Gender Effects of Dietary Omega-3 Fatty Acids From Plant and Marine Sources on Oxylipins in Healthy Humans

Healthy Clinical Trial

— OXGEN-2014  

Official title:

Gender Effects of Dietary Omega-3 Fatty Acids From Plant and Marine Sources on Oxylipins in Healthy Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02317588
• Other study ID #: B2014:036
• Status: Completed
• Phase: Phase 1
• First received: December 11, 2014
• Last updated: March 9, 2016
• Start date: December 2014
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This study is single site, double-blind, randomized, cross-over study designed to compare the effects of flax oil and fish oil supplementation on the oxylipin profile in healthy males and females. Eligible participants will complete two (2) Supplementation Phases (flax oil versus fish oil) and will be asked to attend 6 in-person clinic visits (0, 1, 3, 7, 14 and 28 days) for blood and urine collection during each phase. Participants will consume 8 capsules a day for 28 days containing either A) Flax Oil at 4 grams of ALA per day ,in one phase and B) Fish Oil at a dose of 4 grams DHA + 0.8 grams EPA per day in the next phase. Participants will be randomized and blinded and will therefore no know what supplement they are taking in either phase.

Description:

This is a single site, double-blind, randomized, crossover study designed to compare the effects of dietary omega-3 fatty acids from flax oil versus fish oil supplementation on oxylipin profiles over time (0 to 4 weeks) and between healthy males and females.

Recruitment will consist of a total of six (6) male and six (6) female participants. Participants will be recruited through advertisement from the local community. The study will be conducted at the Asper Centre for Clinical Research, St. Boniface Hospital. Participants will be asked to provide written informed consent prior to participation in the study. Participants who have provided written consent will be asked to attend an in-patient visit to provide a fasting blood sample. Should the participant be eligible to participate, they will be scheduled for a minimum 6 week Run-in Period, a 4 week Supplementation Phase, a minimum 6 week Wash-out Period and then a second 4 week Supplementation Phase; each Supplementation Phase will have 6 in-person visits (0, 1, 3, 7, 14 and 28 days) to obtain fasting blood and urine samples and for completion of the Study Checklist. During each 4 week Supplementation Phase, participants will consume capsules containing flax oil and at a dose of 4 grams of ALA/day, or capsules containing fish oil and at a dose of 4 grams DHA + 0.8 grams EPA/day. A 3-Day Food Record and Activity Questionnaire will be completed before the Day 0 visit and during week 3 of each Supplementation Phase.

Provision of flax oil or fish oil in capsules will allow this study to be double-blinded. Blinding will reduce potential bias during data collection and evaluation of study endpoints. Both the research team and the participant are blinded from the time of randomization and for the duration of the study. Randomization will be used to avoid bias in the assignment; to increase the likelihood that known and unknown participant characteristics are evenly balanced across the various test groups; and to enhance the validity of statistical comparisons across test groups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

Participants must meet the following criteria to be eligible for participation in the study:

1. Male, or non-pregnant, non-lactating premenopausal female, =18 and =50 years of age;

2. Normal blood lipid profile (total cholesterol <5.2 mmol/L, LDL-cholesterol <3.4 mmol/L, HDL-cholesterol >0.9 mmol/L, triglycerides <1.7 mmol/L), plasma creatinine <1.5× upper limit of normal (ULN) where the normal range is 50-97 µmol/L, and glycated hemoglobin <6%; aspartate transaminase (AST) <2× ULN where the normal range is 10 - 32 U/L, and alanine transaminase (ALT) <2× ULN where the normal range is <25 U/L;

3. Blood pressure <140/90;

4. Body mass index (BMI) of 18 to 28;

5. Stable regime if taking vitamin and mineral/dietary/herbal supplements for the past 1 months and while participating in the study;

6. Willing to maintain a stable level of activity while participating in the study;

7. Willing to maintain dietary routine and to refrain from consuming omega-3 supplements or omega-3 rich foods (>0.3 grams ALA/serving, or >0.1 grams EPA + DHA/serving) from acceptance into the study until the final study visit;

8. Females must have normal menses and can be on birth control;

9. Agrees to not donate blood while participating in the study and for 2 months after participation in the study.

10. Willing to comply with the protocol requirements and procedures;

11. Willing to provide informed consent.

Exclusion Criteria:

Participants will be excluded if they have any of the following:

1. Presence of a clinically diagnosed disease affecting the circulatory, respiratory, immune, skeletal, urinary, muscular, endocrine, digestive, nervous or reproductive system, or a disease condition that has required or currently requires medical treatment;

2. Taking any prescribed medication, regular use of acetylsalicylic acid (e.g. Aspirin), ibuprofen (e.g. Advil) or acetaminophen (e.g. Tylenol) within the last 3 months;

3. Allergy or sensitivity to any of the study product ingredients, such as flax, flax oil, or marine source oils such as fish or shellfish.

4. Cigarette/cigar smoking or use of tobacco products within the past 12 months or during the study;

5. Body weight has not been stable (±3 kg) over the past 6 months;

6. Consumption of >15 alcoholic beverages per week (according to Canada's Low-Risk Alcohol Drinking Guidelines, 2012) within the last 3 months or while participating in the study;

7. Current (within the past 30 days) bacterial, viral or fungal infection;

8. Unable to obtain blood sample at the screening and/or week 0 visit.

9. Donated or had blood collected in the 2 months prior to participation the study.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• Flax Oil
Participants will consume capsules containing flax oil at a dose of 4 grams of ALA per day (8 capsules a day) with a meal for 28 days (4 weeks).
• Fish Oil
Participants will consume capsules containing fish oil at a dose of 4 grams DHA + 0.8 grams EPA per day (8 capsules) for 28 days (4 weeks).

Locations

Country	Name	City	State
Canada	St. Boniface General Hospital	Winnipeg	Manitoba

Sponsors (3)

Lead Sponsor	Collaborator
University of Manitoba	Canadian Institutes of Health Research (CIHR), Manitoba Health Research Council

Country where clinical trial is conducted

Canada, 

References & Publications (20)

Caligiuri SP, Love K, Winter T, Gauthier J, Taylor CG, Blydt-Hansen T, Zahradka P, Aukema HM. Dietary linoleic acid and a-linolenic acid differentially affect renal oxylipins and phospholipid fatty acids in diet-induced obese rats. J Nutr. 2013 Sep;143(9):1421-31. doi: 10.3945/jn.113.177360. Epub 2013 Jul 31. — View Citation

Czernichow S, Thomas D, Bruckert E. n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations. Br J Nutr. 2010 Sep;104(6):788-96. doi: 10.1017/S0007114510002096. Epub 2010 Jun 4. Review. — View Citation

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Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1. — View Citation

Harkewicz R, Fahy E, Andreyev A, Dennis EA. Arachidonate-derived dihomoprostaglandin production observed in endotoxin-stimulated macrophage-like cells. J Biol Chem. 2007 Feb 2;282(5):2899-910. Epub 2006 Nov 29. Erratum in: J Biol Chem. 2007 Sep 28;282(39):29068. — View Citation

Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009 Feb 17;119(6):902-7. doi: 10.1161/CIRCULATIONAHA.108.191627. Epub 2009 Jan 26. — View Citation

Kakutani S, Kawashima H, Tanaka T, Shiraishi-Tateishi A, Kiso Y. Uptake of dihomo-gamma-linolenic acid by murine macrophages increases series-1 prostaglandin release following lipopolysaccharide treatment. Prostaglandins Leukot Essent Fatty Acids. 2010 Jul;83(1):23-9. doi: 10.1016/j.plefa.2010.02.032. Epub 2010 Mar 26. — View Citation

Keenan AH, Pedersen TL, Fillaus K, Larson MK, Shearer GC, Newman JW. Basal omega-3 fatty acid status affects fatty acid and oxylipin responses to high-dose n3-HUFA in healthy volunteers. J Lipid Res. 2012 Aug;53(8):1662-9. doi: 10.1194/jlr.P025577. Epub 2012 May 24. — View Citation

Khaw KT, Friesen MD, Riboli E, Luben R, Wareham N. Plasma phospholipid fatty acid concentration and incident coronary heart disease in men and women: the EPIC-Norfolk prospective study. PLoS Med. 2012;9(7):e1001255. doi: 10.1371/journal.pmed.1001255. Epub 2012 Jul 3. — View Citation

