Very Low Calorie Ketogenic Low-fat Diet (VLCKLFD) (Zelé2021)

Comparative Study of the Response to Weight Loss and Metabolic Conditions Using Two Non-pharmacological Nutritional Programs

This study aimed to assess the efficacy and safety of the Zélé program, a controlled ketogenic diet, for weight loss and maintenance. It involved a randomized clinical trial with participants aged 18-60, BMI between 30-34.9 kg/m², and no severe health issues

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Low-fat normoprotein Controlled Ketogenic Diet.; Other: Hypocaloric Balanced Diet

Detailed Description

The study will be conducted in Mexico City under the sponsorship of Zélé® and in collaboration with the VIME Weight Loss and Wellness Center of Mexico. During the year 2021 and with follow-up for 24 months. An open call will be made through different media including social networks for the recruitment of patients who meet the inclusion criteria and must present themselves for a clinical evaluation in which pathological history, clinical status, heart rate, blood pressure, oxygenation and temperature will be recorded. Nutritional assessment, and a Complete Blood Count, a biochemical profile. Patients who meet all the inclusion criteria will be selected and will have an interview with the principal investigator in which they will sign their letter of commitment and informed consent, then they will be subjected to the randomization process with a 2:1 allocation for treatment and controls, respectively. Subsequently, they will be submitted to the two nutritional treatments and will be clinically evaluated every week and will receive nutritional, psycho emotional and physical activity counseling. At each visit, adverse effects, changes in clinical status will be recorded and the presence of ketone bodies in capillary blood will be determined. Subsequently, only clinical and nutritional follow-up will be given along with psycho-emotional support and physical activity advice every 3 months up to 12 months and every 6 months up to 24 months.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Ciudad de Mexico, Mexico
    • Francisco J Nachón García

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients of either sex, between 18 and 60 years old, with a body mass index (BMI) between 30 and 34.9 kg/m2 were eligible to participate in the study. We recruited participants from Mexico City through different media including social networks (Facebook and Instagram). The selection was consecutive according to the order of response of the interested participants. All participants read and signed the Informed Consent form

Exclusion Criteria:

• Pregnant or breastfeeding patients, patients with severe eating disorders, alcoholism, or drug addiction, patients with severe psychiatric disorders (e.g., schizophrenia, bipolar disorder, mayor depression), patients with hepatic alteration defined as increase of ALT, AST, GGT more than 4 folds the reference value, patients with renal impairment defined as a glomerular filtration rate below 60 ml/min. Patients with type 1 or insulin-dependent DM, or DM2 on insulin therapy, patients with obesity caused by endocrinological diseases (except type 2 DM), patients with hemopathies, cancer patients, patients with active cardiovascular or cerebrovascular disease (heart rhythm disorders, recent infarction [<6m], unstable angina, decompensated heart failure, recent vascular accident [<6m]), patients with gout, patients with known renal lithiasis or cholelithiasis, patients with electrolyte disorders, patients with orthostatic hypotension, patients with known an altered or abnormal electrocardiogram.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Very low calorie ketogenic low-fat diet (VLCKLFD); Frank ketosis: between 650 and 730 kcal/day in 5 mealtimes. This stage in the nutritional intervention was done during the first 4 weeks. Mixed Ketosis: in this stage, one intake of commercial preparations was replaced by proteins, which discreetly increased by 100 to 150 Kcal/day. This stage was done during the next 4 weeks.	Other: Low-fat normoprotein Controlled Ketogenic Diet.; Frank ketosis will consist of between 650 and 730 kcal/day in 5 meal times, based on commercial and vegetable preparations with low glycemic index, an average of 1.2 g of protein/kg of ideal weight/day, 20 g/day of lipids based on essential fatty acids and less than 60 g/day of absorbable carbohydrates. Patients will receive vitamin and sodium chloride, magnesium oxide, calcium carbonate. Mixed Ketosis one or two intakes of commercial preparations will be progressively replaced by proteins, which will increase by 100 to 150 Kcal/day, supplementation of vitamins and minerals will continue. Transition Stage simple carbohydrates and some complex carbohydrates are added to the previous program, in an approximate proportion of 30 to 35% protein, 25% fat and 40 to 45 % carbohydrates. Integral and maintenance phase: may vary between 1300 and 2250 kcal/day, with a macronutrient distribution of 50% carbohydrates, 25% proteins and 25% fats.; Other Names: Zelé
Active Comparator: Low-Calorie Diet (LCD); The usual caloric intake of a balanced LCD is between 1,200 and 1,500 kcal per day with a macronutrient distribution of 50% carbohydrates, 25% proteins and 25% fats, according to the Diogenes study	Other: Hypocaloric Balanced Diet; Balanced hypocaloric diet (caloric intake 20% below basal metabolic expenditure measured by Multifrequency Bioelectrical Impedance or calculated according to the FAO/WHO/UN formula (FAO/WHO/UNU (1985). Energy and Protein requirements. Technical Report Series No 724, World Health Organization, Geneva). The usual caloric intake of a balanced hypocaloric diet is between 1,200 and 1,400 kcal per day with a macronutrient distribution of 50% carbohydrates, 25% proteins and 25% fats, according to the Diogenes study; Other Names: Low-Calorie Diet (CD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy of this nutritional intervention	The primary outcome measure was body weight operationalized as the change in an individual's mass or weight loss in kilograms.	Every week for 4 months, then every month for two years
Volume of total body tissue corresponding to muscle	It will be measured with unit Kilogram, minimun 10, maximum 150, with a Multi-frequency Bioelectrical Impedance Equipment	Every week for 4 months, then every month for two years
Percentage of body weight made up of adipose tissue	It will be measured with unit percentaje, minimum 9, maximum 90, with a Multi-frequency Bioelectrical Impedance Equipment	Every week for 4 months, then every month for two years
Visceral Fat	It will be measured with unit index, from 1 to 40, with a Multi-frequency Bioelectrical Impedance Equipment	Every week for 4 months, then every month for two years
Bone mass	the skeletal weight will be measured with unit kilograms (kg), from 1 to 70 kg, with a Multi-frequency Bioelectrical Impedance Equipment	Every week for 4 months, then every month for two years
Total body water	Percentage of the body that corresponds to water, unit % (percentaje) and/ or kilograms (kg) from 0 to 150 with a Multi-frequency bioelectrical impedance equipment	Every week for 4 months, then every month for two years
Waist circumference	Measurement made with a tape measure directly on the skin (without clothing). It will be measured at the height of the middle of the armpit, at the point between the bottom of the last rib and the highest part of the hip. Unit centimeters (cm), minimum 30, maximum 200, Using tape measure	Every week for 4 months, then every month for two years
Hip circumference	Circumference of the widest part above the buttocks. Unit cm, minimum 30, maximum 200. Measuring with tape measure	Every week for 4 months, then every month for two years
Muscular strenght	Isometric muscle strenght in the dominant hand, unit kilograms (kg)/ Strength, registration form digital dynamometer	Every week for 4 months, then every month for two years
Weight	it will be measured in unit kilograms, in a weighing machine	Every week for 4 months, then every month for two years
Height	The size will be measured in meters with a stadiometer	Every week for 4 months, then every month for two years
BMI Body index mass	Body mass index is an index composed of weight/height squared in kg/m2.	Every week for 4 months, then every month for two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin	It will be measured by a Clinical laboratory determination, unit gr/L (grams/liters)	Every 2 months for the first 6 months, then every 6 months for two years
Hematocrit	It will be measured by a Clinical laboratory determination, unit percentage (%), minimumm 10, maximum 16	Every 2 months for the first 6 months, then every 6 months for two years
