Conjugated Linoleic Acid Supplementation Study

NCT01234636 | Completed

• 1 other identifier: RINH_1000
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular disease is a major cause of mortality worldwide resulting in one out of three global deaths. One of the main characteristics of cardiovascular disease is impaired blood flow and increased formation of clots. Platelets are clot-forming cells responsible for prevention of bleeding. However, in disease state they may be overly activated and tend to stick to each other, promoting blood clots and blockage of vessels. Conjugated linoleic acids (CLA) are unique fatty acids present in dairy food products and beef which would help to prevent platelets from clotting and thus help to prevent cardiovascular disease. However, the mechanisms by which those fatty acids affect platelet function are not yet fully understood. We designed a human intervention study assessing the mechanisms by which CLA beneficially affect platelet function and markers of haemostasis and inflammation in humans.

Conditions

Cardiovascular Disease

Keywords

Platelets; Platelet aggregation; Platelet activation; Platelet function; Light transmission aggregometry; Flow cytometry; Platelet function analyzer-100 (PFA-100); Linoleic acid, conjugated; cis9, trans11 conjugated linoleic acid; dietary supplement; short-term intervention

Outcome Measures

Primary Outcomes (3)

• Change of expression of P-selectin and fibrinogen receptor activation on platelets by flow cytometry

  Using fluorescently-conjugated monoclonal antibodies and whole blood flow cytometry after ex vivo stimulation with adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP) P-selectin expression as early marker of platelet activation Activated fibrinogen receptor as late marker of platelet activation

  At 2 weeks

• Change of in vitro bleeding time using the Platelet Function Analyzer (PFA-100)

  Using collagen-epinephrine coated cartridges Using collagen-adenosine diphosphate coated cartridges

  At 2 weeks supplementation

• Change of coagulation marker assessed as fibrinogen levels in plasma

  Using semi-automated coagulometer using fibrinogen assay according to Clauss method

  At 2 weeks supplementation

Secondary Outcomes (2)

• Change in light transmission aggregometry of platelet rich plasma induced by collagen and arachidonic acid

  At 2 weeks supplementation

• Change in plasma levels of von Willebrand factor (vWF), soluble ICAM (s-ICAM) and soluble P-selectin (sP-selectin) as markers of endothelial activation

  At 2 weeks supplementation

Study Arms (2)

cis9,trans 11 CLA oil

ACTIVE COMPARATOR

50 volunteers on cross over design , receiving 4g/day of cis9,trans11 CLA

Dietary Supplement: Placebo oil

Placebo oil

PLACEBO COMPARATOR

50 volunteers cross over design, placebo oil 4g/day

Dietary Supplement: Placebo oil

Interventions

Placebo oil DIETARY_SUPPLEMENT

Placebo oil of 4g/day

Placebo oil; cis9,trans 11 CLA oil

Eligibility Criteria

• Age: 30 Years - 74 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• blood pressure below 160/90 mmHg;
• fasting plasma glucose \< 7 mmol/L;
• total cholesterol \< 8 mmol/L,with cholesterol/HDL ratio \< 6 and/or ASSIGN score \< 20%)
• platelet count \> 170x109/L
• haematocrit above 40 % for males and above 35 % for females
• haemoglobin above 130 g/L for males and above 115 g/L for females
• having a 10-20% risk for developing cardiovascular disease within the next 10 years based on the ASSIGN calculation (http://cvrisk.mvm.ed.ac.uk/index.htm) including the following factors: age, gender, number of cigarettes smoked per day, Scottish Index of Multiple Deprivation (SIMD)/postcode, systolic blood pressure, levels of total and HDL cholesterol and family history of cardiovascular disease or having at least one additional risk factor such as being over 50 years old, BMI above 25 kg/m2, elevated triglyceride levels (\> 1.7 mmol/L) or elevated glucose levels (\> 5.6 mmol/L);

You may not qualify if:

• They are regularly taking aspirin or aspirin-containing drugs, or other anti-inflammatory drugs;
• They are taking drugs or herbal medicines known to alter platelet function or the haemostatic system in general;
• They are diagnosed with diabetes, hypertension, renal, hepatic, haematological disease or coronary heart disease;
• They are undertaking more than 6 hours vigorous exercise per week
• They are pregnant (or planning to become pregnant) or lactating;
• They have given a pint of blood for transfusion purposes within the last month;
• They have unsuitable veins for blood sampling;
• They are inability to understand the participant information sheet or inability to speak, read and understand the English language.

