weight loss

A growing body of literature suggests that inflammation

is pivotal in all phases of atherosclerosis, and biomar-
kers of inflammation (Table 1), especially high sensitivity
C-reactive protein (CRP), have been shown in various studies
to predict cardiovascular events.1,2
The role of dietary factors in the prevention of cardiovas-
cular disease (CVD) has been the subject of considerable
attention. The Third Report of the National Cholesterol
Education Program (NCEP) Adult Treatment Panel III (ATP
III) focuses on therapeutic lifestyle changes as the corner-
stone of therapy for CVD. The components include reduced
intakes of saturated fat and cholesterol, increased dietary
fiber, inclusion of plant sterols/stanols, increased physical
activity, and weight control.3 The goal of this review is to
examine the efficacy of the different dietary components on
biomarkers of inflammation. Particular attention will be paid
to various dietary factors which possibly retard inflammation,
as well as those that potentially promote this process. Al-
though observational studies are mentioned, the major focus
will be on dietary intervention studies in human volunteers,
which will allow for a better appreciation of dietary factors
that can be targeted clinically to attenuate inflammation.
We searched for all reports of reviews, observational studies,
as well as clinical trials that tested the effects of dietary
modifications, nutrient supplementation, and weight loss on bio-
markers of inflammation in human subjects. A PubMed search
was conducted from 1995 through December 2005, by using the
terms: biomarkers of inflammation, c-reactive protein, IL-6, fats,
cholesterol, carbohydrates, proteins, vitamins, minerals, fiber,
antioxidants, weight loss, alcohol, clinical trials, reviews, and
epidemiological observations. Our inclusion criteria for clinical
trials were random allocation of participants, and study sample
limited to men or nonpregnant women.
Weight Loss/Hypocaloric Diets and Inflammation
Elevated CRP levels have been associated with obesity.4
Several studies have been conducted in obese subjects and in

Original received August 25, 2005; final version accepted February 3, 2006.
From the Laboratory for Atherosclerosis and Metabolic Research, University of California Davis Medical Center, Sacramento, Calif.
Correspondence to I. Jialal, MD, PhD, Laboratory for Atherosclerosis and Metabolic Research, University of California Davis Medical Center, 4635
2nd Ave, Research Bldg 1, Room 3000, Sacramento, CA 95817. E-mail ishwarlal.jialal@ucdmc.ucdavis.edu
© 2006 American Heart Association, Inc.
Arterioscler Thromb Vasc Biol. is available at http://www.atvbaha.org DOI: 10.1161/01.ATV.0000214295.86079.d1

995
 996 Arterioscler Thromb Vasc Biol. May 2006

TABLE 1. Relevant Biomarkers of Inflammation and Their Possible Role in Atherosclerosis1,2,6

Biomarkers of Inflammation
CRP, SAA, fibrinogen (acute phase proteins)
Cytokines (IL-1␤, IL-6, TNF, IL-7, TNF-␣,
IL-18 etc)
Chemokines (MCP-1, IL-8)
Adhesion molecules (ICAM, VCAM, E-selectin,
P-selectin)
PAI-1 (inhibitor of fibrinolysis)
ICAM indicates intercellular adhesion molecule; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; SAA, Serum amyloid A;
VCAM, vascular cell adhesion molecule.
