Creatine is a naturally occurring compound that is critical in storing and releasing cellular energy. It also participates in many biological processes driving pregnancy outcomes, maintaining bone mineral density and muscle mass in older adults, improving neurological function, and aiding the immune system to fight cancer. Creatine is best known for its widespread use as a dietary supplement to enhance physical performance.
Creatine, phosphocreatine, creatine transporters, and creatine kinase enzymes are expressed in the endothelial cells that line our blood vessels and play an integral role in delivering high-energy phosphates to ion channels that maintain vascular tone and regulate endothelial function.[1] Creatine may positively impact vascular health through several mechanisms, including its role as an antioxidant, its effects on nitric oxide (NO) bioavailability, its support of endothelium-derived hyperpolarization factors (EDHFs), its maintenance of endothelial cell (EC) integrity, and its protection of cellular DNA and RNA.[2]
Specifically, creatine may benefit vascular health by:
Furthermore, creatine can increase natural endothelial cell stores of high-energy metabolites, improve mitochondrial function and reduce mitochondrial-specific reactive oxygen species production, increase microvascular density, and reduce circulating levels of damaging lipids. Creatine may also help reduce inflammation and homocysteine, both of which are linked to cardiovascular disease development.
It's important to note that while these mechanisms are supported by in vitro and in vivo studies, there is a lack of clinical trials in humans specifically examining the impact of creatine on vascular health. However, a few smaller randomized controlled trials hint at a benefit.
"Furthermore, creatine can increase natural endothelial cell stores of high-energy metabolites, improve mitochondrial function and reduce mitochondrial-specific reactive oxygen species production, increase microvascular density, and reduce circulating levels of damaging lipids. Creatine may also help reduce inflammation and homocysteine, both of which are linked to cardiovascular disease development."- Dr. Rhonda Patrick Click To Tweet
To investigate creatine's effects on blood vessel health—specifically by measuring the ability of arteries and small blood vessels to increase in size to accommodate blood flow (known as endothelial function)—one study recruited 12 healthy men and women with an average age of 59 and supplemented them with creatine or a placebo for 28 days each.[3]
Supplementing involved two phases: A 5-day loading phase during which the participants took 5 grams of creatine four times per day for 20 grams total per day and a 23-day maintenance phase where they just took 5 grams once per day.
After creatine supplementation, endothelial function increased in larger arteries (macrovascular function) by 1.2% and smaller arteries (microvascular function) by 1.4%—this magnitude of change has been associated with a 13% decrease in the risk of having a cardiovascular event like a heart attack or a stroke.
More importantly, both measures of endothelial function were higher after creatine supplementation compared to placebo, indicating that creatine has notable benefits on vascular health and, by extension, cardiovascular disease risk.
Despite a beneficial improvement in vascular health, creatine did not improve biomarkers of oxidative stress but did improve fasting blood glucose from 103 to 99 mg/dL and triglycerides from 100 to 84 mg/dL. Both of these are traditional cardiovascular disease risk factors. In fact, the participants' blood glucose levels dropped from just above prediabetic levels to slightly below.
In another study conducted on older men, supplementing with 20 grams of creatine daily for 7 days resulted in a lowering of their cardio-ankle vascular index—a measure of artery stiffness—and a non-significant 8-mmHg decrease in their systolic blood pressure.[4] Thus, it would appear that both long-term and short-term (acute) creatine supplementation has the potential to positively affect vascular health parameters.
"Collectively, these studies seems to indicate that in addition to experiencing the usual benefits of creatine—stronger and larger muscles and better brain health and cognitive function—creatine may also have some"off target"effects for the heart and blood vessels without the side effects that accompany some medications."- Dr. Rhonda Patrick Click To Tweet
Creatine is not typically considered to be a cardiovascular health supplement and the fact that less than a month of supplementing with it led to improvements in cardiovascular health biomarkers should be seen as a major point of interest.
Collectively, these studies seems to indicate that in addition to experiencing the usual benefits of creatine—stronger and larger muscles and better brain health and cognitive function—creatine may also have some "off target" effects for the heart and blood vessels without the side effects that accompany some medications.
Creatine probably won't become an overnight sensation in the world of heart health supplements. In fact, there were several outcomes in these studies that creatine didn't improve: Blood pressure, arterial stiffness, and cholesterol, for example. It isn't a miracle supplement and it definitely shouldn't take the place of exercise or other lifestyle practices.
However, as the evidence continues to grow for creatine, it does seem like something nearly everyone should be taking daily. People will get a small amount from their diet, but supplementing can help top off the body's stores—ensuring high levels to support athletic performance, brain health, and now heart health.