Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome

Abstract

A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.

Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review

“…Two comparative studies reported improvement in quality of life after supplementation of acetyl‐ l ‐carnitine and propionyl‐ l ‐carnitine , as well as l ‐carnitine . No studies reported improvement in physical activity level; however, one study reported significant improvement in quadriceps isometric strength and VO 2 max after 3 months of supplementation of guanidinoacetic acid in patients compared with controls . All other studies observed no difference of the nutrition intervention on any of the secondary outcomes .…”

“…Ostojic et al (26) SF-36 Significant improvement in physical (P = 0.04) and mental common scores (P = 0.00) Maric et al (30) SF-36 NS Sathyapalan et al (32) London Handicap Scale Significant increase in residual function (P = 0.01) Sullivan et al (33) SF-12 Health Survey NS Hobday et al (27) MOS SF-36 NS The et al (23) SIP-8 score NS McDermott et al (22) WHO QOL-BREF Social wellbeing subscale only (P = 0.02) Vermeulen et al (28) CGI Within group analysis showed improvement in ALC and PLC but not ALC + PLC Brouwers et al (20) CDC symptom checklist SIP-8 score NS NS Plioplys et al (29) CFS Impairment Index CFS Severity Index…”

“…The et al (23) Actigraphic assessment NS Brouwers et al (20) Actigraphic assessment NS dietary interventions in CFS/ME patients. The included studies were six randomised control trial (RCT) parallel designs (15,(20)(21)(22)(23)(24) ; three RCT cross-over designs where patients were their own control (6,25,26) ; three comparative studies without concurrent control (two-or three-arm parallel groups) (27)(28)(29) ; one prospective cohort study (before and after) (30) ; and four pilot studies (15,(31)(32)(33) . All RCT (parallel and cross-over) (6,15,(20)(21)(22)(23)(24)(25)(26) and two pilot studies (31,32) reported using a double-blind design.…”

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

“…In addition, creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions (Kornblum et al 2005). Guanidinoacetic acid, a direct precursor of creatine, improved work capacity in women with chronic fatigue syndrome yet markers of tissue bioenergetics were not improved by the intervention (Ostojic et al 2016), suggesting non-energy related role of this compound. Oral L-arginine, another precursor of creatine, positively affected energy metabolism in MELAS syndrome, an inherited disorder of mitochondrial energy metabolism (Rodan et al 2015), while its effectiveness to improve brain bioenergetics in patients with X-linked creatine transporter defect was absent (Fons et al 2008) or minimal (Chilosi et al 2012).…”

Effects of Guanidinoacetic Acid Loading on Biomarkers of Cardiometabolic Risk and Inflammation

“…However, a few isolated human studies evaluated supplemental GAA in kidney failure and diabetes [4]. In recent days, a scientific interest for GAA has developed, with a few studies investigating its effectiveness and safety in healthy humans [5] and in women with chronic fatigue syndrome [6]. It appears that dietary GAA increases methylation demand and provokes mild hyperhomocysteinemia [7], a risk factor for cardiometabolic diseases.…”