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Beta Alanine Supplement Benefits and Side EffectsBeta-alanine and muscle fatigue prevention -
Carnosinase, the enzyme that catalyzes the breakdown of carnosine, is present in serum and various tissues in humans, but is absent in skeletal muscle [ 25 ] and many animals. It is important to note that carnosinase is not present in most non-primate mammals [ 26 ], which must be considered when evaluating carnosine supplementation and data obtained from animal models.
Therefore, oral carnosine supplementation is an inefficient method of augmenting muscle carnosine levels in humans, as ingested carnosine is ultimately metabolized before reaching skeletal muscle [ 27 ]. in [ 28 ], who demonstrated that the absence of carnosine resulted in more rapid fatigue and acidosis.
By virtue of a pKa of 6. More evidence documenting the contribution of carnosine in muscle buffering is needed to further identify its role in exercise performance.
Nonetheless, beta-alanine supplementation has been shown to increase muscle carnosine concentrations [ 1 , 3 ] and attenuate exercise-induced reductions in pH [ 32 ], supporting the concept that carnosine plays a significant role in buffering exercise-induced acidosis.
The potential physiological roles of carnosine extend beyond its function as a proton buffer. Previous research has suggested that reactive oxygen species ROS , which are produced at an elevated rate during exercise [ 33 ], may contribute to muscle fatigue and exercise-induced muscle damage under certain circumstances [ 34 , 35 ].
Carnosine has been shown to act as an antioxidant by scavenging free radicals and singlet oxygen [ 36 , 37 ], thereby reducing oxidative stress. Carnosine can further reduce oxidative stress by chelating transition metals, such as copper and iron [ 37 ].
In doing so, these transition metals are prevented from reacting with peroxides in the Fenton reaction, which results in the production of free radicals. Carnosine is abundant in human skeletal muscle, and may influence these contributors to fatigue and oxidative stress by buffering excess protons [ 28 ], scavenging free radicals [ 36 , 37 ], and chelating transition metals [ 37 ].
The supplementation strategy for beta-alanine is important to maximize its effects. To increase muscle carnosine, a larger dose of 6 g, divided into 4 equal doses would be more advantageous. Additionally, if supplementing with a non-time release version, consuming a total daily dose of 6 g would be important for augmenting muscle carnosine [ 40 ].
Single large boluses of beta-alanine have been shown to induce paraesthesia i. tingling , and have not been effective for performance outcomes likely due to strong paraesthesia, rapid changes in pH, higher excretion rates, and inability to effectively load the muscle contents.
Combining beta-alanine consumption with a meal during beta-alanine loading has also been shown to be effective for further augmenting muscle carnosine levels [ 41 ].
In addition, a recent meta-analysis [ 42 ] suggested that supplementation with a total ingestion of g of beta-alanine the average dose across all studies resulted in a median performance improvement of 2. Washout time, or time required for values to return to baseline, may vary between non-responders and responders, requiring 6 to 15 weeks to return to normal [ 4 ].
Despite these findings, the maximal concentration or retention of carnosine in human muscle is not well known; thus, we cannot yet provide information on the optimal loading or maintenance doses. A loading phase ~4 weeks of beta-alanine supplementation is essential for increasing carnosine levels.
Paraesthesia i. It appears that the symptoms of paraesthesia are substantially reduced with the use of sustained-release formulations. In studies using the non-sustained release supplement, paraesthesia has generally been reported to disappear within 60 to 90 min following supplementation [ 40 ].
It is hypothesized that beta-alanine activates Mas-related genes Mrg [ 43 ], or sensory neuron specific G-protein coupled receptors. Specifically, MrgD, which is expressed in the dorsal root ganglion, terminates in the skin [ 44 ].
It is likely that activation of MrgD from beta-alanine results in paraesthesia on the skin. To date, there is no evidence to support that this tingling is harmful in any way. The paraesthesia side effect is typically experienced in the face, neck, and back of hands. Although not all individuals will experience paraesthesia, it is typically dose-dependent, with higher doses resulting in greater side effects.
Recent data also suggests that males of Asian descent may experience a reduced effect, with Asian females experiencing greater paraesthesia [ 45 ]. Moreover, there is no known mechanism to explain why certain individuals may be predisposed to experiencing paraesthesia.
Currently, there is no safety data on the long-term use of beta-alanine i. However, due to the non-essential nature of this constituent i. A secondary effect of beta-alanine supplementation is a potential decrease in taurine concentrations.
