Creatine Supplementation: A Review of Current Research
Creatine is known for its influence on muscle building and brain function. Because women going through the menopause transition are at risk for loss of lean muscle mass and cognitive difficulties such as depression and lack of mental clarity, supplemental creatine could be a useful tool in improving well-being.
Creatine is made by the pancreas, kidneys, and liver and stored mainly in the muscles to be used as a quick and accessible energy source. Small amounts of creatine are also synthesized in the brain and utilized for cognitive function. While the body does produce creatine, the amount is small which is why for some people, supplemental creatine can be helpful. Three amino acids are needed to produce creatine, glycine, arginine, and methionine. Dietary creatine comes from red meat and seafood. Research has found several ways that supplementing with creatine can be helpful, particularly for women during perimenopause and in the years following, to both mitigate health risk and to improve well-being. As with any supplement, please consult your doctor before using.
Review of Literature
Bone Health
To provide cellular energy, creatine combines with phosphate to become phosphocreatine. This can be used as a source of energy for bone cells. Previous studies have concluded that in some circumstances creatine can reduce bone resorption (the process of breakdown and removal of old bone tissue) and one found that in postmenopausal women creatine supplementation combined with resistance training improved the bone mineral density (BMD) in the femoral neck. This is important because as women age, the resorption of bone can outpace the formation of new bone leading to a loss of bone mineral density and increased fracture risk. A further study tried to replicate these findings and found that supplemental creatine combined with resistance training and a walking program did not improve the BMD of the hip, femoral neck, or lumbar spine. They did find positive bone changes as compared to the placebo group which may show creatine to be beneficial for reducing fracture risk. These changes are potentially due to the improvement in lean muscle mass that results from creatine supplementation.
In addition, there is some evidence that creatine can reduce oxidative stress and inflammation. For women post menopause, the decrease in estrogen is responsible for loss of bone mass. Low levels of estrogen are also linked to oxidative stress and inflammation. Supplemental creatine may be a way to counter the loss of BMD through a reduction in inflammation.
Mood and Cognition
Multiple studies have shown that creatine supplementation can have positive effects on mood and cognitive functioning. This includes improvements in working memory, mental fatigue, and processing speed. Several reports have suggested that the availability of creatine in the body influences depression. Because of these studies, the use of the creatine precursor SAMe has been used in the treatment of depression and has been found effective. In mice studies, the addition of creatine to exercise promoted an improvement in depressive symptoms and behaviors. There is also some evidence that creatine supplementation combined with choline supplementation can improve both depression and anxiety.
These findings are of particular importance as females suffer from depression rates twice the rate of males. This is linked to hormonal changes such as puberty, pregnancy, during the luteal phase of the menstrual cycle, and perimenopause. Most of this is due to the sensitivity of the brain to estrogen and progesterone. Women have lower concentrations of creatine phosphate than men. This is likely due to the importance of estrogen in maintaining creatine homeostasis. Researchers looking at the connection between creatine metabolism and depression measured cerebral spinal fluid and found a relationship between depression and creatine, dopamine, and metabolites (byproducts) of serotonin. They believe that the neurotransmission of mood affecting metabolites is dependent on the creatine-phosphocreatine system. Because females have been shown to have lower levels of creatine in their brain and especially in the frontal lobe which is responsible for cognitive functions such as memory, emotion, and mood, supplemental creatine can be particularly useful for treating depression in females.
The addition of supplemental creatine to antidepressants has been shown to be beneficial. There is evidence that increased intake of animal protein can improve mood disorders in females and is especially important during the phases of hormonal change. Vegetarians who supplement with creatine have improved cognitive function. It is uncertain if the increase in depression in vegetarians is due solely to the creatine in animal protein, or the synergistic value of multiple nutrients found most abundantly in animal protein. But supplemental creatine has been shown to be effective and can be used therapeutically for the treatment of depression.
Creatine supplementation can also help mitigate the impacts of sleep loss which is of particular concern for females. The hormonal phases of the female leave them susceptible to poor sleep quality during specific periods and creatine supplementation can be helpful in increasing cognition and mental capacity under poor sleep conditions.
