Ab1802

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

D.A. Fraser^1,4, J. Thoen¹, S. Bondhus¹, M. Haugen¹, J.E. Reseland² O. Djøseland³, Ø. Førre¹, J. Kjeldsen-Kragh⁴

¹Centre for Rheumatic Diseases, The National Hospital; ²Institute for Nutrition Research, University of Oslo; ³Department of Endocrinology, The National Hospital; ⁴Department of Immunology and Transfusion Medicine, Ullevaal University Hospital, Oslo, Norway.

ABSTRACT
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, b-hydroxybutyrate (b-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 b-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.

Key words
Rheumatoid arthritis, ketogenic diet, leptin, IGF-1, fasting, immune.

Please address correspondence and reprint requests to: David A. Fraser, Department of Immunology and Transfusion Medicine, Ullevaal University Hospital, N-0407, Oslo, Norway.
E-mail: DFRA@nycomed.com