Beta-alanine and taurine share the same transporter Tau-T into skeletal muscle, with beta-alanine thereby inhibiting taurine uptake within the muscle [ 46 ]. Interestingly, Harris et al. While taurine has a number of essential physiological functions, to date there is no human data to support decreases with beta-alanine supplementation.
Additionally, when extrapolated to humans, the decrease in taurine would not be of physiological significance. Current, although limited information, suggests that beta-alanine is safe in healthy individuals at recommended doses.
To gain a better consensus of published findings, this review includes an analysis of the relative effects RE of literature obtained from PubMed and Google Scholar databases.
The primary search terms included beta-alanine AND supplementation AND carnosine AND exercise. The search was limited to articles published as of March and written in English. To construct figures, literature with similar outcome variables was reviewed to identify studies evaluating the effects of beta-alanine supplementation for a open-ended exercise tasks, such as time to exhaustion TTE , b fixed end-point exercise such as time trials, or c indices of neuromuscular fatigue.
To graphically depict the RE of beta-alanine in in comparison to placebo, RE was calculated using the following equation [ 48 , 49 ]:.
Where Pre PL is the pre-test value in the placebo group, Post PL is the post-test value in the placebo group, Pre BA is the pre-test value in the beta-alanine group, and Post BA is the post-test value in the beta-alanine group.
For Figures 1 and 3 , an RE greater than represents an increase or improvement in performance versus a placebo group. In Fig. The relative effects of beta-alanine supplementation on time to exhaustion TTE lasting A 0— s 0—6 min and B lasting — s 8—25 min.
For time to exhaustion and neuromuscular fatigue Figs. Relative effects of beta-alanine on neuromuscular fatigue i. For time trial or fixed end-point data Fig. It has been suggested that chronic beta-alanine supplementation improves high-intensity exercise performance by increasing muscle carnosine content, thereby enhancing intracellular proton buffering [ 50 , 51 ].
Excess protons are also buffered independently of carnosine by a number of physicochemical buffering constituents; extracellular bicarbonate is the most relevant for increasing muscle buffering capacity [ 52 ], thereby acting to maintain intramuscular pH.
A collective view of the literature on anaerobic 0—4 min and aerobic performance, neuromuscular fatigue, strength, and tactical challenges has been included. The primary physiological mechanism associated with beta-alanine supplementation is most likely related to enhancing intracellular buffering capacity, consequently it has been hypothesized that beta-alanine supplementation would have ergogenic potential for activities that are primarily reliant on anaerobic metabolism.
A meta-analysis on beta-alanine supplementation [ 42 ] indicated that supplementation improved exercise capacity in tasks lasting 60 to s, but not in tasks lasting under 60 s in which acidosis is not likely the primary limiting factor.
Additionally, literature evaluating repeated short-duration sprint tasks do not seem to demonstrate an effect: Sweeney et al.
The effects of beta-alanine supplementation on time to exhaustion TTE are presented in Fig. Similar to the results of Hobson et al. For example, Hill et al. In a critical velocity test, Smith-Ryan et al.
It should be noted that results are not entirely consistent, as relative effects below are seen for anaerobic exercise tests between 1 to 4 min, as reported in Fig.
According to data from Jagim et al. Further, data from Smith-Ryan et al. In a recent meta-analysis, Hobson et al. Relative effects for fixed-endpoint performance are displayed in Fig. In agreement with Hobson et al. Nonetheless, the three largest relative effects were observed in exercise bouts lasting Taken together, research currently suggests that beta-alanine has the greatest potential to improve performance in high-intensity exercise lasting over 60 s, with more pronounced effects observed in open end-point exercise tasks taken to volitional exhaustion.
Beta-alanine generally enhances high intensity exercise lasting over 60 s, with greater effects on open end point exercise bouts, such as time to exhaustion tasks. For exercise bouts lasting greater than four minutes, ATP demand is increasingly met via aerobic metabolic pathways.
As such, it has been suggested that beta-alanine is not beneficial for exercise bouts lasting over 4 min. To the contrary, however, Hobson et al. Research has demonstrated a modest benefit of beta-alanine supplementation on TTE in exercise tests over 4 min in duration Fig.
In conjunction with 6 weeks of interval training, Smith et al. Participants consuming a placebo improved TTE from Similarly, Stout et al. In aerobic, open end-point exercise, beta-alanine appears to result in modest improvements that, nonetheless, could be meaningful in competitive athletics, such as running, cycling, etc.