Potential Sources
Liver, adipose tissue, macrophages, smooth
muscle cells, endothelial cells
Endothelial cells, macrophages, adipose
tissue
Endothelial cells, macrophages
Endothelial cells
Endothelial cells, adipose tissue,
macrophages
Possible Role in Atherosclerosis
CRP associated with production of inflammatory cytokines,
chemokines, tissue factor expression, chemotaxis of
monocytes
Downregulation of eNOS and prostacyclin;
Predisposition to a state of hypercoagulability (increased
PAI-1, and decreased tPA)
Pro-atherogenic and augment monocyte-endothelial
adhesion;
IL-7 activates monocytes and enhances production of
inflammatory cytokines;
IL-18, a strong independent predictor of mortality in
patients with coronary artery disease
Stimulate chemotaxis
Promote monocyte–endothelial adhesion
Reduced plasma fibrinolysis
Promotes atherothrombosis

obese patients with hyperinsulinemia, diabetes, or rheumatoid
arthritis. Weight loss achieved through different diet pro-
grams (low-fat, high-protein, or hypocaloric diet), in combi-
nation with exercise or nutritional counseling, ranged from 3
to 15 kg resulting in concomitant reduction of CRP levels by
7% to 48%. Figure shows the correlation between weight loss
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Saturated and Trans Fatty Acids
Several observational studies have reported a positive correlation
between diets with a high content of saturated and trans fatty
acids and biomarkers of inflammation.7–9 Fung et al found a
positive correlation between CRP and the Western diet versus a
healthier prudent diet. Although the authors do not correlate

and percentage reduction of CRP levels from pooled data
from several dietary intervention trials.5 Although much re-
search is needed to elucidate the mechanisms by which weight
loss results in decreased inflammation, lowering of CRP levels
can be attributed to a decrease in fat mass which lowers IL-6
levels, which in turn decreases CRP synthesis by the liver, and
from other cellular sources.6
Dietary Fatty Acids and Biomarkers
of Inflammation
Table 2 summarizes the role of dietary fatty acids in modu-
lating biomarkers of inflammation in human subjects.
CRP with the individual foods or nutrients in the western diet,
the overall discussion suggests a positive association between
high fat intake, particularly saturated and trans fatty acids from
red and processed meats, full-fat dairy products, and french fries,
high glycemic index carbohydrates in the Western diet, and
inflammation.7 King et al further examined the National Health
and Nutrition Examination survey (NHANES; 1999 to 2000)
data, and revealed a modest association between saturated fat
consumption and elevated CRP.8 Analysis of data from the
Nurses’ Health Study I cohort revealed a 73% higher level of
CRP in women in the highest quintile of trans fat intake
compared with the lowest quintile.9
Intervention trials with trans fatty acids have been some-
what conflicting. CRP levels increased with trans fatty acid
substitution in a high-fat diet (39% fat) in healthy subjects,10
whereas, 6% substitution of trans fatty acids in a standard fat
diet (30% fat), showed no effects on CRP in moderately
hypercholesterolemic subjects,11 although it increased tumor
necrosis factor (TNF)␣ and IL-6 levels in these subjects.12
Because a high-fat diet (59% fat) has also been shown to
promote inflammation in healthy and type 2 diabetic patients,13
the level of dietary fat may influence the pro-inflammatory
actions of saturated or trans fatty acids, which, in turn, may exert
differential effects on acute phase proteins and inflammatory
cytokines.

Monounsaturated Fatty Acids (MUFA)

The Lyon Diet Heart Study demonstrates the cardioprotective
Correlation between weight loss (kg) and % C-reactive protein
(CRP) reduction from intervention trials as reviewed5 is provided. effects of a Mediterranean diet on composite measures of
Correlation coefficient : r2⫽0.8693; P⬍0.05. coronary recurrence rate after a first myocardial infarction but

TABLE 2. Summary of Randomized Clinical Trials Examining the Effects of Dietary Interventions (Whole Diet Approach or
Enrichment) With Fatty Acids (Saturated, Trans, Monounsaturated, Polyunsaturated, or Conjugated Linoleic Acid) on Biomarkers
of Inflammation.
