Reduction in serum leptin and IGF-1 but preserved T-lymphocyte numbers and activation after a ketogenic diet in rheumatoid arthritis patients

Clin Exp Rheumatol. Mar-Apr 2000;18(2):209-14.


Objective: To assess the clinical, immunological and hormonal effects of carbohydrate restriction in rheumatoid arthritis (RA) patients via the provision of a ketogenic diet.

Methods: Thirteen RA patients with active disease consumed a ketogenic diet for 7 days, providing the estimated requirements for energy and protein whilst restricting their carbohydrate intake to < 40 g/day. This was followed by a 2-week re-feeding period. Clinical and laboratory evaluations were carried out on days 0, 7 and 21. Changes in serum glucose, beta-hydroxybutyrate (beta-HB), leptin, insulin-like growth factor-1 (IGF-1) and cortisol were also measured at these time points. To study CD4+ and CD8+ lymphocyte responses, mitogen stimulated T-cell activation was assessed in heparinised whole blood via flow-cytometric analysis of CD69 expression.

Results: After the 7-day ketogenic diet, there were significant increases in serum beta-HB and cortisol, and significant decreases in body weight, the total lymphocyte count, serum leptin, IGF-1 and glucose. However, with the exception of morning stiffness, there were no significant changes in any of the clinical or laboratory measures of disease activity, or in early T-lymphocyte activation and the absolute numbers of CD4+ and CD8+ cells.

Conclusion: In RA patients several of the metabolic and hormonal responses to a ketogenic diet, such as a fall in serum IGF-1 and leptin, resemble those which occur in response to acute starvation. However, the clinical and immunological changes which occur in response to acute starvation do not take place with a ketogenic diet and thus may be dependent upon energy and/or protein restriction.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diet therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Blood Glucose
  • Body Weight
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dietary Carbohydrates / administration & dosage
  • Dietary Proteins / administration & dosage
  • Humans
  • Hydrocortisone / blood
  • Insulin-Like Growth Factor I / metabolism*
  • Ketones / metabolism*
  • Leptin / blood*
  • Lymphocyte Activation*
  • Lymphocyte Count
  • Severity of Illness Index


  • Blood Glucose
  • Dietary Carbohydrates
  • Dietary Proteins
  • Ketones
  • Leptin
  • Insulin-Like Growth Factor I
  • 3-Hydroxybutyric Acid
  • Hydrocortisone