References – Benefits of Fish Oil, Omega 3 and 6 EFAs

- Updated on November 10, 2021

Quotes and references (dangers in fish oil and fish due to pollution)
Quotes and references about conversion rates of ALA (alpha-linolenic acid) to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid)
Quotes and references (fish oil versus flaxseed oil)
Quotes and references (krill oil medical research)
Quotes and references (long-term use causes negative effects)
Quotes and references (dangers in fish oil and fish due to pollution)
Quotes and References (Increased bleeding myth)
Quotes and references about conversion rates of ALA (alpha-linolenic acid) to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid)
Quotes and references (fish oil versus flaxseed oil)
Quotes and References (Krill oil medical research)
Quotes and references (long-term use causes negative effects)

All quotes and references for this web page

Quotes and references (dangers in fish oil and fish due to pollution)

“Five types of oil derived from various Baltic fish were purified. Reduction in the PCDD/Fs content was 77.0-93.6% on average, whereas in the dioxin-like polychlorinated biphenyls (dl-PCBs)-it was 42.7-50.5% on average, with insignificant changes in the total amount of EPA and DHA content. Furthermore, a significant reduction in the content of arsenic was noted (by about 62% on average), with insignificant changes in the content of organochlorine pesticides (OCPs), and marker polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), cadmium, lead, and mercury. Purification provided fish oil having standardized parameters that allow for its use as feed additives, whilst retaining its favorable fatty acid content.”

Usydus Z, Szlinder-Richert J, Polak-Juszczak L, Malesa-Ciecwierz M, Dobrzanski Z, Study on the raw fish oil purification from PCDD/F and dl-PCB-industrial tests, Chemosphere. 2009 Mar; 74(11): p. 1495-1501.

“This paper reviews the state of the science regarding recent literature on PCDD/F (polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans) and PCB (polychlorinated biphenyls) levels in marine species and human nutrients intake through fish and seafood consumption. The concentrations of these pollutants depend basically on the environment in which the respective species are caught. It is concluded that some groups of population frequently consuming high quantities of certain species could be significantly increasing health risks due to PCDD/F and PCB exposure.”

Domingo JL, Bocio A, Levels of PCDD/PCDFs and PCBs in edible marine species and human intake: a literature review, Environ Int. 2007 Apr; 33(3): p. 397-405.

“… Several studies have shown an inverse correlation between omega-3 fatty acids from fish in serum/adipose tissue and coronary heart disease. However, a high content of mercury in hair/toe nail had a negative effect, and in one study the odds ratio for myocardial infarction in those with the highest content of mercury was 2.16. A positive correlation between mercury in hair and the progression of carotid atherosclerosis has been found. Intake of fish is a major source of exposure to mercury, and a high content of mercury probably inhibits the beneficial effects of omega-3 fatty acids on the development of coronary artery disease.”

Landmark K, Aursnes I, Mercury, fish, fish oil and the risk of cardiovascular disease [Article in Norwegian], Tidsskr Nor Laegeforen. 2004 Jan 22; 124(2): p.198-200.

“… CONCLUSIONS: High content of mercury in hair may be a risk factor for acute coronary events and CVD, CHD, and all-cause mortality in middle-aged eastern Finnish men. Mercury may also attenuate the protective effects of fish on cardiovascular health.”

Virtanen JK, Voutilainen S, Rissanen TH, Mursu J, Tuomainen TP, Korhonen MJ, Valkonen VP, Seppnen K, Laukkanen JA, Salonen JT, Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland, Arterioscler Thromb Vasc Biol. 2005 Jan; 25(1): p. 228-233.

“The mercury content of fish oil was similar to the basal concentration normally found in human blood. CONCLUSIONS: Fish are rich in omega-3 fatty acids, and their consumption is recommended to decrease the risk of coronary artery disease. However, fish such as swordfish and shark are also a source of exposure to the heavy metal toxin, mercury. The fish oil brands examined in this manuscript have negligible amounts of mercury and may provide a safer alternative to fish consumption.”

