Fish Oil

Summary (The Good, The Bad, and all other Essential Benefits/Effects/Facts Information)

Fish oil is an omega-3 fat mixture which is comprised of a multitude of fatty acids. The two main fatty acids that exert benefits in the body are Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA).

Fish oil, via EPA or DHA, has been implicated in acting as ^[1]:

• An anti-inflammatory
• An anxiolytic
• A brain booster
• A heart health compound
• A liver health compound

Fish oil is likely the best way to get omega-3 fatty acids in the diet, as the EPA and DHA are closer to the final products in the body. Supplementing with other forms of omega-3 fatty acids such as Alpha-Linoleic Acid (ALA) instead of fish oil will result in less of an effect due to inefficiency of conversion in the body.

Also Known As

Eicosapentaenoic Acid, EPA, Docosahexaenoic Acid, DHA, Omega-3 fatty acids, Omega-3, Omega 3, N-3 Fatty Acids

Do Not Confuse With

Alpha-Linoleic Acid (the plant-based omega-3)

Is a Form of

• Health Support
• Nootropic

Goes Well With

• Anti-lipid peroxidation agents (Vitamin E, Milk Thistle)

• Curcumin for breast cancer risk reduction

• Fucoxanthin for increasing fucoxanthin's effects

• Fenugreek Oil, for reducing after-meal glucose spikes

• Green Tea Catechins (increases bioavailability of green tea catechins)

Does Not Go Well With

• Fat-blockers

• Alpha-Linoleic Acid (reduces effectiveness of lowering Triglycerides)

How to Take (recommended dosage, active amounts, other details)

For primary prevention (taking some 'just because'), a dose of 250mg or above seems to be the minimum.^[2] The American Heart Association recommends 1g daily^[3] and it is advised for pregnant women to increase intake of DHA by at least 200mg daily (although mercury should be a concern).^[4] These doses are effective, but would not result in any short-term (less than a week) changes.

For more acute and dramatic effects such as reducing soreness or attempting to increase metabolic flux of muscle cells, a higher dose nearing 6g may be used over the course of a day.

Things to Note

• Not a classical stimulant, but increases brain activity. Stimulatory effects may be felt, but are less potent than and unlike classical stimulants like Caffeine.

• Most benefits of fish oil come from normalizing or preventing changes in a phospholipid omega3:6 ratio, so the effects will be seen over a matter of days or weeks rather than immediately

• Fish 'burps' with supplementation can be prevented by either consuming the fish oil with food, or (anecdotally) freezing the capsules

Frequently Asked Questions Related to Fish Oil

• Can I eat flax seeds instead of fish or fish oil for omega 3s?
• When should I take Vitamin D?
• Should I take Fish Oil if I am sick?

Caution Notice (just some FYI - if needed)

• If left out in the sun or warmth, fish oil can be oxidized. Please see the Synergism section on 'Lipid Peroxidation' for more detail, but it's generally not the worst thing for healthy persons but it would be prudent to refrigerate the fish oil.

• Fish oil, as an anti-inflammatory, may be immunosuppressive and should not be taken in high doses during a state of sickness or during an outbreak of sickness in your area (if worried about getting sick)

• As a potential oxidant and as an immunosuppressive agent, more is not better with fish oil in all regards. If you wish to superload fish oil, have a method to your madness rather than just blindly consuming 10+ grams.

Detailed Summary

1. Sources and Active Molecules
   1. Fish oil contents and sources
   2. Active components of fish oil
   3. Avoiding Mercury
2. Importance of Omega-3 forms and Vegetarianism
   1. Fish Oils (EPA and DHA) and Plant Omega-3s (ALA)
   2. Comparing forms of Omega-3 fatty acids
   3. Vegetarianism or Veganism
3. Dosage and the 3:6 Ratio
   1. Membrane Rheology
4. Fish oil Metabolism and Pharmacokinetics
   1. Intestinal transit
   2. Serum values
5. Fish Oil as ligands
   1. PPAR-agonism
   2. AMPK Agonism
6. Heart Health and Fish Oil
   1. Effects on Lipoproteins and Total Cholesterol
   2. Effects on Triglycerides
   3. Effects on the endothelium
   4. Overall risk
7. Effects on Diabetes and Glycemic Control/Insulin Sensitivity
   1. Effects on blood glucose and glycemic control
   2. Effects on insulin sensitivity
   3. Diabetes and Renal function (Diabetic Nephropathy)
8. Effects on Fat Metabolism and Obesity
   1. Mechanisms of action
   2. In Vivo Studies
9. Effects on muscle cells
   1. Hypertrophy and Muscle Size
   2. Effects on Muscle Bioenergetics
   3. Health Effects
   4. Muscle healing and atrophy
10. Fish oil and Inflammation
    1. Systemic inflammation factors
    2. Response to pro-inflammatory insult
    3. Localized inflammation
    4. Effects on Cell Adhesion factors
    5. Other notables
11. Fish Oil and Cognition
    1. Neural glucose metabolism
    2. Mood Disorders related to Depression
    3. Mood Disorders related to Aggression
    4. Stress
12. Fish Oil Synergisms
    1. Lipid anti-oxidants
    2. Curcumin
    3. Fucoxanthin
    4. Fenugreek

Edit1. Sources and Active Molecules

1.1. Fish oil contents and sources

Fish oil is a solution of various fatty acids which comprise a high percentage of omega-3 PolyUnsaturated Fatty Acids (PUFAs). Of these PUFAs, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are the two most biologically active forms. Most fish oil supplements label the amount of EPA and DHA per serving, with a 180mg/120mg being the standard and most common dose per serving. Specifically, fish oil contains:

• Eicosapentaenoic Acid (EPA)

• Docosahexaenoic Acid (DHA)

• Potentially may include methylmercury contamination^[5][6][7] although this is dependent on initial source of the oil (fish) and company dependent processing.

• May contain PCB/dioxin contamination^[8][9] and organochlorine contamination.^[5][10] Again, this is dependent on the fish source and company processing.

Generally any toxin which is released into the water and is fat-soluble in nature (and thus can be stored in the tissues of fish) has potential to be found in fish oil supplementation. If possible, fish oil supplements from non-predatory and non-bottom feeding fish (such as sardines, herring, or mackeral) should be used, as mercury levels (used as a standard by which to assess 'contaminants' in general) typically are elevated in fish that consume other fish and build up stores of mercury and PCBs^[11][12], and bottom-feeders that feed on carcasses of fish and accumulate toxins and minerals.^[13] Depth of forage may also be correlated with mercury levels, making surface fish safer.^[14]

Fish itself (especially fatty fish such as mackeral) may also be a source of other nutrients such as Phosphatidylserine.

Vegetarian/Vegan sources of EPA and DHA include microalgae and flax seed oil.^[15]

1.2. Active components of fish oil

The active components of fish oil are generally considered to be the two omega-3 fatty acids, Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). Both fatty acids are similar in structure, although DHA a tad longer.

The name 'omega3' (also written as n3) comes from the greek meaning of Omega for the end. Specifically, however many carbons away from the end of the fatty acid the first double bond appears is what 'omega' the fatty acid is. As both EPA and DHA have a double bond on the third carbon from the end, they are called 'omega3 fatty acids'.

1.3. Avoiding Mercury

Although there are numerous toxins associated with fish consumption, mercury is the one at the forefront of concern due to its correlation with omega-3 intake in fish^[16][2] and its adverse effects on child cognition when consumed by pregnant mothers, as mercury can pass the placental barrier^[17] and reach the child; as assessed by umbilical cord exposure.^[18] Other toxins do not have as strong a correlation in children, such as PCBs and Dioxins^[19] and although a concern, are less of a concern relative to mercury.

Additionally, mercury just has an adverse pharmacokinetic profile. When fish is cooked, the methylmercury binds to meat proteins^[20] and 95% of ingested mercury is absorbed within 2 days^[21] where it persists in the body for 70-90 days.^[22]

In some epidemiological research, high consumption of mercury is related to heart disease risk, mostly with whale meat^[23] but related to the mercury intake itself.^[24][25] The omega3s offer a protective effect though, and avoiding the highest sources of mercury reduces a lot of risk on cardiovascular disease.^[26][27] Only the highest sources of mercury (shark and whale) seem to cause enough of an effect for significance to arise in this epidemiological research, although the effect of mercury per se may be dose dependent.

