Trial Report Six-Week Supplementation with Creatine in ME/CFS: A Magnetic Resonance Spectroscopy, 2024, Godlewska et al

InitialConditions

InitialConditions

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Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS.

Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments.

Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment.

Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

https://www.mdpi.com/2072-6643/16/19/3308
 
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"In all participants, the diagnosis of ME/CFS had been made originally by an appropriate professional (ME/CFS service); additionally, a clinically trained member of the research team (B.R.G.) confirmed the presence of the symptoms at the time of the study according to the Center for Disease Control and Prevention 94 (CDC-94) criteria for ME/CFS"

"Fatigue was measured with the Chalder Fatigue Scale (ChFS) [22] and Fatigue Severity Scale (FSS) [23], and mood was measured with the Beck Depression Inventory II (BDI-II) [24]. We also assessed two other key ME/CFS symptoms: sleep using Pittsburgh Sleep Quality Inventory (PSQI) [25] and pain with Brief Pain Inventory (BPI; severity and interference scores)"

"In our study, participants reported an improvement in fatigue, reflected by a significant decrease in scores on self-reported fatigue severity and Chalder Chronic Fatigue Scales. This change, however, did not correlate with changes in creatine levels. With the lack of a placebo, it cannot be excluded that this subjective improvement was related to the study participation or taking a new treatment rather than to a specific benefit of creatine."
 
Hand grip strength seems to be the most significant change.
There was a significant increase in hand-grip strength (visit 1: mean 48.9, SEM 4.5; visit 2: mean 61.9, SEM 4.9; t(df6) = −7.201, p = 0.0004; effect size 2.722) following creatine treatment.
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Side effects weren't too bad for such a high dose.
Creatine was generally well tolerated, and none of the participants stopped treatment. One participant, however, gained weight during the study (5.2 kg), one reported nausea and vomiting, and one had problems sleeping if creatine was taken at night (this resolved when they took creatine earlier in the day).
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Will be much more convincing with a placebo group.
 
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I tried creatine back in 2003 when I was body building but was suffering from Autistic Burnout. It made no difference what so ever, my cognitive fatigue and brain fog were just as bad as before I took creatine. I'm not hopeful what so ever for this supplement.
 
DigitalDrifter said:
I tried creatine back in 2003 when I was body building but was suffering from Autistic Burnout. It made no difference what so ever, my cognitive fatigue and brain fog were just as bad as before I took creatine. I'm not hopeful what so ever for this supplement.
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How high a dose did you take though? I think they tried a pretty high dose.

Paper said:
The following three factors were also taken into account when deciding the dose and duration of the intervention in the current study: (1) higher doses (10–20 g/day) and longer supplementation periods seemed to consistently produce increases in the brain creatine level in other populations (the only MRS studies that showed no increase in creatine were those using lower doses) [9]; (2) it was suggested that a dose and treatment period may need to be higher to influence disease states, in particular creatine deficiencies and mitochondrial-related diseases, and mitochondrial dysfunction was suggested in ME/CFS [18]; and (3) it is possible that ME/CFS might be associated with blood–brain barrier dysfunction [19].
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I agree with Andy, that this sort of study, with hard-to-measure outcomes, doesn't have much value. It's far too easy to get positive looking results just by how the study is set up, and maybe adjusted at the end to make the numbers look good. It doesn't make me want to spend money on it.
 
Creekside said:
I agree with Andy, that this sort of study, with hard-to-measure outcomes, doesn't have much value. It's far too easy to get positive looking results just by how the study is set up, and maybe adjusted at the end to make the numbers look good. It doesn't make me want to spend money on it.
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Is hand grip strength hard to measure though? That produced the largest difference. I think the biggest weakness for this test is that it could be placebo, or due to confounders.
 
forestglip said:
Is hand grip strength hard to measure though?
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It may not be hard to measure, but it's hard to know what the numbers mean. Does it mean low ATP in those muscles, or weaker nerve impulses, or it is a psychological response to how the test is done? I haven't noticed any change in hand grip strength in my ME, regardless of changes in diet, PEM or not-PEM, or any other variations, so I'm skeptical that taking creatine would produce a noticeable change.
 
