Creatine Research

Creatine represents an endogenous amino acid produced in the body, as well as obtained through dietary sources - especially meat and fish. It is used widely as a supplement to produce lean muscle mass. Approximately 95 percent of the creatine in the body is present in skeletal muscle.

Creatine is increasingly being used as an ergogenic aid, as well as to help individuals with specific aging-related degenerative conditions or hereditary disorders involving muscle weakness. It is mostly used in the oral form, as creatine monohydrate.

Creatine Formulations and Protocols

Much research has been carried out on how and when creatine supplementation should be pursued, as well as on the best formulation and type of side effects that may be expected. Different combinations of creatine with other compounds have been tested, including those which include carbohydrates, proteins and taurine.

Many forms of creatine are available, including the following;

  • Creatine anhydrous
  • Creatine monohydrate
  • Creatine salts including pyruvate, citrate, and malate
  • Creatine with sodium bicarbonate
  • Creatine effervescent which contains citrate or monohydrate forms of creatine with sodium bicarbonate and citric acid
  • Creatine esters such as the ethyl ester

Important Areas of Research

The various formulations need to be further tested with respect to pharmacodynamic parameters such as peak concentrations, time to peak concentrations, absorption and elimination velocity constants, effective increase in muscle creatine uptake, as well as effects on endurance capacity, muscle fatigability and muscle power. Protocols of creatine administration also need to be tested for their relative efficacy and safety.

Another area in which research is required is the mechanism of action of creatine, concentrating on its anabolic and strength-promoting effects. Various studies suggest that creatine induces the proliferation of satellite cells, stimulates myogenic transcription factors, and promotes signaling via insulin-like growth factor-1.

It also seems that creatine inhibits the production of myostatin, a protein which prevents the growth of skeletal muscle fibers. Another action might be the effect of creatine on the anaerobic threshold. Creatine also increases the glycogen stores in muscle fibers, along with the expression of GLUT-4 receptors, when its administration is during a period of intense exercise.

Creatine and the Brain

Creatine has a potent anti-oxidant activity which has been instrumental in delaying aging-related neurodegeneration, as well as preventing or improving other creatine-depleted conditions. This is probably by replenishing brain stores of phosphocreatine and creatine, which are vital for the normal mitochondrial function. Sleep deprivation also causes neuronal stress which can be prevented to some extent by creatine supplementation.

Creatine and Other Areas of health

Creatine in the elderly acts in similar ways to provide reduction in muscle fatigability, but also to provide increases in muscle strength and improvements in bone mineral density. These have been shown to produce greater ease in performing activities of daily living, which in turn helps to promote independence in older adults.

Certain specific inflammatory myopathies have also been helped by creatine supplementation, probably due to the anti-oxidant properties of this molecule. However, some studies fail to show benefit.

Thus research is needed to confirm the presence of any positive effect in the following conditions, though early work shows some promise:

  • Skin aging
  • Chronic obstructive pulmonary disease
  • Congestive cardiac failure
  • Depression, schizophrenia and bipolar disorder
  • Diabetes mellitus
  • Fibromyalgia, muscle cramps, polymyositis and other autoimmune muscle disorders
  • Mitochondrial myopathies and muscular dystrophies
  • Gyrate atrophy
  • Hereditary neuropathies of some types
  • Amnesia following traumatic brain injury in childhood and following spinal injury
  • Osteoarthritis and rheumatoid arthritis

The long-term effects of prolonged creatine administration should also be looked into as its use is becoming indiscriminate, most notably among young athletes and children.


Further Reading

Last Updated: Feb 26, 2019

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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