The primary outcome was glycosylated hemoglobin HbA1c. Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed.

The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation.

In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps. Keywords: dietary supplements; exercise; glycemic control; skeletal muscle; type 2 diabetes mellitus.

Abstract Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance.

Publication types Review. Here are a few examples:. A study published in the Journal of Diabetes Science and Technology in found that people with type 2 diabetes who took 5 grams of creatine every day for 5 days had better blood sugar control and more lean body mass.

In the study, researchers investigated the effects of creatine supplementation on 15 type 2 diabetic participants who were receiving stable blood sugar control with oral anti-diabetic medications. They found that creatine supplementation led to improved insulin sensitivity and increased lean body mass, suggesting potential benefits for those with diabetes.

A PLoS One systematic review and meta-analysis of 14 randomised controlled trials found that creatine supplementation can improve glycemic control and lower insulin secretion in people with type 2 diabetes.

However, the researchers warned that the long-term effects of creatine supplementation in diabetic people need more research.

If you are a diabetic individual considering creatine supplementation, here are some recommendations to keep in mind:. It is important to get advice from your healthcare provider about the potential risks and benefits of creatine supplementation before starting to take it.

Your healthcare provider can help you determine if creatine is safe and appropriate for your individual situation and can monitor your progress while taking it. Creatine made of amino acids can affect blood sugar levels, so it is important to monitor your blood sugar levels closely if you decide to take creatine.

Make sure to track any changes in your blood sugar levels while taking creatine and inform your healthcare provider of any dramatic changes. Creatine supplementation can lead to increased water retention, so it is important to drink a lot of water while taking creatine supplements.

When taking creatine supplements, it is important to start with a low dose in order to minimize the risk of adverse effects.

Aim for a low dose of 2—5 g per day and gradually increase the amount as tolerated. Research suggests that taking higher doses of up to 20 g per day can improve muscle strength and physical function in individuals with type 2 diabetes, but these doses should be monitored closely. Creatine supplements can cause gastric upset, so it is important to take them with a meal or snack to minimize this risk.

Be sure to consume plenty of fluids when taking creatine supplements, as they can lead to dehydration. Creatine supplementation can lead to increased levels of creatinine in the body, so it is important to monitor impair kidney function if taking creatine.

This is especially important if you have diabetes or any other condition that may put you at risk for kidney damage. Make sure to discuss this with your healthcare provider before starting creatine supplementation.

Follow the prescriptions provided by the manufacturer of your creatine supplement. The dose and timing of supplementation may differ depending on the product, so make sure that you read and understand the label before taking it. Additionally, always purchase from a reputable source to ensure quality and safety.

Creatine supplements can be a good way for people with type 2 diabetes to improve their muscle strength and physical function. However, it is important to discuss the potential risks and benefits of oral creatine supplementation with your healthcare provider before starting to take it.

Hespel; Effect of Oral Creatine Supplementation on Human Muscle GLUT4 Protein Content After Immobilization. Diabetes 1 January ; 50 1 : 18— The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training.

A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a week heavy resistance training program involving the knee-extensor muscles three sessions per week.

Half of the subjects received creatine monohydrate supplements 20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively , whereas the other 11 subjects ingested placebo maltodextrine.

Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training.

Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable.

We concluded that 1 oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2 oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.

It is well established that high-dose g per day oral creatine intake can rapidly days raise muscle total creatine content. This elevation in muscle creatine storage is associated with increased muscle power output during short high-intensity exercise.

In addition, it has been shown that long-term creatine intake can enhance the effects of weight training on muscle volume and strength 1 , 2. The use of creatine as an ergogenic supplement in sports has prompted interest in the potential of oral creatine supplementation to treat muscle atrophy and neuromuscular diseases.

Thus, the recovery of muscle disuse atrophy due to immobilization was significantly enhanced by creatine supplementation P.

Van Leemputte, B. Labarque, S. Dymarkowski, P. Van Hecke, E. R, unpublished observations. Furthermore, creatine supplementation was found to have a beneficial impact on muscle functional capacity in various modes of mitochondrial cytopathies 3 and muscle dystrophies 4.

At the same time, evidence is accumulating to suggest that creatine supplementation may be an effective neuroprotective agent to treat neurodegenerative diseases 5 , 6 , 7. Interestingly, a number of recent observations also indicate that creatine supplementation might have a beneficial impact on glucoregulation.