Sponsors & Collaborators

• University of Aberdeen: lead

Study Sites (1)

Rowett Institute of Nutrition and Health

Aberdeen, Scotland, AB21 9SB, United Kingdom

Location

Related Publications (15)

• Benito P, Nelson GJ, Kelley DS, Bartolini G, Schmidt PC, Simon V. The effect of conjugated linoleic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids. 2001 Mar;36(3):221-7. doi: 10.1007/s11745-001-0711-y.

  PMID: 11337976 BACKGROUND

• Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem. 2006 Dec;17(12):789-810. doi: 10.1016/j.jnutbio.2006.02.009. Epub 2006 May 2.

  PMID: 16650752 BACKGROUND

• Malpuech-Brugere C, Verboeket-van de Venne WP, Mensink RP, Arnal MA, Morio B, Brandolini M, Saebo A, Lassel TS, Chardigny JM, Sebedio JL, Beaufrere B. Effects of two conjugated linoleic Acid isomers on body fat mass in overweight humans. Obes Res. 2004 Apr;12(4):591-8. doi: 10.1038/oby.2004.68.

  PMID: 15090626 BACKGROUND

• Zhila VV, Shodmonova ZR, Rublevskii VP, Chernenko PS. [High resection of the left testicular vein and ligation of the internal iliac artery using a retroperitoneoscope]. Klin Khir (1962). 1991;(5):49-51. Russian.

  PMID: 1875623 BACKGROUND

• Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004 Oct;80(4):887-95. doi: 10.1093/ajcn/80.4.887.

  PMID: 15447895 BACKGROUND

• Brewerton TD, Murphy DL, Lesem MD, Brandt HA, Jimerson DC. Headache responses following m-chlorophenylpiperazine in bulimics and controls. Headache. 1992 May;32(5):217-22. doi: 10.1111/j.1526-4610.1992.hed3205217.x.

  PMID: 1628957 BACKGROUND

• Noone EJ, Roche HM, Nugent AP, Gibney MJ. The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. Br J Nutr. 2002 Sep;88(3):243-51. doi: 10.1079/BJN2002615.

  PMID: 12207834 BACKGROUND

• Riserus U, Vessby B, Arnlov J, Basu S. Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr. 2004 Aug;80(2):279-83. doi: 10.1093/ajcn/80.2.279.

  PMID: 15277146 BACKGROUND

• Riserus U, Vessby B, Arner P, Zethelius B. Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia. 2004 Jun;47(6):1016-9. doi: 10.1007/s00125-004-1421-8. Epub 2004 May 28.

  PMID: 15168020 BACKGROUND

• Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B. Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance. Circulation. 2002 Oct 8;106(15):1925-9. doi: 10.1161/01.cir.0000033589.15413.48.

  PMID: 12370214 BACKGROUND

• Riserus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care. 2002 Sep;25(9):1516-21. doi: 10.2337/diacare.25.9.1516.

  PMID: 12196420 BACKGROUND

• Tholstrup T, Raff M, Straarup EM, Lund P, Basu S, Bruun JM. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. J Nutr. 2008 Aug;138(8):1445-51. doi: 10.1093/jn/138.8.1445.

  PMID: 18641189 BACKGROUND

• Tricon S, Burdge GC, Kew S, Banerjee T, Russell JJ, Jones EL, Grimble RF, Williams CM, Yaqoob P, Calder PC. Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. Am J Clin Nutr. 2004 Sep;80(3):614-20. doi: 10.1093/ajcn/80.3.614.

  PMID: 15321800 BACKGROUND

• Truitt A, McNeill G, Vanderhoek JY. Antiplatelet effects of conjugated linoleic acid isomers. Biochim Biophys Acta. 1999 May 18;1438(2):239-46. doi: 10.1016/s1388-1981(99)00055-4.

  PMID: 10320806 BACKGROUND

• Bachmair EM, Wood SG, Keizer HG, Horgan GW, Ford I, de Roos B. Supplementation with a 9c,11t-rich conjugated linoleic acid blend shows no clear inhibitory effects on platelet function in healthy subjects at low and moderate cardiovascular risk: a randomized controlled trial. Mol Nutr Food Res. 2015 Apr;59(4):741-50. doi: 10.1002/mnfr.201400495. Epub 2015 Feb 23.

  PMID: 25641922 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Baukje De Roos, PhD

  Univeristy of Aberdeen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 4, 2010
• Study Start: November 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 13, 2015

Record last verified: 2015-11

Locations

GB (1)