Benefits have also been reported using fixed end-point exercise bouts lasting over 4 min Fig. Similarly, Ducker et al. Currently, limited research is available for exercise over 25 min in duration.
In a graded exercise test, Van Thienen et al. Although the beta-alanine group did improve TTE from Chung et al. Although beta-alanine supplementation substantially increased muscle carnosine concentrations, both the beta-alanine and placebo groups saw performance decrements following six weeks of supplementation [ 70 ].
Overall, available research indicates that beta-alanine provides a modest benefit for exercise lasting up to approximately 25 min in duration. To date, research beyond this time frame is limited and does not demonstrate a consistent positive effect.
Beta-alanine may improve exercise duration during tasks requiring a greater contribution from aerobic energy pathways. The physical working capacity at fatigue threshold PWC FT indicates the highest cycling power output that results in a non-significant increase in vastus lateralis muscle activation.
This measurement is a validated and reliable method of determining the power output at which the onset of neuromuscular fatigue occurs [ 71 ], and has been used to determine the effects of beta-alanine supplementation on neuromuscular fatigue.
In , Stout et al. Similar results were reported in female participants the following year During 6 weeks of high-intensity interval training, Smith et al. Despite marked improvements, the relative effect calculated was below , as the group consuming a placebo improved by Using slightly different methodology to quantify neuromuscular fatigue, Smith-Ryan et al.
The effects of beta-alanine on neuromuscular fatigue appear to be more pronounced in longer studies utilizing older subjects. Collectively, the evidence suggests that beta-alanine supplementation attenuates neuromuscular fatigue, particularly in older subjects.
Improvements in fatigue threshold may be augmented with concurrent participation in high-intensity interval training. Studies investigating the effects of beta-alanine on strength outcomes have reported mixed findings. While short-term 30 days studies by Hoffman et al. In a similar length study 4 weeks , Derave et al.
In contrast, Sale et al. It has been hypothesized that the documented improvements in training volume and fatigue may translate to meaningful changes over prolonged interventions.
Despite improvements from baseline testing, Kern and Robinson [ 66 ] did not show eight weeks of beta-alanine supplementation to significantly improve flexed arm hang performance in wrestlers or football players compared to placebo. In a week intervention, Kendrick et al. Finally, Hoffman et al.
Collectively, the evidence suggests that beta-alanine may improve indices of training volume and fatigue for resistance exercise, but more long-term studies are needed to clarify potential effects on strength and body composition compared to placebo. Beta-alanine appears to increase training volume, however, current research does not indicate an additive benefit on strength gains during resistance training.
The training and duties of military personnel and other tactical athletes often consist of prolonged and rigorous exercise, resulting in reductions in physical and cognitive performance [ 77 ].
Beta-alanine supplementation may be advantageous in this population, potentially attenuating fatigue, enhancing neuromuscular performance, and reducing oxidative stress. In , an expert panel published a review regarding the use of beta-alanine in military personnel [ 78 ].
The panel concluded that there was insufficient evidence to recommend the use of beta-alanine by military personnel [ 78 ]. More recently, the use of beta-alanine in tactical personnel was directly investigated by Hoffman et al. Soldiers involved in military training supplemented with either beta-alanine or placebo for 28 days, with researchers testing a number of outcomes pertaining to physical and cognitive performance.
While cognitive performance was not affected, beta-alanine resulted in moderate improvements in peak power, marksmanship, and target engagement speed, compared to placebo [ 77 ]. A subsequent study by Hoffman et al. Recently, it was reported that beta-alanine had no significant effect on brain carnosine or cognitive function in non-tactical athletes [ 80 ].
While evidence in this population is scarce, it would appear that beta-alanine supplementation yields promising results for tasks relevant to tactical personnel. More research is needed to determine which tasks are consistently improved with supplementation. The combined effects of beta-alanine with other ergogenic aids, such as sodium bicarbonate, creatine, and multi-ingredient pre-workout formulas, have gained popularity.
Due to the potential positive effects of beta-alanine during high-intensity exercise, it has been hypothesized that combining it with other ergogenic aids may further augment performance and proton buffering. Sodium bicarbonate SB supplementation has been shown to acutely increase bicarbonate levels, blood pH, and high-intensity exercise performance [ 81 ], prompting interest in combined supplementation with beta-alanine.