For instance, it has been shown that the ingestion of creatine in combination with carbohydrate supplements can stimulate postexercise muscle glycogen resynthesis 8 , which is conceivably due to enhanced insulin-mediated muscle glucose uptake 9. Similarly, creatine intake in conjunction with carbohydrates was found to result in greater muscle creatine accumulation than creatine intake alone 10 , which may be due to the fact that both glucose transport and creatine transport 11 in muscle cells are stimulated by insulin.

On the other hand, a number of in vitro studies have found that high extracellular concentrations of guanidine compounds, including creatine, stimulate pancreatic insulin secretion 12 , However, the extracellular creatine concentrations obtained by oral creatine intake in humans do not affect insulin secretion 14 , Perhaps the most striking evidence to suggest that creatine supplementation might be an effective strategy to treat insulin resistance comes from a recent study on transgenic Huntington mice.

The addition of creatine to the diet of the Huntington mice resulted in a marked neuroprotective effect and significantly reduced the hyperglycemia typical of these mice, while improving the glucose response to intravenous glucose injection 5. Based on the above evidence, we speculate that creatine supplementation may enhance insulin-mediated muscle glucose uptake and glycogen synthesis, thereby beneficially impacting whole-body glucose homeostasis.

Furthermore, it is well established that muscle inactivity and training are effective stimuli to down- and upregulate muscle GLUT4 content and peripheral insulin sensitivity, respectively Therefore, we investigated the effect of creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen concentration in healthy volunteers during 2 weeks of leg immobilization and during 10 weeks of subsequent rehabilitation training.

This report is part of a larger study P. R that investigated the effects of creatine supplementation on muscle functional capacity during disuse atrophy in healthy subjects.

A total of 13 men and 9 women, aged years, gave their informed written consent to participate in the study. They were instructed to abstain from taking any medication and to avoid making any changes in their usual physical activity level and other living habits during the period of the study.

However, three of the women were taking oral contraceptives for the duration of the study. The local ethics committee approved the study protocol. Study protocol. A double-blind study was performed over a week period. At the start of the study, subjects were systematically assigned to either a creatine or a placebo group based on quadriceps muscle cross-sectional area and maximal isometric knee-extension torque to obtain two groups of similar distribution P.

Thereafter, the cast was removed, and the subjects underwent a standardized week rehabilitation program. Maximal knee-extension torque was measured at a 90° knee-angle at the start of each session using a calibrated force transducer. During the final 7 weeks of the training period, the series of four unilateral knee-extensions was increased to six.

All training sessions were supervised by one of the investigators. During immobilization, the creatine group received 5 g creatine monohydrate four times per day, whereas the placebo group received placebo supplements 5 g maltodextrine, four times per day. During the training period, creatine and placebo supplementation was reduced to 5 g three times per day from week 1 to 3 and then to a single 5-g daily dose from week 4 to Creatine and placebo powders were identical in taste and appearance.

Before and after 2 weeks of immobilization, and after 3 and 10 weeks of rehabilitation, a percutaneous needle biopsy from the vastus lateralis muscle was obtained. The last training session preceded muscle sampling by at least 48 h.

During sessions , the incision was made either proximal or distal to the incision made at an earlier session. On removal from the limb, a piece of each muscle biopsy was immediately blotted and cleaned from visible connective tissue, rapidly frozen in liquid nitrogen, and stored at °C for subsequent biochemical and immunochemical analyses.

Biochemical and immunochemical analyses. The biopsy samples were first freeze-dried, then washed twice in petroleum ether to remove fat, and finally dissected free of the remaining visible blood and connective tissue.

A fraction of each sample was pulverized, and the powdered extracts were used for spectrophotometric determination of glycogen and free creatine and phosphocreatine concentrations Another fraction was used for GLUT4 determination.

The homogenate was incubated on ice for 1 h and spun for 15 min at 13, g , and the supernatant extract was collected for analysis. Then, μg of the extract were resolved by SDS-PAGE before electroblotting to polyvinylidine fluoride membranes.

Finally, GLUT4 was visualized by an alkaline phosphatase-labeled antibody and quantified on a phosphoimager STORM; Molecular Dynamics, Sunnyvale, CA. Data analysis. Data are means ± SE. Muscle total creatine concentration was calculated as the sum of free creatine and phosphocreatine.

Treatment effects creatine versus placebo were evaluated by a two-way analysis of variance, which was covariate adjusted for the baseline values Statistica; Statsoft, Tulsa, OK. In addition to these primary analyses, we did a one-way analysis of variance to compare the values after immobilization and rehabilitation with the corresponding baseline values within each group.

The statistical analyses of the GLUT4 data were performed on the raw data densitometric counts. Muscle GLUT4 content.

