Skip to main content

Thank you for visiting 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.

Low-carbohydrate–high-protein diet and long-term survival in a general population cohort



We have evaluated the effects on mortality of habitual low carbohydrate–high-protein diets that are thought to contribute to weight control.


Cohort investigation.


Adult Greek population.

Subjects methods:

Follow-up was performed from 1993 to 2003 in the context of the Greek component of the European Prospective Investigation into Cancer and nutrition. Participants were 22 944 healthy adults, whose diet was assessed through a validated questionnaire. Participants were distributed by increasing deciles according to protein intake or carbohydrate intake, as well as by an additive score generated by increasing decile intake of protein and decreasing decile intake of carbohydrates. Proportional hazards regression was used to assess the relation between high protein, high carbohydrate and the low carbohydrate–high protein score on the one hand and mortality on the other.


During 113 230 persons years of follow-up, there were 455 deaths. In models with energy adjustment, higher intake of carbohydrates was associated with significant reduction of total mortality, whereas higher intake of protein was associated with nonsignificant increase of total mortality (per decile, mortality ratios 0.94 with 95% CI 0.89 –0.99, and 1.02 with 95% CI 0.98 –1.07 respectively). Even more predictive of higher mortality were high values of the additive low carbohydrate–high protein score (per 5 units, mortality ratio 1.22 with 95% CI 1.09 –to 1.36). Positive associations of this score were noted with respect to both cardiovascular and cancer mortality.


Prolonged consumption of diets low in carbohydrates and high in protein is associated with an increase in total mortality.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  • Ainsworth BE, Haskell WL, Leon AS, Jacobs Jr DR, Montoye HJ, Sallis JF et al. (1993). Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25, 71–80.

    CAS  Article  Google Scholar 

  • Astrup A, Meinert Larsen T, Harper A (2004). Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet 364, 897–899.

    Article  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (2004). Department of Health and Human Services. Morbility and Mortality weekly report. Trends in intake of energy and macronutrients – United States – 1971–2000, 53 (04), 80–82 January 20, 2006).

  • Chen TY, Smith W, Rosenstock JL, Lessnau KD (2006). A life-threatening complication of Atkins diet. Lancet 367, 958.

    Article  Google Scholar 

  • Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ (2005). Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA 293, 43–53.

    CAS  Article  Google Scholar 

  • Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS et al. (2003). A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 348, 2082–2090.

    CAS  Article  Google Scholar 

  • Gnardellis C, Trichopoulou A, Katsouyanni K, Polychronopoulos E, Rimm EB, Trichopoulos D (1995). Reproducibility and validity of an extensive semiquantitative food frequency questionnaire among Greek school teachers. Epidemiology 6, 74–77.

    CAS  Article  Google Scholar 

  • Goldbohm RA, van't Veer P, van den Brandt PA, van'Hof MA, Brants HA, Sturmans F et al. (1995). Reproducibility of a food frequency questionnaire and stability of dietary habits determined from five annually repeated measurements. Eur J Clin Nutr 49, 420–429.

    CAS  PubMed  Google Scholar 

  • Kelemen LE, Kushi LH, Jacobs Jr DR, Cerhan JR (2005). Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. Am J Epidemiol 161, 239–249.

    Article  Google Scholar 

  • Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A et al. (2004). Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292, 1433–1439.

    Article  Google Scholar 

  • Lara-Castro C, Garvey WT (2004). Diet, insulin resistance and obesity: zoning in on data for Atkins dieters living in South Beach. J Clin Endocrinol Metab 89, 4197–4205.

    CAS  Article  Google Scholar 

  • McCullough M, Feskanich D, Stampfer M, Giovanucci EL, Rimm EB, Hu FB et al. (2002). Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr 76, 1261–1271.

    CAS  Article  Google Scholar 

  • Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M et al. (2002). European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5, 1113–1124.

    CAS  Article  Google Scholar 

  • Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J et al. (2003). A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 348, 2074–2081.

    CAS  Article  Google Scholar 

  • Smith-Warner S, Spiegelman D, Adami HO, Beeson WL, van den Brandt PA, Folsom AR et al. (2001). Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int J Cancer 92, 767–774.

    CAS  Article  Google Scholar 

  • St Jeor ST, Howard BV, Prewitt TE, Bovee V, Bazarre T, Eckel RH (2001). Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation 104, 1869–1874.

    CAS  Article  Google Scholar 

  • Stanton R, Crowe T (2006). Risks of a high-protein diet outweigh the benefits. Nature 440 (7086), 868.