Study (Reference) Subjects
Saturated and Trans Fatty Acids
Baer et al (10) 50 healthy adult males
Lichtenstein et al (11) 36 moderately
hypercholesterolemic adults
Han et al (12) 19 moderately
hypercholesterolemic adults
Nappo et al (13) 20 type 2 diabetic patients and
20 matched healthy subjects
Pirro et al. (37) 35 patients with primary
hypercholesterolemia and 15
normal control subjects
Monounsaturated Fatty Acids
Esposito et al (15) 180 patients with metabolic
syndrome
Michalsen et al (16) 101 patients with established
and treated CAD
Polyunsaturated Fatty Acids
Rallidis et al (19) 76 male dyslipidemic patients
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Bemelmans et al (20) 103 moderately
hypercholesterolemic adults
Zhao et al. (21) 23 hypercholesterolemic adults
Chan et al (25) 48 obese individuals and 10
lean normolipidemic men
Vega-Lopez et al (26) 80 healthy subjects
Jellema et al (27) 11 obese men
Mori et al (28) 51 treated-hypertensive type 2
diabetic subjects
Geelen et al. (29) 43 men and 41
postmenopausal women
Ciubotaru et al (30) 30 postmenopausal women
using HRT
Conjugated Linoleic Acid
Riserus et al (33) 60 men with metabolic
syndrome
Moloney et al (34) 32 adults with diet-controlled
type 2 diabetes
Smedman et al (35) 53 healthy volunteers
AAD indicates average American diet; HRT, hormone replacement therapy.
1 indicates increased and 2 indicates decreased.
Basu et al Dietary Factors and Inflammation
Type and duration of dietary intervention/enrichment
Control diet (30% fat) or experimental diets (39% fat) with 8%
substitution of oleic acid, trans fatty acid, saturated fatty
acids, stearic acid, or trans⫹stearic acid; duration 5 weeks
Experimental diets (30% fat) two-thirds fats substituted with
soybean oil, semi-liquid margarine, soft margarine, shortening,
stick margarine, or butter; duration 35 days
Experimental diets (30% fat) two-thirds fats substituted with
soybean oil, soybeal oil-based stick margarine, or butter;
duration 32 days
High-fat diet (59% fat) or high-carbohydrate diet (73%
carbohydrates), with or without antioxidants; duration 4-day
study, 1 week apart
Low-cholesterol/low-saturated fat diet (30% fat, 5% saturated
fat, cholesterol ⬍200 mg); duration 8 weeks
Mediterranean-style diet or prudent diet; duration 2 years
Mediterranean diet group or written advice-only group;
duration 1 year
15 mL linseed oil (8 grams ALA) or 15 mL safflower oil (11
grams LA); duration 12 weeks
ALA-enriched (15% ALA, 46% LA) or LA-enriched (58% LA,
0.3% ALA) margarine; duration 2 years
ALA diet (6.5% ALA, 10.5% LA), LA diet (12.6% LA, 3.6%
ALA) or AAD (7.7% LA, 0.8% ALA); duration 6 weeks
4 grams EPA⫹DHA, with or without atorvastatin (40 mg)
Duration- 6 weeks
1.5 grams EPA⫹DHA, with or without 800 IU all-rac
alpha-tocopherol; duration 12 weeks
1.35 grams of EPA⫹DHA or placebo capsules; duration
6 weeks
4 grams, DHA, or placebo; duration 6 weeks
1.5 grams EPA⫹DHA or placebo; duration- 12 weeks
1.33 grams EPA⫹DHA, or 2.56 grams EPA⫹DHA, or placebo;
duration 5 weeks
3.4 g CLA, or 3.4g purified t 10c12 CLA, or placebo Duration-
12 weeks
3.0 grams CLA isomer mixture or placebo; duration 8 weeks
4.2 grams CLA isomer mixture or placebo; duration 12 weeks
997
Change in biomarkers of Inflammation
1CRP and E-selectin levels with trans fat diet compared
with control; 1fibrinogen in stearic acid diet vs control;
no difference in any marker between oleic acid diet and
control; (P⬍0.05)
No effect on CRP with any dietary fat type (P⬎0.05)
1IL-6 and TNF-␣ with stick margarine diet vs soybean
oil diet (P⬍0.05)
1IL-6, TNF-␣, ICAM-1, VCAM-1 in healthy and diabetic
subjects with high-fat meal; increased levels only in
diabetics with high-carbohydrate meal (P⬍0.05)
2CRP levels in hypercholesterolemic patients compared
to baseline (P⬍0.05)
