Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects

A Corrigendum to this article was published on 16 August 2004

Abstract

OBJECTIVE: To compare the long-term compliance and effects of two low-fat diets differing in carbohydrate to protein ratio on body composition and biomarkers of cardiovascular disease risk in obese subjects with hyperinsulinemia.

DESIGN: Outpatient, parallel, clinical intervention study of two groups of subjects randomly assigned to either a standard protein (SP; 15% protein, 55% carbohydrate) or high-protein (HP; 30% protein, 40% carbohydrate) diet, during 12 weeks of energy restriction (6.5 MJ/day) and 4 weeks of energy balance (8.3 MJ/day). Subsequently, subjects were asked to maintain the same dietary pattern for the succeeding 52 weeks with minimal professional support.

SUBJECTS: A total of 58 obese, nondietetic subjects with hyperinsulinemia (13 males/45 females, mean age 50.2 y, mean body mass index (BMI) 34.0 kg/m2, mean fasting insulin 17.8 mU/l) participated in the study.

MEASUREMENTS: Body composition, blood pressure, blood lipids, fasting glucose, insulin, CRP and sICAM-1 were measured at baseline and at weeks 16 and 68. Urinary urea/creatinine ratio was measured at baseline, week 16 and at 3 monthly intervals thereafter.

RESULTS: In total, 43 subjects completed the study with similar dropouts in each group (P=0.76). At week 68, there was net weight loss (SP −2.9±3.6%, HP −4.1±5.8%; P<0.01) due entirely to fat loss (P<0.001) with no diet effect. Both diets significantly increased HDL cholesterol concentrations (P<0.001) and decreased fasting insulin, insulin resistance, sICAM-1 and CRP levels (P<0.05). Protein intake was significantly greater in HP during the initial 16 weeks (P<0.001), but decreased in HP and increased in SP during 52-week follow-up, with no difference between groups at week 68, indicating poor long-term dietary adherence behaviour to both dietary patterns.

CONCLUSION: Without active ongoing dietary advice, adherence to dietary intervention is poor. Nonetheless, both dietary patterns achieved net weight loss and improvements in cardiovascular risk factors.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2

References

  1. Bonow RO, Eckel RH . Diet, obesity, and cardiovascular risk. N Engl J Med 2003; 348: 2057–2058.

    Article  Google Scholar 

  2. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH . The disease burden associated with overweight and obesity. JAMA 1999; 282: 1523–1529.

    CAS  Article  Google Scholar 

  3. Flegal KM, Carroll MD, Ogden CL, Johnson CL . Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002; 288: 1723–1727.

    Article  Google Scholar 

  4. Cameron AJ, Welborn TA, Zimmet PZ, Dunstan DW, Owen N, Salmon J, Dalton M, Jolley D, Shaw JE . Overweight and obesity in Australia: the 1999–2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Med J Aust 2003; 178: 427–432.

    PubMed  Google Scholar 

  5. Visscher TL, Seidell JC . The public health impact of obesity. Annu Rev Public Health 2001; 22: 355–375.

    CAS  Article  Google Scholar 

  6. Seidell JC . The impact of obesity on health status: some implications for health care costs. Int J Obes Relat Metab Disord 1995; 19 (Suppl 6): S13–S16.

    PubMed  Google Scholar 

  7. Serdula MK, Mokdad AH, Williamson DF, Galuska DA, Mendlein JM, Heath GW . Prevalence of attempting weight loss and strategies for controlling weight. JAMA 1999; 282: 1353–1358.

    CAS  Article  Google Scholar 

  8. Eisenstein J, Roberts SB, Dallal G, Saltzman E . High-protein weight-loss diets: are they safe and do they work? A review of the experimental and epidemiologic data. Nutr Rev 2002; 60: 189–200.