Sale et al. Tobias et al. Despite non-significant differences between groups, authors of other studies have calculated the probability of an additive effect with combined beta-alanine and SB supplementation.
In a 2,m rowing time trial, Hobson et al. In swimmers, de Salles Painelli et al. In contrast to these studies, other findings do not suggest a synergistic effect between beta-alanine and SB.
In a series of two repeated m sprints in swimmers, Mero et al. Ducker et al. Results demonstrated that SB supplementation improved performance more than placebo, beta-alanine, or a combination of beta-alanine and SB.
Saunders et al. Results indicated that neither beta-alanine, SB, nor beta-alanine plus SB improved performance on the sprint test. Bellinger et al. It is also important to note that the protocols employed by Ducker et al.
Collectively, the body of literature suggests a modest additive effect when adding SB to beta-alanine supplementation in exercise bouts in which metabolic acidosis may be performance-limiting.
While this additive benefit is not typically revealed with traditional statistical analyses, studies using magnitude-based inferences have suggested that a modest additive effect is likely to exist [ 62 , 65 , 68 ].
The studies reviewed have used supplement dosages ranging from 4. However, the only study to indicate a statistically significant synergistic effect of beta-alanine and SB [ 82 ] employed a unique dosing protocol for SB, providing daily doses of 0.
Individual responses to SB supplementation may vary, likely due to side effects including headache and gastrointestinal discomfort [ 68 , 85 , 87 ].
In terms of practical application, those wishing to combine beta-alanine and SB supplementation must carefully evaluate the dosage and timing with which SB is consumed and weigh the modest additive benefit against the risk of potentially ergolytic side effects. Given the proton-buffering capacity of muscle carnosine [ 51 ], beta-alanine is most commonly purported to improve performance in exercise of high enough intensity to induce intramuscular acidosis.
Creatine supplementation has been consistently shown to improve high-intensity exercise performance, primarily by increasing phosphorylcreatine and adenosine triphosphate ATP availability [ 88 ].
The first study investigating co-ingestion of these ingredients was reported in a published abstract by Harris et al. Similarly, Hoffman et al. Notably, these studies did not include a treatment arm ingesting beta-alanine alone. Zoeller et al. Stout et al. Kresta et al. The creatine group trended toward an increase in VO 2 max, while the beta-alanine group trended toward an improvement in rate of fatigue on a series of two Wingate tests.
However, no significant effects on performance were noted for any treatment arm, and results did not suggest a synergistic effect between creatine and beta-alanine.
Two studies have shown additive ergogenic effects when beta-alanine is combined with creatine supplementation [ 76 , 89 ], but did not include a treatment group ingesting beta-alanine only. Other studies including a beta-alanine treatment arm have not demonstrated a synergistic effect between beta-alanine and creatine [ 71 , 90 ].
Despite promising findings from initial studies [ 76 , 89 ], more research is needed to evaluate potential synergy between creatine and beta-alanine supplementation.
Multi-ingredient pre- and post-workout supplements have become increasingly popular, with formulations that include a number of purportedly ergogenic ingredients including creatine, caffeine, branched-chain amino acids, whey protein, nitric oxide precursors, and other isolated amino acids [ 91 — 98 ].
Such supplements are typically consumed once per day prior to training, with beta-alanine doses generally ranging from 2 to 4 g single boluses. When ingested acutely before exercise, previous studies have shown these multi-ingredient supplements to improve muscular endurance [ 92 , 98 ], running time to exhaustion [ 91 ], and power output [ 98 ].
Some studies have documented improvements in subjective feelings of energy and focus [ 91 , 92 ], while Gonzalez et al. When taken chronically for a period of 4 to 8 weeks, multi-ingredient pre-workout supplements have been shown to increase measures of strength [ 93 , 94 , 97 ], power output [ 96 ], and lean mass [ 93 — 95 ].
In contrast, Outlaw et al. These discrepant findings may be attributed to the short duration of supplementation 8 days , or the substantial improvements in lean mass, strength, and peak power output displayed by the placebo group. Overall, the body of literature suggests that acute and chronic ingestion of multi-ingredient pre-workout supplements can contribute to improvements in performance and body composition.
It is difficult to attribute these ergogenic effects directly to beta-alanine, as multi-ingredient supplements include a wide range of ergogenic ingredients that may improve performance independently e. It typically takes a number of weeks at least 2 weeks for beta-alanine supplementation to yield meaningful increases in muscle carnosine content [ 3 , 19 ].