Foran SE, Flood JG, Lewandrowski KB, Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med. 2003 Dec; 127(12): p. 1603-1605.

“CONCLUSIONS: For major health outcomes among adults, based on both the strength of the evidence and the potential magnitudes of effect, the benefits of fish intake exceed the potential risks. For women of childbearing age, benefits of modest fish intake, excepting a few selected species, also outweigh risks.”

Mozaffarian D, Rimm EB, Fish intake, contaminants, and human health: evaluating the risks and the benefits, JAMA. 2006 Oct 18; 296(15): p. 1885-1899.

“We studied 22 commercial fish oil and menhaden oil preparations in respect to accompanying substances that could be harmful. The substances measured were: cholesterol as determined by gas liquid chromatography, heavy metals measured by atomic absorption, and vitamin A as determined by high-performance liquid chromatography (HPLC). The contents of cholesterol and heavy metals were in ranges which can be regarded as negligible; the content of vitamin A in menhaden oils, however, was found in amounts which warrant that pregnant women do not exceed the dosage as recommended by the manufacturers.”

Koller H, Luley C, Klein B, Baum H, Biesalski HK, Contaminating substances in 22 over-the-counter fish oil and cod liver oil preparations: cholesterol, heavy metals and vitamin A [Article in German], Z Ernahrungswiss. 1989 Mar; 28(1): p. 76-83.

Quotes and References (Increased bleeding myth)

“It has been suggested that the potential antithrombotic effect of fish oils may theoretically increase the risk for bleeding, which may be a safety concern for individual patients. However, clinical trial evidence has not supported increased bleeding with omega-3 fatty acid intake, even when combined with other agents that might also increase bleeding (such as aspirin and warfarin). Another potential safety concern is the susceptibility of omega-3 fatty acid preparations to undergo oxidation, which contributes to patient intolerance and potential toxicity. Finally, large amounts of fish consumption may result in adverse experiences due to the potential presence of environmental toxins such as mercury, polychlorinated biphenyls, dioxins, and other contaminants. The risks of exposure to environmental toxins and hypervitaminosis with fish consumption are substantially reduced through purification processes used to develop selected concentrated fish oil supplements and prescription preparations. Thus, in choosing which fish oil therapies to recommend, clinicians should be aware of available information to best assess their relative safety, which includes the US Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) advisory statement regarding fish consumption, the meaning of certain labeling (such as “verification” through the US Pharmacopeia) and the differences in FDA regulatory requirements between nonprescription fish oil supplements and prescription fish oil preparations, and how all of this is important to the optimal treatment of patients.”

Bays HE, Safety considerations with omega-3 fatty acid therapy, Am J Cardiol. 2007 Mar 19;99(6A):35C-43C. Epub 2006 Nov 28.
Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky 40213, USA.

“Omega-3 fatty acid ethyl esters have well-known triglyceride-lowering properties and were shown >30 years ago to inhibit platelet function. With the recent US Food and Drug Administration (FDA) approval of these agents for treating severe triglyceride elevations, concerns about excess bleeding naturally arise. However, an objective assessment of the evidence for clinically significant bleeding reveals that such concerns are unfounded. As such, the benefits of triglyceride lowering with omega-3 fatty acids more than outweigh any theoretical risks for increased bleeding.”

Harris WS, Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol. 2007 Mar 19; 99(6A): 44C-46C.
Sanford School of Medicine of University of South Dakota, Sioux Falls, South Dakota 57105, USA.


Quotes and references about conversion rates of ALA (alpha-linolenic acid) to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid)

“The use of ALA labelled with radioisotopes suggested that with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%… These findings indicate that future attention will have to focus on the adequate provision of DHA which can reliably be achieved only with the supply of the preformed long-chain metabolite.”