In food, one recent review noted that the safest fish in terms of "High omega3, low Mercury" were salmon, trout and shrimp.^[25] They examined those three, as well as other common fish (cod, halibut, shark, three forms of tuna, mackeral, seabass, snapper, tilapia and swordfish) for mercury content. Their results were:

• Mackeral, Cod, Trout, Catfish, Farm Raised and Canned Salmon, Shrimp, and Tilapia were all under 0.1mcg/g (0.044, 0.026, 0.020, 0.014-0.015, 0.027-0.076, 0.012, and 0.020; respectively)
• Halibut and Canned Light Tuna crossed over 0.1mcg/g (0.069-0.160, 0.030-0.102)
• Albacore Tuna, Snapper, Ahi Tuna, Chilean Sea Bass, Swordfish and Shark all were above 0.1mcg/g (0.148-0.259, 0.465, 0.291, 0.194, 0.293 and 0.541; respectively)

They^[25] also averaged the omega-3 content of said species by doing a literature review of a few studies^{[28][29][30][31][32]}, their averages were:

• Tilapia and Snapper had less than 0.2g/3oz (0.115 and 0.170)
• Cod, Light Tuna, Catfish, and Shrimp had between 0.2-0.4g/3oz (0.204, 0.238, 0.260, 0.301)
• Seabass and Swordfish had beteen 0.4-0.6g/3oz (0.417, 0.493)
• Shark, Ahi Tuna, and Albacore Tuna had between 0.6-0.8g/3oz (0.711, 0.716, 0.732)
• Halibut and Trout were between 0.8-1g/3oz (0.800, 0.818)
• Salmon and Mackeral were above 1g/3oz (1.090-1.582, with farm raised salmon having more; canned mackeral at 1.251)

In supplements, fish oil capsules and cod liver oil seem to be relatively low in mercury. Although products will vary in concentrations (depending on the fish used), one study noted a range of 0.013ng/g-2.03ng/g Mercury and no detectable methylmercury in capsules and 0.233ng/g in cod liver oil.^[6] A study conducted in the US looking at three (unnamed) brands noted values of 9.89ng/g, 38.8ng/g, and 123ng/g in one salmon oil product.^[33]

A letter to the Editors in which independent testing was done^[34] mentioned that many popular fish oil products sold in North America have below 0.1mcg/g; TwinLab, Kyolic, Nature's Way, Natrol, Health from the Sun, and Nordic were cited in this letter.^[34]

Organochlorines and PCBs are at a minute level in supplementation, below the detection limit of many studies looking at them.^[35] Some studies do note detection, however, and tend to be by far highest in predatory oils like shark oil (usually supplemented for the Squalene content).^[5]

Edit2. Importance of Omega-3 forms and Vegetarianism

2.1. Fish Oils (EPA and DHA) and Plant Omega-3s (ALA)

Fish oil, specifically the EPA and DHA components, are known as essential fatty acids to human metabolism and are required for human survival. Specifically, omega-3 fatty acids and omega-6 fatty acids are required for survival. This need is due to humans lacking enzymes (delta 15 and 12 desaturases, respectively) to convert endogenously created fatty acids into those with the specified omega denotation^[36]. EPA and DHA are not needed per se, as the parent omega-3 fatty acid Alpha-Linoleic Acid can be used (and later converted into EPA and DHA) since it also bypasses the inherent lack of a delta-15 desaturase enzyme. There is a biological need for 'omega3', but any form can be consumed.

However, the conversion rates of ALA into EPA and DHA is subpar, as the delta 6 desaturase enzyme is the rate limiting step^[37][38] and determines conversion of ALA into the bioactive EPA and DHA range from 2-10% of ingested ALA.^[39][40] Although the conversion rates seem to be flexible according to omega-3 state^[41][42] (which may help to explain why true omega-3 deficiencies are low in society) competition at this enzyme can also occur with high levels of the omega-6 fatty acid 'linoleic acid'; one of the reasons a ratio of omega-3 to omega-6 is touted.^[43][44]

As there are benefits that are attributed to EPA and DHA, rather than the parent ALA, sometimes fish oil supplementation or fish consumption is needed to circumvent the poor conversion.

It should be noted that fish or fish oil supplementation is not needed for survival, as the standard diet has enough trace ALA to supply life.

2.2. Comparing forms of Omega-3 fatty acids

There are three main forms of omega-3 fatty acids from fish oils (excluding algal oil and flax); they are fish oil triglycerides (the standard), fish oil ethyl esters (Lovaza) and fish oil phospholipids (otherwise known as Krill Oil).

These three forms of fish oils are all effective, but differ in bioavailability. If fish oil triglycerides are used as a standard of 100%, then ethyl esters seem to have a relative bioavailability of 73%^[45]. Studies comparing ethyl esters against triglyceride formulations tend to show greater blood increases in EPA with triglycerides, and also the effects of EPA.^[46][47] Aside from being less well absorbed than triglycerides, ethyl esters are also less absorbed than free fatty acids.^[48]

When natural fish oils (fish, cod liver oil) are re-esterified, they have an increase in relative bioavailability (124%); otherwise they do not differ between each other.^[45]

On the other hand, phospholipid bound fish oils from Krill Oil appear to be more bioavailable than triglyceride forms. An equipotent dose of Krill Oil appears to be 2/3rds that of fish oil.^[49][50]

2.3. Vegetarianism or Veganism

As all fish oil supplementation is derived from fish, these products are animal byproducts. Their usage would thus not be vegan.

There is research into Algae oil (or Microalgae oil), which is a vegan source of EPA and DHA.^[15] The DHA component is equivalent to fish oils in heart health^[51][52] and seems to have comparable safety.^[53]

Additionally, supplements that are not omega-3s in structure may change the body's amounts of omega-3s; either by affecting the ratio of 3:6, or by beneficially affecting the delta-6-desaturase enzyme. For example, Fucoxanthin is able to increase liver DHA levels independent of fish oil supplementation.^[54][55] One does not need fish oil per se, but just needs to alter the 3:6 ratio or otherwise increase blood levels of omega3s. There is a research mouse line, the FAT-1 mouse, that can synthesis its own omega-3 fatty acids (due to genetic upregulation of delta-6-desaturase) that harbors the benefits of fish oil supplementation without ever consuming omega3s.^[56][57][58]

Edit3. Dosage and the 3:6 Ratio

Omega 3 fatty acids tend to be dosed in relation to their omega 6 counterparts.

The actual 'ratio' refers not to dietary intake, but to the amount of omega3 to omega6 in the cellular membrane. Fish oil intake is redundant if you can get the ratio by other means, but fish oil remains the simplest means to the desired end. There is even a particular mouse line, the Fat-1 mouse, which synthesizes enough EPA and DHA to achieve a 1:1 ratio or close of omega3 to 6 fatty acids.^[56][57][58]

3.1. Membrane Rheology

Membrane rheology is the study of membrane fluidity. Due to the highly unsaturated and 'bendy' nature of long-chain omega-3 fatty acids, they are able to make membranes more flexible.

This flexibility is highly associated with increased glucose uptake and insulin sensitivity in muscle cells.^{[58][58][59][60]} No 'best' ratio is noted as of yet for muscle health, but the studies on increased protein synthesis note a doubling of the total amount of omega3s in the cell membrane.

The standard american diet tends to have an omega6:omega3 ratio of around 15-20:1 (numbers vary depending on source)^[61] and many benefits are seen in bringing the ratio closer to a 1:1 ratio.

Edit4. Fish oil Metabolism and Pharmacokinetics

4.1. Intestinal transit

EPA and DHA tend to be digested and taken up as normal dietary fats, by getting packaged into micelles in the intestines and being subsequently dropped off at fat cells and muscle cells by chylomicrons (a transport molecule) before the chylomicron remnant goes to the liver.

If the fish oils are microencapsulated (which occurs in some functional foods to avoid a fishy taste) they tend to be absorbed in the upper small intestines^[62] although a large bit is incorporated into the intestinal wall as well.^[63]

4.2. Serum values

After 28 days loading, EPA levels dose dependently increase while serum increases in DHA have a lesser drastic increase with increasing dosage.^[64] One study noted that with 3g,6g, and 12g n3 fatty acids daily (210-630mg EPA, 150-450mg DHA) serum levels seemed to reach highest levels at day 21 of supplementation.^[64]

Edit5. Fish Oil as ligands

Individual fatty acids, free from the glycerol backbone associated with storage, can act as ligands (activators) of receptors. By this manner fish oils may be peroxisome proliferator-activated receptor (PPAR) agonists through their metabolites^[65][66], GRP120 agonists^[67] RXR(y) agonist^[68] and AMPK.^[69]

Fish oil can induce long-term effects through being incorporated into receptors; although ligand dynamics are a main area to look at for more acute effects of fish oil.

