Cardiovascular Risk Prevention With a Mediterranean Dietary Pattern Reduced in Saturated Fat

NCT05778656 | Completed

• 1 other identifier: CADIMED2022
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 1

Brief Summary

The Cardiovascular Risk Prevention With a Mediterranean Dietary Pattern Reduced in Saturated Fat (CADIMED) study is a randomized, controlled intervention trial aiming to develop a dietary intervention that promotes saturated fat (SFA) reduction through eliminating red and processed meat consumption and to evaluate its impact on lipid and cardiovascular disease (CVD) risk biomarkers. The main research question is: \* Does lowering SFA intake from specific foods (e.g., red and processed meat) modify cardiovascular risk factors in a Mediterranean dietary pattern context? The aim is to compare, in a sample of 156 adult subjects (\>18 years) with dyslipidemia, the effect of an intervention that promotes the elimination of red and processed meat intake vs. the control group that will follow the usual health advice for CVD prevention. Changes in CVD risk biomarkers, blood metabolomics and the microbiome will be investigated after 8 weeks of intervention.

Conditions

LDL Cholesterol

Keywords

cardiovascular disease; Mediterranean diet; saturated fat; LDL cholesterol; red meat; fatty acids

Outcome Measures

Primary Outcomes (2)

• LDL-Cholesterol (mg/dL)

  To investigate changes in LDL-C after 8 weeks in the intervention group compared to control

  8 weeks

• Fatty acid profile (%)

  The initial plan was to investigate changes in palmitic acid after 8 weeks in the intervention group compared to control. However, after careful consideration with experts in Biochemistry, it is proposed to measure the overall fatty acid profile in erytrocyte membranes (instead of measuring palmitic acid individually for the primary outcome and the rest of individual fatty acids for the secondary outcome measures). Given the nature of this dietary intervention and the homeostatic metabolic processes that regulate individual fatty acids, it is advised to look at changes in the overall fatty acid profile (ie. their relative proportion within the overall profile) in response to the intervention. This change does not affect any methodological aspect of the trial because the sample size was calculated based on the primary outcome LDL-cholesterol change (see Statistical Analysis in Study Description)

  8 weeks

Secondary Outcomes (22)

• Metabolites derived from lipid and metabolomic profile analysis (mg/dL)

  8 weeks

• Metabolites derived from lipid and metabolomic profile analysis (percentage)

  8 weeks

• CVD risk related markers: C-reactive protein, IL-6, IL8/CXCL8, IL10, IL23, TNF-alpha, IFNgamma, ICAM1, VCAM1, ELAM1, MPO, endotelin I, angiotensin II (ng/mL)

  8 weeks

• CVD risk related markers: Glucose (mg/dL)

  8 weeks

• CVD risk related markers: Insulin (mU/ml)

  8 weeks

Other Outcomes (3)

• Process Evaluation Outcomes: feasibility outcomes

  8 weeks

• Process Evaluation Outcomes: acceptance and use of the intervention

  8 weeks

• Exploratory subgroup analyses by SES

  8 weeks

Study Arms (2)

Mediterranean diet without red and/or processed meat

EXPERIMENTAL

They will receive motivation and behavioral support through a study specific website which will be accessed after randomization. The research team will give participants further information on the use of this website. One of the features of the website will allow participants to collect and self-monitor their dietary intakes using 24h dietary recalls. Participants will be instructed to fill in as many recalls as possible throughout the study, with a minimum of 2 recalls at baseline and 2 recalls at follow up. Other features of the website include specific indications to eliminate red and processed meat in the context of a healthy Mediterranean dietary pattern, considering the key elements proposed in the dietary guidelines to improve cardiovascular health. The website will also provide them general information about the Mediterranean diet, as well as recipes, tips, and alternatives to replace meat when cooking at home or eating out. The rest of the clinical care will be as usual.

Behavioral: Cardiovascular Risk Prevention with a Mediterranean Dietary Pattern Reduced in Saturated Fat

General advice based on the Mediterranean diet

NO INTERVENTION

The control group will be guided to use the same website although they will only have access to a restricted version of it, with the dietary recall feature plus general information about the Mediterranean diet. They will not receive specific recommendations to reduce red and processed meat or any other support or advice. Participants will be instructed to fill in as many 24h dietary recalls as possible throughout the study, with a minimum of 2 recalls at baseline and 2 recalls at follow up. The rest of the clinical care will be as usual.

Interventions

Cardiovascular Risk Prevention with a Mediterranean Dietary Pattern Reduced in Saturated Fat BEHAVIORAL

Eight-week behavioral intervention consisting of a Mediterranean dietary pattern with elimination of red and processed meat

Also known as: CADIMED

Mediterranean diet without red and/or processed meat

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form.
• Age ≥18 years to ≤75 years.
• With indication to start lifestyle intervention based on recent values (e.g., last 3-6 months) of LDL-C ≥ 116 mg/dl and \< 190 mg/dl; or as long as pharmacological treatment has not been advised and started (ESC/EAS Guide, Rev Esp Cardiol. 2020).
• Access to a device (e.g., smartphone, tablet, computer) with internet and digital skills to use the website.
• Motivation and willingness to be assigned to any group to improve their diet and commitment to perform the designated protocol.