Levy BD. Resolvins and protectins: natural pharmacophores for resolution biology. Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):327-32. doi: 10.1016/j.plefa.2010.02.003. Epub 2010 Mar 15. Review. — View Citation

MacLean CH, Mojica WA, Morton SC, Pencharz J, Hasenfeld Garland R, Tu W, Newberry SJ, Jungvig LK, Grossman J, Khanna P, Rhodes S, Shekelle P. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid Rep Technol Assess (Summ). 2004 Mar;(89):1-4. — View Citation

Marcantoni E, Di Francesco L, Totani L, Piccoli A, Evangelista V, Tacconelli S, Patrignani P. Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression. Prostaglandins Other Lipid Mediat. 2012 Aug;98(3-4):122-8. doi: 10.1016/j.prostaglandins.2012.01.006. Epub 2012 Feb 6. — View Citation

Miles EA, Calder PC. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr. 2012 Jun;107 Suppl 2:S171-84. doi: 10.1017/S0007114512001560. Review. — View Citation

Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I, Krishnamurthy R, Eisner R, Gautam B, Young N, Xia J, Knox C, Dong E, Huang P, Hollander Z, Pedersen TL, Smith SR, Bamforth F, Greiner R, McManus B, Newman JW, Goodfriend T, Wishart DS. The human serum metabolome. PLoS One. 2011 Feb 16;6(2):e16957. doi: 10.1371/journal.pone.0016957. — View Citation

Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010 Nov;51(11):3299-305. doi: 10.1194/jlr.M009449. Epub 2010 Jul 29. — View Citation

Ramsden CE, Ringel A, Feldstein AE, Taha AY, MacIntosh BA, Hibbeln JR, Majchrzak-Hong SF, Faurot KR, Rapoport SI, Cheon Y, Chung YM, Berk M, Mann JD. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):135-41. doi: 10.1016/j.plefa.2012.08.004. Epub 2012 Sep 5. — View Citation

Robinson LE, Buchholz AC, Mazurak VC. Inflammation, obesity, and fatty acid metabolism: influence of n-3 polyunsaturated fatty acids on factors contributing to metabolic syndrome. Appl Physiol Nutr Metab. 2007 Dec;32(6):1008-24. Review. — View Citation

Schuchardt JP, Schmidt S, Kressel G, Dong H, Willenberg I, Hammock BD, Hahn A, Schebb NH. Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men. Prostaglandins Leukot Essent Fatty Acids. 2013 Jul;89(1):19-29. doi: 10.1016/j.plefa.2013.04.001. Epub 2013 May 19. — View Citation

Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008 May;8(5):349-61. doi: 10.1038/nri2294. Review. — View Citation

Wang X, Lin H, Gu Y. Multiple roles of dihomo-?-linolenic acid against proliferation diseases. Lipids Health Dis. 2012 Feb 14;11:25. doi: 10.1186/1476-511X-11-25. Review. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of Blood Lipids Day 0 vs. Day 28	At the Day 0 and 28 visits, additional blood fasting venous blood will be obtained from the participant for measurement of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides.	28 Days	No
Other	Comparison of Serum Oxylipins vs. Plasma Oxylipins	At the Day 0 and 28 visits a fasting venous blood will be obtained for comparison of oxylipins in clotted (serum) versus unclotted (plasma) samples.	28 Days	No
Primary	Plasma oxylipin concentrations over time	A fasting venous blood sample will be obtained from the participant on Days 0, 1, 3, 7, 14 and 28 of each 'Supplementation Phase' for the assessment of plasma oxylipin profile.	28 Days	No
Secondary	Fatty Acid Composition Over Time	A fasting venous blood sample will be obtained from the participant on Days 0, 1, 3, 7, 14 and 28 of each 'Supplementation Phase' for the assessment of fatty acid composition.	28 Days	No
Secondary	Assessment of Markers of Metabolism, Oxidative Stress & Inflammation Over Time	A fasting venous blood sample will be obtained from the participant at Day 0, 1, 3, 7, 14 and 28 of each Supplementation Phase for assessment of markers of markers of metabolism, oxidative stress and inflammation.	28 Days	No

External Links

•   Canadian Centre for Agri-Food Research in Health and Medicine