Leukocytes	It will be measured by a Clinical laboratory determination, unit quantity per cc, minimumm 4000, maximum 18000.	Every 2 months for the first 6 months, then every 6 months for two years
Fasting Blood Glucose	It will be measured by a blood tests, unit mg/dl (miligrams/deciliters), Normoglycemia in fasting 70 to 100 mg/dl. Hyperglycemia higher than 100 mg/dl in fasting. Diabetes 126 mg/Dl of fasting blood glucose.	Every 2 months for the first 6 months, then every 6 months for two years
Glycated hemoglobin (HbA1c)	It will be measured by a blood tests, unit percentage (%), 6% very low, 7% moderate, 8% high, 9% very high, 10% risk.	Every 2 months for the first 6 months, then every 6 months for two years
Insulin	It will be measured by a blood tests, unit UI/ml (Interantional unit/ mililiter), hyperinsulinemia >6UI/ml	Every 2 months for the first 6 months, then every 6 months for two years
Creatinine	It will be measured by a blood tests, unit mg/dl (miligrams/deciliters), minimum 0.4, maximum 1.3	Every 2 months for the first 6 months, then every 6 months for two years
Urea	It will be measured by a blood tests, unit mg/dl (miligrams/deciliters), minimum 8, maximum 54	Every 2 months for the first 6 months, then every 6 months for two years
Uric acid	It will be measured by a blood tests, unit mg/dl (miligrams/deciliters), minimum 2.4, maximum 9.	Every 2 months for the first 6 months, then every 6 months for two years
Sodium	It will be measured by a blood tests, unit mEq/l (miliequivalents/ litre), minimum 90, maximum 110.	Every 2 months for the first 6 months, then every 6 months for two years
Potassium	It will be measured by a blood tests, unit mEq/l (miliequivalents/ litre), minimum 3.5, maximum 5.5	Every 2 months for the first 6 months, then every 6 months for two years
Calcium	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 8.5, maximum 10.5	Every 2 months for the first 6 months, then every 6 months for two years
Phosphorus	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 2.5, maximum 4.5,	Every 2 months for the first 6 months, then every 6 months for two years
Magnesium	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 1.5, maximum 2.5,	Every 2 months for the first 6 months, then every 6 months for two years
Albumin	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 3.4, maximum 5.4,	Every 2 months for the first 6 months, then every 6 months for two years
Direct bilirubin	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), normal value less than 0.3 mg/dl (0 less than 5.1mg/dl)	Every 2 months for the first 6 months, then every 6 months for two years
Indirect bilirubin	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 0.1, maximum 0.5	Every 2 months for the first 6 months, then every 6 months for two years
Total bilirubin	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 0.1, maximum 1.2	Every 2 months for the first 6 months, then every 6 months for two years
Alanine aminotransferase	It will be measured by a blood tests, unit IU/L (interantional unit/ liters), minimum 10, maximum 41.	Every 2 months for the first 6 months, then every 6 months for two years
Aspartate Amino Transferase	It will be measured by a blood tests, unit IU/L (interantional unit/ liters), minimum 5, maximum 37	Every 2 months for the first 6 months, then every 6 months for two years
Total cholesterol	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 100, maximum 200	Every 2 months for the first 6 months, then every 6 months for two years
Triglycerides	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), minimum 100, maximum 500	Every 2 months for the first 6 months, then every 6 months for two years
High Density Lipoproteins	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), greater than 40 mg/dl	Every 2 months for the first 6 months, then every 6 months for two years
Low Density lipoproteins	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), less than 100 mg/dl	Every 2 months for the first 6 months, then every 6 months for two years
Protein C Reactive	It will be measured by a blood tests, unit mg/dl (miligrams/ deciliters), less than 10 mg/dl	Every 2 months for the first 6 months, then every 6 months for two years
Thyroid stimulating hormone	It will be measured by a blood tests, unit IU/L (interantional unit/ liters), from 0.3 to 3 IU	Every 2 months for the first 6 months, then every 6 months for two years
Triiodothyronine	It will be measured by a blood tests, unit IU/L (nanograms/ mililiters), from 0.8 to 2 ng/ml	Every 2 months for the first 6 months, then every 6 months for two years
Thyroxine	It will be measured by a blood tests, unit pg/ml (picograms/ mililiters), from 5.4 to 11.5 pg/ml	Every 2 months for the first 6 months, then every 6 months for two years
Cholecalciferol	It will be measured by a blood tests, unit ng/ml (nanograms/ mililiters), from 25 to 90 ng/ml	Every 2 months for the first 6 months, then every 6 months for two years
Gasometric variables, Partial pressure of oxygen (PaO2)	It will be measured by a blood tests, unit mmHg (milimeters of mercury), minimum 75, maximum 100	Every 2 months for the first 6 months, then every 6 months for two years
HCO3 (Bicarbonate ion plasma concentration)	It will be measured by a blood tests, unit mEq/L (miliequivalents per litre), minimum 21, maximum 30	Every 2 months for the first 6 months, then every 6 months for two years
Arterial pH	It will be measured by a blood tests, minimum 7.35, maximum 7.45	Every 2 months for the first 6 months, then every 6 months for two years
Lactic acid	It will be measured by a blood tests, unit mg/L (miligrams/liters), from 4.5 to 19 mg/L	Every 2 months for the first 6 months, then every 6 months for two years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to this nutritional intervention	It will be measured by complied or did not comply with the program, making a question.	Every week for 4 months, then every month for a two years
Satisfaction survey	Interrogation very satified to very dissatisfied	Every week for 4 months, then every month for a two years