You may not qualify if:

• Patients with familial hypercholesterolemia and/or on treatment with lipid-lowering drugs (including statins, ezetimibe, PCSK9 inhibitors, fibrates, bile acid sequestrants, omega-3 fatty acids, nicotinic acid/Vit B3), dietary supplements or functional foods for the treatment of dyslipidemia (plant sterols, monacolin, red yeast rice, fiber supplements 3-10 g (Plantago), policosanol, berberine, and soy protein/lecithin) in the last 3 months.
• High cardiovascular risk that requires pharmacological treatment, for example, patients with recent and/or established CVD, type 1 and 2 diabetes.
• Uncompensated thyroid function disorders; relevant comorbidities (including liver failure and cholestasis, chronic kidney disease, Cushing's syndrome, nephrotic syndrome, class III obesity - BMI ≥ 40 kg/m²); cancer; psychiatric disorders and/or that in the opinion of the investigator hinder the fulfillment or follow-up of the study.
• Excessive alcohol consumption: \> 40 g/d (4 UBEs/day) in men and \> 20-25 g/d (2-2.5 UBEs/day) in women (Ministry of Health, July 2020).
• Pregnancy, lactation, perimenopause (amenorrhea \< 1 year) and women who change, start, or finish their treatment with hormonal contraceptives during the study.
• Enrollment in other research studies or following restricted eating patterns (e.g., vegetarians and vegans) that could interfere with study requirements.
• Failure to grant informed consent or not complete the initial assessment.

Sponsors & Collaborators

• University Hospital Virgen de las Nieves: collaborator
• Universidad de Granada: lead
• University of Oxford: collaborator
• University of Copenhagen: collaborator
• Norwegian Veterinary Institute: collaborator
• Harvard University: collaborator

Study Sites (1)

University of Granada

Granada, Granada, 18008, Spain

Location

Related Publications (19)

• World Health Organization. Cardiovascular diseases (CVDs). WHO: Copenhagen; 2021. Available in: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

  BACKGROUND

• Verschuren WMM, Boer JMA, Temme EHM. Optimal diet for cardiovascular and planetary health. Heart. 2022 Jul 13;108(15):1234-1239. doi: 10.1136/heartjnl-2019-316373. No abstract available.

  PMID: 34635484 BACKGROUND

• Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004 Jun 15;109(23 Suppl 1):III27-32. doi: 10.1161/01.CIR.0000131515.03336.f8.

  PMID: 15198963 BACKGROUND

• SEC Working Group for the 2021 ESC guidelines on cardiovascular disease prevention in clinical practice and SEC Guidelines Committee. Comments on the 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Rev Esp Cardiol (Engl Ed). 2022 May;75(5):364-369. doi: 10.1016/j.rec.2021.10.023. Epub 2022 Feb 11. No abstract available. English, Spanish.

  PMID: 35165071 BACKGROUND

• American Heart Association. Saturated Fat. AHA: Texas: 2021. Available in: https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/fats/saturated-fats

  BACKGROUND

• Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2020 Aug 21;8(8):CD011737. doi: 10.1002/14651858.CD011737.pub3.

  PMID: 32827219 BACKGROUND

• Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Aug 18;76(7):844-857. doi: 10.1016/j.jacc.2020.05.077. Epub 2020 Jun 17.

  PMID: 32562735 BACKGROUND

• Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406. doi: 10.7326/M13-1788.

  PMID: 24723079 BACKGROUND

• Zong G, Li Y, Wanders AJ, Alssema M, Zock PL, Willett WC, Hu FB, Sun Q. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies. BMJ. 2016 Nov 23;355:i5796. doi: 10.1136/bmj.i5796.

  PMID: 27881409 BACKGROUND

• Guasch-Ferre M, Satija A, Blondin SA, Janiszewski M, Emlen E, O'Connor LE, Campbell WW, Hu FB, Willett WC, Stampfer MJ. Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors. Circulation. 2019 Apr 9;139(15):1828-1845. doi: 10.1161/CIRCULATIONAHA.118.035225.