5.1. PPAR-agonism

PPAR (Peroxisome Proliferator Activating Receptor) is a family of receptors found on cell nuclei. They consist of three classes, the alpha subclass (PPARa), the gamma class (PPARy) and the beta/delta class (PPARd). Fish oil is a positive agonist for PPARa^[70][71] and in adipose tissue an agonist of PPARy.^[72][73] However,

Through these agonisms, fish oil can increase adiponectin secretion from fat cells.^[74][75] Surprisingly, though, it seems to take up to 6 weeks for this effect to be physiologically relevant in humans at a dose of 2g fish oil daily.^[76] Higher levels of circulating adiponectin are seen with diets higher in fish oil omega-3s.^[77]

EPA is more potent at increasing adiponectin relative to DHA, and this increase in mediated mostly through PPARy activation.^[72][74] Fish oils can also positively regulate leptin in the same manner.^[78]

5.2. AMPK Agonism

Fish oil, specifically EPA, appears to stimulate AMPK^[69] directly rather through PI3K related means (insulin signalling). Due to this interaction, fish oil can stimulate downstream effects of AMPK, such as increasing adipokine signalling (visfatin secretion and transcription,^[69] which are dose-dependent)

Edit6. Heart Health and Fish Oil

6.1. Effects on Lipoproteins and Total Cholesterol

6.2. Effects on Triglycerides

Fish oil appears to be highly reliable in reducing triglycerides over a period of 8-16 weeks, and tends to reduce triglycerides by about 10-20% in persons with high triglycerides supplementing with a moderate dose.

The effect on triglycerides is chronic, as it does not influence TG levels after a test meal.^[79]

Fish oil may be inhibited in part by Alpha-Linoleic acid in reference to triglycerides. One study noted a 51% decrease of TGs in a low ALA group compared to 21% in a high TG group.^[80] This antagonism does not appear to carry over to incorporation into immune cells though, and may be unique to triglycerides.^[81]

6.3. Effects on the endothelium

The mechanistic basis for the improved endothelium-triggered relaxation with n - 3 PUFAs may include the suppression of thromboxane A2 or cyclic endoperoxides, a reduced production of cytokines, the augmented endothelial synthesis of nitric oxide, an improvement of vascular smooth muscle cell sensitivity to nitric oxide, and a reduced expression of endothelial adhesion molecules^[82].

6.4. Overall risk

In secondary prevention of cardiovascular disease, a ratio of 4:1 omega6:3 or lower is associated with a 70% decrease in total mortality^[61] as assessed by a single blind prospective study.^[83]

Edit7. Effects on Diabetes and Glycemic Control/Insulin Sensitivity

In regards to metabolic syndrome and diabetes, and their relation to omega-3 fatty acids, there appear to be a large amount of correlational and epidemiological research which suggests that persons with a better 3:6 ratio and higher omega-3 intake have less risk of these diseases.^[84][85][86]

7.1. Effects on blood glucose and glycemic control

There is some evidence that fish oil, when taken with a meal, can increase post-prandial glucose levels by about 2-3mg/dL by decreasing the responsiveness of the pancreas.^[87]

7.2. Effects on insulin sensitivity

In healthy persons, fish oil may not increase insulin sensitivity with a high fat (37%) diet when weight loss or gain prevented, at a dose of 3.6 EPA+DHA daily.^[88] This study did note nonsignificant trends of improved sensitivity in individuals who had higher 6:3 ratios at baseline. Other studies note similar results in healthy persons^[89] but did not record phospholipid ratios.

In otherwise healthy males, even pairing exercise with fish oil did not yeild any changes to insulin sensitivity that were attributable to the fish oil.^[90] Fish oil seems to be additive to but not synergistic with exercise.

Other studies suggest improvement in insulin sensitivity in populations who typically have worse 3:6 ratios, such as the elderly^[91] the metabolically unhealthy,^[87][92] and the obese.^[93] It should be noted that this body of evidence is not bullet-proof, and notable studies do detect no changes in insulin sensitivity even in the above populations.^{[94][95][96][97]} Furthermore, information from out rubric show that a large amount of systematic meta-analysis' show no significant ability for fish oil to change fasting glucose or fasting insulin in type II diabetics.^{[98][99][100][101]}

The above mechanism of increasing insulin sensitivity may be by preserving cell fluidity and rheology, or bringing an aberrant omega3:6 ratio back to a normal range (or preventing aberration in the first place) with no therapeutic benefit beyond that. This is supported by Haugaard et al. who demonstrate a correlation between membrane PUFA content (independent of being omega 3 or 6) but additionally the 3:6 ratio, and insulin sensitivity.^[102] Finally; in those who develop insulin resistance from fructose overfeeding, fish oil appears to be ineffective at alleviating the insulin resistance (although it still reduces triglycerides).^[103] This lends credence to the notion that fish oil's insulin sensitizing effects are at the level of the cell, as fructose causes insulin resistance at the level of the liver and pancreas.^[104]

7.3. Diabetes and Renal function (Diabetic Nephropathy)

Fish oil supplementation beneficially effects kidney function in those with diabetes (and at risk for diabetic nephropathy) at 4g daily,^[105] whereas animal models with higher doses show more dramatic protection.^[106] The mechanism may be through reducing pro-inflammatory cytokines in the kidney and through eicosanoid production.^[107][108] There isn't the largest body of literature on this function exclusively, and at least one recent review suggests that a final conclusion on fish oil's effects on renal function is preliminary.^[109]

There have been correlations established between dietary PUFA (Polyunsaturated fat) intake of omega3s and prevention of renal disease, suggesting a preventative role may also exist.^[85]

Edit8. Effects on Fat Metabolism and Obesity

8.1. Mechanisms of action

Fish oil can exert anti-obesity effects in a few manners. One is suppression of pro-adipocyte differentiation gene factors (such as PPARy), appetite suppression, and possibly via inducing adipocyte apoptosis.^[110]

Fish oil supplementation can also potentially increase metabolic rate via influence of the PPAR nuclear receptor family^[111] and increase expression of the Carnitine Palmitoyltransferase-1 (CMPT-1) enzyme in cardiac tissue while increasing the specific activity in myocytes.^[112] Fish oil also increases muscle UCP3 expression and peroxisomal acyl-CoA oxidase at high doses (40% of dietary intake) which resulted in reduced metabolic efficiency (more on this in the section on 'Muscle Bioenergetics').^[113]

Aside from the genetic improvements in energy metabolism (in regards to fat loss) in myocytes (COMT-1, UCP3, Acyl-CoA), energy metabolism in white adipocytes is also upregulated in favor of fat loss. Genetic transcription for COMT-1, nuclear respiratory factor-1, and PPAR-alpha^[114] the latter of which is a metabolic lever which upregulates motichondrial activity by multiple mechanisms of action.^[115]

8.2. In Vivo Studies

Fish oil, when supplemented in animal feed, reduces the expected weight gain associated with an obesogenic diet and thus proves itself as a preventative supplement.^[116][117] It also shows this effect in animals that are already obese, and are further given the obesogenic stimuli,^[118] and has been shown to slightly increase rates of lipid peroxidation in humans.^[119]

Many animal studies note high consumption of fish oil (primarily the EPA component) in doses in the range of 15% total energy intake, or 30-40% of total fat intake on a high fat diet(50-60% overall).^[120] Due to this, dose should be paid attention to when extrapolating animal results onto humans.

In humans, the effects are not as predictable. Large epidemiological studies have noted an inverse correlation with fish intake (indicative of the EPA/DHA components) and obesity^[121] while other studies have noted the opposite.^[122] Both studies (due to the nature of epidemiological studies) were confounded with activity level, energy intake, and possible other unforeseen and unaccounted for factors.

Double-blind controlled studies on humans show conflicting results as well. Although there is more positive results (weight loss) than no results, significance varies widely. Fish oil supplementation appears to be more effective for the purpose of weight loss in those who are obese, dyslipidemic, and exercising.^{[123][124][125][95][126][127][128]} One study noted an increase in energy expenditure and reduced metabolic efficiency in humans at 6g fish oil a day without energy restriction nor exercise, but these results were not replicated. These may be due to the in vitro mechanisms explained in the previous section.