Muscle GLUT4 concentrations were expressed relative to the corresponding baseline values that were set equal to 1 Fig. Muscle GLUT4 content at baseline was similar between the groups. In the placebo group, the rehabilitation training restored muscle GLUT4 content within 3 weeks to the baseline value, where it remained.

Effect of creatine supplementation on muscle GLUT4 protein content during immobilization and subsequent rehabilitation training. Muscle samples were taken from the vastus lateralis muscle before and after 2 weeks of immobilization and after 3 and 10 weeks of rehabilitation of the right leg.

See RESEARCH DESIGN AND METHODS for further details. Muscle glycogen. Immobilization did not change muscle glycogen concentration in either group.

However, during the final 7 weeks of rehabilitation training, muscle glycogen reverted to baseline values in both groups. Effect of creatine supplementation on muscle glycogen concentration during immobilization and subsequent rehabilitation training.

Muscle creatine content. The muscle phosphocreatine and free creatine concentrations at baseline were similar between both groups Table 1.

In the placebo group, muscle phosphocreatine concentration returned to the preimmobilization baseline level within the initial 3 weeks of the rehabilitation period, after which it remained stable.

However, this increase above baseline in phosphocreatine was reversed during the final stage of the rehabilitation period. Throughout the study, the muscle free creatine concentrations were not significantly different between the placebo and the creatine groups.

In the placebo group, muscle total creatine concentration was not significantly changed compared with the baseline value during either immobilization or rehabilitation. However, along with the declining muscle phosphocreatine levels, muscle total creatine returned to baseline by the end of the study.

Our study investigated the impact of creatine supplementation on muscle GLUT4 content and glycogen and total creatine concentrations in healthy subjects during 2 weeks of voluntary leg immobilization followed by 10 weeks of rehabilitation training. Our data are the first to show that creatine supplementation prevents the loss of GLUT4 protein during muscle disuse and increases muscle GLUT4 content above normal levels during subsequent rehabilitation.

Furthermore, muscle glycogen concentration was increased during the initial stages of the creatine supplementation. Glucose transport across the plasma membrane is the rate-limiting step for glucose metabolism.

Hence, muscle GLUT4 content is a primary determinant of insulin-stimulated muscle glucose uptake and metabolism Thus, increasing muscle GLUT4 content by transgenic overexpression or by increased contractile activity enhances maximal insulin-stimulated muscle glucose uptake.

Conversely, reducing the content of GLUT4 by GLUT4 knockout, denervation, or aging impairs insulin-mediated muscle glucose uptake Our data, therefore, suggest that creatine supplementation in humans may increase insulin sensitivity by increasing muscle GLUT4 content.

Over the last decade, substantial evidence has accumulated to show that endurance exercise training elevates muscle GLUT4 content and insulin-stimulated glucose uptake in both healthy 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 and insulin-resistant muscles 29 , Ten weeks of rehabilitation training per se did not increase muscle GLUT4 content above the baseline level Fig.

However, the same training regimen in conjunction with oral creatine supplementation resulted in a marked increase of muscle GLUT4 protein content.

In fact, our observations indicate that oral creatine supplementation can probably increase GLUT4 protein content in skeletal musculature independent of exercise training. Based on the current knowledge, it is difficult to reveal the molecular basis for the increase in muscle GLUT4 content that occurs during creatine supplementation.

It has recently been observed in rats that short-term administration of amino-imidazolecarboximide riboside, an AMP-activated protein kinase AMPK agonist, increases muscle GLUT4 content Creatine administration that increases AMPK activity by decreasing the phosphocreatine-to-creatine ratio 34 may, thus, explain the increase in GLUT4 protein content in the creatine group.

And yet, in both groups the phosphocreatine-to-creatine ratio decreased to the same degree during immobilization and remained below the baseline value during the subsequent rehabilitation period. Furthermore, it has recently been shown that the creatine kinase CK and AMPK enzymes colocalize in muscle cells According to the prevailing opinion, in skeletal muscle, such coupling should serve to suppress muscle AMPK activity by maintaining high local ATP:AMP and phosphocreatine-to-creatine ratios in conditions of cellular stress, such as contractions If anything, this inhibitory action is enhanced by the increased muscle phosphocreatine concentration established during the creatine supplementation Table 1.

Thus, evidence for a possible creatine-induced increase in AMPK activity has not been found. Alternatively, there is substantial evidence to suggest that cellular hydration status is an important factor controlling cellular protein turnover 36 , which in muscle cells, excluding the contractile proteins, may involve other proteins important to energy homeostasis, such as GLUT4.

