Creatine for ME/CFS & Fibromyalgia
Historically, creatine supplementation has been reserved for athletes. For many decades professional and amateur athletes have supplemented with creatine to improve strength gains and augment performance and recovery. Countless studies have supported the supplement for these purposes for more than 150 years. New research illustrates the many other properties of creatine, suggesting supplementation may be beneficial in ME/CFS, depression, and fibromyalgia.
Creatine is found abundantly in skeletal muscle but also in the brain. Dietary sources of creatine can contribute to body stores with regular consumption of milk, meat, and fish. A pound of uncooked fish or beef contains 1-2 g of creatine, but is partially degraded with cooking. Creatine is metabolized to creatinine and excreted in the urine.
*As an aside, serum creatinine is a common laboratory measurement predictive of kidney function. Those with a high meat intake, strenuous weight lifting, or creatine supplementation may have elevated levels of serum creatinine. This however, is not completely indicative of kidney damage and one must also consider the rate of kidney filtration. Creatinine may increase with certain medications, fever, or inflammatory conditions. There is a large body of evidence and long history of safety surrounding creatine supplementation and kidney health. Routine kidney function testing may be warranted in those with a renal disease history.
Creatine & the Mitochondria
Creatine is an excellent energy source for the cell’s powerhouse, the mitochondria. Its effects on the mitochondria are two-fold; protective and enhancing. It acts as an antioxidant, quenching free radicals and lactic acid. Creatine is converted to phosphocreatine (PCr) by the enzyme creatine kinase, which is found in the inner mitochondrial membrane. This PCr can be stored and contributes to a cellular energy (ATP) pool.
Creatine helps stabilize the mitochondrial membrane by increasing cardiolipin—a protein that acts like scaffolding for the delicate mitochondrial membrane. It also interacts with a protein associated with mitochondrial permeability—the mitochondrial permeability transition pore (MPTP). This pore controls influxes of calcium into the mitochondria. Excess calcium influx leads to mitochondrial dysfunction and death. Creatine inhibits this pore to preserve mitochondria. The MPTP is implicated in several neurological conditions—brain injury, Parkinson’s, stroke, etc. In these conditions, the MPTP is stimulated to promote mitochondrial dysfunction and death. Individuals with traumatic brain injury received creatine for 6 months and showed significant improvement in communication, cognition, personality/behavior, and self-care as compared to individuals who did not receive creatine.
Creatine Problems in ME/CFS
A new 2019 study from Dr. Nacul’s group found reduced serum creatine kinase (CK) concentrations in severe ME/CFS compared to less severe cases. This enzyme is typically increased in serum due to skeletal muscle injury (CK-MM) or cardiac muscle injury (CK-MB). Here, measured levels of this important enzyme were markedly reduced in skeletal muscle but not cardiac muscle. A 2010 study of 14 ME/CFS patients found plasma creatine kinase levels (measured from muscle biospy), before and after an exercise challenge, to be low in patients. These two studies suggest insufficiency of the important energy system enzyme. There is a third form of the CK enzyme, CK-BB, which is found in the central nervous system. No study has measured this form of the enzyme as of yet in ME/CFS. Sampling of cerebrospinal fluid would provide the best sampling.
Creatine & Fibromyalgia
Creatine may lessen muscle pain and soreness in fibromyalgia by scavenging lactic acid. Lactic acid build-up also occurs in some subsets of ME/CFS as a consequence of post-exertion. This happens to me! Since creatine can be stored, it also may provide a boost in energy for those with chronic fatigue syndrome. A 16-week double-blind, randomized control study in fibromyalgia patients showed creatine supplementation increased intramuscular phosphorylcreatine content by ~80% (more ATP available) and improved lower- and upper-body muscle function, with some additional effects in general symptoms.
Creatine & Methylation
The body’s production of creatine represents a large proportion of methylation demands. Up to 40% of the body’s methyl groups are consumed during synthesis of creatine at the kidney and liver. Those with MTHFR mutations that supplement with creatine should also support methylation with vitamin B2 to balance high demands.