Most studies on fish oil supplementation with energy restriction and exercise on weight loss used doses ranging from 2-4g fish oil, with approximately 2g of active EPA/DHA giving 1.6g EPA and 0.4g DHA.

In both animals and humans, the effects on fat loss seem confounded during states of insulin resistance with fat loss being less and some subjects experiencing weight gain upon fish oil intervention. This may be due to possible interactions with carbohydrates.^[129]

Edit9. Effects on muscle cells

9.1. Hypertrophy and Muscle Size

Fish oil supplementation has been linked in older and young (of both genders) adults to augmenting muscle protein synthesis that is induced from amino acids.^[130] This effect also seems to occur in healthy youth, and seems to be from augmenting the anabolic response to leucine.^[131] This mechanism may be mediated by a beneficial influence on SMAD signalling, particularily suppression of SMAD2 and increased expression of SMAD7 (inhibitory SMAD)^[132] while preventing the SMAD2/3 complex from entering the nucleus to hinder protein synthesis.^[133] SMAD manipulation is in a way similar to Myostatin inhibition as the SMAD signalling cascade is activated from Myostatin, and Myostatin appears to not increase protein synthesis per se, but to drastically augment other means of anabolism.

9.2. Effects on Muscle Bioenergetics

A very high dose (1g/kg bodyweight; about 28% EPA+DHA content) fish oil in rats shows increased glycogen resynthesis rates and increased glucose oxidation independent of insulin,^[134] and 14% increase lactate concentration that was dependent of insulin stimulation. The increased glucose oxidation and uptake may be downstream effects of increasing transcription of AMPK.^[135] Activation of AMPK has been noted in other tissues by DHA, such as the intestines^[136] and can do so vicariously though adiponectin.^[77] This increase in glucose oxidation (possibly by AMPK) was also noted at intakes of 1.8g omega3 (1.1 EPA, 0.7 DHA), which quantified the same glucose oxidation rates despite a 17% lesser AUC for insulin.^[137]

Fish oil seems to upregulate mRNA for uncoupling proteins (heat production) in mouse muscle UCP3, brown adipose tissue UCP2, and liver UCP2^[138][139] although a drop is seen in white adipose tissue UCP2. Muscle upregulation is seen in bovine as well.^[140] Although increased UCP expression is correlated with decreased energy efficiency, a dose of 7.2g fish oil (1.1g EPA, 0.7g DHA) does not significantly impair energy efficiency in otherwise healthy males.^[90] This study did not a trend of increasing fat utilization over carbohydrates, however; uncoupling proteins were not measured. This may be a dose issue, as metabolic efficiency is greatly reduced when fish oil is superloaded at 40% of energy intake in rats.^[113]

Fish oil (technically, EPA) incubation in muscle cells is associated with a greater ability for the muscle cell to switch from glucose to fat as primary substrate for oxidation, a phenomena known as 'bioenergetic flexibility' of 'metabolic switching'.^[141]

9.3. Health Effects

In mice and over longer periods of time, fish oil can preserve the effects of some hormones (insulin, adiponectin) on muscle cells when normally exposed to an obesogenic diet.^[142][77] This may be due to the fish oil component DHA being able to partially reverse the reduction seen in muscle glucose uptake with Palmitic Acid, a saturated fatty acid.^[135] Normalizing the phospholipid ratio (independent of fish oil) does seem to increase adiponectin secretion, however.^[143] It is not clear whether the means to the end (fish oil) or the end (ratio) are the cause of health benefits seen.

In muscle cells, fish oil can also increase AMPK mRNA levels, particularly the AMPKa2 subset.^[135] It has been implicated in doing so in white adipose tissue as well.^[144]

High doses of EPA (0.5g/kg) have been shown to reduce PPARd and PPARy expression in muscle cells, and interfere with the production of pro-inflammatory TNF-a and IL-6, which lend credence to its anti-inflammatory claims.^[144] Increased GLUT4 expression was seen at this dose, although lower doses show only increases in GLUT1 translocation.^[145]

Possibly through AMPK, a decreased n6/n3 ratio (more omega 3 relative to omega 6) in muscle cells is associated with increased glucose uptake and better whole-body glucose tolerance independent of mitochondria.^[58] The ratio was approximately 0.5:1-1.5:1 (fish oil) relative to 17.5:1-29.7:1 (control), as measured in the cell membrane.^[58] The muscle cell membrane seems highly response to dietary changes in omega fatty acid intake^[59] and has been associated in vivo with human insulin sensitivity.^[60]

9.4. Muscle healing and atrophy

In mice subject to immobilization, fish oil supplementation has been implicated in decreasing the rate of muscle degeneration.^[146] However, it also hinders recovery after the fact for a few days via the same pathway.^[147]

Some studies in post-surgery situations note increased retention of lean body mass when EPA is added to enteral nutrition.^[148][149] Its still under investigation, however, as some studies note no difference.^[150]

Edit10. Fish oil and Inflammation

10.1. Systemic inflammation factors

Overall, fish oil supplementation does not tend to decrease systemic inflammation factors; most commonly researched are IL-6, TNF-a and IL-1.^{[151][152][153][154]}

In studies done on wholly healthy subjects, fish oil does not show an anti-inflammatory effect.^[155] In persons with metabolic syndrome or similar pathology (obesity, high blood triglycerides, pre-diabetes) fish oil still does not reduce systemic inflammation.^[156]

It appears an exception to the above may be children of those with diabetes type II, in which fish oil may reduce systemic inflammation as measured by TNF-a.^[157] Additionally, at least one study noted less inflammation in adolescents using fish oil.^[158]

10.2. Response to pro-inflammatory insult

Fish oil seems to be able to suppress the pro-inflammatory response by various factors, which exerts an overall anti-inflammatory effect that is dependent on a metabolic insult.

It has been shown to reduce inflammation after exercise^[159] and after Lipopolysaccharide insult (a experimental test to induce systemic inflammation)^[160][161]

10.3. Localized inflammation

Some in vivo studies note less expression of pro-inflammatory genes in adipocytes (fat cells) after fish oil supplementation.^[162]

10.4. Effects on Cell Adhesion factors

Cell adhesion factors are responsible for attracting and 'pulling' immune cells into tissues that express pro-inflammatory signals.

Fish oil tends to show a slightly anti-inflammatory effect in middle aged and older men by reducing the expression of cell adhesion factors^[163]

10.5. Other notables

Fish oil's anti-inflammatory effects seem to be more effective in a low-sucrose (possibly low-carbohydrate) diet when compared against diets with a higher sucrose content.^[129]

Edit11. Fish Oil and Cognition

11.1. Neural glucose metabolism

When a deficiency state is enforced upon a lab animal, deficiencies in omega-3 fatty acids (especially EPA and DHA) are associated with reduced glucose uptake and utilization into neurons^[164] which may be associated with reduced transporters.^[165] Supplementing this deficiency state with omega-3s appears to fix the problems with glucose metabolism in neurons.^[166][167]

One study noted DHA supplementation in elderly but otherwise healthy monkeys (at 150mg/kg bodyweight) increased neuronal glucose uptake.^[168]

In healthy humans, fish oil per se does not appear to increase neurological glucose uptake (metabolic rate of glucose), although by reducing triglycerides it may help (as TGs reduce neural usage of glucose).^[169]

In some disease states or mental disorders, however, a low level of omega-3 is associated with the standard pathology^[170] and thus fish oil may have a therapeutic effect. At least one review indicated anxiety disorders, attention disorders, and mood disorders as potential avenues.^[171]

11.2. Mood Disorders related to Depression

It is hypothesized that a deficiency of EPA results in depressive symptoms in humans.

In otherwise healthy persons with depressive-like symptoms, fish oil does not appear to further increase well-being at 1800mg EPA+DHA in elderly adults,^[172] completely healthy adults.^[173] In line with the deficiency theory.

11.3. Mood Disorders related to Aggression

It has been hypothesized that aggression is a symptom of DHA deficiency,^[174] in which case supplemental DHA would alleviate this deficiency.

