Effect of Consuming n-3 Polyunsaturated Fatty Acids Rich Foods on Triglyceride Concentration and Lipoprotein Composition

Official title

Effect of Consuming n-3 Polyunsaturated Fatty Acids Rich Foods on Triglyceride Concentration and Lipoprotein Composition in Individuals With Hypertriglyceridemia. Controlled Clinical Trial.

Overview

Hypertriglyceridemia is one of the most prevalent lipid profile disorders and is linked to a large proportion of mortality in Mexico and around the world. Various international treatment guidelines for hypertriglyceridemia have suggested the consumption of foods rich in n-3 polyunsaturated fatty acids or their intake through supplementation as a complement to lifestyle changes. However, adherence to the consumption of foods and supplements containing these fatty acids is often limited due to lack of acceptance or unaffordability. For this reason the objective of the study is to evaluate the effect of including Mexican foods rich in n-3 polyunsaturated fatty acids (chia seeds and pumpkin seeds) within a diet based on NCEP-ATPIII recommendations on triacylglycerol concentration and fatty acid profile in people with hypertriglyceridemia. The study will consist of a 4-week period in which one group of participants will be randomized into two treatment groups: 1)isocaloric diet based on the NCEP-ATPIII dietary recommendations; 2) isocaloric diet based on the NCEP-ATPIII dietary recommendations plus chia and pumpkin seeds. The effect of the dietary intervention will be assessed by concentration of triglycerides, fatty acids profile and lipoprotein analysis.

Detailed description

The study will consist of a 4-week period in which one group of participants will be given a diet based on the NCEP-ATPIII dietary recommendations, and another group will receive the same diet plus chia and pumpkin seeds. If participants maintain triglyceride levels \>200 mg/dL, they will be given fish oil supplementation for an additional 4 weeks to reinforce the dietary treatment (NCEP-ATPIII dietary recommendations).

Participants will be screened to ensure they meet the inclusion criteria. Those who agree to participate will be required to sign an informed consent form. At both the beginning and the end of the 4-week period, participants will undergo a medical history assessment, anthropometric measurements (weight, height, and waist circumference), body composition analysis (including body fat percentage, skeletal muscle mass percentage, and lean body mass percentage), blood pressure measurement, evaluation of hepatic steatosis using transient elastography and; pulse wave velocity.

In addition, blood samples will be collected to determine serum glucose levels; lipid profile parameters (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides); inflammatory, oxidative, and endothelial markers; and genetic polymorphisms related to lipid metabolism, particularly n-3 polyunsaturated fatty acids (PUFAs) (FADS1 and FADS2). Monocytes will also be isolated to assess mitochondrial function.

Furthermore, serum concentrations of phosphatidylcholine species (16:0\_20:5 and 16:0\_22:6), lipoprotein composition, and fatty acid profiles will be analyzed using gas chromatography.

Participants with hypertriglyceridemia will be randomly assigned to two groups. Both groups will be prescribed an isocaloric diet; however, only one group will additionally include a food rich in n-3 PUFAs:

* An isocaloric diet based on NCEP-ATPIII dietary recommendations. * An isocaloric diet based on NCEP-ATPIII dietary recommendations including chia and pumpkin seeds.

Resting energy expenditure wil be measured by indirect calorimetry to determine energy requirement of each participant. Distribution of micronutrients of the dietary intervention will be as follow: 50% carbohydrates, 20% protein, and 30% lipids .

This dietary intervention will last 4 weeks. To promote adherence, participants will be given foods rich in n-3 PUFA.

Participants with triglyceride levels \>200 mg/dL after the 4-week dietary intervention period will receive fish oil supplementation for an additional 4 weeks. At the end of this period, anthropometric measurements (weight, height, and waist circumference), body composition analysis (including body fat percentage, skeletal muscle mass percentage, and lean body mass percentage), blood pressure measurement, and hepatic steatosis assessment using transient elastography will be repeated. Blood samples will be collected again to determine serum glucose levels and lipid profile parameters (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides).

During the whole study dietary intake and the adherence to dietary treatment will be monitored using 24-hour dietary recalls, which will be conducted during all visits, as well as through phone calls 2 times per week and text messages.

In addition to the above, the concentration of fatty acids in serum will be evaluated and compared over a 24-hour period following the intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements (fish oil) vs. that of foods rich in n-3 polyunsaturated fatty acids (salmon fish, Sierra fish and chia seeds and pumpkin seeds).

Interventions

• Dietary supplement Isocaloric diet including chia and pumpkin seeds
  Diet based on participant-specific energy expenditure. With the following macronutrient distribution: 50% carbohydrates, protein 20% and 30% fats. This dietary intervention consists of a four-week follow-up period and incorporates the intake of pumpkin and chia seeds.
• Other Isocaloric diet
  Diet based on participant-specific energy expenditure. With the following macronutrient distribution: 50% carbohydrates, protein 20% and 30% fats. This dietary intervention consists of a four-week follow-up period.

