Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet


To investigate safety, compliance, and efficacy, on weight loss and cardiovascular risk factors of a multiphasic dietary intervention based on meal replacements, including a period of very low calorie diet (VLCD) in a population of obese patients. Anthropometric parameters, blood tests (including insulin), dual-energy-X-ray absorptiometry (DXA), and questionnaires for the assessment of safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day, normoproteic, 50 g/day carbohydrate, four meal replacements; (phase II) a 30-day low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein plate; (phase III) 60-day LCD, 1,100 kcal/day, two meal replacements plus two protein plates and reintroduction of small amounts of carbohydrates; (phase IV) 60-day hypocaloric balanced diet (HBD), 1,200 kcal/day, one meal replacement, two protein plates and the reintroduction of carbohydrates. 24 patients (17 females, 7 males, mean BMI 33.8 ± 3.2 kg/m2, mean age 35.1 ± 10.2 years) completed the study. The average weight loss was 15.4 ± 6.7 %, with a significant reduction of fat mass (from 32.8 ± 4.7 to 26.1 ± 6.3 % p < 0.05) and a relative increase of lean mass (from 61.9 ± 4.8 to 67.1 ± 5.9 % p < 0.05). An improvement of metabolic parameters and no variations of the liver and kidney functions were found. A high safety profile and an excellent dietary compliance were seen. The VLCD dietary program and the replacement dietary system described here is an effective, safe, and well-tolerated treatment for weight control.

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  1. 1.

    D.W. Haslam, W.P. James, Obes. Lancet. 366, 1197–1209 (2005)

    Article  Google Scholar 

  2. 2.

    V.I. Kraak, B. Swinburn, M. Lawrence, P. Harrison, An accountability framework to promote healthy food environments. Public Health Nutr. 25, 1–17 (2014)

    Google Scholar 

  3. 3.

    L.M. Donini, M. Cuzzolaro, L. Gnessi, C. Lubrano, S. Migliaccio, A. Aversa et al., Obesity treatment: results after 4 years of a Nutritional and Psycho-Physical Rehabilitation Program in an outpatient setting. Eat Weight Disord. 1 Mar (2014)

  4. 4.

    S. Desroches, A. Lapointe, S. Ratté, K. Gravel, F. Légaré, S. Turcotte, Interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults. Cochrane Database Syst. Rev. 2, CD008722 (2013). doi:10.1002/14651858

  5. 5.

    M.J. Munsters, W.H. Saris, Body weight regulation and obesity: dietary strategies to improve the metabolic profile. Annu. Rev. Food Sci. Technol. 5, 39–51 (2014)

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    S. Melotto, Clinical pharmacology of eating and not eating. Curr. Opin. Pharmacol. 14C, 1–5 (2014)

    Article  Google Scholar 

  7. 7.

    N. Vogels, P. Westerterp, Successful long-term weight maintenance: a 2-year follow-up. Obesity (Silver Spring) 15, 1258–1266 (2007)

    Article  Google Scholar 

  8. 8.

    C. Rolland, K.L. Johnston, S. Lula, I. Macdonald, J. Broom, Long-term weight loss maintenance and management following a VLCD: a 3-year outcome. Int. J. Clin. Pract. 68, 379–387 (2014)

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    S. Ramage, A. Farmer, K. Apps Eccles, L. McCargar, Healthy strategies for successful weight loss and weight maintenance: a systematic review. Appl. Physiol. Nutr. Metab. 39, 1–20 (2014)

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    R.U. Pliquett, D. Fuhrer, The effect of insulin on the central nervous system-focus on appetite regulation. Horm. Metab. Res. 38, 442–446 (2006)

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    D. Weigle, P. Breen, C. Matthys, A high protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am. J. Clin. Nutr. 82, 41–48 (2005)

    CAS  PubMed  Google Scholar 

  12. 12.

    R. Vettor, R. Fabris, Neuroendocrine regulation of eating behavior. J. Endocrinol. Investig. 25, 836–854 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    P. Björntorp, Obes. Lancet 350, 423–426 (1997)

    Article  Google Scholar 

  14. 14.

    S. Rössner, J.S. Torgerson, VLCD a safe and simple treatment of obesity. Lakartidningen 97, 3876–3879 (2000)

    PubMed  Google Scholar 

  15. 15.