In otherwise healthy persons, DHA appears to prevent excessive aggression in times of stress^[175][176] and has been found to prevent a decline in aggression during destressing follow-up periods.^[177] These effects are seen (like depression and stress) in the range of 1.5g daily, and don't appear to occur at 150mg DHA daily.^[176] An exception may be schoolchildren, who showed benefit at 3.6g per week.^[178]

11.4. Stress

Fish oil supplementation in rats (at 5% food intake) was found to normalize the stress response after being subject to footshock, a research test used to mimic long-term environmental stress.^[179] This has been replicated in other models on animals and in humans with DHA supplementation at high doses (1.5-1.8g DHA) daily in which adrenaline response to stress is attenuated.^[174][180] In longer term models to assess cortisol (long term stress hormone), students taking 20 exams had a similar decrease in noradrenaline (-31%) at 1.5g DHA daily, although no changes in cortisol were noted.^[181]

In regards to stress, both EPA and DHA seem to have implications. EPA from modulating some immune functions associated with stress^[182] and DHA is tied in with aggressive increases during stressful times.^[183]

Interestingly, a low dose of 762mg EPA+DHA daily can reduce noradrenaline levels even in healthy non-stressed persons.^[184]

Edit12. Fish Oil Synergisms

12.1. Lipid anti-oxidants

Fish oil, as it is a highly unsaturated fatty acid, can be subject to 'lipid peroxidation' which is when the double bonds (unsaturated segments) become oxidized. This converts the fatty acid into a pro-oxidant compound.^[185] In theory this is quite a bad (pro-oxidant) reaction, although it doesn't appear to be a large concern in otherwise healthy individuals.^[186]

Additionally, fish oil supplementation might increase markers of lipid peroxidation in vivo.^[187][188] This topic, however, is not clear cut as some studies do not note changes in oxidation biomarkers.^[189][190]

In vivo research notes that pair fish oil with anti-lipid peroxidation compounds (research standard is vitamin E) show delayed oxidation and preserving bodily amounts of vitamin E.^[191][192] Supplementing vitamin E may also reduce the anti-oxidative response by the body by inhibiting the pro-oxidative insult by fish oil.^[193]

In regards to supplementation though, not all lipid peroxidation can be negated with added anti-oxidants although a good deal is reduced.^[194]

12.2. Curcumin

One in vitro study noted that although the fish oil compound Docosahexaenoic acid (DHA) and Curcumin were both beneficial for breast cancer cells, they showed synergism in 5 cell models. The cells showed enhanced curcumin uptake, and both compounds acted on different (and thus not overlapping) signalling pathways.^[195]

Additionally, curcumin has been shown in vitro to be synergistic with both EPA and DHA in a cell line of macrophages (immune cells) and suppressing a pro-inflammatory response.^[196]

Both curcumin and fish oil positively affect Brain Derived Neurotropic Factor (BDNF) and may be synergistic in cognitive enhancement, although this is speculative.^[197]

12.3. Fucoxanthin

The carotenoid from seaweed, Fucoxanthin, has been found to be slightly synergistic with fish oil for attenuating weight gain in obese and diabetic mice.^[198] The addition of fish oil at 6.9% of the diet (quite a high dose) was found to make 0.1% dietary fucoxanthin as effective at suppressing fat gain as double the dose.^[198]

Interestingly, fucoxanthin can increase liver levels of DHA independent of fish oil consumption.^[55]

12.4. Fenugreek

When a Fenugreek oil (formulated with 15% fish oil by weight) was given to diabetic rats at 5% of food intake, it resulted in a 51% decrease in blood glucose levels after a meal due to decrease the activity of carbohydrate digesting enzymes in the pancreas (46% reduction in α-amylase, 37% reduction in maltase) and plasma (52% α-amylase, 35% maltase).^[199] The combination 5% group was slightly more potent than the 5% Fenugreek group and much more than the 5% fish oil group.

A protective effect on pancreatic beta-cells was also noted with this combination^[199] as well as decreases in triglycerides attributed to the fish oil component. Said infusion also normalized the increase in ACE that diabetic rats experience.^[199]

Human Clinical Trial Results

Confidence	Attribute	Result in Studies	References
A	Triglycerides		Show 22 Studies
A	Cell Adhesion Factors (Elderly)		Show 3 Studies
A	ADHD in Children		Show 7 Studies
A	Muscle Soreness		Show 3 Studies
A	C-Reactive Protein		Show 11 Studies
A	Inflammation		Show 16 Studies
A	Blood Pressure		Show 4 Studies
A	Total Cholesterol		Show 4 Studies
A	Weight		Show 6 Studies
A	LDL-C		Show 5 Studies
A	HDL-C		Show 4 Studies
A	Arterial Stiffness		Show 4 Studies
A	Depression		Show 4 Studies
B	Cell Adhesion Factors (Youth)		Show 4 Studies
B	Cortisol		Show 2 Studies
B	HbA1c		Show 3 Studies
B	Homocysteine		Show Study
B	General Oxidation		Show 2 Studies
B	Treatment of NAFLD		Show Study
B	Insulin Sensitivity		Show Study
B	Treatment of PCOS		Show 2 Studies
B	vLDL-C		Show Study
B	Platlet Aggregation		Show 2 Studies
B	Anxiety		Show Study

