Creatine and Heart Health: Cardiovascular Research Summary

The heart is the body's most metabolically active muscle. It beats approximately 100,000 times per day and relies heavily on phosphocreatine to buffer ATP demand during periods of increased cardiac work. This makes the relationship between creatine supplementation and cardiovascular health both biologically interesting and clinically relevant. The research addresses two distinct questions: does creatine harm the heart, and might it help it?

Creatine in Cardiac Metabolism

The myocardium uses the creatine-phosphocreatine system as a critical energy shuttle. The enzyme creatine kinase facilitates the rapid transfer of a phosphate group from phosphocreatine to ADP, regenerating ATP during periods of high energy demand. This system is particularly important during transient increases in cardiac work, such as exercise, stress responses, and recovery from ischemic events.

Cardiac creatine levels are depleted in heart failure. This observation, documented in multiple studies including the work of Neubauer et al. (1997), led researchers to hypothesize that creatine supplementation might benefit the failing heart by replenishing depleted energy reserves. This hypothesis positioned creatine not as a cardiovascular risk but as a potential therapeutic agent.

Safety: Blood Pressure

One of the earliest cardiovascular safety questions was whether creatine supplementation raises blood pressure. The concern was rooted in the water retention associated with creatine loading. Increased total body water could theoretically increase blood volume and elevate blood pressure.

The evidence does not support this concern. Multiple studies have measured blood pressure before and after creatine supplementation, including during loading phases. Persky and Brazeau (2001), in their comprehensive pharmacological review published in Pharmacological Reviews, summarized the available blood pressure data and found no consistent evidence that creatine supplementation elevates blood pressure in normotensive individuals.

Earnest et al. (1996) examined lipid profiles and blood pressure in creatine-supplementing subjects and found no significant changes in systolic or diastolic blood pressure. The ISSN position stand (Kreider et al., 2017) confirmed that no adverse cardiovascular effects, including hypertension, have been attributed to creatine supplementation in the literature.

Safety: Lipid Profiles

Lipid profiles (total cholesterol, LDL, HDL, and triglycerides) are important cardiovascular risk markers. Several studies have assessed these markers in creatine users. The results have been neutral or mildly favorable.

Earnest et al. (1996) conducted one of the earlier investigations and reported that creatine supplementation was associated with reductions in total cholesterol and triglycerides, with no adverse effects on LDL or HDL levels. This study was preliminary and the lipid effects were not the primary outcome, but the direction of the findings was reassuring from a cardiovascular perspective.

Kreider et al. (2003), in their long-term follow-up study, measured lipid profiles across supplementation periods of up to 21 months. No adverse changes in lipid parameters were observed. The consistency of these findings across multiple studies and time periods indicates that creatine supplementation does not worsen cardiovascular risk as measured by standard lipid panels.

Safety: Homocysteine

One theoretical cardiovascular concern relates to homocysteine. Creatine biosynthesis is the largest consumer of methyl groups in the body, accounting for approximately 40% of all S-adenosylmethionine (SAM) utilization. When creatine is synthesized endogenously, this methylation process generates S-adenosylhomocysteine (SAH), which is subsequently converted to homocysteine. Elevated homocysteine is an independent risk factor for cardiovascular disease.

Exogenous creatine supplementation reduces the need for endogenous creatine synthesis. This means supplementation should decrease, not increase, the methylation demand and the resultant homocysteine production. Steenge et al. (2001) investigated this hypothesis and found that creatine supplementation reduced plasma homocysteine levels. This finding, while preliminary, suggests that creatine may have a mildly favorable effect on this cardiovascular risk marker.

Deminice et al. (2011) further explored this relationship and confirmed that creatine supplementation can reduce plasma homocysteine, particularly in individuals with initially elevated levels. The effect is mediated through the reduction in SAM utilization for endogenous creatine synthesis, leaving more methyl groups available for homocysteine remethylation to methionine.

Potential Therapeutic Applications

Beyond safety, research has explored whether creatine supplementation might benefit cardiovascular health in specific clinical contexts:

Heart failure. The phosphocreatine/creatine energy system is impaired in the failing heart. Studies have investigated creatine supplementation as a means to improve cardiac energy metabolism. Gordon et al. (1995) reported that creatine supplementation improved ejection fraction and exercise capacity in patients with chronic heart failure. While subsequent studies have produced mixed results, the finding that creatine could improve cardiac function in heart failure patients further undercuts the notion that creatine harms the heart.

Ischemia-reperfusion. Animal studies have examined whether creatine loading prior to ischemic events (such as heart attacks) provides cardioprotection through enhanced phosphocreatine reserves. The results are promising in preclinical models, though translation to human clinical care remains investigational.

Endothelial function. Preliminary research has examined creatine's effects on vascular endothelial function, an important determinant of cardiovascular health. No adverse effects on endothelial function have been reported, and some data suggests potential benefits mediated through reduced oxidative stress and homocysteine levels.

Cardiac Arrhythmias

No controlled study has linked creatine supplementation to cardiac arrhythmias. This is relevant because some ergogenic substances (stimulants, certain pre-workout compounds, high-dose caffeine) can provoke arrhythmias. Creatine's mechanism of action, enhancing the phosphocreatine energy shuttle rather than stimulating the sympathetic nervous system, does not predispose to arrhythmogenic effects. The electrolyte stability observed in creatine users further reduces any theoretical arrhythmia risk.

The Weight Gain Consideration

The one cardiovascular-adjacent concern with genuine biological plausibility is the weight gain associated with creatine. A 1-3 kg increase in body mass from water retention during loading is physiologically trivial from a cardiovascular standpoint. However, in individuals already obese or with hypertension, any weight gain could theoretically contribute marginally to cardiovascular burden. In practice, this concern has not materialized in any clinical study, and the weight gain from creatine (water, not fat) is metabolically distinct from adiposity-related weight gain.

Summary

The cardiovascular safety data for creatine is robust and uniformly favorable. Blood pressure, lipid profiles, homocysteine levels, and cardiac function markers are either unaffected or mildly improved by creatine supplementation. The heart itself relies on the creatine-phosphocreatine system for energy buffering, and depletion of cardiac creatine is a hallmark of heart failure. No mechanism by which creatine supplementation would harm the cardiovascular system has been identified, and no controlled study has observed cardiovascular adverse effects. The balance of evidence suggests that creatine is cardiovascularly neutral to mildly beneficial.