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 Journal of Vitam Nutr Res. 1998; 68(3): p. 159-73.
Vitamin Research Department, F. Hoffman-Roche Ltd, Basel, Switzerland.

“… in vivo studies in humans show that asymptotically equal to 5 percent of ALA is converted to EPA and <0.5 percent of ALA is converted to DHA. … even large amounts of dietary ALA have a negligible effect on plasma DHA”

Plourde M & Cunnane SC, Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements, Applied Physiology of Nutr Metab. 2007 Aug;32(4): p. 619-634.
Research Center on Aging, Departments of Medicine, and Physiology and Biophysics, Universit de Sherbrooke, 1036 Belvedere St, South, Sherbrooke, QC J1H 4C4, Canada

“Stable isotope tracer studies indicate that conversion of alphaLNA to EPA occurs but is limited in men and that further transformation to DHA is very low.”

Burdge GC & Calder PC, Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults, Reproductive Nutrition Dev. 2005 Sep-Oct; 45(5): p. 581-597.
Institute of Human Nutrition, University of Southampton, Southampton, UK.

“… alphaLNA-feeding studies and stable-isotope studies using alphaLNA, which have addressed the question of bioconversion of alphaLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0.1%).”

Williams CM & Burdge G, Long-chain n-3 PUFA: plant versus marine sources, Proceedings of the Nutritional Society, 2006 Feb; 65(1): p. 42-50.
Hihj Sinclair Unit Human Nutrition, School of Food Biosciences, University of Reading, UK.

Quotes and references (fish oil versus flaxseed oil)

“PURPOSE: Evaluate the effect of flaxseed, olive and fish oil on the lipid profile, preservation of villosities and lymphocyte migration in the intestinal mucosa of Wistar rats… RESULTS: The group which was fed fish oil presented lower values when compared to the other treatments for Total Cholesterol, High-density Lipoprotein Cholesterol and Triacylglycerol (p<0.05). The animals treated with fish and olive oils presented better intestinal villosities preservation. Less deposition of lymphocytes was observed in the flaxseed group (p<0.001). CONCLUSIONS: This study demonstrated that flaxseed, olive and fish oils present different responses than soy oil for the intestinal mucosa preservation and lymphocyte proliferation in Wistar rats.”

Rosa DD, de Sales RL, Moraes LF, Loureno FC, Neves CA, Sabarense CM, Ribeiro SM, Peluzio Mdo C, Flaxseed, olive and fish oil influence plasmatic lipids, lymphocyte migration and morphometry of the intestinal of Wistar rats, Acta Cir Bras. 2010 Jun;25(3):275-80.
Department of Nutrition and Health, UFV, Viosa, MG, Brazil.

“The atheroprotective potential of n-3 alpha-linolenic acid (ALA) has not yet been fully determined, even in murine models of atherosclerosis. We tested whether ALA-derived, n-3 long chain polyunsaturated fatty acids (LCPUFA) could offer atheroprotection in a dose-dependent manner. Apolipoprotein B (ApoB)100/100LDLr-/- mice were fed with diets containing two levels of ALA from flaxseed oil for 16 weeks. Fish oil- and cis-monounsaturated-fat-enriched diets were used as positive and negative controls, respectively. The mice fed cis-monounsaturated fat and ALA-enriched diets exhibited equivalent plasma total cholesterol (TPC) and LDL-cholesterol (LDL-c) levels; only mice fed the fish-oil diet had lower TPC and LDL-c concentrations. Plasma LDL-CE fatty acid composition analysis showed that ALA-enriched diets lowered the percentage of atherogenic cholesteryl oleate compared with cis-monounsaturated-fat diet (44% versus 55.6%) but not as efficiently as the fish-oil diet (32.4%). Although both ALA and fish-oil diets equally enriched hepatic phospholipids with eicosapentaenoic acid (EPA) and ALA-enriched diets lowered hepatic cholesteryl ester (CE) levels compared with cis-monounsaturated-fat diet, only fish oil strongly protected from atherosclerosis. These outcomes indicate that dietary n-3 LCPUFA from fish oil and n-3 LCPUFA (mostly EPA) synthesized endogenously from ALA were not equally atheroprotective in these mice.”