Scientific Support & Reference Citations

References

1. Effects of omega-3 fatty acids on cytokines and adhesion molecules
2. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. (2006)
3. Kris-Etherton PM, Harris WS, Appel LJ; AHA Nutrition Committee. American Heart Association. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol. (2003)
4. Koletzko B, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. (2008)
5. Rawn DF, et al. Persistent organic pollutants in fish oil supplements on the Canadian market: polychlorinated biphenyls and organochlorine insecticides. J Food Sci. (2009)
6. Smutna M, et al. Fish oil and cod liver as safe and healthy food supplements. Neuro Endocrinol Lett. (2009)
7. Jordan RG. Prenatal omega-3 fatty acids: review and recommendations. J Midwifery Womens Health. (2010)
8. Fernandes AR, et al. Dioxins and polychlorinated biphenyls (PCBs) in fish oil dietary supplements: occurrence and human exposure in the UK. Food Addit Contam. (2006)
9. Bourdon JA, et al. Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements: implications for daily intake of dioxins and PCBs. Food Chem Toxicol. (2010)
10. Jacobs MN, et al. Organochlorine residues in fish oil dietary supplements: comparison with industrial grade oils. Chemosphere. (1998)
11. Akutsu K, Tanaka Y, Hayakawa K. Occurrence of polybrominated diphenyl ethers and polychlorinated biphenyls in shark liver oil supplements. Food Addit Contam. (2006)
12. Mahaffey KR. Methylmercury: a new look at the risks. Public Health Rep. (1999)
13. Guéguen M, et al. Shellfish and residual chemical contaminants: hazards, monitoring, and health risk assessment along French coasts. Rev Environ Contam Toxicol. (2011)
14. Choy CA, et al. The influence of depth on mercury levels in pelagic fishes and their prey. Proc Natl Acad Sci U S A. (2009)
15. Doughman SD, Krupanidhi S, Sanjeevi CB. Omega-3 fatty acids for nutrition and medicine: considering microalgae oil as a vegetarian source of EPA and DHA. Curr Diabetes Rev. (2007)
16. Tsuji M, et al. Relationship between RBC mercury levels and serum n3 polyunsaturated fatty acid concentrations among Japanese men and women. J Environ Public Health. (2012)
17. Boadi WY, et al. In vitro effect of mercury on enzyme activities and its accumulation in the first-trimester human placenta. Environ Res. (1992)
18. Grandjean P, et al. Impact of maternal seafood diet on fetal exposure to mercury, selenium, and lead. Arch Environ Health. (1992)
19. Huang MC, et al. Placental docosahexaenoic and arachidonic acids correlate weakly with placental polychlorinated dibenzofurans (PCDF) and are uncorrelated with polychlorinated dibenzo-p-dioxins (PCDD) or polychlorinated biphenyls (PCB) at delivery: a pilot study. Food Chem Toxicol. (2011)
20. Domingo JL, et al. Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. Toxicology. (2007)
21. Hightower JM, Moore D. Mercury levels in high-end consumers of fish. Environ Health Perspect. (2003)
22. Health benefits and potential risks related to consumption of fish or fish oil
23. Choi AL, et al. Methylmercury exposure and adverse cardiovascular effects in Faroese whaling men. Environ Health Perspect. (2009)
24. Mercury as a risk factor for cardiovascular diseases
25. Smith KL, Guentzel JL. Mercury concentrations and omega-3 fatty acids in fish and shrimp: Preferential consumption for maximum health benefits. Mar Pollut Bull. (2010)
26. Mozaffarian D, et al. Mercury exposure and risk of cardiovascular disease in two U.S. cohorts. N Engl J Med. (2011)
27. Yoshizawa K, et al. Mercury and the risk of coronary heart disease in men. N Engl J Med. (2002)
28. Mahaffey KR, Clickner RP, Jeffries RA. Methylmercury and omega-3 fatty acids: co-occurrence of dietary sources with emphasis on fish and shellfish. Environ Res. (2008)
29. Harris WS, Kris-Etherton PM, Harris KA. Intakes of long-chain omega-3 fatty acid associated with reduced risk for death from coronary heart disease in healthy adults. Curr Atheroscler Rep. (2008)
30. Psota TL, Gebauer SK, Kris-Etherton P. Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol. (2006)
31. Connor WE, DeFrancesco CA, Connor SL. N-3 fatty acids from fish oil. Effects on plasma lipoproteins and hypertriglyceridemic patients. Ann N Y Acad Sci. (1993)
32. Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease
33. Levine KE, et al. Determination of mercury in an assortment of dietary supplements using an inexpensive combustion atomic absorption spectrometry technique. J Autom Methods Manag Chem. (2005)
34. Schaller JL. Mercury and fish oil supplements. MedGenMed. (2001)
35. Melanson SF, et al. Measurement of organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. Arch Pathol Lab Med. (2005)
36. Tvrzicka E, et al. Fatty acids as biocompounds: their role in human metabolism, health and disease--a review. Part 1: classification, dietary sources and biological functions. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. (2011)
37. Brenna JT, et al. alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. (2009)
38. Yamazaki K, et al. Comparison of the conversion rates of alpha-linolenic acid (18:3(n - 3)) and stearidonic acid (18:4(n - 3)) to longer polyunsaturated fatty acids in rats. Biochim Biophys Acta. (1992)
39. Anderson BM, Ma DW. Are all n-3 polyunsaturated fatty acids created equal. Lipids Health Dis. (2009)
40. Dietary n-6 and n-3 Fatty Acid Balance and Cardiovascular Health
41. Igarashi M, et al. Low liver conversion rate of alpha-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet. J Lipid Res. (2006)
42. Igarashi M, et al. Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. J Lipid Res. (2007)
43. Kinsella JE, Broughton KS, Whelan JW. Dietary unsaturated fatty acids: interactions and possible needs in relation to eicosanoid synthesis. J Nutr Biochem. (1990)
44. Harnack K, Andersen G, Somoza V. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids. Nutr Metab (Lond). (2009)
45. Dyerberg J, et al. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. (2010)
46. Neubronner J, et al. Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. Eur J Clin Nutr. (2011)
47. Hansen JB, et al. Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, haemostasis and platelet function in normolipaemic men. Eur J Clin Nutr. (1993)
48. el Boustani S, et al. Enteral absorption in man of eicosapentaenoic acid in different chemical forms. Lipids. (1987)
49. Maki KC, et al. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women. Nutr Res. (2009)
50. Schuchardt JP, et al. Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations--a comparative bioavailability study of fish oil vs. krill oil. Lipids Health Dis. (2011)
51. Bernstein AM, et al. A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease. J Nutr. (2012)
52. Wu WH, et al. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr. (2006)
53. Hadley KB, et al. Preclinical safety evaluation in rats using a highly purified ethyl ester of algal-docosahexaenoic acid. Food Chem Toxicol. (2010)
54. Airanthi MK, et al. Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver. J Agric Food Chem. (2011)
55. Tsukui T, et al. Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese/diabetic mice. J Agric Food Chem. (2007)
56. Orr SK, et al. The fat-1 mouse has brain docosahexaenoic acid levels achievable through fish oil feeding. Neurochem Res. (2010)
57. Das UN, Puskás LG. Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular, neurological and psychiatric disorders. Lipids Health Dis. (2009)
58. Smith BK, et al. A decreased n-6/n-3 ratio in the fat-1 mouse is associated with improved glucose tolerance. Appl Physiol Nutr Metab. (2010)
59. Abbott SK, Else PL, Hulbert AJ. Membrane fatty acid composition of rat skeletal muscle is most responsive to the balance of dietary n-3 and n-6 PUFA. Br J Nutr. (2010)
60. Haugaard SB, et al. Skeletal muscle structural lipids improve during weight-maintenance after a very low calorie dietary intervention. Lipids Health Dis. (2009)
61. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). (2008)
62. Augustin MA, et al. Intestinal passage of microencapsulated fish oil in rats following oral administration. Food Funct. (2011)
63. Patten GS, et al. Site specific delivery of microencapsulated fish oil to the gastrointestinal tract of the rat. Dig Dis Sci. (2009)
64. Marsen TA, et al. Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations. Prostaglandins Leukot Essent Fatty Acids. (1992)
65. Gani OA. Are fish oil omega-3 long-chain fatty acids and their derivatives peroxisome proliferator-activated receptor agonists. Cardiovasc Diabetol. (2008)
66. Xu HE, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. (1999)
67. Burns RN, Moniri NH. Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem Biophys Res Commun. (2010)
68. Wietrzych-Schindler M, et al. Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry. (2011)
69. Lorente-Cebrián S, et al. Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond). (2009)
70. Neschen S, et al. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes. (2007)
71. Litherland NB, et al. Effects of the peroxisome proliferator-activated receptor-alpha agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves. J Dairy Sci. (2010)
72. Tishinsky JM, Ma DW, Robinson LE. Eicosapentaenoic acid and rosiglitazone increase adiponectin in an additive and PPARγ-dependent manner in human adipocytes. Obesity (Silver Spring). (2011)
73. Oster RT, et al. Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes. Appl Physiol Nutr Metab. (2010)
74. Neschen S, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. (2006)
75. Shirai N, Suzuki H. Effects of simultaneous intakes of fish oil and green tea extracts on plasma, glucose, insulin, C-peptide, and adiponectin and on liver lipid concentrations in mice fed low- and high-fat diets. Ann Nutr Metab. (2008)
76. Gammelmark A, et al. Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects. Nutr Res. (2012)
77. Flachs P, et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. (2006)
78. Rossi AS, et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol. (2005)
79. Hanwell HE, et al. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. J Nutr. (2009)
80. Damsgaard CT, et al. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. J Nutr. (2008)
81. Damsgaard CT, Frøkiaer H, Lauritzen L. The effects of fish oil and high or low linoleic acid intake on fatty acid composition of human peripheral blood mononuclear cells. Br J Nutr. (2008)
82. Impact of n-3 fatty acids on endothelial function: results from human interventions studies