2hs-CRP, IL-6, Il-7, IL-18, with Mediterranean diet vs
prudent diet (P⬍0.05)
No effects on biomarkers of inflammation (P⬎0.05)
2CRP, SAA, and IL-6 in ALA group; no effects with LA
(P⬍0.05)
2CRP in the ALA group vs LA (P⬍0.05)
2CRP, VCAM-1, and E-selectin in ALA group vs LA;
Decreased ICAM-1 in ALA and LA groups vs AAD
(P⬍0.05)
2CRP and IL-6 with fish oil⫹atorvastatin, but not with
fish oil alone (P⬎0.05)
No effects on biomarkers of inflammation (P⬎0.05)
No effects on biomarkers of inflammation (P⬎0.05)
No effects on biomarkers of inflammation (P⬎0.05)
No effects on biomarkers of inflammation (P⬎0.05)
2CRP and IL-6 with fish oil vs placebo (P⬍0.05)
1CRP with t10c12 CLA supplementation vs placebo
(P⬍0.01)
CLA 2fibrinogen (P⬍0.01); no effects on CRP, IL-6
(P⬎0.05)
1CRP with CLA mixture vs placebo (P⬍0.01) No effects
on TNF-␣ and VCAM-1 (P⬎0.05)
 998 Arterioscler Thromb Vasc Biol. May 2006
did not measure biomarkers of inflammation in these sub-
jects. Whereas the authors ascribe part of the benefit to
␣-linolenic acid (ALA), the role of individual dietary factors
(oleic acid, ␣-linolenic acid, or antioxidants) in the Mediter-
ranean diet, in modulating inflammation is not yet defined.14
Esposito et al reported the anti-inflammatory effects of a
Mediterranean-style diet in patients with metabolic syn-
drome, without CVD, who randomly received instructions to
follow either a control diet or the Mediterranean-style diet.
Although the macronutrient composition of the 2 diets were
similar (carbohydrates 50% to 60%, proteins 15% to 20%,
total fat ⬍30%), the patients consuming the Mediterranean-
style diet had higher intakes of fruits, vegetables, nuts, whole
grains, and olive oil in comparison to the control group. These
patients showed a concomitant decrease in serum concentrations
of hsCRP and cytokines (IL-6, IL-7, and IL-18, P⬍0.05), and
decreased insulin resistance compared with the control group.15
However, Michalsen et al reported null effects with a Mediter-
ranean diet in patients with medically treated coronary artery
disease (CAD), on biomarkers of inflammation.16 Thus, a
Mediterranean-style diet, high in oleic acid or monounsatu-
rated fatty acid content, fiber, and antioxidants may reduce
inflammation, and corresponding coronary events in middle-
aged adults; however, their effects in patients with heart
disease need further investigation. Baer et al also demon-
strated that 8% substitution of oleic acid led to a significant
decrease in IL-6 concentrations, compared with consumption
of a saturated or trans fatty acid-substituted diet. Furthermore,
there was no difference in biomarkers of inflammation bet ween
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oleic acid diet (39% fat) and the standard fat control diet (30%
fat). Thus, oleic acid does not promote inflammation, and may
actually offset the pro-inflammatory effects of a high-fat diet, or
those seen with substitution of saturated or trans fatty acids.10
Polyunsaturated Fatty Acids (PUFA)
The relationship between dietary n-3 fatty acids [␣-linolenic
acid (ALA), eicosapentaenoic acid (EPA), and docosahexae-
noic acid (DHA)], and inflammation has been relatively
well-studied among the major dietary macronutrients. Epide-
miological studies indicate that there is an inverse association
between dietary ALA and risk of myocardial infarction.17,18
Randomized trials have reported anti-inflammatory effects of
ALA. Rallidis et al reported a significant reduction of CRP
and IL-6 levels (P⬍0.01), after ALA supplementation (8g
ALA), whereas LA supplementation (11 grams LA) de-
creased cholesterol levels with no significant effects on
inflammation in male dyslipidemic patients. The ratio of
n-6:n-3 was 1.3:1 in ALA supplemented group, and 13.2:1 in
LA supplemented group.19 Bemelmans et al also reported a