Muscle Mass
People typically lose muscle mass and strength with aging. This is accompanied by a loss of bone mass and an increase in body fat and can lead to a condition called sarcopenia which is a significant loss of muscle mass and strength resulting in lowered function. The lowered function leads to further loss of muscle and strength resulting in lowered life quality and well-being. Creatine supplementation has been most often studied for its impact on strength, performance, and muscle building. There is evidence that supplementation along with resistance training is beneficial for increasing lean muscle mass, strength, and endurance. This is especially significant for older individuals as they seek to maintain muscle mass as they age. Most studies found that supplementation accompanied with resistance training proved the most effective. For individuals attempting to lose weight and restrict calories, the addition of creatine was important for preventing muscle loss and promoting fat loss.
It is likely that phosphocreatine stores decrease as we age. This is particularly evident in the lower body as muscles atrophy, activity is decreased, and often consumption of meat is reduced. Strength loss is also more pronounced in lower body muscles as we age, and creatine supplementation could help mitigate this loss.
Results were seen with a creatine supplementation of equal to or greater than five grams either daily or on resistance training days. By maintaining muscle mass during aging, individuals can help prevent sarcopenia which is often accompanied by osteoporosis and frailty.
Antioxidant Capacity
With age, the body increases its production of free radicals while antioxidant production decreases. This leads to oxidative damage and inflammation. Resistance training alone can help prevent some of the consequences of aging and can increase the body’s production of antioxidant enzymes while reducing harmful byproducts of oxidative damage. A ten-week resistance training program reduced oxidative damage and strengthened antioxidant capacity. The addition of creatine supplementation did not increase the reduction of oxidative damage, but it did increase the levels of the antioxidant enzyme glutathione peroxidase. (Glutathione peroxidase protects cells from damage by neutralizing free radicals and reactive oxygen species which are harmful, inflammatory molecules.) This study hoped to show a greater antioxidant potential for creatine supplementation, but it did not. It did however demonstrate that resistance training itself can have an important role in increasing antioxidant production in the body and reducing oxidative damage.
Safety Profile
Creatine supplementation is generally safe. There are some reports of gastrointestinal distress in study participants, but overall, it is well tolerated. Individuals who have pre-existing kidney conditions should avoid creatine supplementation. For older adults, it is particularly important to monitor usage due to the decrease in the glomerular filtration rate (the efficiency at which kidneys filter the blood) that accompanies aging. However, most studies have shown that creatine is safe, even in older individuals. One study looked at postmenopausal women who supplemented with three grams of creatine per day for two years and found no adverse effects. Individuals using statins or glucocorticoids should use caution as these drugs may impact the effectiveness of creatine supplementation. One meta-analysis found creatine supplementation to be both safe and well-tolerated and can be safely recommended for postmenopausal females.
Dosage
Studies do not have a consensus for the most beneficial dosage and have experimented with a variety of methodologies. In some instances, participants engaged in a loading phase with an intake of 20 grams for 5-7 days followed by a maintenance dose of five grams per day going forward. Studies using low dose supplementation often saw little to no benefits. The dose that proved most consistent throughout the studies was approximately five grams per day. Supplementation is also potentially most beneficial when consumed within 60 minutes of exercise participation.
Summary
Creatine supplementation has been shown to be effective for increasing muscle mass and strength when combined with weight training. This is especially important in women following the menopause transition as lean muscle mass decreases. There is some evidence that it can improve bone health and lower the risk of fractures. Creatine has been shown to improve mood disorders, particularly depression, both through supplementation and through increased consumption of animal protein. It also has a potential to improve antioxidant capacity in the body, but this is inconclusive in the studies. This review of literature concludes that creatine supplementation is both safe and beneficial for postmenopausal women and can be useful in improving life and health quality.
Conflicts of Interest
Several of the studies used were funded by German chemical company Alzchem who manufactures creatine monohydrate. This is a significant conflict of interest. In addition, some study authors are connected to Alzchem in professional capacities.
Limitations
There was no consistency in dosage or metrics to determine benefit. The studies made many claims but were often not able to be replicated. This was sometimes potentially due to a lower dosage used in the new study, but overall, a consistent approach wasn’t used throughout the research. While it does appear safe and many studies have shown benefit, the fact that much of the research was funded by Alzchem is a potential reason to question the results.
Further Directions
This supplement holds promise for the overall population and can be of particular value to women during and after the menopause transition. More independent research is needed. Of most importance is finding a reliable recommended dosage. While the safety profile is positive, the parameters of dosage that are considered safe are unknown.
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