This document discusses research on the effects of omega-3 polyunsaturated fatty acids (PUFAs) on metabolic syndrome. Early epidemiological studies found lower rates of cardiovascular and inflammatory diseases in populations with high fish/omega-3 intake. Further studies showed that omega-3 supplementation improved metabolic abnormalities in rats and human subjects, reducing triglycerides, cholesterol, blood pressure, glucose, inflammation, and endothelial dysfunction. The document concludes that omega-3 PUFAs from fish oil supplements of 1-2g per day can effectively treat metabolic syndrome with minimal side effects.

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Omega-3 Polyunsaturated Fatty Acids and
Metabolic Syndrome
Josh Nooner, BS, CSCS
4/5/16
NSCI-5960

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Introduction
Metabolic syndrome (MetS) rates have reached alarming heights, affecting 1 in 4 people
globally. Prevalence rates in America have also increased in every age group, affecting 10% of
children, 34% of adults, and 50% of those aged >50 years. Due to this distressing increase,
research has focused on ways to treat or prevent the metabolic syndrome. The use of omega-3
polyunsaturated fatty acids (PUFAs) is one potential treatment option that is being investigated.
The PUFAs, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA), are the two main
fatty acids being investigated, due to their reported ability to modulate abnormalities of MetS as
reported in early studies.
Metabolic syndrome is a collection of 5 abnormalities that increase an individual’s risk
for developing cardiovascular disease and diabetes. These include (1) Hypertriglyceridemia, (2)
hyperglycemia, (3) low HDL, (4) hypertension, and (5) high waist circumference. An individual
must present with 3 of the 5 risk factors to be diagnosed with MetS. In addition to the diagnostic
criteria, there are other abnormalities that are associated with MetS, including chronic, low-grade
inflammation, oxidative stress, and endothelial dysfunction. Studies have reported that n-3
PUFAs exert positive effects on hypertriglyceridemia, hypertension, abdominal obesity,
inflammation, oxidative stress, and endothelial dysfunction.
Early studies on omega-3 PUFAs were epidemiological studies looking at disease rates in
different cultures. In 1978, Dyerberg reported that higher EPA levels are protective against
thrombosis and atherosclerosis (Dyerberg, 1978). Then in 1980, it was reported there was a
higher EPA/Arachidonic Acid ratio in a Japanese fishing village with lower incidence of
cardiovascular and inflammatory diseases (Hirai, 1980). Furthermore, Kromann reported lower
incidence of inflammatory disorders in Greenland Eskimos with high fish intake (Kromann,

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1980). Then in 1985, a study reported an inverse relation between fish consumption and 20-year
mortality from coronary heart disease (Kromhout, 1985). Moving forward, Joel reported that fish
oil supplementation resulted in alleviation of active rheumatoid arthritis (Joel, 1987). Next,
Stenson reported fish oil supplementation results in significant improvements in ulcerative colitis
(Stenson, 1991). Lastly, it was reported that higher consumption of fish and N-3 PUFAs is
associated with a lower risk of CHD death (Hu, 2002). Taking all of these early studies into
account we can see that omega-3 PUFAs are affective at ameliorating many of the abnormalities
that present in MetS, specifically cardiovascular and inflammatory risk factors.
Furthering the strength of the argument for the use of n-3 PUFAs for the treatment of
metabolic syndrome is a study by Lombardo et al. that was published in 2007 (Lombardo, 2007).
The purpose of this study was to investigate the effectiveness of fish oil to reverse dyslipidemia,
insulin resistance, and adiposity induced by long term feeding of a sucrose-rich diet. Wistar rats
were randomly divided to receive either a control diet or a sucrose-rich diet. After 6 months, the
sucrose rich diet group were further divided to either continue the sucrose rich diet or to
supplement with fish oil for the remaining two months. At the end of the trial, blood samples and
tissue assays were taken. The results of this study showed that dietary fish oil supplementation
reverses dyslipidemia and improves insulin action and adiposity in SRD fed rats.
Then in 2009, a study was published that investigated the effect of n-3 PUFAs on
established cardiovascular risk factors including anthropometric and biochemical parameters and
heat shock protein (Hsp) 27 antibody titers in subjects with metabolic syndrome (Ebrahimi,
2009). Subjects were randomly divided to either eat their normal diet or to eat their normal diet
plus supplement with 1g of fish oil/day. Anthropometric and lab data were collected at the end of
the 6 month intervention period. Results showed that the fish oil group had a significantly

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lowered weight, BMI, systolic blood pressure, triglycerides, total cholesterol, LDL-cholesterol,
CRP level, and Hsp 27 levels. The authors concluded that, “Omega-3 PUFA supplementation
improves the cardiovascular risk profile of subjects with MetS (Ebrahimi, 2009)”
Lastly, in 2014 Tousoulis published a study that evaluated the effects of n-3 PUFAs on
vascular function and inflammatory processes in subjects with MetS (Tousoulis, 2014). This
study was a placebo-controlled, double-blind, crossover trial that randomly divided subjects into
a control group, which was to eat their normal diet plus a placebo capsule, or an experimental
group, which was to eat their normal diet plus a daily 2g fish oil capsule. At the end of the 12
week intervention period anthropometric and lab data were taken. The results showed significant
reduction in triglycerides, total cholesterol, LDL-cholesterol, fasting glucose, IL-6 levels, and
markers of endothelial dysfunction such as flow mediated dilation and pulse wave velocity. The
authors concluded that “Treatment with omega-3 PUFAs may favorably affect endothelial
function and the elastic properties of the arterial tree in MetS subjects, with a parallel anti-
inflammatory effect (Tousoulis, 2014).”
Almost every study published over this topic shows a beneficial effect from omega-3
PUFA supplementation. However, there are a few instances were using n-3 PUFA supplements,
such as fish oil, could possibly be harmful. Most of the reported side effects are minimal and not
harmful such as fishy taste, fish burps, steatorrhea, and GI upset. However, some studies have
shown that at very high doses omega-3 PUFAs can cause an increased risk for bleeding. For this
reason it is advised to avoid high doses if you are taking blood thinning medications such as
Warfarin. However, an expert opinion was published in 2007 that concluded, “We are confident
that omega-3 fatty acids do not increase risk for adverse bleeding episodes… given the number
of randomized, controlled clinical trials in which these agents were found to be safe (Harris,

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2007).” This study looked at 19 randomized clinical trials, all of them reporting no significant
increase in bleeding in the omega-3 supplemented groups.
After taking each of these studies into account, it is clear that the use of omega-3 PUFAs
for the treatment of MetS is supported by ample scientific evidence, will be highly beneficial to
the patient, and causes very minimal if any side effects. Individuals with metabolic syndrome
should supplement with 1-2g of fish oil/day, which is shown to be an effective dose for
producing significant reductions in triglycerides, total cholesterol, LDL-cholesterol, systolic
blood pressure, abdominal obesity, blood glucose, inflammation, and oxidative stress. Future
research should focus on defining the optimal N-6/N-3 ratio for metabolic syndrome,
differentiating the independent effects of EPA vs. DHA vs. ALA, and understanding the long
term effects of omega-3 PUFA supplementation.
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