83. de Lorgeril M, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. (1994)
84. Huang T, et al. Plasma phospholipids n-3 polyunsaturated fatty acid is associated with metabolic syndrome. Mol Nutr Food Res. (2010)
85. Lauretani F, et al. Omega-3 and renal function in older adults. Curr Pharm Des. (2009)
86. Huang T, et al. Increased plasma n-3 polyunsaturated fatty acid is associated with improved insulin sensitivity in type 2 diabetes in China. Mol Nutr Food Res. (2010)
87. Maki KC, et al. Prescription omega-3-acid ethyl esters reduce fasting and postprandial triglycerides and modestly reduce pancreatic β-cell response in subjects with primary hypertriglyceridemia. Prostaglandins Leukot Essent Fatty Acids. (2011)
88. Giacco R, et al. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids. Nutr Metab Cardiovasc Dis. (2007)
89. Egert S, et al. Effects of dietary alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on parameters of glucose metabolism in healthy volunteers. Ann Nutr Metab. (2008)
90. Bortolotti M, Tappy L, Schneiter P. Fish oil supplementation does not alter energy efficiency in healthy males. Clin Nutr. (2007)
91. Tsitouras PD, et al. High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults. Horm Metab Res. (2008)
92. Fedor D, Kelley DS. Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. (2009)
93. Ramel A, et al. Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults. Diabetologia. (2008)
94. Rivellese AA, et al. Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care. (1996)
95. Krebs JD, et al. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women. Int J Obes (Lond). (2006)
96. Browning LM, et al. The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab. (2007)
97. Treatment for 2 mo with n–3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study
98. Hendrich S. (n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes. Adv Nutr. (2010)
99. Hartweg J, et al. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst Rev. (2008)
100. Montori VM, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. (2000)
101. Friedberg CE, et al. Fish oil and glycemic control in diabetes. A meta-analysis. Diabetes Care. (1998)
102. Haugaard SB, et al. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity. Clin Endocrinol {Oxf}. (2006)
103. Faeh D, et al. Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. Diabetes. (2005)
104. Dekker MJ, et al. Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab. (2010)
105. Wong CY, et al. Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with Type 2 diabetes mellitus. Diabet Med. (2010)
106. Garman JH, et al. Omega-3 fatty acid rich diet prevents diabetic renal disease. Am J Physiol Renal Physiol. (2009)
107. Logan JL, Benson B, Lee SM. Dietary fish oil enhances renal hypertrophy in experimental diabetes. Diabetes Res Clin Pract. (1990)
108. Hagiwara S, et al. Eicosapentaenoic acid ameliorates diabetic nephropathy of type 2 diabetic KKAy/Ta mice: involvement of MCP-1 suppression and decreased ERK1/2 and p38 phosphorylation. Nephrol Dial Transplant. (2006)
109. Shapiro H, et al. Effects of polyunsaturated fatty acid consumption in diabetic nephropathy. Nat Rev Nephrol. (2011)
110. Buckley JD, Howe PR. Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids. Obes Rev. (2009)
111. Mascaró C, et al. Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J Biol Chem. (1998)
112. Dietary Fatty Acids Influence the Activity and Metabolic Control of Mitochondrial Carnitine Palmitoyltransferase I in Rat Heart and Skeletal Muscle
113. Baillie RA, et al. Coordinate induction of peroxisomal acyl-CoA oxidase and UCP-3 by dietary fish oil: a mechanism for decreased body fat deposition. Prostaglandins Leukot Essent Fatty Acids. (1999)
114. Flachs P, et al. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia. (2005)
115. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. (2004)
116. Hainault I, et al. Fish oil in a high lard diet prevents obesity, hyperlipemia, and adipocyte insulin resistance in rats. Ann N Y Acad Sci. (1993)
117. Pérez-Matute P, et al. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr. (2007)
118. Huang XF, et al. Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. Diabetes Obes Metab. (2004)
119. Couet C, et al. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. Int J Obes Relat Metab Disord. (1997)
120. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue
121. Fish consumption and risk of stroke in man
122. Iso H, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. (2001)
123. Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors
124. Kunesová M, et al. The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Physiol Res. (2006)
125. Warner JG Jr, et al. Combined effects of aerobic exercise and omega-3 fatty acids in hyperlipidemic persons. Med Sci Sports Exerc. (1989)
126. Fontani G, et al. Blood profiles, body fat and mood state in healthy subjects on different diets supplemented with Omega-3 polyunsaturated fatty acids. Eur J Clin Invest. (2005)
127. Lauritzen L, et al. Maternal fish oil supplementation in lactation and growth during the first 2.5 years of life. Pediatr Res. (2005)
128. Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults
129. Ma T, et al. Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice. PLoS One. (2011)
130. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial
131. Smith GI, et al. Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia-hyperaminoacidaemia in healthy young and middle-aged men and women. Clin Sci (Lond). (2011)
132. An WS, et al. Omega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney. Am J Physiol Renal Physiol. (2009)
133. Chen J, et al. Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP/protein kinase G signaling in cardiac fibroblasts. Circulation. (2011)
134. Yamazaki RK, et al. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats. Lipids Health Dis. (2011)
135. Lam YY, et al. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids. Biochim Biophys Acta. (2011)
136. Gabler NK, et al. Feeding long-chain n-3 polyunsaturated fatty acids during gestation increases intestinal glucose absorption potentially via the acute activation of AMPK. J Nutr Biochem. (2009)
137. Delarue J, et al. Interaction of fish oil and a glucocorticoid on metabolic responses to an oral glucose load in healthy human subjects. Br J Nutr. (2006)
138. Tsuboyama-Kasaoka N, et al. Up-regulation of liver uncoupling protein-2 mRNA by either fish oil feeding or fibrate administration in mice. Biochem Biophys Res Commun. (1999)
139. Cha SH, et al. Chronic docosahexaenoic acid intake enhances expression of the gene for uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of aged C57BL/6NJcl mice. J Nutr. (2001)
140. Perez R, Cañón J, Dunner S. Genes associated with long-chain omega-3 fatty acids in bovine skeletal muscle. J Appl Genet. (2010)
141. Hessvik NP, et al. Metabolic switching of human myotubes is improved by n-3 fatty acids. J Lipid Res. (2010)
142. Tishinsky JM, et al. Fish oil prevents high saturated fat diet-induced impairments in adiponectin and insulin response in rodent soleus muscle. Am J Physiol Regul Integr Comp Physiol. (2011)
143. Guebre-Egziabher F, et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects. Eur J Clin Nutr. (2008)
144. Figueras M, et al. Effects of eicosapentaenoic acid (EPA) treatment on insulin sensitivity in an animal model of diabetes: improvement of the inflammatory status. Obesity (Silver Spring). (2011)
145. Aas V, et al. Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells. J Lipid Res. (2006)
146. You JS, et al. Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats. Appl Physiol Nutr Metab. (2010)
147. You JS, Park MN, Lee YS. Dietary fish oil inhibits the early stage of recovery of atrophied soleus muscle in rats via Akt-p70s6k signaling and PGF2α. J Nutr Biochem. (2010)
148. Ryan AM, et al. Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial. Ann Surg. (2009)
149. Read JA, et al. Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial. Support Care Cancer. (2007)
150. Fearon KC, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. (2003)
151. Vega-López S, et al. Supplementation with omega3 polyunsaturated fatty acids and all-rac alpha-tocopherol alone and in combination failed to exert an anti-inflammatory effect in human volunteers. Metabolism. (2004)
152. Pot GK, et al. No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals. Eur J Clin Nutr. (2009)
153. Poppitt SD, et al. Effects of moderate-dose omega-3 fish oil on cardiovascular risk factors and mood after ischemic stroke: a randomized, controlled trial. Stroke. (2009)
154. Deike E, et al. The Effects of Fish Oil Supplementation on Markers of Inflammation in Chronic Kidney Disease Patients. J Ren Nutr. (2012)
155. Fujioka S, et al. The effects of eicosapentaenoic acid-fortified food on inflammatory markers in healthy subjects--A randomized, placebo-controlled, double-blind study. J Nutr Sci Vitaminol (Tokyo). (2006)
156. Skulas-Ray AC, et al. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr. (2011)
157. Rizza S, et al. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis. (2009)
158. Dangardt F, et al. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis. (2010)
159. Bloomer RJ, et al. Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study. Lipids Health Dis. (2009)
160. Ciubotaru I, Lee YS, Wander RC. Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT. J Nutr Biochem. (2003)
161. Kiecolt-Glaser JK, et al. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav Immun. (2011)
162. Kabir M, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr. (2007)
163. Yusof HM, Miles EA, Calder P. Influence of very long-chain n-3 fatty acids on plasma markers of inflammation in middle-aged men. Prostaglandins Leukot Essent Fatty Acids. (2008)
164. Ximenes da Silva A, et al. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem. (2002)
165. Pifferi F, et al. (n-3) polyunsaturated fatty acid deficiency reduces the expression of both isoforms of the brain glucose transporter GLUT1 in rats. J Nutr. (2005)
166. Pifferi F, et al. n-3 Fatty acids modulate brain glucose transport in endothelial cells of the blood-brain barrier. Prostaglandins Leukot Essent Fatty Acids. (2007)
167. Pifferi F, et al. n-3 long-chain fatty acids and regulation of glucose transport in two models of rat brain endothelial cells. Neurochem Int. (2010)
168. Tsukada H, et al. Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys. Brain Res. (2000)