Degirolamo C, Kelley KL, Wilson MD, Rudel LL, Dietary n-3 LCPUFA from fish oil but not alpha-linolenic acid-derived LCPUFA confers atheroprotection in mice, J Lipid Res. 2010 Jul;51(7):1897-905. Epub 2010 Feb 11.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

“Whether preformed dietary docosahexaenoic acid (DHA) is required for brain accretion has not been clearly determined. In this study, we investigated in mice the different effects of dietary longer-chain n-3 polyunsaturated fatty acids (PUFAs) and alpha-linolenic acid (LNA) on brain accretion of DHA and the expression of associated desaturases and transcription factors. C57 BL/6J mice were fed for 3 months with four fish oil n-3 PUFA diets – lower, low, high and higher (0.46%, 0.91%, 1.73% and 4.29% total energy, respectively); a flaxseed oil n-3 PUFA (5.01% total energy) diet; and an n-3 PUFA-deficient diet, respectively. Either fish oil or flaxseed oil n-3 PUFA diets increased DHA concentrations in the brain. However, the flaxseed oil n-3 PUFA diet was less effective than the fish oil diet with higher amount of n-3 PUFA in increasing brain DHA content. Furthermore, the expressions of delta-6 desaturase (D6D) and sterol regulatory element binding protein 1 (SREBP-1) in the liver were down-regulated by all fish oil diets with different amounts of n-3 PUFAs, as well as by the flaxseed oil n-3 PUFA diet, whereas in the brain, D6D, delta-5 desaturase (D5D) and SREBP-1 expressions were down-regulated by the higher fish oil n-3 PUFA diet rather than by other fish oil n-3 PUFA and the flaxseed oil n-3 PUFA diets. These results suggest that preformed dietary DHA, different from those converted by LNA inside the body, is better for brain accretion. Dietary longer-chain n-3 PUFAs affect expressions of D6D, D5D and SREBP-1 in the brain differently from their precursor LNA.”

Zhu H, Fan C, Xu F, Tian C, Zhang F, Qi K, Dietary fish oil n-3 polyunsaturated fatty acids and alpha-linolenic acid differently affect brain accretion of docosahexaenoic acid and expression of desaturases and sterol regulatory element-binding protein 1 in mice, J Nutr Biochem. 2009 Nov 30.
Clinical Nutrition Center, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China.

“Thirty adults with ADHD were randomized to 12 weeks of supplementation with olive oil (< 1% omega-3 fatty acids), flax oil (source of alpha-linolenic acid; 18:3n-3; alpha-LNA) or fish oil (source of EPA and docosahexaenoic acid; 22:6n-3; DHA). Serum PL fatty acid levels were determined at baseline and at 12 weeks. Flax oil supplementation resulted in an increase in alpha-LNA and a slight decrease in the ratio of AA/EPA, while fish oil supplementation resulted in increases in EPA, DHA and total omega-3 fatty acids and a decrease in the AA/EPA ratio to values seen in the Japanese population. These data suggest that in order to increase levels of EPA and DHA in adults with ADHD, and decrease the AA/EPA ratio to levels seen in high fish consuming populations, high dose fish oil may be preferable to high dose flax oil.”

Young GS, Conquer JA, Thomas R, Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder, Reprod Nutr Dev. 2005 Sep-Oct; 45(5): p.549-558.

“Fish oil caused a significant reduction (mean decline: 48%) in NK (natural killer) cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA (eicosapentaenoic acid; i.e. fish oil component) but not of other n-6 or n-3 polyunsaturated fatty acids (i.e, components of flaxseed oil) can decrease NK cell activity in healthy subjects.”

Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC, Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y, Am J Clin Nutr. 2001 Mar; 73(3): p. 539-548.

“The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid a-linolenic acid is not as effective.”

Breslow JL, n-3 fatty acids and cardiovascular disease, Am J Clin Nutr. 2006 Jun; 83(6 Suppl): p. 1477S-1482S.

“CONCLUSIONS: Long-chain n -3 PUFA (polyunsaturated fatty acids) from fish are possible promising nutrients for the dietary prevention of PCa (prostate cancer), but to-date with little epidemiological support. In contrast, studies suggest that alpha-linolenic acid intake might be a risk factor.”

Astorg P, Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence, Cancer Causes Control. 2004 May; 15(4): p. 367-386.

Quotes and References (Krill oil medical research)

J Am Coll Nutr. 2007 Feb;26(1):39-48.
Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms.
Deutsch L.
Sciopsis Inc. Evidence Based NutraMedicine, 18 Corso Court, Richmond Hill, Ontario L4S 1H4, CANADA.
OBJECTIVES: a) To evaluate the effect of Neptune Krill Oil (NKO) on C-reactive protein (CRP) on patients with chronic inflammation and b) to evaluate the effectiveness of NKO on arthritic symptoms.
METHODS: Randomized, double blind, placebo controlled study. Ninety patients were recruited with confirmed diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis and with increased levels of CRP (>1.0 mg/dl) upon three consecutive weekly blood analysis. Group A received NKO (300 mg daily) and Group B received a placebo. CRP and Western Ontario and McMaster Universities (WOMAC) osteoarthritis score were measured at baseline and days 7, 14 and 30.
RESULTS: After 7 days of treatment NKO reduced CRP by 19.3% compared to an increase by 15.7% observed in the placebo group (p = 0.049). After 14 and 30 days of treatment NKO further decreased CRP by 29.7% and 30.9% respectively (p < 0.001). The CRP levels of the placebo group increased to 32.1% after 14 days and then decreased to 25.1% at day 30. The between group difference was statistically significant; p = 0.004 at day 14 and p = 0.008 at day 30. NKO showed a significant reduction in all three WOMAC scores. After 7 days of treatment, NKO reduced pain scores by 28.9% (p = 0.050), reduced stiffness by 20.3% (p = 0.001) and reduced functional impairment by 22.8% (p = 0.008).
CONCLUSION: The results of the present study clearly indicate that NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and 14 days.

BMC Musculoskelet Disord. 2010 Jun 29;11:136.
Supplementation of diet with krill oil protects against experimental rheumatoid arthritis.
Ierna M, Kerr A, Scales H, Berge K, Griinari M.
MD Biosciences Gmbh Postfach, Gewerbestrasse 9, 8132 Egg b Zrich, Switzerland.
BACKGROUND: Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis.
METHODS: Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1alpha, IL-1beta, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-beta were determined by a Luminex assay system.
RESULTS: Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1alpha and IL-13.
CONCLUSIONS: The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis.

Altern Med Rev. 2003 May;8(2):171-9.
Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea.
Sampalis F, Bunea R, Pelland MF, Kowalski O, Duguet N, Dupuis S.
Department of Experimental Surgery, University of Montreal, Montreal, Quebec, Canada.
PRIMARY OBJECTIVE: To evaluate the effectiveness of Neptune Krill Oil (NKO) for the management of premenstrual syndrome and dysmenorrhea. SECONDARY
OBJECTIVE: To compare the effectiveness of NKO for the management of premenstrual syndrome and dysmenorrhea with that of omega-3 fish oil. METHODS/
DESIGN: Double-blind, randomized clinical trial.
SETTING: Outpatient clinic.
PARTICIPANTS: Seventy patients of reproductive age diagnosed with premenstrual syndrome according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R).
INTERVENTIONS: Treatment period of three months with either NKO or omega-3 fish oil.
OUTCOME MEASURES: Self-Assessment Questionnaire based on the American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria for premenstrual syndrome and dysmenorrhea and number of analgesics used for dysmenorrhea.
RESULTS: In 70 patients with complete data, a statistically significant improvement was demonstrated among baseline, interim, and final evaluations in the self assessment questionnaire (P < 0.001) within the NKO group as well as between-group comparison to fish oil, after three cycles or 45 and 90 days of treatment. Data analysis showed a significant reduction of the number of analgesics used for dysmenorrhea within the NKO group (comparing baseline vs. 45- vs. 90-day visit). The between-groups analysis illustrated that women taking NKO consumed significantly fewer analgesics during the 10-day treatment period than women receiving omega-3 fish oil (P < 0.03).
CONCLUSION: Neptune Krill Oil can significantly reduce dysmenorrhea and the emotional symptoms of premenstrual syndrome and is shown to be significantly more effective for the complete management of premenstrual symptoms compared to omega-3 fish oil.