As such, it is unlikely that beta-alanine is the primary ingredient improving performance outcomes in studies utilizing acute, one-time supplementation. In studies extending over 4 to 8 weeks, the likelihood of beta-alanine contributing to improvements in performance and indirect effects on body composition is greater.
While it is difficult to determine the relative contributions of individual ingredients, research has demonstrated that multi-ingredient pre-workout supplements containing 2 to 4 g of beta-alanine are safe and efficacious when taken acutely, or chronically for up to 8 weeks.
Co-ingestion of beta-alanine with sodium bicarbonate or creatine have modest additive ergogenic benefits; ingestion of beta-alanine as part of a multi-ingredient pre-workout product may be effective, if the supplementation period is sufficient to increase carnosine levels and the product is taken for at least 4 weeks.
Decades of literature support a potential for carnosine to influence some mechanisms related to health including antioxidant properties, anti-aging, immune enhancing, and neurotransmitter actions.
However, the majority of these health benefits have been explored in vitro and in animal models. Carnosine is widely considered an important anti-glycating agent that serves to prevent reactions that threaten to impact the structure and function of proteins in the body.
Advanced glycation end products are associated with the aging process and diabetic complications, but carnosine is thought to reduce the formation of these end products [ , ].
Carnosine is also known to be an antioxidant that is capable of preventing the accumulation of oxidized products derived from lipid components of biological membranes [ , ]. The antioxidant mechanism of carnosine has been postulated to be due to metal chelation or free radical scavenging [ ].
The combination of histidine-containing compounds, such as carnosine, at near physiological concentrations, have resulted in synergistic antioxidant activity [ 37 ]. Minimal data in humans exists regarding the potential antioxidant effect of increasing muscle carnosine vis-a-vis beta-alanine.
Initial research suggests that beta-alanine may effectively reduce lipid peroxidation and mitigate accumulation of free radicals when combined with aerobic exercise in men and women [ , ]. Future research evaluating potential anti-aging effects and the impact of potential antioxidant properties in humans would be important to explore, especially due to the positive effects beta-alanine has shown in older populations [ 24 , 73 ].
Interestingly, humans also have carnosine within the brain, eye, and heart tissue [ 37 , ]. Therefore some initial data has explored the neuronal effects of carnosine [ 80 , ], as well as potential effects on cardiac tissue and heart rate [ 60 ].
Future research exploring the effects of beta-alanine to induce changes in carnosine concentrations in these tissues would be beneficial, as well as explorations of potential physiological effects in humans. An additional potential function of carnosine has been linked to improvements in calcium sensitivity in muscle fibers [ , ].
As a result of improved calcium sensitivity, there may be a direct impact on muscular performance. This mechanism has not yet been fully explored in humans. One recent paper by Hannah et al. Future studies should further explore this mechanism.
Lastly, there is a need for long-term safety data on beta-alanine supplementation as well as more information on potential benefits in special populations such as elderly and tactical athletes.
Four weeks of beta-alanine supplementation 4—6 g daily significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer. Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses.
The only reported side effect is paraesthesia i. Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance.
Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when the dose of beta-alanine is sufficient i.
More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine.
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β-alanine is thought to bind specifically, to MrgD, a receptor that is primarily expressed in the sensory dorsal root ganglion neurons that is found under the skin Crozier et al. The MrgD receptor is extensively involved in pruriception and may be responsible for the itchy sensation that is associated with β-alanine supplementation Bader et al.
Symptoms of paresthesia may indicate that some of the ingested β-alanine is bound to MrgD receptors; however whether this affects β-alanine availability to the muscle is unknown. In comparison to a sustained-release formulation of β-alanine which extends the β-alanine concentrations in the plasma for longer duration, a rapid-release formulation is likely to have a higher proportion of its content excreted via the urine Decombaz et al.
The sustained-release formulation may, therefore, provide greater β-alanine availability to the muscle and result in a greater percentage from each single dose of supplemented β-alanine to be retained in muscle as carnosine.
However, β-alanine retention may not be a good indication of carnosine formation. In a previous study, comparing the effects of sustained-release β-alanine supplementation in a tablet to rapid-release β-alanine supplementation in a powder filled gel capsule 3.