    CAS  Article  Google Scholar 

  • Steffen L, Nettleton JA (2006). Carbohydrates: how low can you go? Lancet 267, 880–881.

    Article  Google Scholar 

  • Swan G (2004). Findings from the latest National Diet and Nutrition Survey. Proc Nutr Soc 63, 505–512.

    CAS  Article  Google Scholar 

  • Trichopoulou A, Bamia C, Trichopoulos D (2005a). Mediterranean diet and survival among patients with coronary heart disease in Greece. Arch Intern Med 165 (8), 929–935.

    Article  Google Scholar 

  • Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003). Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348, 2599–2608.

    Article  Google Scholar 

  • Trichopoulou A, Georga K (eds) (2004). Composition Tables of Simple and Composite Foods. Parisianos: Athens, Greece, pp 1–158.

    Google Scholar 

  • Trichopoulou A, Gnardellis C, Lagiou A, Benetou V, Trichopoulos D (2000). Body mass index in relation to energy intake and expenditure among adults in Greece. Epidemiology 11, 333–336.

    CAS  Article  Google Scholar 

  • Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocke MC, Peeters PH et al. (2005b). Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ 330, 991–997.

    Article  Google Scholar 

  • Trichopoulou A, Psaltopoulou T, Orfanos P, Trichopoulos D (2006). Diet and physical activity in relation to overall mortality amongst adult diabetics in a general population cohort. J Intern Med 259 (6), 583–591.

    CAS  Article  Google Scholar 

  • Truby H, Baic S, deLooy A, Fox KR, Livingstone MB, Logan CM et al. (2006). Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC ‘diet trials’. BMJ 332 (7553), 1309–1314.

    Article  Google Scholar 

  • Tsai CJ, Leitzmann M, Willett W, Giovannucci E (2004). Dietary protein and the risk of cholecystectomy in a cohort of US women. The Nurses' Health Study. Am J Epidemiol 160, 11–18.

    Article  Google Scholar 

  • Volek J, Westman E (2002). Very-low-carbohydrate weight-loss diets revisited. Cleve Cl J Med 69, 849–858.

    Article  Google Scholar 

  • Wacholder S, Schatzkin A, Freedman LS, Kipnis V, Hartman A, Brown CC (1994). Can energy adjustment separate the effects of energy from those of specific macronutrients? Am J Epidemiol 140, 848–855.

    CAS  Article  Google Scholar 

  • Willett WC (2004). Reduced-carbohydrate diets: no roll in weight management? Ann Intern Med 140, 836–837.

    Article  Google Scholar 

  • Willett W, Stampfer M (1998). Implications of total energy intake for epidemiological analyses. In: Willett W (ed). Nutritional Epidemiology, 2nd edn, Oxford University Press: New York, US, pp 273–301.

    Chapter  Google Scholar 

  • Willett WC, Sampson L, Browne ML, Stampfer MJ, Rosner B, Hennekens CH et al. (1988). The use of a self-administered questionnaire to assess diet four years in the past. Am J Epidemiol 127, 188–199.

    CAS  Article  Google Scholar 

  • World Cancer Research Fund (1997). Food, nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Prevention: Washington, DC, pp. 92–361.

  • World Health Organization (1992). International Statistical Classification of Diseases and Related Health Problems (ICD, vol 1,2,3). 10th revision, Geneva, Switzerland.

  • Yang E, Kerver J, Park Y, Kayitsinga J, Allison D, Song W (2003). Carbohydrate intake and biomarkers of glycemic control among US adults: the third National Health and Nutrition Examination Survey (NHANES III). Am J Clin Nutr 77, 1426–1433.

    CAS  Article  Google Scholar 

Download references


This work was supported by the Europe Against Cancer Program of the European Commission, the Greek Ministry of Health, the Greek Ministry of Education, and an unrestricted grant to the University of Athens in honour of ‘Vasilios and Nafsika Tricha’ (all supporting the collection and management of the data).

Author information

Authors and Affiliations


Corresponding author

Correspondence to A Trichopoulou.

Additional information

Guarantor: A Trichopoulou.

Contributors: AT is the principal investigator of the Greek EPIC project and has the supervising responsibility for all aspects of this project. TP is the physician directly involved in the implementation of this study. PO is the coordinator for data analysis. C-CH and DT are the epidemiology consultants.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Trichopoulou, A., Psaltopoulou, T., Orfanos, P. et al. Low-carbohydrate–high-protein diet and long-term survival in a general population cohort. Eur J Clin Nutr 61, 575–581 (2007).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • diet
  • survival
  • protein intake
  • carbohydrate intake
  • cohort study

Further reading


Quick links