This study evaluates the effectiveness of medium-term supplementation with creatine to improve clinical outcomes in well-defined adult CFS population. Half of the participants will receive creatine while the other half will receive placebo.

Chronic fatigue syndrome (CFS) is a debilitating and complex condition characterized by profound fatigue of unknown cause, which is permanent and limits the person's functional capacity, producing various degrees of disability. It seems that inadequate or impaired energy provision through cellular metabolism may contribute to the pathogenic initiation and maintenance of CFS.

A variety of dietary interventions have been used in the management of CFS, yet no therapeutic modality demonstrated overall positive results in terms of effectiveness. Previous studies have evaluated the effects of essential fatty acids, vitamins, minerals and/or enzymes, with findings that do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms. Considering the fact that patients with CFS have lower levels of high-energy compounds (e.g. phosphocreatine, adenosine triphosphate), effective dietary treatment of CFS should be focused on providing compounds that facilitates cellular bioenergetics. Besides other candidate agents, creatine (Cr) could be of particular interest since it occurs naturally in the human body.

Placebo-controlled, randomized, double-blind, cross-over clinical trial examining the effectiveness of Cr for the treatment of CFS will be organized according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Inclusion Criteria:

• older than 18 years
• fulfilled CDC criteria for CFS

Exclusion Criteria:

• psychiatric co-morbidity
• use of dietary supplement within 4-weeks prior to the study commencing
• pregnancy