Despite similar increases in carnosine content, the effects of each formulation on exercise performance and muscle metabolites were not examined in this investigation. Furthermore, differences in supplement formulation tablet vs. gel capsule may also have affected absorption rates. Recent research by Blancquaert et al.
These researchers observed that 23 days of β-alanine supplementation 6. However, recent investigations by Church et al.
A decrease in muscle histidine levels may compromise physiological function by reducing protein synthesis and lowering hematocrit and hemoglobin levels Kriengsinyos et al.
An interesting difference between these studies is that Church et al. It is possible that the different pharmacokinetic properties of sustained-release and rapid-release β-alanine may affect concentrations of intramuscular histidine content in a different manner.
In addition, the effect of these different β-alanine formulations on changes in muscle performance was also examined. Each participant reported to the Human Performance Laboratory at the University of Central Florida on two occasions separated by a period of four weeks 28 days.
Informed consent was obtained from all individual participants included in the study. On the first day of testing, each participant was randomly assigned into one of three groups: rapid-release β-alanine RR , sustained-release β-alanine SR , or placebo PLA. This was a double-blinded experimental design.
Prior to each testing session, participants were instructed to fast for a minimum of 2 h and avoid lower body physical activity for 48 h prior to testing. During each visit, body composition measures and a muscle biopsy were obtained from participants prior to completing a fatiguing knee extensor protocol.
Thirty-seven physically active men and women were recruited for this study. Participants were stratified into one of the three groups SR, RR, or PLA in a counterbalanced fashion based on the peak torque PT values obtained during unilateral maximal voluntary isometric contraction MVIC performed on the first testing day.
Participants were instructed to maintain normal food and exercise habits throughout the duration of the study. This investigation was approved by the New England Institutional Review Board for human subjects, and all procedures were in accordance with the ethical standards of the Helsinki Declaration and its later amendments.
Following an explanation of all procedures, risks, and benefits, each participant provided their written informed consent to participate in the study. All participants were required to be free of any physical limitations as determined by medical history questionnaire and PAR-Q and not to have consumed β-alanine for at least 9 weeks prior to enrollment in the study.
Although being a vegetarian was not part of the exclusion criteria, none of the participants recruited reported to be a vegetarian. The demographics of each group can be seen in Table 1. Participants were instructed to consume their supplements with regular meals breakfast, lunch, dinner.
Both RR and SR supplements were provided in tablet form 1 g and were identical in appearance. Participants in the placebo group were provided with the same number of tablets that were also identical in appearance to the β-alanine tablets.
Active and placebo tablets were provided by Natural Alternatives International Carlsbad, CA, USA. Supplementation compliance was tracked by self-reported supplement logs and by inspection of the number of tablets remaining in each bottle upon return for follow-up testing.
Anthropometric measurements were assessed for each participant during both visits to the laboratory. Upon arrival to the laboratory, participants were instructed to void their bladder in order to properly assess body composition. Body composition was assessed via air displacement plethysmography BodPod ® , COSMED, Chicago, IL, USA.
Anthropometric measures of each group are depicted in Table 1. The muscle biopsy procedures used in this investigation have been previously reported Varanoske et al. Prior to testing, all participants were instructed to wear shorts on testing day to expose the upper portion of their thigh.
A B-mode, linear probe ultrasound General Electric LOGIQe, Wauwatosa, WI, USA , coated with transmission gel Aquasonic ® , Parker Laboratories, Inc. The biopsy area was washed with antiseptic soap and cleaned with rubbing alcohol.
A small area of the clean skin approximately 2 cm in diameter was then anesthetized with a 2. The biopsy site was further cleansed by swabbing the area with betadine.
Once anesthetized, a spring loaded reusable microbiopsy instrument with a disposable gauge needle Argon Medical Devices Inc. Approximately, 5—6 muscle samples were extracted from each participant on each occasion, with the goal of obtaining about 15—20 mg of total wet tissue weight.
After removal, each muscle sample was transferred to a petri dish placed on ice to trim adipose tissue from the muscle specimens. The isometric testing and the muscle-fatiguing protocol used in this investigation have been previously reported Varanoske et al.
Due to the participants not being specifically trained in resistance exercise, an isokinetic dynamometer was used to elicit muscle fatigue and evaluate muscle strength while preventing injury.
Briefly, as participants were reporting to the lab on a 2-h minimum fast, 8 oz of a carbohydrate-containing beverage 60 calories, 16 g carbohydrates, 0 g fat, and 0 g protein was provided to the participants following the muscle biopsy, minutes prior to the isokinetic muscle-fatiguing protocol.