Primary outcome measures

• Serum triglycerides concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum fatty acid profile analysis by gas chromatography in microgram [Time frame: From baseline to week 4 of the intervention]

Secondary outcome measures (12)

• Serum total cholesterol concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum LDL cholesterol concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum HDL cholesterol concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum lipids concentration in relative peak area [Time frame: From baseline to week 4 of the intervention]
• Serum C-reactive protein concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Plasma malondialdehyde concentration in nmol/mL [Time frame: From baseline to week 4 of the intervention]
• Serum Intercellular Adhesion Molecule-1 (ICAM-1) concentration in pg/mL [Time frame: From baseline to week 4 of the intervention]
• Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) concentration in pg/mL [Time frame: From baseline to week 4 of the intervention]
• Serum plasminogen concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum glucose concentration in mg/dL [Time frame: From baseline to week 4 of the intervention]
• Serum aspartate aminotransferase concentration in IU/mL [Time frame: From baseline to week 4 of the intervention]
• Serum alanine aminotransferase concentration in IU/mL [Time frame: From baseline to week 4 of the intervention]

Eligibility criteria

Inclusion criteria

• Signing of the informed consent form
• Both sexes.
• Adults over 18 years of age.
• BMI >18.5 kg/m2.
• Triglycerides between 200 and 500 mg/dL.
• Total cholesterol less than 240 mg/dL

Exclusion criteria

• Any type of diabetes.
• kidney disease diagnosed by a physician.
• Acquired diseases that secondarily cause obesity and diabetes.
• Patients who have suffered a cardiovascular event.
• Weight loss >3 kg in the last 3 months.
• Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
• Pregnancy.
• Treatment with any medication:
• Treatment with antihypertensive drugs (tricyclic, loop, or potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, alpha-blockers, calcium channel blockers, beta-blockers).
• Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or - insulin and antidiabetics.
• Treatment with statins, fibrates, or other drugs to control dyslipidemia.
• Use of steroid medications, chemotherapy, immunosuppressants, or radiation therapy.
• Anorectic agents or those that accelerate weight loss.
• Treatment with any medication that influences inflammation (corticosteroids, nonsteroidal anti-inflammatory drugs, colchicine, interleukin-1 inhibitors) or triglyceride metabolism (metformin, glitazones, SGLT2 inhibitors, fibrates, statins, cholesterol ester transporter protein (CETP) inhibitors, pancreatic lipase inhibitors).
• Anticoagulants and antiplatelets (warfarin, aspirin, clopidogrel).
• People with a smoking cessation index (SCI) greater than 21.
• People with a tobacco Index greater than 21.
• Consumption of large amounts of alcohol (14 drinks for women or 21 drinks for men in a typical week).
• Consumption of any recreational psychoactive substance.
• Allergy or intolerance to any food listed in the proposed pantry.
• Unwillingness to consume any of the foods listed in the proposed pantry.
• Previous n-3 PUFA supplementation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Mexico · 1 center

• Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán — Mexico City

Publications

• Ly R, MacIntyre BC, Philips SM, McGlory C, Mutch DM, Britz-McKibbin P. Lipidomic studies reveal two specific circulating phosphatidylcholines as surrogate biomarkers of the omega-3 index. J Lipid Res. 2023 Nov;64(11):100445. doi: 10.1016/j.jlr.2023.100445. Epub 2023 Sep 18. PMID 37730162
• Ottestad I, Hassani S, Borge GI, Kohler A, Vogt G, Hyotylainen T, Oresic M, Bronner KW, Holven KB, Ulven SM, Myhrstad MC. Fish oil supplementation alters the plasma lipidomic profile and increases long-chain PUFAs of phospholipids and triglycerides in healthy subjects. PLoS One. 2012;7(8):e42550. doi: 10.1371/journal.pone.0042550. Epub 2012 Aug 28. PMID 22952598
• Erkkila AT, Manninen S, Fredrikson L, Bhalke M, Holopainen M, Ruuth M, Lankinen M, Kakela R, Oorni K, Schwab US. Lipidomic changes of LDL after consumption of Camelina sativa oil, fatty fish and lean fish in subjects with impaired glucose metabolism-A randomized controlled trial. J Clin Lipidol. 2021 Sep-Oct;15(5):743-751. doi: 10.1016/j.jacl.2021.08.060. Epub 2021 Sep 7. PMID 34548243
• Tatsuno I, Kudou K, Kagawa T. Effect of TAK-085 on Low-density Lipoprotein Particle Size in Patients with Hypertriglyceridemia: A Double-blind Randomized Clinical Study. Cardiovasc Ther. 2015 Dec;33(6):317-23. doi: 10.1111/1755-5922.12146. PMID 26222126
• Makni M, Fetoui H, Gargouri NK, Garoui el M, Jaber H, Makni J, Boudawara T, Zeghal N. Hypolipidemic and hepatoprotective effects of flax and pumpkin seed mixture rich in omega-3 and omega-6 fatty acids in hypercholesterolemic rats. Food Chem Toxicol. 2008 Dec;46(12):3714-20. doi: 10.1016/j.fct.2008.09.057. Epub 2008 Oct 1. PMID 18938206
• Avila-Nava A, Noriega LG, Tovar AR, Granados O, Perez-Cruz C, Pedraza-Chaverri J, Torres N. Food combination based on a pre-hispanic Mexican diet decreases metabolic and cognitive abnormalities and gut microbiota dysbiosis caused by a sucrose-enriched high-fat diet in rats. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201501023. Epub 2016 Aug 8. PMID 27352915
• Bhatt DL, Steg PG, Brinton EA, Jacobson TA, Miller M, Tardif JC, Ketchum SB, Doyle RT Jr, Murphy SA, Soni PN, Braeckman RA, Juliano RA, Ballantyne CM; REDUCE-IT Investigators. Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial. Clin Cardiol. 2017 Mar;40(3):138-148. doi: 10.1002/clc.22692. Epub 2017 Mar 15. PMID 28294373
• Zheng J, Huang T, Yu Y, Hu X, Yang B, Li D. Fish consumption and CHD mortality: an updated meta-analysis of seventeen cohort studies. Public Health Nutr. 2012 Apr;15(4):725-37. doi: 10.1017/S1368980011002254. Epub 2011 Sep 14. PMID 21914258

Identifiers

NCT: NCT07004777 · FNU-5515-25-27-1 · INCMNSZ

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