lowering of CRP levels in moderately hypercholesterolemic
men and women after consumption of an ALA-enriched mar-
garine than in those consuming a LA-enriched margarine.20
However, in a substitution study in hypercholesterolemic men
and women, reported by Zhao et al, both ALA and LA
significantly reduced CRP and intercellular cell adhesion
molecule-1 (intercellular adhesion molecule-1 [ICAM-1]),
respectively. It should be noted that in this study, both
substitution diets had high levels of LA (10.5% and 12.6%),
and had half of the total fats derived from walnuts, walnut oil,
and flaxseed oil, and saturated fatty acids provided only 8%
of the total energy. The n-6:n-3 ratio was 4:1 and 2:1, respec-
tively, in LA-substituted and ALA-substituted diets. Although
the authors do not discuss the protein content of walnuts in
modulating inflammation, there might be a role of specific
amino acids in walnuts (eg, arginine), which may also
contribute to a decrease in inflammation in the two dietary
groups. In this study, both ALA and LA substituted diets
(17% of total energy) were found to lower serum lipids (total
and low-density lipoprotein [LDL] cholesterol, and triglycer-
ides) as well as biomarkers of inflammation.21 Thus, a low
ratio of n-6:n-3 PUFA is desirable. The average American
diet comprises of an excess of n-6 fatty acids compared with
n-3 fatty acids, amounting to a ratio of 10 to 20:1, and it has
been suggested that this imbalance could potentially promote
a prothrombotic state.22
Although some epidemiological studies have shown an
inverse correlation between dietary fish or fish oil (EPA and
DHA) consumption and biomarkers of inflammation,23,24
intervention trials have not yet confirmed these effects. Chan
et al reported a significant decrease of hsCRP in obese
dyslipidemic individuals after a 6-week treatment with 40
mg/d of atorvastatin alone, and in combination with 4 g/d of
fish oil (Omacor capsules; 45% EPA and 39% DHA), but no
effects in the group treated with fish oil alone.25 Similarly null
effects with EPA and DHA supplementation were seen in
healthy subjects,26 in slightly obese individuals,27 in treated
hypertensive type 2 diabetic subjects,28 and also in postmeno-
pausal women.29 In contrast to the null effects reported by
several studies following fish oil consumption on biomarkers
of inflammation, Ciubotaru et al reported a significant de-
crease in CRP and IL-6 levels in postmenopausal women on
hormone replacement therapy (HRT) after a 5-week con-
sumption of 1.3g/d of n-3 fatty acids from fish oil compared
with placebo (safflower oil). However, it needs to be pointed
out that these women on HRT, had high levels of CRP to start
with and in the same study, the group that received 2.56 g/d
of n-3 fatty acids from fish oil did not have a decrease in CRP
or IL-6 that was significant from placebo.30 Thus, among
the n3 fatty acids, ALA appears to be anti-inflammatory.
ALA is the precursor of EPA, and there is limited conversion
of ALA to DHA.31 EPA has been inversely associated with
IL-6 in observational studies, and further intervention trials
with n3 fatty acids, alone or in combination, will confirm
these observations.32
Conjugated Linoleic Acid (CLA)
and Inflammation
A supplementation study of t10c12 CLA, CLA mixture
(t10c12⫹c9t11), or placebo in men with metabolic syndrome,
revealed that t10c12 CLA significantly increased CRP levels
(110%) compared with placebo. There was no difference in CRP
levels between CLA mixture and placebo groups, suggesting an
unfavorable effect of t10c12 CLA in inflammation and cardio-
vascular disease. Recently, Smedman et al reported a significant
increase in CRP levels, compared with placebo, after a 3-month
supplementation of CLA mixture (4.2 g/d) in healthy volunteers.