Unilateral MVICs and an isokinetic muscle-fatiguing protocol were performed on an isokinetic dynamometer System 4, Biodex Medical System, Inc. To avoid any residual effects of the muscle biopsy, the right leg of each participant was tested. The lower portion of the leg was secured to the dynamometer arm just above the medial and lateral malleoli.
Participants were seated in the dynamometer with a hip angle of ° and strapped to the chair at the waist, shoulders, and across the left thigh. Chair and dynamometer settings were adjusted for each participant but kept consistent between visits to properly align the axis of rotation of the knee with the lateral condyle of the femur.
Range of motion was assessed for each participant. All participants were able to achieve a range of motion of 90—° without discomfort. The gravity effect of moment was measured at ° of knee flexion ° representing full extension and subsequently corrected during testing Beyer et al.
Each contraction was initiated from a position of 90° knee flexion and was continued to the point of full knee extension.
Each bout of 50 contractions was separated by a s recovery period. Participants were encouraged during the first three contractions to make sure that they were contracting maximally from the start of each bout. Two MVICs were performed prior to the isokinetic muscle-fatiguing protocol, separated by a period of 3 min.
Of the two MVICs performed prior to the isokinetic muscle-fatiguing protocol, the one that produced the greatest PT was saved and used for later analysis MVIC1.
Additionally, one MVIC was performed s after the final set of the muscle-fatiguing protocol was completed MVIC2.
During these tests, the knee angle was fixed at °, and all MVICs were held for a total of 6 s. PT was recorded during each MVIC. Torque signals were sampled at 1 kHz with a Biopac data acquisition system MP Biopac Systems, Inc.
PT was identified as the greatest torque achieved on the torque-time curve. Participants were instructed to maintain their normal dietary intake habits throughout the investigation. Total energy, macronutrient, and histidine intakes were monitored using recorded food logs during the h period prior to each visit.
The FoodWorks Dietary Analysis Software, Version 13 The Nutrition Company, Long Valley, NJ, USA was used to analyze dietary recalls. Participants were required to record side effects that were associated with consuming the supplement on a daily calendar.
Side effects were recorded subjectively, through explanation of the symptom and by noting the time during which the symptom occurred.
Side effects were analyzed by quantifying the total amount of days during which paresthesia was encountered over the day supplementation period for each subject. Muscle biopsy samples were homogenized with three volumes of 0. Louis, MO, USA and subsequently centrifuged at 4 °C for 20 min at 10, rpm.
Muscle homogenates were deproteinized with three volumes of acetonitrile BDH VWR Analytical, Radnor, PA, USA , and left to stand at 4 °C for 20 min.
Then, the sample was centrifuged at 4 °C for 10 min at 10, rpm. The supernatant was collected and subsequently analyzed. The experimental methods were performed as described by Mora et al.
Calibration standards were prepared in the range of 0. Chromatography was performed on an Agilent Infinity HPLC Agilent Technologies, Santa Clara, CA, USA and separation was carried out using an Atlantis hydrophilic interaction chromatography HILIC silica column 4.
Mobile phase consisted of solvent A, containing 0. Louis, MO, USA , pH 5. Solvents were filtered through a 0. The column was equilibrated for 10 min under initial conditions before each injection. The separation was monitored using a diode array detector at a wavelength of nm for carnosine and histidine.
Peak areas were correlated to compound concentration by interpolation in the corresponding calibration curve. Duplication of retention times for a known standard was used to verify column equilibrium prior to analysis. Each sample was run in duplicate; the average intra-assay CV of carnosine was 1.
Calibration standards were prepared in the range of 1—0. Louis, MO, USA. Norvaline Nva; Ark Pharm, Arlington Heights, IL, USA was used as an internal standard at a concentration of 0.
Afterwards, the supernatant was transferred to vials and automatic pre-column derivatization with ortho-phthalaldehyde OPA; Agilent Technologies, Santa Clara, CA, USA was performed at room temperature. Separation was carried out using a Poroshell HPH-C18 column 3. Mobile phase consisted of solvent A which contained 10 mM sodium phosphate dibasic Sigma-Aldrich, St.
Louis, MO, USA , 10 mM sodium tetraborate decahydrate Alfa Aesar, Tewksbury, MA, USA , and 5 mM sodium azide BDH VWR Analytical, Radnor, PA, USA , pH 8.