    Article  Google Scholar 

  9. Hill JO, Peters JC . Environmental contributions to the obesity epidemic. Science 1998; 280: 1371–1374.

    CAS  Article  Google Scholar 

  10. Westerterp KR, Verboeket-van de Venne WP, Westerterp-Plantenga MS, Velthuis-te Wierik EJ, de Graaf C, Weststrate JA . Dietary fat and body fat: an intervention study. Int J Obes Relat Metab Disord 1996; 20: 1022–1026.

    CAS  PubMed  Google Scholar 

  11. Toubro S, Astrup A . Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake. BMJ 1997; 314: 29–34.

    CAS  Article  Google Scholar 

  12. Baba NH, Sawaya S, Torbay N, Habbal Z, Azar S, Hashim SA . High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord 1999; 23: 1202–1206.

    CAS  Article  Google Scholar 

  13. Skov AR, Toubro S, Ronn B, Holm L, Astrup A . Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes Relat Metab Disord 1999; 23: 528–536.

    CAS  Article  Google Scholar 

  14. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, Christou DD . A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. J Nutr 2003; 133: 411–417.

    CAS  Article  Google Scholar 

  15. Parker B, Noakes M, Luscombe N, Clifton P . Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 2002; 25: 425–430.

    Article  Google Scholar 

  16. Piatti PM, Monti F, Fermo I, Baruffaldi L, Nasser R, Santambrogio G, Librenti MC, Galli-Kienle M, Pontiroli AE, Pozza G . Hypocaloric high-protein diet improves glucose oxidation and spares lean body mass: comparison to hypocaloric high-carbohydrate diet. Metabolism 1994; 43: 1481–1487.

    CAS  Article  Google Scholar 

  17. Farnsworth E, Luscombe ND, Noakes M, Wittert G, Argyiou E, Clifton PM . Effect of a high-protein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. Am J Clin Nutr 2003; 78: 31–39.

    CAS  Article  Google Scholar 

  18. Wolfe BM, Giovannetti PM . Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human subjects. Metabolism 1991; 40: 338–343.

    CAS  Article  Google Scholar 

  19. Hodge A, Patterson AJ, Brown WJ, Ireland P, Giles G . The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation. Aust N Z J Public Health 2000; 24: 576–583.

    CAS  Article  Google Scholar 

  20. Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  Google Scholar 

  21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    CAS  Article  Google Scholar 

  22. Hallynck TH, Soep HH, Thomis JA, Boelaert J, Daneels R, Dettli L . Should clearance be normalised to body surface or to lean body mass? Br J Clin Pharmacol 1981; 11: 523–526.

    CAS  Article  Google Scholar 

  23. Skov AR, Toubro S, Bulow J, Krabbe K, Parving HH, Astrup A . Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects. Int J Obes Relat Metab Disord 1999; 23: 1170–1177.

    CAS  Article  Google Scholar 

  24. Poppitt SD, McCormack D, Buffenstein R . Short-term effects of macronutrient preloads on appetite and energy intake in lean women. Physiol Behav 1998; 64: 279–285.

    CAS  Article  Google Scholar 

  25. Latner JD, Schwartz M . The effects of a high-carbohydrate, high-protein or balanced lunch upon later food intake and hunger ratings. Appetite 1999; 33: 119–128.

    CAS  Article  Google Scholar 

  26. Bray GA, Popkin BM . Dietary fat intake does affect obesity! Am J Clin Nutr 1998; 68: 1157–1173.

    CAS  Article  Google Scholar 

  27. Heshka S, Greenway F, Anderson JW, Atkinson RL, Hill JO, Phinney SD, Miller-Kovach K, Xavier Pi-Sunyer F . Self-help weight loss versus a structured commercial program after 26 weeks: a randomized controlled study. Am J Med 2000; 109: 282–287.

    CAS  Article  Google Scholar 

  28. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–1350.

    CAS  Article  Google Scholar 

  29. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.

    CAS  Article  Google Scholar 

  30. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, Szapary PO, Rader DJ, Edman JS, Klein S . A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003; 348: 2082–2090.

    CAS  Article  Google Scholar 

  31. Thomas PR, (ed), The Food and Nutrition Board, Institute of Medicine Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity. Weighing the options: criteria for evaluating weight management programs. National Academy Press: Washington, DC; 1995.

