What the Heck is Guanidinoacetic Acid And Why Might It Help ME/CFS?

Cort

Founder of Health Rising and Phoenix Rising
Staff member
I have not looked at this study (it's a freebie by the way). The idea of something assisting with muscle strength and aerobic power is of course intriguing.

http://www.ncbi.nlm.nih.gov/pubmed/26840330


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.

Source: Ostojic, S.M.; Stojanovic, M.; Drid, P.; Hoffman, J.R.; Sekulic, D.; Zenic, N. Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome. Nutrients 2016, 8, 72.
 

Remy

Administrator
Interesting. It looks like it's also called glycocyamine.

It doesn't look like it's available as a supplement yet though.

Wikipedia has this to say...
A series of studies showed that a combination of betaine and glycocyamine improves the symptoms of patients with chronic illness, including heart disease, without toxicity. Betaine can provide a methyl group to glycocyamine, via methionine, for the formation of creatine. [1] In overall, such treatment led to less fatigue, greater strength and endurance, and an improved sense of well-being. The patients with cardiac decompensation (arteriosclerosis or rheumatic disease) [2] and congestive heart failure[3] had improved cardiac function. The patients gained weight (improved nitrogen balance) and saw lessened symptoms of arthritis and asthma and increased libido, and those people suffering from hypertension experienced transient reduced blood pressure. Also the studies shows the increase of glucose tolerance in both diabetic subjects and subjects without diabetes. [4]
So apparently it depletes methyl groups which causes a rise in homocysteine. Now I'm curious if a problem in this pathway isn't responsible for high homocysteine rather than a methylation cycle defect?
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Interesting. It looks like it's also called glycocyamine.

It doesn't look like it's available as a supplement yet though.

Wikipedia has this to say...


So apparently it depletes methyl groups which causes a rise in homocysteine. Now I'm curious if a problem in this pathway isn't responsible for high homocysteine rather than a methylation cycle defect?
I can see why they tried it in ME/CFS....
 

Not dead yet!

Well-Known Member
I have not looked at this study (it's a freebie by the way). The idea of something assisting with muscle strength and aerobic power is of course intriguing.

http://www.ncbi.nlm.nih.gov/pubmed/26840330


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.

Source: Ostojic, S.M.; Stojanovic, M.; Drid, P.; Hoffman, J.R.; Sekulic, D.; Zenic, N. Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome. Nutrients 2016, 8, 72.
For all we know that might mean it's blocking the metabolism of creatine so it builds up instead of being used. I'm not sure how they're getting a positive effect on "work capacity" if the fatigue and pain are the same.

This is also troubling: "A total of 14 participants completed the follow-up measures. Seven participants were lost during the intervention period due to reasons not connected to the study per se. "

If they lost that many people to get p values like this, then I wouldn't put a lot of faith into it:

"Changes in exercise performance from baseline to three months post-administration are presented in Figure 2. Significant differences in the percent change in total quadriceps isometric strength and maximal oxygen uptake were observed between the interventions (p < 0.05), while no differences were noted for daily energy expenditure (p = 0.98), physical activity duration (p = 0.23) and intensity (p = 0.22). A trend (p = 0.08) towards a difference was noted in maximal workload during ergometry between the GAA and placebo groups. "

However, I'm glad they went back to a 1950s era study (and idea) and re-examined it. It looks like it needs more biochemical explanation, like a clear mechanism of action. Meaning, how does it increase creatine? And how is that different from taking extra creatine? Maybe I missed it but they didn't seem to focus on those questions in this particular study.
 

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