Human supplementation with CLA is thus not recommended
until further information from studies on the mechanisms of
 Basu et al
CLA and specific CLA isomers at the molecular level are
conducted.33,34,35
Cholesterol
Whole-egg supplementation significantly increased CRP levels
in healthy, lean, insulin-sensitive subjects, but had no effects in
obese or insulin resistant groups whose inflammatory marker
levels were already elevated at baseline. It has been shown
earlier that obesity or insulin resistance is associated with an
impaired cholesterol absorption. This may explain the lack of
effects of cholesterol feeding in these groups.36 Pirro et al have
demonstrated the attenuation of inflammation after an 8-week
dietary intervention with a low-cholesterol/low-saturated-fat diet
in patients with primary hypercholesterolemia.37
Thus, from the studies discussed so far it appears that the
overall quantity of fat intake, the sources and type of dietary
fat, with special emphasis on ALA and oleic acid, and the
ratio of n-6:n-3 fatty acids in the diet, collectively play a
crucial role in modulating inflammation. Although the com-
bination of fatty acids (oleic acid and ␣-linolenic acid) in the
Mediterranean diet seems to exert anti-inflammatory effects,
their individual role in attenuating inflammation remains
inconclusive and should be the focus of future research.
Carbohydrates, Dietary Fiber,
and Inflammation
Esposito et al emphasized meal modulation of cytokines (IL-8,
IL-18, and adiponectin) as a therapeutic approach toward atten-
uating atherogenic inflammatory activities in diabetic patients.
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Thirty patients with newly diagnosed type 2 diabetes mellitus
and 30 matched healthy subjects were randomly assigned to
consume 3 isoenergetic meals (780 kcal), separated by 1-week
interval; a high-fat meal (28% carbohydrates, 12% protein, and
60% fat, 2.8 grams fiber), a high-carbohydrate low-fiber meal
(70% carbohydrate, 11% protein, 19% fat, 4.5 grams fiber), and
a high-carbohydrate high-fiber meal (67% carbohydrate, 11%
protein, 22% fat, 16.8 grams fiber). Whereas the high-fat meal
increased IL-18 concentrations and decreased adiponectin con-
centrations from baseline in both nondiabetic and diabetic
subjects, the high-carbohydrate high-fiber meal, decreased IL-
18, from baseline, in both types of subjects. The high-
carbohydrate low-fiber meal significantly decreased adiponectin
concentrations in diabetic subjects, whereas IL-8 concentrations
were not affected by any of the 3 meals. However, there were no
significant differences in any biomarkers of inflammation be-
tween the 3 dietary groups.38 Jenkins et al further postulated the
anti-inflammatory effects of a dietary portfolio treatment in
hyperlipidemic adults, wherein a combination of soy proteins,
viscous fiber, plant sterols, and almonds lowered CRP levels,
similar to the statin-treated group.39 Thus, although a diet high in
fiber and complex carbohydrates is a better choice than refined
carbohydrates, but their role in reducing inflammation needs
further investigation.
Alcohol and Inflammation
Moderate alcohol intake has been associated with beneficial
effects on markers of inflammation in type 2 diabetic patients.40
A 4-week consumption of 30 g/d of alcohol from red wine led to
a significant decrease in serum concentrations of hsCRP (21%),
Dietary Factors and Inflammation 999
as well as endothelial adhesion molecules (vascular cell adhe-
sion molecule-1 [VCAM-1], ICAM-1) in healthy adult men.41
Whereas this amount of red wine exceeds the dose for moderate
drinking, however, as an essential component of the Mediterra-
nean diet,14 red wine consumption (1 to 2 glasses/d) has been
associated with reduced inflammation.