    W.Y. Lin, C.H. Wu, N.F. Chu, Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter randomized, controlled trial. Nutrition 25, 1129–1136 (2009)

    Article  PubMed  Google Scholar 

  16. 16.

    P. Dhindsa, A.R. Scott, R. Donnelly, Metabolic and cardiovascular effects of very-low-calorie-diet therapy in obese patients with type 2 diabetes in secondary failure: outcome after 1 year. Diabet. Med. 20, 319–324 (2003)

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    G.F. Cahill Jr, R.L. Veech, Ketoacidosis? Good medicine? Trans. Am. Clin. Climatol. Assoc. 114, 149–161 (2003)

    PubMed Central  PubMed  Google Scholar 

  18. 18.

    K. Casazza, K.R. Fontaine, A. Astrup, L.L. Birch, A.W. Brown, M.M. Bohan Brown et al., Myths, presumptions, and facts about obesity. N. Engl. J. Med. 368, 446–454 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 19.

    K.R. Ryttig, H. Flaten, S. Rössner, Long-term effects of a very low calorie diet (Nutrilett) in obesity treatment. A prospective, randomized, comparison between VLCD and a hypocaloric diet + behavior modification and their combination. Int. J. Obes. Relat. Metab. Disord. 21, 574–579 (1997)

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    J.L. Childs, M.D. Yates, M.A. Drake, Sensory properties of meal replacement bars and beverages made from whey and soy proteins. J. Food Sci. 72, S425–S434 (2007)

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    S. Sette, C. Le Donne, R. Piccinelli, L. Mistura, M. Ferrari, C. Leclercq, INRAN-SCAI 2005–06 study group. The third National Food Consumption Survey, INRAN-SCAI 2005–06: major dietary sources of nutrients in Italy. Int J Food Sci Nutr. 64, 1014–1021 (2013)

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    D. Machin, M.J. Campbell, S.B. Tan, S.H. Tan, Sample Size Tables for Clinical Studies, 3rd edn. (Wiley-Blackwell, Oxford, 2009)

    Google Scholar 

  23. 23.

    P. Sumithran, L.A. Prendergast, E. Delbridge, Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur. J. Clin. Nutr. 67, 1–6 (2013)

  24. 24.

    Y. Gu, A. Zhao, F. Huang, Y. Zhang, J. Liu, C. Wang et al., Very low carbohydrate diet significantly alters the serum metabolic profiles in obese subjects. J. Proteome Res. 12, 5801–5811 (2013)

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    M. Hession, C. Rolland, U. Kulkarni, A. Wise, J. Broom, Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes. Rev. 10, 36–50 (2009)

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    A. Paoli, A. Rubini, J.S. Volek, K.A. Grimaldi, Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur. J. Clin. Nutr. 67, 789–796 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. 27.

    K. Esposito, P. Chiodini, MI. Maiorino, G. Bellastella, D. Panagiotakos, D. Giugliano. Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies. Endocrine 18, (2014). doi:10.1007/s12020-014-0264-4

  28. 28.

    L. Velázquez-López, E. González-Figueroa, P. Medina-Bravo, I. Pineda-Del Aguila, L. Avila-Jiménez, R. Ramos-Hernández et al., Low calorie and carbohydrate diet: to improve the cardiovascular risk indicators in overweight or obese adults with prediabetes. Endocrine 43, 593–602 (2013)

    Article  PubMed  Google Scholar 

  29. 29.

    N.B. Bueno, I.S. Vieira, S. Lima, T. Rocha, Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br. J. Nutr. 110, 1178–1187 (2013)

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    C.B. Ebbeling, J.F. Swain, H.A. Feldman, W.W. Wong, D.L. Hachey, E. Garcia-Lago et al., Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA 307, 2627–2634 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. 31.

    S.G. Camps, S.P. Verhoef, K.R. Westerterp, Weight loss, weight maintenance, and adaptive thermogenesis. Am. J. Clin. Nutr. 97, 990–994 (2013)

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    B. Moreno, D. Bellido, I. Sajoux, A. Goday, D. Saavedra, A.B. Crujeiras, F.F. Casanueva, Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine (2014). doi:10.1007/s12020-014-0192-3

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Correspondence to Lucio Gnessi.

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Basciani, S., Costantini, D., Contini, S. et al. Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet. Endocrine 48, 863–870 (2015).

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  • Safety
  • Efficacy
  • Diet
  • Very low calorie