169. Nugent S, et al. Brain and systemic glucose metabolism in the healthy elderly following fish oil supplementation. Prostaglandins Leukot Essent Fatty Acids. (2011)
170. Lavialle M, et al. Involvement of omega-3 fatty acids in emotional responses and hyperactive symptoms. J Nutr Biochem. (2010)
171. Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid. Lipids Health Dis. (2007)
172. van de Rest O, et al. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. (2008)
173. van de Rest O, et al. Effect of fish oil supplementation on quality of life in a general population of older Dutch subjects: a randomized, double-blind, placebo-controlled trial. J Am Geriatr Soc. (2009)
174. Hamazaki T, et al. Anti-stress effects of DHA. Biofactors. (2000)
175. Hamazaki T, et al. The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J Clin Invest. (1996)
176. Hamazaki T, et al. The effect of docosahexaenoic acid on aggression in elderly Thai subjects--a placebo-controlled double-blind study. Nutr Neurosci. (2002)
177. Hamazaki T, et al. Docosahexaenoic acid does not affect aggression of normal volunteers under nonstressful conditions. A randomized, placebo-controlled, double-blind study. Lipids. (1998)
178. Itomura M, et al. The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial. J Nutr Biochem. (2005)
179. Eguchi R, et al. Fish oil consumption prevents glucose intolerance and hypercorticosteronemy in footshock-stressed rats. Lipids Health Dis. (2011)
180. Hamazaki T, et al. Administration of docosahexaenoic acid influences behavior and plasma catecholamine levels at times of psychological stress. Lipids. (1999)
181. Sawazaki S, et al. The effect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study. J Nutr Sci Vitaminol (Tokyo). (1999)
182. Song C, et al. Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats. J Lipid Res. (2003)
183. Takeuchi T, Iwanaga M, Harada E. Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res. (2003)
184. Hamazaki K, et al. Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Nutrition. (2005)
185. Fritsche KL, Johnston PV. Rapid autoxidation of fish oil in diets without added antioxidants. J Nutr. (1988)
186. Ottestad I, et al. Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial. Br J Nutr. (2011)
187. Davis TA, et al. In vivo and in vitro lipid peroxidation of arachidonate esters: the effect of fish oil omega-3 lipids on product distribution. J Am Chem Soc. (2006)
188. Polavarapu R, et al. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology. (1998)
189. Higdon JV, et al. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Am J Clin Nutr. (2000)
190. Higdon JV, et al. Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. J Lipid Res. (2001)
191. Oostenbrug GS, et al. Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E. J Appl Physiol. (1997)
192. Sen CK, et al. Fish oil and vitamin E supplementation in oxidative stress at rest and after physical exercise. J Appl Physiol. (1997)
193. Atalay M, et al. Vitamin E regulates changes in tissue antioxidants induced by fish oil and acute exercise. Med Sci Sports Exerc. (2000)
194. Gonzalez MJ, et al. Lipid peroxidation products are elevated in fish oil diets even in the presence of added antioxidants. J Nutr. (1992)
195. Altenburg JD, et al. A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone. BMC Cancer. (2011)
196. Saw CL, Huang Y, Kong AN. Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol. (2010)
197. Gomez-Pinilla F. Collaborative effects of diet and exercise on cognitive enhancement. Nutr Health. (2011)
198. Maeda H, et al. Dietary combination of fucoxanthin and fish oil attenuates the weight gain of white adipose tissue and decreases blood glucose in obese/diabetic KK-Ay mice. J Agric Food Chem. (2007)
199. Hamden K, et al. Inhibitory potential of omega-3 fatty and fenugreek essential oil on key enzymes of carbohydrate-digestion and hypertension in diabetes rats. Lipids Health Dis. (2011)
200. Cazzola R, et al. Age- and dose-dependent effects of an eicosapentaenoic acid-rich oil on cardiovascular risk factors in healthy male subjects. Atherosclerosis. (2007)
201. Shidfar F, et al. Effects of omega-3 fatty acid supplements on serum lipids, apolipoproteins and malondialdehyde in type 2 diabetes patients. East Mediterr Health J. (2008)
202. Eslick GD, et al. Benefits of fish oil supplementation in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. (2009)
203. Thusgaard M, et al. Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study. Scand J Infect Dis. (2009)
204. Dawczynski C, et al. n-3 LC-PUFA-enriched dairy products are able to reduce cardiovascular risk factors: a double-blind, cross-over study. Clin Nutr. (2010)
205. Fakhrzadeh H, et al. The effects of low dose n-3 fatty acids on serum lipid profiles and insulin resistance of the elderly: a randomized controlled clinical trial. Int J Vitam Nutr Res. (2010)
206. Filaire E, et al. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes. Int J Sport Nutr Exerc Metab. (2010)
207. Nobili V, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child. (2011)
208. Maki KC, et al. Effects of prescription omega-3-acid ethyl esters on fasting lipid profile in subjects with primary hypercholesterolemia. J Cardiovasc Pharmacol. (2011)
209. Vargas ML, et al. Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome. Metabolism. (2011)
210. Schuchardt JP, et al. Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial. Prostaglandins Leukot Essent Fatty Acids. (2011)
211. Oelrich B, Dewell A, Gardner CD. Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults. Nutr Metab Cardiovasc Dis. (2011)
212. Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. (2011)
213. Olendzki BC, et al. Treatment of rheumatoid arthritis with marine and botanical oils: influence on serum lipids. Evid Based Complement Alternat Med. (2011)
214. Oliveira JM, Rondó PH. Omega-3 fatty acids and hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: systematic review and meta-analysis. HIV Clin Trials. (2011)
215. Miles EA, et al. Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clin Sci (Lond). (2001)
216. Paulo MC, et al. Influence of n-3 polyunsaturated fatty acids on soluble cellular adhesion molecules as biomarkers of cardiovascular risk in young healthy subjects. Nutr Metab Cardiovasc Dis. (2008)
217. Kooshki A, et al. Effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients. Ann Nutr Metab. (2011)
218. Voigt RG, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. (2001)
219. Richardson AJ, Puri BK. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog Neuropsychopharmacol Biol Psychiatry. (2002)
220. Stevens L, et al. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids. (2003)
221. Sinn N, Bryan J. Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD. J Dev Behav Pediatr. (2007)
222. Bélanger SA, et al. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. Paediatr Child Health. (2009)
223. Gustafsson PA, et al. EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr. (2010)
224. Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. (2011)
225. Lenn J, et al. The effects of fish oil and isoflavones on delayed onset muscle soreness. Med Sci Sports Exerc. (2002)
226. Tartibian B, Maleki BH, Abbasi A. The effects of ingestion of omega-3 fatty acids on perceived pain and external symptoms of delayed onset muscle soreness in untrained men. Clin J Sport Med. (2009)
227. Madsen T, et al. The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study. Br J Nutr. (2003)
228. Geelen A, et al. Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects. Eur J Clin Nutr. (2004)
229. Pooya Sh, et al. The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Nutr Metab Cardiovasc Dis. (2010)
230. Finocchiaro C, et al. Effect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study. Br J Nutr. (2011)
231. Mackay I, et al. Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease. Atherosclerosis. (2012)
232. Ramel A, et al. Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction. Nutrition. (2010)
233. Simão AN, et al. Blood pressure decrease with ingestion of a soya product (kinako) or fish oil in women with the metabolic syndrome: role of adiponectin and nitric oxide. Br J Nutr. (2012)
234. Campbell F, et al. A systematic review of fish-oil supplements for the prevention and treatment of hypertension. Eur J Prev Cardiolog. (2012)
235. Michaeli B, et al. Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers. Clin Nutr. (2007)
236. Pittet YK, et al. Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil. Intensive Care Med. (2010)
237. Bays HE, et al. The effect of prescription omega-3 fatty acids on body weight after 8 to 16 weeks of treatment for very high triglyceride levels. Postgrad Med. (2009)
238. Munro IA, Garg ML. Dietary supplementation with n-3 PUFA does not promote weight loss when combined with a very-low-energy diet. Br J Nutr. (2012)
239. Sanders TA, et al. Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial. Am J Clin Nutr. (2011)
240. Pase MP, Grima NA, Sarris J. Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials. Br J Nutr. (2011)
241. Phelan N, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial. Am J Clin Nutr. (2011)
242. Nahas R, Sheikh O. Complementary and alternative medicine for the treatment of major depressive disorder. Can Fam Physician. (2011)
243. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry. (2012)
244. Sublette ME, et al. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. (2011)
245. Serebruany VL, et al. Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia. Cardiology. (2011)
246. Wang C, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. (2006)
247. Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3). Int J Vitam Nutr Res. (1998)
248. Brenna JT. Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man. Curr Opin Clin Nutr Metab Care. (2002)
249. Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr. (1996)
250. Fokkema MR, et al. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent. Prostaglandins Leukot Essent Fatty Acids. (2000)
251. Byleveld PM, et al. Fish oil feeding delays influenza virus clearance and impairs production of interferon-gamma and virus-specific immunoglobulin A in the lungs of mice. J Nutr. (1999)
252. Schwerbrock NM, et al. Fish oil-fed mice have impaired resistance to influenza infection. J Nutr. (2009)
253. Byleveld M, et al. Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus. Clin Exp Immunol. (2000)

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