Collaborators and Investigators

• Sponsor: Universidad Veracruzana

Publications and helpful links

General Publications

• Larsen TM, Dalskov SM, van Baak M, Jebb SA, Papadaki A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunesova M, Pihlsgard M, Stender S, Holst C, Saris WH, Astrup A; Diet, Obesity, and Genes (Diogenes) Project. Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med. 2010 Nov 25;363(22):2102-13. doi: 10.1056/NEJMoa1007137.
• Tsai AG, Wadden TA. The evolution of very-low-calorie diets: an update and meta-analysis. Obesity (Silver Spring). 2006 Aug;14(8):1283-93. doi: 10.1038/oby.2006.146.
• Palgi A, Read JL, Greenberg I, Hoefer MA, Bistrian BR, Blackburn GL. Multidisciplinary treatment of obesity with a protein-sparing modified fast: results in 668 outpatients. Am J Public Health. 1985 Oct;75(10):1190-4. doi: 10.2105/ajph.75.10.1190.
• Hemmingsson E, Johansson K, Eriksson J, Sundstrom J, Neovius M, Marcus C. Weight loss and dropout during a commercial weight-loss program including a very-low-calorie diet, a low-calorie diet, or restricted normal food: observational cohort study. Am J Clin Nutr. 2012 Nov;96(5):953-61. doi: 10.3945/ajcn.112.038265. Epub 2012 Sep 18.
• Lartey S, Si L, Lung T, Magnussen CG, Boateng GO, Minicuci N, Kowal P, Hayes A, de Graaff B, Blizzard L, Palmer AJ. Impact of overweight and obesity on life expectancy, quality-adjusted life years and lifetime costs in the adult population of Ghana. BMJ Glob Health. 2020 Sep;5(9):e003332. doi: 10.1136/bmjgh-2020-003332.
• Foster D, Sanchez-Collins S, Cheskin LJ. Multidisciplinary Team-Based Obesity Treatment in Patients With Diabetes: Current Practices and the State of the Science. Diabetes Spectr. 2017 Nov;30(4):244-249. doi: 10.2337/ds17-0045. Erratum In: Diabetes Spectr. 2018 Feb;31(1):119.
• Pirozzo S, Summerbell C, Cameron C, Glasziou P. Should we recommend low-fat diets for obesity? Obes Rev. 2003 May;4(2):83-90. doi: 10.1046/j.1467-789x.2003.00099.x. Erratum In: Obes Rev. 2003 Aug;4(3):185.
• Blackburn GL, Bistrian BR. Careers in nutrition from the clinical viewpoint. Nutr Rev. 1976 Apr;34(4):97-104. doi: 10.1111/j.1753-4887.1976.tb05719.x. No abstract available.
• Goday A, Bellido D, Sajoux I, Crujeiras AB, Burguera B, Garcia-Luna PP, Oleaga A, Moreno B, Casanueva FF. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes. 2016 Sep 19;6(9):e230. doi: 10.1038/nutd.2016.36.
• Elfhag K, Rossner S. Initial weight loss is the best predictor for success in obesity treatment and sociodemographic liabilities increase risk for drop-out. Patient Educ Couns. 2010 Jun;79(3):361-6. doi: 10.1016/j.pec.2010.02.006. Epub 2010 Mar 11.
• Handjieva-Darlenska T, Handjiev S, Larsen TM, van Baak MA, Jebb S, Papadaki A, Pfeiffer AF, Martinez JA, Kunesova M, Holst C, Saris WH, Astrup A. Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study. Eur J Clin Nutr. 2010 Sep;64(9):994-9. doi: 10.1038/ejcn.2010.110. Epub 2010 Jun 30.
• Nackers LM, Ross KM, Perri MG. The association between rate of initial weight loss and long-term success in obesity treatment: does slow and steady win the race? Int J Behav Med. 2010 Sep;17(3):161-7. doi: 10.1007/s12529-010-9092-y.
• Blackburn GL. Weight of the nation: moving forward, reversing the trend using medical care. Am J Clin Nutr. 2012 Nov;96(5):949-50. doi: 10.3945/ajcn.112.049643. Epub 2012 Oct 3. No abstract available.