  PMID: 30958719 BACKGROUND

• Key TJ, Appleby PN, Bradbury KE, Sweeting M, Wood A, Johansson I, Kuhn T, Steur M, Weiderpass E, Wennberg M, Lund Wurtz AM, Agudo A, Andersson J, Arriola L, Boeing H, Boer JMA, Bonnet F, Boutron-Ruault MC, Cross AJ, Ericson U, Fagherazzi G, Ferrari P, Gunter M, Huerta JM, Katzke V, Khaw KT, Krogh V, La Vecchia C, Matullo G, Moreno-Iribas C, Naska A, Nilsson LM, Olsen A, Overvad K, Palli D, Panico S, Molina-Portillo E, Quiros JR, Skeie G, Sluijs I, Sonestedt E, Stepien M, Tjonneland A, Trichopoulou A, Tumino R, Tzoulaki I, van der Schouw YT, Verschuren WMM, di Angelantonio E, Langenberg C, Forouhi N, Wareham N, Butterworth A, Riboli E, Danesh J. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease. Circulation. 2019 Jun 18;139(25):2835-2845. doi: 10.1161/CIRCULATIONAHA.118.038813. Epub 2019 Apr 22.

  PMID: 31006335 BACKGROUND

• Visioli F, Poli A. Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence. Nutrients. 2020 Dec 9;12(12):3782. doi: 10.3390/nu12123782.

  PMID: 33317164 BACKGROUND

• de Oliveira Otto MC, Mozaffarian D, Kromhout D, Bertoni AG, Sibley CT, Jacobs DR Jr, Nettleton JA. Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr. 2012 Aug;96(2):397-404. doi: 10.3945/ajcn.112.037770. Epub 2012 Jul 3.

  PMID: 22760560 BACKGROUND

• Piernas C, Aveyard P, Lee C, Tsiountsioura M, Noreik M, Astbury NM, Oke J, Madigan C, Jebb SA. Evaluation of an intervention to provide brief support and personalized feedback on food shopping to reduce saturated fat intake (PC-SHOP): A randomized controlled trial. PLoS Med. 2020 Nov 5;17(11):e1003385. doi: 10.1371/journal.pmed.1003385. eCollection 2020 Nov.

  PMID: 33151934 BACKGROUND

• Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Fito M, Gea A, Hernan MA, Martinez-Gonzalez MA; PREDIMED Study Investigators. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018 Jun 21;378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13.

  PMID: 29897866 BACKGROUND

• Reidlinger DP, Darzi J, Hall WL, Seed PT, Chowienczyk PJ, Sanders TA; Cardiovascular disease risk REduction Study (CRESSIDA) investigators. How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial. Am J Clin Nutr. 2015 May;101(5):922-30. doi: 10.3945/ajcn.114.097352. Epub 2015 Mar 18.

  PMID: 25787998 BACKGROUND

• Vafeiadou K, Weech M, Altowaijri H, Todd S, Yaqoob P, Jackson KG, Lovegrove JA. Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study. Am J Clin Nutr. 2015 Jul;102(1):40-8. doi: 10.3945/ajcn.114.097089. Epub 2015 May 27.

  PMID: 26016869 BACKGROUND

• Lin JS, O'Connor E, Whitlock EP, Beil TL. Behavioral counseling to promote physical activity and a healthful diet to prevent cardiovascular disease in adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010 Dec 7;153(11):736-50. doi: 10.7326/0003-4819-153-11-201012070-00007.

  PMID: 21135297 BACKGROUND

• Chavez-Alfaro L, Tenorio Jimenez C, Silveira-Sanguino V, Noguera Gomez MJ, Fernandez-Moreno C, Rodriguez Cuesta AM, Lebron Arana AF, Segura Calvo O, Merino De Haro I, Aguilera CM, Gomez-Llorente C, Rangel-Huerta OD, Astbury N, Perez-Cornago A, Guasch-Ferre M, Piernas C. Intervention design and adherence to Mediterranean diet in the Cardiovascular Risk Prevention with a Mediterranean Dietary Pattern Reduced in Saturated Fat (CADIMED) randomized trial. Nutr Res. 2025 Apr;136:120-132. doi: 10.1016/j.nutres.2025.03.001. Epub 2025 Mar 10.

  PMID: 40187224 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Fatty Acids

Intervention Hierarchy (Ancestors)

Lipids

Study Officials

• Carmen Piernas, PhD

  Universidad de Granada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A computer-generated randomization with a stratified block design will be used, with sex, age, obesity, and fiber intake as stratification variables using randomly permuted blocks of size 2 and 4. The computer program (RedCap) will reveal the group allocation to the researcher, with no option to visualize the groups that will be assigned to future patients. It will not be possible to blind patients to the intervention group due to the nature of the intervention. However, the effectiveness measure comparing trial arms (primary outcomes) are objectively measured outcomes (blood lipids and metabolites) and not subject to interpretation by researchers, limiting the effect that researcher knowledge of the intervention group could have on outcomes. Where possible, the study team taking all the outcome measurements will remain blind to group allocation throughout the trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior researcher

Model Details: The CADIMED study is a randomized, controlled nutritional intervention study (two-arm parallel group design with a 1:1 ratio)

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: March 21, 2023
• Study Start: March 19, 2023
• Primary Completion: August 6, 2025
• Study Completion: August 6, 2025
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

ES (1)