The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.

This investigation aimed to determine the effect of a multi-ingredient pre-workout supplement (MIPS) on heart rate (HR), perceived exertion (RPE), lactate concentration, and time to fatigue (TTF) during a running task to volitional exhaustion. Eleven NCAA Division I cross-country runners (20 ± 2 year; height: 171 ± 14 cm; weight: 63.5 ± 9.1 kg) participated in this randomized, double-blind, placebo-controlled cross-over study. Bayesian statistical methods were utilized, and parameter estimates were interpreted as statistically significant if the 95% highest-density intervals (HDIs) did not include zero. TTF was increased in the MIPS condition with a posterior Mean_diff = 154 ± 4.2 s (95% HDI: −167, 465) and a 0.84 posterior probability that the supplement would increase TTF relative to PL. Blood lactate concentration immediately post-exercise was also higher in the MIPS condition compared to PL with an estimated posterior Mean_diff = 3.99 ± 2.1 mmol (95% HDI: −0.16, 7.68). There were no differences in HR or RPE between trials. These findings suggest that a MIPS ingested prior to sustained running at lactate threshold has an 84% chance of increasing TTF in highly trained runners and may allow athletes to handle a higher level of circulating lactate before reaching exhaustion.

Background: Doxorubicin (DOX) is associated with profound skeletal muscle dysfunction. Resistance training (RT) and creatine (Cr) monohydrate have been independently shown to protect against DOX-induced muscle dysfunction. However, no investigation has examined their combined effects on DOX-induced muscle dysfunction. Methods: Male Sprague-Dawley rats were randomly assigned to a RT or sedentary group. After 6 wk of training, the soleus (SOL) and extensor digitorum longus (EDL) were excised and placed in a tissue bath containing Krebs buffer (K) or a K containing Cr (25 mM) for 30 min. The buffers were refreshed with new K or K containing DOX (24 μM) and incubated for 30 min. Muscles were then subjected to maximal twitch and fatigue testing. Results: DOX-induced fatigue occurred at 40 s in the SOL and EDL. RT delayed DOX-induced fatigue by 20 s in the SOL and 10 s in the EDL. Cr treatment delayed the onset of DOX-induced fatigue by 10 s in the EDL. The combination of RT and Cr delayed DOX-induced fatigue by 50 s in the SOL and 20 s in the EDL. Conclusion: This study showed that a combined treatment with RT and Cr minimized DOX-induced fatigue in the SOL and EDL.

Previous research has shown that resistance training (RT) before doxorubicin (DOX) treatment attenuates the decline in muscle dysfunction; however, the effect of RT during DOX treatment is less known. Purpose: Investigate the effects of RT before and during a 4-wk course of incremental DOX treatment on skeletal muscle function. Methods: Male, Sprague-Dawley rats (N = 36) were randomly assigned to the following groups: sedentary+saline (SED + SAL), sedentary+DOX (SED + DOX), RT + SAL, or RT + DOX. The RT protocol utilized a raised cage model, which provided progressive hindlimb loading throughout the 14-wk study, whereas SED animals were kept in normal housing. Starting at week 10, DOX-treated animals received 3 mg·kg⁻¹ DOX weekly for 4 wk (12 mg·kg⁻¹ cumulative); whereas SAL-treated groups received 0.9% NaCl as a placebo. Grip strength was recorded at 0, 10, 12, and 14 wk. Ex vivo muscle function was performed on excised soleus (SOL) and extensor digitorum longus (EDL) from the right hind limb 5 d after the last injection and were analyzed for expression of creatine kinase (CK) and creatine transporters. Results: SED + DOX–treated animals had significantly lower EDL mass compared with SED + SAL– and RT + DOX–treated animals. Grip strength, EDL maximal force, and EDL force development were significantly lower in SED + DOX–treated animals compared with RT + SAL and SED + SAL. No significant differences in EDL function were found between RT + DOX and RT + SAL animals. DOX treatment reduced expression of CK in the SOL, which abated with RT. Conclusions: Low-intensity RT may attenuate the decline in skeletal muscle function during incremental DOX treatment.

Doxorubicin (DOX), an effective anticancer agent, can damage cardiac and skeletal muscle tissue via excessive generation of reactive oxygen species (ROS). Supplemental creatine (Cr) has been shown to have a therapeutic role in disease states characterized by increased oxidative stress. To investigate the effects of Cr and creatinine (CrN) on DOX-induced cytotoxicity. Cultured L6 and H9C2 myoblasts were exposed to 25 μM DOX, 10 mM Cr, 10 mM CrN, 25 μM DOX + 10 mM Cr, 25 μM DOX + 10 mM CrN, or control media for 12 h. Viability was assessed using Confocal and Widefield imaging. Immunoblotting was used to determine protein expression. Viability was lowest in the DOX-treated group regardless of cell type; however, when DOX was combined with Cr or CrN, viability was improved. Levels of oxidative stress, as measured by 4-hydroxynonenal (4HNE), were significantly (p < 0.05) higher in the DOX treated cells vs. controls; however, Cr + DOX and CrN + DOX significantly lowered 4HNE levels compared to DOX-treated cells. Creatine kinase (CK), a key marker of cellular damage, was significantly higher in DOX-treated H9c2 cells vs. controls. However, Cr or CrN in combination with DOX, resulted in no significant differences in CK vs. controls. Supplementation with Cr or CrN may preserve cell viability during DOX treatment.

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (p < 0.05). Additionally, cardiac mass was significantly greater in RT + CR + DOX SED + DOX animals (p < 0.05). These results suggest RT and CR supplementation, separately and in combination, could attenuate some measures of DOX-induced cardiotoxicity and may offer a cost-effective way to complement cancer treatments and enhance patient outcomes. More investigations are essential to better understand CR’s prolonged effects during DOX therapy and its clinical implications.