Paragraph in the paper about previous creatine research (line breaks added by me):

"Although this is the only study on ME/CFS showing a change in brain creatine concentration in response to dietary supplementation with creatine monohydrate, it can be placed in the context of a few studies using creatine or creatine-related compounds in conditions sharing similarities with ME/CFS.

For example, the above-mentioned long COVID trial [16] involving twelve patients (six on 4 g of creatine monohydrate per day and six on a placebo over six months) showed an increase in creatine in the skeletal muscle (vastus medialis muscle) and the brain (left frontal white matter and right parietal white matter) at 3 and 6 months. Creatine significantly decreased subjective feelings of fatigue and improved concentration; no correlations with changes in the creatine brain levels were presented.

In a placebo-controlled 16-week trial using 20 g of creatine monohydrate for the first 5 days followed by 5 g per day in patients with fibromyalgia [46], creatine increased muscle phosphocreatine content and improved lower- and upper-body muscle strength, but no change in cognitive function, including Stroop test measures, was noted.

A randomised controlled trial in women with CFS showed that 12-week supplementation with the creatine precursor guanidinoacetic acid increased muscle creatine concentration, functional performance, and specific fatigue subdomains [47].

One study [48] in patients with CFS failed to show benefits of a creatine-containing polynutrient supplement on fatigue severity and functional impairment. However, the dose used in this study was low (13 μg/100 mL, 125 mL single dose)."

16. Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome, 2023, Slankamenac et al

46. Creatine supplementation in fibromyalgia: a randomized, double‐blind, placebo‐controlled trial, 2013, Alves et al

47. Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome, 2016, Ostojic et al

48. The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double‐blind randomized controlled trial, 2002, Browers et al
 
forestglip said:
One study [48] in patients with CFS failed to show benefits of a creatine-containing polynutrient supplement on fatigue severity and functional impairment. However, the dose used in this study was low (13 μg/100 mL, 125 mL single dose)."
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I think they read the chart wrong. It looks like the real amount was 1200 mg/100 mL, 125 mL dose. So 1500 mg of creatine. Chromium was 13 ug/100mL.
 
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Yann04 said:
I was thinking about how people who have benefited from drugs tend to be far more likely to share the results. Which made me think I should share my negative results to this thread.
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@Yann04 made a good point in another thread about reporting negative results.

I tried taking 16g/day of creatine monohydrate for 3.5 weeks in October and did not notice any effects.
 
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Examine Study Summary.
Quick Summary
In this uncontrolled trial in adults with chronic fatigue syndrome, supplementation with creatine increased brain creatine levels, improved handgrip strength, and reduced fatigue.

What was studied?
The effects of creatine in adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

The primary outcomes were creatine levels in the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC) regions of brain, which were assessed using magnetic resonance spectroscopy.

Additional outcomes included fatigue severity, as assessed on the Chalder Fatigue Scale and Fatigue Severity Scale. The Stroop Test was used to assess various aspects of cognition and reaction time, and handgrip strength was assessed using a dynamometer.

Who was studied?
11 adults (average age of 40; 7 women, 4 men) in the United Kingdom who were diagnosed with ME/CFS.

How was it studied?
In this 6-week noncontrolled trial, all of the participants received 16 grams of creatine monohydrate per day. Assessments were conducted at baseline (prior to supplementation) and on the last day of supplementation.

What were the results?
After 6 weeks of supplementation, creatine concentrations were increased by 8.3% in the pgACC and by 2.9% in the DLPFC.

Fatigue severity was reduced on both scales, and handgrip strength was increased after 6 weeks.

Reaction times on the Stroop test were reduced (improved) after 6 weeks of creatine supplementation, and an association was found between increased pgACC creatine concentrations and improvements in reaction time.
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https://examine.com/research-feed/s...0g_dimqqmWQVTTjygoml4AancOPENMwZvf1IttYdGUb48
 
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