Altern Med Rev. 2004 Dec;9(4):420-8.
Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia.
Bunea R, El Farrah K, Deutsch L.
Department of Internal Medicine, McGill University, Montreal, Quebec, Canada.
OBJECTIVE: To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
METHODS: A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by Neptune Technologies and Bioresources, Laval, Quebec, Canada.
OUTCOME MEASURES: Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose.
RESULTS: Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo.
CONCLUSIONS: The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.

Nutr Res. 2009 Sep;29(9):609-15.
Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women.
Maki KC, Reeves MS, Farmer M, Griinari M, Berge K, Vik H, Hubacher R, Rains TM.
Provident Clinical Research, Bloomington, IN 47403, USA; Provident Clinical Research, Glen Ellyn, IL 60137, USA.
Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.

Alterntive Medicine Review 2010 Apr;15(1): p.84-86.
Krill oil. Monograph.

Quotes and references (long-term use causes negative effects)

“OBJECTIVE: The effects of fish oil including omega-3 polyunsaturated fatty acids on aging and lifespan arXu X, Jiang M, Wang Y, Smith T, Baumgarten C, Wood M, Tseng G, Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model, PLoS One. 2010 Apr 13; 5(4): e10140.
Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, USA.
e not well understood. In this study, the influence of long-term ingestion of fish oil on lifespan was examined in senescence-accelerated (SAMP8) mice. METHODS: We investigated the effects of dietary fish oil on lifespan and on lipid composition and oxidative stress in plasma and liver in SAMP8 mice. Male mice were fed a fish oil diet (5% fish oil and 5% safflower oil) or a safflower oil diet (10% safflower oil) from 12 wk of age. RESULTS: The SAMP8 mice fed fish oil did not have a longer maximum lifespan and had a shorter average lifespan than mice fed safflower oil. To examine the mechanism underlying these results, the effects on oxidative stress of long-term ingestion of fish oil were also examined. SAMP8 mice fed fish oil for 28 wk showed strong oxidative stress that caused hyperoxidation of membrane phospholipids and a diminished antioxidant defense system due to a decrease in tocopherol compared with mice fed safflower oil. CONCLUSION: These findings suggest that intake of fish oil increases oxidative stress, decreases cellular function, and causes organ dysfunction in SAMP8 mice, thereby promoting aging and shortening the lifespan of the mice.”

Tsuduki T, Honma TD, Nakagawa KH, Ikeda I, & Miyazawa T, Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice, Nutrition. 2010 Jul 10. [Epub ahead of print] Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai, Japan.

