, Volume 193, Issue 6, pp 939–945 | Cite as

Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects

  • Rubini Alessandro
  • Bosco Gerardo
  • Lodi Alessandra
  • Cenci Lorenzo
  • Parmagnani Andrea
  • Grimaldi Keith
  • Zhongjin YangEmail author
  • Paoli Antonio



The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects.


Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40t 2m). The MD group followed a MD for 20 days (MD t 0t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20t 40), and completed the study with the MD for 2 months (MD t 40t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point.


A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet.


The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.


Ketogenic diet Respiration parameters Metabolism Resting energy expenditure 



We wish to thank Kim Hare and Marcelyn Cook for their English editorial assistance.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Hartman AL, Vining EP (2007) Clinical aspects of the ketogenic diet. Epilepsia 48:31–42CrossRefPubMedGoogle Scholar
  2. 2.
    Paoli A, Rubini A, Volek JS, Grimaldi KA (2013) Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 67:789–796. doi: 10.1038/ejcn.2013.116 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Cross JH, McLellan A, Neal EG, Philip S, Williams E, Williams RE (2010) The ketogenic diet in childhood epilepsy: where are we now? Arch Dis Child 95:550–553. doi: 10.1136/adc.2009.159848 CrossRefPubMedGoogle Scholar
  4. 4.
    Volek JS, Sharman MJ (2004) Cardiovascular and hormonal aspects of very-low-carbohydrate ketogenic diets. Obes Res 12:115S–123S. doi: 10.1186/1475-2891-10-112 CrossRefPubMedGoogle Scholar
  5. 5.
    Paoli A, Cenci L, Grimaldi KA (2011) Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees. Nutr J 10:112CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Langfort J, Pilis W, Zarzeczny R, Nazar K, Kaciuba-Uscilko H (1996) Effect of low-carbohydrate-ketogenic diet on metabolic and hormonal responses to graded exercise in men. J Physiol Pharmacol 47:361–371PubMedGoogle Scholar
  7. 7.
    Tagliabue A, Bertoli S, Trentani C, Borrelli P, Veggiotti P (2012) Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: a 6-month prospective observational study. Clin Nutr 31:246–249. doi: 10.1016/j.clnu.2011.09.012 CrossRefPubMedGoogle Scholar
  8. 8.
    Perez-Guisado J, Munoz-Serrano A, Alonso-Moraga A (2008) Spanish Ketogenic Mediterranean Diet: a healthy cardiovascular diet for weight loss. Nutr J 7:30. doi: 10.1186/1550-2783-9-34 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Paoli A, Grimaldi K, D’Agostino D, Cenci L, Moro T, Bianco A, Palma A (2012) Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr 9:34. doi: 10.1186/1550-2783-9-34 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Paoli A, Moro T, Marcolin G, Neri M, Bianco A, Palma A, Grimaldi K (2012) High-intensity interval resistance training (HIRT) influences resting energy expenditure and respiratory ratio in non-dieting individuals. J Transl Med 10:237. doi: 10.1186/1479-5876-10-237 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schrauwen P, van MarkenLichtenbelt WD, Saris WH, Westerterp KR (1997) The adaptation of nutrient oxidation to nutrient intake on a high-fat diet. Z Ernahrungswiss 36:306e9CrossRefGoogle Scholar
  12. 12.
    Schrauwen P, van MarkenLichtenbelt WD, Westerterp KR (2000) Fat and carbohydrate balances during adaptation to a high-fat diet. Am J Clin Nutr 72:1239e44Google Scholar
  13. 13.
    Sabapathy S, Morris NR, Schneider DA (2006) Ventilatory and gas-exchange responses to incremental exercise performed with reduced muscle glycogen content. J Sci Med Sport 9:267–273CrossRefPubMedGoogle Scholar
  14. 14.
    Cai B, Zhu Y, Ma Y, Xu Z, Zao Y, Wang J, Lin Y, Comer GM (2003) Effect of supplementing a high-fat, low-carbohydrate enteral formula in COPD patients. Nutrition 19:229–232CrossRefPubMedGoogle Scholar
  15. 15.
    Srivastava S, Kashiwaya Y, King MT, Baxa U, Tam J, Niu G, Veech RL (2012) Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB 26:2351–2362. doi: 10.1096/fj.11-200410 CrossRefGoogle Scholar
  16. 16.
    Malli F, Papaioannou AI, Gourgoulianis KI, Daniil Z (2010) The role of leptin in the respiratory system: an overview. Respir Res 11:152. doi: 10.1186/1465-9921-11-152 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Makinodan K, Yoshikawa M, Fukuoka A, Tamaki S, Koyama N, Yamauchi M, Tomoda K, Hamada K, Kimura H (2008) Effect of serum leptin levels on hypercapnic ventilatory response in obstructive sleep apnea. Respiration 75:257–264CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Rubini Alessandro
    • 1
  • Bosco Gerardo
    • 1
  • Lodi Alessandra
    • 1
  • Cenci Lorenzo
    • 1
  • Parmagnani Andrea
    • 1
  • Grimaldi Keith
    • 2
  • Zhongjin Yang
    • 3
    Email author
  • Paoli Antonio
    • 1
  1. 1.Department of Biomedical SciencesUniversity of PadovaPaduaItaly
  2. 2.Biomedical Engineering LaboratoryUniversity of AtheneAthensGreece
  3. 3.The Institute for Human PerformanceSUNY Upstate Medical UniversitySyracuseUSA

Personalised recommendations