Proteins and Inflammation
Consumption of arginine-rich foods, like nuts and fish, have
been shown to lower CVD risk by reduction of inflammatory
markers.42 However, clinical trials have shown null effects with
soy isoflavones or soy proteins on biomarkers of inflamma-
tion.43,44 A soy-based meal replacement (MR) plan (SlimFast
Soy), replacing 2 meals per day with the continuing use of fruits
and vegetables as snacks and a third regular meal, has been
shown to promote weight loss, improve metabolic profile, and
lower CRP levels in diabetic subjects at 6 months in comparison
to those on an individualized diet plan (IDP).45 Although it
suggests that substitution of soy protein to a calorie-restricted
diet may promote weight loss, which in turn has been shown to
reduce CRP, as discussed earlier in this review, it does not
support the conclusion that soy proteins lower inflammation.
Micronutrients and Inflammatory Markers
Among the various micronutrients, the existing body of data
reveal RRR-␣-tocopherol, and to some extent ␥-enriched
mixed tocopherols, to be anti-inflammatory, whereas in case
of other micronutrients, data remain insufficient and inconclu-
sive.46 – 49 Limited observational studies have shown a strong
inverse association between dietary total antioxidant capacity,
individual serum carotenoids and vitamins, and magnesium, and
markers of inflammation.50 –53 Recently, Miller et al performed
a meta-analysis of 19 randomized controlled trials, using
either vitamin E alone, or in combination with other micro-
nutrients, and reported an increase in all-cause mortality with
high dosages of vitamin E (ⱖ400 IU/d).54 Their conclusions
were strongly contested by various experts who argued that
the authors did not take into consideration the different forms
of vitamin E on inflammation, and the wide heterogeneity in
the studies selected cannot support the application of the
results to general or healthy population.55 Furthermore, the
recently reported data from the Women’s Health Study
showed a highly significant 24% reduction in the secondary
end point of cardiovascular deaths, and a significant 26%
reduction in major cardiovascular events among the subgroup
of women aged at least 65 years. The study administered 600
IU of RRR-␣-tocopherol on alternate days in 39 876 healthy
US women for 10 years.56 Thus, whereas RRR-␣-tocopherol
is anti-inflammatory (ⱖ600 to 800 IU/d),46 the effects of high
doses of natural forms of vitamin E on cardiovascular end
points have essentially been negative. Further research needs
to focus on other forms of vitamin E, such as ␥-tocopherol or
combination of natural tocopherols, with weight loss to
determine whether their effects are additive.
In addition to individual dietary nutrients, research has also
focused on the anti-inflammatory factors in foods such as the
flavonoids and catechins. A 4-week consumption of green tea
(600 mL/d) significantly decreased plasma soluble P-selectin
levels in adult male smokers but had no effects on CRP
 1000 Arterioscler Thromb Vasc Biol. May 2006
levels. Phillips et al reported a significant decrease in CRP
levels after dietary supplementation of a combination of
mixed tocopherols, flavanoids, and docosahexaenoate in un-
trained healthy nonsmoking males undergoing eccentric ex-
ercise.57,58 Thus, it is difficult to attribute benefit to a single
dietary factor, and the possibility of synergy between dietary
factors needs to be borne in mind.
It appears from the available literature that a combination
of dietary factors, such as, in the Mediterranean diet, portfolio
diet, or the prudent diet may retard inflammation, possibly by
nutrient–nutrient synergy, but does not clarify the role of
individual factors in the process. Weight loss/hypocaloric
diets are definitely associated with reduced inflammation and
overall risk reduction of CVD. Also, most of the studies have
reported effects on CRP, whereas a few have focused on
pro-inflammatory cytokines such as IL-1␤, IL-6, or TNF-␣.
Future research needs to focus on the role of specific dietary
factors on biomarkers of inflammation, because they may
modulate inflammation through different mechanisms. Ther-
apeutic lifestyle changes remain the cornerstone in modulat-
ing inflammation and cardiovascular disease and much fur-
ther research is needed to define the anti-inflammatory or
pro-inflammatory effects of specific dietary factors.
Acknowledgments
This work was supported by grants from NIH K24AT00596 and
NIH HL074360.
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