Since the 1990s, creatine supplementation has been hailed as a shortcut to improving or recovering from physical demands on our body. Most studies concentrated on improvements with athletic performance or recovery. Creatine is formed in our bodies from three amino acids, methionine, arginine, and glycine, all of which can be found in any animal protein source that we consume. Creatine is made from these three amino acids in the liver, but also to a lesser extent the kidneys and pancreas also make creatine and store it in the form of phosphocreatine. It is the phosphocreatine compound donating the P to convert ADP to ATP, the primary energy carrier within the mitochondria that is showing many more health benefits than previously imagined with creatine supplementation.
There have been numerous studies showing that muscle growth, strength and exercise performance improved with supplementing creatine over taking the individual amino acids, perhaps because taking it exogenously either through diet or supplementation is more efficient than having the body make it. It has also helped boost water content in the muscles to reduce dehydration and muscle cramps. Creatine can help those with muscular dystrophy. It can also help those who often suffer from sarcopenia (lowered muscle mass) and cachexia (muscle loss from disease), both of which are more common as we age. In one study senior males who took creatine while using resistance training, gained twice as much muscle mass as those taking a placebo. It can also simultaneously decrease body fat by about one percent.
Where science on creatine supplementation is heading now, it is much more interesting. Creatine also has benefits for cognitive and heart issues. Since most of our mitochondria exist within our heart and brain, making improvements to these areas through improved mitochondrial function by increasing ATP with creatine is showing great promise. In 2021 and 2022 I wrote a series of seven newsletters about mitochondrial health. The last one in the series can be seen here. With the improvement in mitochondrial function from creatine supplementation, science sees improvement in depression, anxiety, recovery from sleep deprivation, memory in older individuals and Long COVID. In the case of depression and anxiety this study was done in conjunction with medication. With Long COVID, brain fog is a common symptom. Creatine helps decrease the persistent inflammation in the brain from mitochondrial stress either from a persistent viral infection, or persistent inflammation from the spike protein. Current research is also showing it has benefits for building bone density by inhibiting osteoclasts which break down bone. Medications such as bisphosphonates like Fosamax and Denosumab have the same mechanism of action to block osteoclasts. Creatine also increases anabolic hormones such as insulin, hGH (human growth hormone), estrogen, testosterone, and sperm motility for infertility issues. It may also benefit people with neurodegenerative diseases, fibromyalgia, or insufficient blood flow to the heart muscle as endothelial cells which line blood vessels have creatine transporters. Creatine also may aid diabetes through glucose disposal, making it a promising aid for vascular and metabolic health.
While our body produces about 1-2 grams of creatine per day, we do lose a lot through urine, so it is important to replenish. We cannot get it from vegetarian sources, and vegans have been evaluated and show lower amounts of creatine. The highest sources of creatine are beef, chicken, organ meats, seafood, and dairy, where we could potentially get about 1-2 grams per day. Intense exercise, and intense use of our cognitive function for work or school may result in a quicker depletion of creatine stores. In addition, we may not be eating enough from our diets to adequately replenish creatine levels, so supplementation is looking to be an option to consider.
The best form for creatine supplementation is creatine monohydrate. It is identical to what is made in the liver, has been around for a long time and has a very safe history, even for children. There are just a few things that you should be aware of so that you do not run into any problems. A good rule of thumb is to not exceed .3 mg per kilogram of body weight. For instance, a maximal dose for a 180-pound person who would be about 80 kilograms is 24 mgs of creatine. You also would want to avoid a large amount of caffeine (250 mg) with creatine not because of it being dangerous but because it disrupts the calcium regulation in muscle cells and would negatively impact performance. The only side effects that have been reported are weight gain because of the water retention, nausea and vomiting, diarrhea, and excessive sweating but most of this can be avoided by gently increasing the dose to see if any reactions are taking place. It is best for pregnant women to avoid creatine. Contrary to what has been reported in the past, it does not adversely affect your kidneys. Creatine does break down to creatinine, and higher levels might show up on a blood test but that does not indicate damage, just the elimination of the extra creatine. It does not increase blood pressure or cause hair loss, or frequency of urination. However, creatine could interfere with a diuretic medication for blood pressure.
Dosing
If you are considering taking it for athletic purposes, to help with muscle growth, recovery, or for preventing the loss of muscle mass from aging, then two to five grams per day is all most people would need to get results, and it would be best to take around exercise time.
However, for the non-athletic considerations, higher doses are most likely needed. For bone loss, eight grams per day may be needed. For cognitive performance to support memory in seniors and the aftereffects of sleep deprivation, up to 20 mg per day may be needed. This higher dose would also apply to someone who recently had a concussion to achieve a faster recovery. However, it may be best for most people to take the creatine in slow loading method in divided doses of 4-5 grams doses two to four times per day to avoid any of the side effects listed above.
Conclusion
Whether it is muscle growth, fatigue and recovery, bone health, or cognitive symptoms from inflammation, creatine in a therapeutic dose is a useful adjunct for consideration that is not widely known outside of the sports world. Creatine’s effect on the COX 2 pathway and the cytokines that the COX 2 pathway produces show promise in lowering chronic inflammation. In addition, T-cells and macrophages which help fight off infections require a lot of energy so it is felt that creatine may aid the immune system. I expect a lot more research to be forthcoming in all these new areas discussed and more.
I want to thank Rhonda Patrick PhD and her interview with Darren Candow PhD, an expert in creatine research, where most of this information was discussed. https://www.youtube.com/watch?v=ICsO-EHI_vM&t=2416s