Creatine is cotransported with Na ions across the sarcolemma, which initiates influx of Cl - and water to balance electroneutrality and osmolality The resulting increase of cell volume may, in turn, act as an anabolic proliferative signal, which involves activation of the mitogen-activated protein kinase MAPK signaling cascade that plays a pivotal role in muscle protein synthesis regulation 37 , It is warranted to further explore the possible role of intracellular creatine content in modulating the concerted actions of CK, AMPK, and MAPK in regulating GLUT4 synthesis and degradation in muscle cells.

The bulk of glucose in the human body is stored as muscle glycogen. The presence of a high muscle glycogen concentration, in general, indicates adequate insulin stimulation of muscle glucose uptake and glycogen synthesis. Furthermore, a high muscle glycogen concentration is a prerequisite for optimal endurance exercise performance Robinson et al.

Given that no dietary instructions were administered to the subjects, our findings suggest that the addition of creatine supplementation to a standard diet may eventually result in a postexercise increment of muscle glycogen concentration similar to that found after a classical carbohydrate-enriched glycogen supercompensation dietary protocol Interestingly, after 5 weeks of creatine supplementation, the increase of muscle glycogen content vanished, despite continued creatine supplementation.

In fact, during both immobilization and rehabilitation, the pattern of muscle glycogen changes closely mimicked the fluctuations of muscle total creatine content Table 1 Fig. In this respect, Low et al. If such an osmotic trigger mechanism indeed regulates insulin action on glycogen synthesis during creatine supplementation, then the decrease in muscle creatine content beyond 3 weeks of training might also explain the concurrent decrease in the muscle glycogen storage.

Studies in rats have demonstrated that long-term high-dose creatine feeding induces a downregulation of muscle total Na-creatine cotransporter protein content In addition, the low creatine transporter content in failing human myocardium has been found to be associated with a decrease in intracellular creatine storage In conclusion, the current findings provide strong evidence to suggest that 1 oral creatine supplementation can offset the decline of muscle GLUT4 protein content in skeletal musculature during disuse atrophy, and 2 oral creatine supplementation increases GLUT4 content during subsequent rehabilitation training.

Its advantages include being relatively inexpensive and having been verified safe when compared with many other sports supplements The large reduction in dopamine levels causes brain cell death and several serious symptoms, including tremors, loss of muscle function, and speech impairments However, there is no evidence that it has the same effect in humans In one study in individuals with this disease, combining creatine with weight training improved strength and daily function to a greater extent than training alone A key factor in several neurological diseases is a reduction of phosphocreatine in your brain Research in animals suggests that taking creatine supplements may treat other diseases too, including 35 , 36 , 37 , 38 :.

Creatine has also shown benefits against amyotrophic lateral sclerosis ALS , a disease that affects the motor neurons that are essential for movement. Although more studies are needed in humans, some researchers believe that creatine supplements can serve as a defense against neurological diseases when used alongside conventional medicines.

Research suggests that creatine supplements may lower blood sugar levels by increasing the function of glucose transporter type 4 GLUT-4 , a molecule that brings blood sugar into your muscles 40 , 41 , 42 , A week study examined how creatine affects blood sugar levels after a high carb meal.

People who combined creatine and exercise exhibited better blood sugar control than those who only exercised Short-term blood sugar response to a meal is an important marker of diabetes risk.

The faster your body clears sugar from the blood, the better Creatine plays an important role in brain health and function Research demonstrates that your brain requires a significant amount of ATP when performing difficult tasks Supplements can increase phosphocreatine stores in your brain to help it produce more ATP.

Creatine may also aid brain function by increasing dopamine levels and mitochondrial function 25 , 45 , As meat is the best dietary source of creatine, vegetarians often have low levels.

For older individuals, supplementing with creatine for 2 weeks significantly improved memory and recall ability In older adults, creatine may boost brain function, protect against neurological diseases, and reduce age-related loss of muscle and strength Despite such positive findings, more research is needed in young, healthy individuals who eat meat or fish regularly.

Creatine supplements may also reduce fatigue and tiredness Another study determined that creatine led to reduced fatigue and increased energy levels during sleep deprivation Creatine also reduced fatigue in athletes taking a cycling test and has been used to decrease fatigue when exercising in high heat 51 , You can find a wide selection online.

It has been researched for more than years, and numerous studies support its safety for long-term use. Clinical trials lasting up to 5 years report no adverse effects in healthy individuals 1. At the end of the day, creatine is an effective supplement with powerful benefits for both athletic performance and health.

It may boost brain function , fight certain neurological diseases, improve exercise performance, and accelerate muscle growth. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Creatine is a well-studied supplement with proven benefits for high intensity exercise.

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