• Cano-Rodríguez I, Ballesteros-Pomar MD, Pérez-Corral B, Aguado R. Dietas bajas en hidratos de carbono frente a dietas bajas en grasas. Endocrinol Nutr 2006;53(3):209-17 dol: http://dx.doi.org/10.1016/s1575-0922(06)71091-9
• Joint WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition. World Health Organ Tech Rep Ser. 2007;(935):1-265, back cover.
• Díaz-Muñoz GA, Castañeda-Gómez ÁM, Belalcázar-Monsalve MP, Zambrano-Salazar JP, Bautista-Velandia MC, Ballesteros-Arbeláez F. Efecto de la dieta cetogénica baja en calorías sobre la composición corporal en adultos con sobrepeso y obesidad: revisión sistemática y metaanálisis. Rev Nutr Clin Metab. 2021;4(3):98-113. http://dx.doi.org/10.35454/rncm.v4n3.273
• Merra G, Gratteri S, De Lorenzo A, Barrucco S, Perrone MA, Avolio E, Bernardini S, Marchetti M, Di Renzo L. Effects of very-low-calorie diet on body composition, metabolic state, and genes expression: a randomized double-blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2017 Jan;21(2):329-345.
• Romano L, Marchetti M, Gualtieri P, Di Renzo L, Belcastro M, De Santis GL, Perrone MA, De Lorenzo A. Effects of a Personalized VLCKD on Body Composition and Resting Energy Expenditure in the Reversal of Diabetes to Prevent Complications. Nutrients. 2019 Jul 4;11(7):1526. doi: 10.3390/nu11071526.
• Colombo O, Ferretti VV, Ferraris C, Trentani C, Vinai P, Villani S, Tagliabue A. Is drop-out from obesity treatment a predictable and preventable event? Nutr J. 2014 Feb 3;13:13. doi: 10.1186/1475-2891-13-13.
• Moreno B, Crujeiras AB, Bellido D, Sajoux I, Casanueva FF. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine. 2016 Dec;54(3):681-690. doi: 10.1007/s12020-016-1050-2. Epub 2016 Sep 13.
• Sajoux I, Lorenzo PM, Gomez-Arbelaez D, Zulet MA, Abete I, Castro AI, Baltar J, Portillo MP, Tinahones FJ, Martinez JA, Crujeiras AB, Casanueva FF. Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity. Nutrients. 2019 Oct 4;11(10):2368. doi: 10.3390/nu11102368.

Helpful Links

• Careers in nutrition from the clinical viewpoint.
• Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.
• Initial weight loss is the best predictor for success in obesity treatment and sociodemographic liabilities increase risk for drop-out
• Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study.
• Clinical correlates of weight loss and attrition during a 10-week dietary intervention study: results from the NUGENOB project.
• The association between rate of initial weight loss and long-term success in obesity treatment: Does slow and steady win the race?
• Weight of the nation: moving forward, reversing the trend using medical care
• Dietas bajas en hidratos de carbono frente a dietas bajas en grasas.
• Multidisciplinary team-based obesity treatment in patients with diabetes: Current practices and the state of the science.
• Efecto de la dieta cetogénica baja en calorías sobre la composición corporal en adultos con sobrepeso y obesidad: revisión sistemática y metaanálisis

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): May 25, 2023

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 19CI 30 087 041; 1/1142021 (Other Identifier: Comite del Centro de alta especialidad del Estado de Veracruz)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No