Creatine & Severe ME/CFS
The muscle atrophy that occurs with prolonged bed rest and immobility of ME/CFS, may be mitigated with creatine supplementation. Studies in those immobilized due to fractures, show reduced amount of muscle atrophy and better insulin sensitivity with supplementation. Another interesting study, showed increases in peak oxygen uptake following creatine supplementation in those immobilized due to spinal cord injury. Meta-analyses of creatine supplementation in the elderly, shows consistent improvement in muscle mass, strength, and bone mineral density when combined with some degree of resistance training. Those with severe ME/CFS who struggle with mobility, may consider supplementation with gentle stretching or isometric exercises as mentioned in an earlier post.
Creatine & Depression
Perhaps most fascinating about creatine is that it also has neuroprotective properties. Creatine can be synthesized in the brain, and it can cross the blood-brain barrier via specific creatine transporters. In the brain, it plays a major role in ATP/ADP balance by providing a steady phosphorous group to ADP to replenish ATP. In addition to an energy substrate, creatine can be released from neurons and function as a neurotransmitter.
In animal studies and human clinical studies of depression, there have been detectable changes in creatine and its enzymes and metabolites. Most, but not all, studies show lower levels of creatine in depressed individuals. Those taking tricyclic or selective serotonin reuptake inhibitors (SSRIs) may positively influence creatine levels in the brain. These medications seem to effect action of the enzyme creatine kinase. The anti-depressive effects of these medications are enhanced by creatine supplementation in some studies.
Animal studies have shown that creatine can interact with dopamine and serotonin systems in the brain. It also seems to inhibit NMDA receptors, resulting in lower levels of the highly excitatory glutamate. In this way, creatine may reduce neuroinflammation by blocking excess glutamate from producing nitrosative and oxidative stress.
Supplementation with creatine in human subjects has been shown to effectively increase creatine levels in the brain. Some research has not supported these findings but that may be due to different clinical conditions of the patients as well as different analytical methods to quantify creatine. Regardless, it is clear that creatine plays some role in depressive conditions. No study I reviewed while writing this showed adverse effect of creatine supplementation or kidney insult.
Consider these clinical studies:
A case study of a 52-year-old woman who suffered from post-traumatic stress disorder, depression and fibromyalgia who was not responsive to treatment with citalopram experienced improvement in depressive symptoms and fibromyalgia lasting up to 8 weeks after the end of supplementation (Amital et al., 2006).
8 unipolar and 2 bipolar patients with treatment-resistant depression treated for 4 weeks with creatine significantly improved their symptoms, and 1 patient had improvement after just 1 week (Roitman et al., 2007).
5 female adolescents with continued depression despite fluoxetine, used creatine as an adjunct for 8 weeks and exhibited increased brain creatine and significant depression improvement (Kondo et al., 2011).
Improvement in depressive symptoms in a group of 52 women that received creatine and escitalopram for 8 weeks. These effects were seen as early as week 2 into treatment and were maintained at weeks 4 and 8, when compared to the placebo group (Lyooet al., 2012).
How to Take
Many forms of creatine are on the market (visit FullScript for a selection) yet there is no consensus that any form is better than the traditional, inexpensive creatine monohydrate. In those with lactic acid issues such as myself, look for an alkalized supplement (e.g. Kre-Alkalyn). This enables enhanced support for lactic acid and metabolic acid buffering. Some may experience water retention with creatine supplementation. This is because it acts in the muscle to increase glycogen, which harbors water. In general, alkaline creatine supplements should not cause water retention.
The International Society of Sport Nutrition has stated that creatine supplementation up to 30 g/day for 5 years is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. For those with chronic disease, 10–30 g per day is suggested to offset deficiencies or provide therapeutic benefit. The highest range is also suggested for severe ME/CFS to facilitate muscle health.
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Pazini, F. L., Cunha, M. P., & Rodrigues, A. L. S. (2018). The possible beneficial effects of creatine for the management of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry.
Tokarska-Schlattner M (2012) Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects. PLoS One. 7(8):e43178. Epub 2012 Aug 17.
Alves CR, et al. (2013) Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 65(9):1449-59.
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