    Book  Google Scholar 

  32. World Health Organisation. Obesity: preventing and managing the global epidemic. WHO Publications: Geneva; 1997.

  33. Granberry MC, Fonseca VA . Insulin resistance syndrome: options for treatment. South Med J 1999; 92: 2–15.

    CAS  Article  Google Scholar 

  34. Ross R . Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340: 115–126.

    CAS  Article  Google Scholar 

  35. Blake GJ, Ridker PM . Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med 2002; 252: 283–294.

    CAS  Article  Google Scholar 

  36. Hak AE, Pols HA, Stehouwer CD, Meijer J, Kiliaan AJ, Hofman A, Breteler MM, Witteman JC . Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study. J Clin Endocrinol Metab 2001; 86: 4398–4405.

    CAS  Article  Google Scholar 

  37. Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J . Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998; 351: 88–92.

    CAS  Article  Google Scholar 

  38. Ridker PM, Hennekens CH, Buring JE, Rifai N . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–843.

    CAS  Article  Google Scholar 

  39. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM . C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327–334.

    CAS  Article  Google Scholar 

  40. Albert MA, Danielson E, Rifai N, Ridker PM . Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001; 286: 64–70.

    CAS  Article  Google Scholar 

  41. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto Jr AM, Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959–1965.

    CAS  Article  Google Scholar 

  42. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E . Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98: 839–844.

    CAS  Article  Google Scholar 

  43. Szapary PO, Rader DJ . Pharmacological management of high triglycerides and low high-density lipoprotein cholesterol. Curr Opin Pharmacol 2001; 1: 113–120.

    CAS  Article  Google Scholar 

  44. Boden WE . High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the Veterans Affairs High-Density Lipoprotein Intervention Trial. Am J Cardiol 2000; 86: 19L–22L.

    CAS  Article  Google Scholar 

  45. Dattilo AM, Kris-Etherton PM . Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 1992; 56: 320–328.

    CAS  Article  Google Scholar 

  46. Yu-Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris-Etherton PM . Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr 1999; 69: 632–646.

    CAS  Article  Google Scholar 

  47. Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DP . Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 2000; 15: 2504–2512.

    CAS  Article  Google Scholar 

  48. Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E . Protein consumption and bone mineral density in the elderly: the Rancho Bernardo Study. Am J Epidemiol 2002; 155: 636–644.

    Article  Google Scholar 

  49. Brandle E, Sieberth HG, Hautmann RE . Effect of chronic dietary protein intake on the renal function in healthy subjects. Eur J Clin Nutr 1996; 50: 734–740.

    CAS  PubMed  Google Scholar 

  50. Skov AR, Haulrik N, Toubro S, Molgaard C, Astrup A . Effect of protein intake on bone mineralization during weight loss: a 6-month trial. Obes Res 2002; 10: 432–438.

    Article  Google Scholar 

  51. Tremblay A, Doucet E, Imbeault P . Physical activity and weight maintenance. Int J Obes Relat Metab Disord 1999; 23 (Suppl 3): S50–S54.

    Article  Google Scholar 

  52. Fogelholm M, Kukkonen-Harjula K . Does physical activity prevent weight gain—a systematic review. Obes Rev 2000; 1: 95–111.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We acknowledge Rosemary McArthur, Anne McGuffin, and Jodie Avery for assistance in performing these studies. This work was supported by a National Health and Medical Research Grant #158012 and a Dairy Research and Development Corporation Grant #CSHN100003

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P M Clifton.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Brinkworth, G., Noakes, M., Keogh, J. et al. Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects. Int J Obes 28, 661–670 (2004). https://doi.org/10.1038/sj.ijo.0802617

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802617

Keywords

  • weight loss
  • diet composition
  • lipids
  • C-reactive protein
  • soluble intracellular adhesion molecule-1
  • dual X-ray absorptiometry
  • insulin sensitivity

Further reading

Search

Quick links