“Hypothalamic serotonin inhibits food intake and stimulates energy expenditure. High-fat feeding is obesogenic, but the role of polyunsaturated fats is not well understood. This study examined the influence of different high-PUFA diets on serotonin-induced hypophagia, hypothalamic serotonin turnover, and hypothalamic protein levels of serotonin transporter (ST), and SR-1B and SR-2C receptors. Male Wistar rats received for 9 weeks from weaning a diet high in either soy oil or fish oil or low fat (control diet). Throughout 9 weeks, daily intake of fat diets decreased such that energy intake was similar to that of the control diet. However, the fish group developed heavier retroperitoneal and epididymal fat depots. After 12 h of either 200 or 300 mug intracerebroventricular serotonin, food intake was significantly inhibited in control group (21-25%) and soy group (37-39%) but not in the fish group. Serotonin turnover was significantly lower in the fish group than in both the control group (-13%) and the soy group (-18%). SR-2C levels of fish group were lower than those of control group (50%, P = 0.02) and soy group (37%, P = 0.09). ST levels tended to decrease in the fish group in comparison to the control group (16%, P = 0.339) and the soy group (21%, P = 0.161). Thus, unlike the soy-oil diet, the fish-oil diet decreased hypothalamic serotonin turnover and SR-2C levels and abolished serotonin-induced hypophagia. Fish-diet rats were potentially hypophagic, suggesting that, at least up to this point in its course, the serotonergic impairment was either compensated by other factors or not of a sufficient extent to affect feeding. That fat pad weight increased in the absence of hyperphagia indicates that energy expenditure was affected by the serotonergic hypofunction.”

Watanabe R, Andrade I, Telles M, Albuquerque K, Nascimento C, Oyama L, CaXu X, Jiang M, Wang Y, Smith T, Baumgarten C, Wood M, Tseng G, Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model, PLoS One. 2010 Apr 13; 5(4): e10140.
Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, USA.
sarini D, & Ribeiro EB, Long-Term Consumption of Fish Oil-Enriched Diet Impairs Serotonin Hypophagia in Rats, Cellular and Molecular Neurobiology, 2010 Jun 5. [Epub ahead of print]
Departamento de Fisiologia, Universidade Federal de So Paulo, Rua Botucatu, 862, 2 masculine andar, So Paulo, SP, Brazil.

“Clinical trials and epidemiological studies have suggested that dietary fish oil (FO) supplementation can provide an anti-arrhythmic benefit in some patient populations. The underlying mXu X, Jiang M, Wang Y, Smith T, Baumgarten C, Wood M, Tseng G, Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model, PLoS One. 2010 Apr 13; 5(4): e10140.
Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, USA.
echanisms are not entirely clear. We wanted to understand how FO supplementation (for 4 weeks) affected the action potential configuration/duration of ventricular myocytes, and the ionic mechanisms/molecular basis for these effects. The experiments were conducted on adult rabbits, a widely used animal model for cardiac electrophysiology and pathophysiology. We used gas chromatography-mass spectroscopy to confirm that FO feeding produced a marked increase in the content of n-3 polyunsaturated fatty acids in the phospholipids of rabbit hearts. Left ventricular myocytes were used in current and voltage clamp experiments to monitor action potentials and ionic currents, respectively. Action potentials of myocytes from FO-fed rabbits exhibited much more positive plateau voltages and prolonged durations. These changes could be explained by an increase in the L-type Ca current (I(CaL)) and a decrease in the transient outward current (I(to)) in these myocytes. FO feeding did not change the delayed rectifier or inward rectifier current. Immunoblot experiments showed that the FO-feeding induced changes in I(CaL) and I(to) were associated with corresponding changes in the protein levels of major pore-forming subunits of these channels: increase in Cav1.2 and decrease in Kv4.2 and Kv1.4. There was no change in other channel subunits (Cav1.1, Kv4.3, KChIP2, and ERG1). We conclude that long-term fish oil supplementation can impact on cardiac electrical activity at least partially by changing channel subunit expression in cardiac myocytes.”

Xu X, Jiang M, Wang Y, Smith T, Baumgarten C, Wood M, Tseng G, Long-term fish oil supplementation induces cardiac electrical remodeling by changing channel protein expression in the rabbit model, PLoS One. 2010 Apr 13; 5(4): e10140.
Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, USA.

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