Primary amino acids derivatized with OPA were detected at nm. Each sample was run in duplicate; the average intra-assay CV for β-alanine was 1.
Prior to statistical procedures, all data were assessed for normality, homogeneity of variance, and sphericity. If the assumption of sphericity was violated, a Greenhouse—Geisser correction was applied. PRE- and POST-values were used as the covariate and dependent variable, respectively.
To analyze differences in supplement compliance, side effects, and participant characteristics between groups, a one-way ANOVA was performed. In the event of a significant F ratio for any of these analyses, LSD post hoc comparisons were performed. Outliers were identified when values exceeded 1.
Recruitment of participants, screening, and progression through the study are presented in Fig. A total of 10 participants withdrew from the study prior to group assignment due to reasons unrelated to the investigation. One participant was removed from the final data analysis due to the lack of compliance to the supplementation protocol.
Four participants were removed from the final data analysis because they were deemed to be outliers. Two additional participants from PLA were excluded from the final analysis due to inabilities to fulfill the time commitments of the study. Additionally, 3 subjects in RR were removed from the final analysis due to errors in data collection.
The demographics of participants included in the final analysis are reported in Table 1. Participant recruitment, sampling, and progression through the study. Dietary analysis revealed that at PRE, the adjusted average nutrient intake for participants during the 72 h prior to the testing session was: No significant difference in supplement compliance was noted between the groups.
Participants consuming RR formulation reported paresthesia on significantly more days Changes in skeletal muscle carnosine are depicted in Fig.
At PRE, the average-adjusted muscle carnosine content was 7. Muscle carnosine content in participants consuming SR The unadjusted change in muscle carnosine values from PRE to POST for participants consuming the SR formulation was 3. These changes reflected a Unadjusted values for PRE- and POST-supplementation skeletal muscle carnosine content.
PRE before 28 days of supplementation; POST after 28 days of supplementation, SR sustained-release formulation of β-alanine, RR rapid-release formulation of β-alanine, PLA placebo.
Changes in skeletal muscle histidine and β-alanine are depicted in Figs. At PRE, the average-adjusted muscle histidine content was 0. PRE before 28 days of supplementation, POST after 28 days of supplementation, SR sustained-release formulation of β-alanine, RR rapid-release formulation of β-alanine, PLA placebo.
The average-adjusted muscle β-alanine content at PRE was 0. Unadjusted values for PRE- and POST-supplementation decline in peak torque.
Initial studies reporting significant increases in skeletal muscle carnosine from β-alanine supplementation used an RR formulation Harris et al. Symptoms of paresthesia were a common side effect associated with β-alanine ingestion, with greater symptoms associated with larger daily doses Decombaz et al.
More recently, an SR form of β-alanine has become available, which delays the release of β-alanine and prevents or attenuates symptoms of paresthesia Decombaz et al.
The present investigation is an initial foray into exploring whether differences in β-alanine formulation differ with regard to their effectiveness in increasing skeletal muscle carnosine and subsequent performance improvement.
The main findings of this study indicate that daily ingestion of 6 g SR formulation of β-alanine for a period of 28 days significantly increased skeletal muscle carnosine content and attenuated the decline in PT after a unilateral, lower body, muscle-fatiguing protocol.
Participants consuming the RR formulation experienced no statistically significant increases in muscle carnosine content, but had significantly attenuated changes in PT.
Although changes in muscle carnosine and performance results were not significantly different between the different β-alanine formulations, participants consuming the RR formulation reported significantly more side effects e.
Elevations in muscle carnosine observed in this investigation were consistent with previous investigations Harris et al. Participants supplementing with the SR formulation experienced an increase in unadjusted muscle carnosine content of Previous studies using dosing strategies ranging from 4.
Interestingly, only participants consuming the SR formulation had elevations in muscle carnosine content that were significantly different than those supplementing with the PLA, while no significant differences were noted between those supplementing with the RR formulation and those participants supplementing with the PLA.
However, a large effect size was observed for changes in carnosine content in participants consuming the RR formulation compared to PLA, suggesting that carnosine content was elevated with the RR formulation. Additionally, despite no significant differences in muscle carnosine at POST were noted between participants consuming the SR and RR formulations, a The estimated retention of β-alanine was calculated at 6.
Previous research comparing the effects of the SR and RR formulations 3. However, that study utilized a tablet form for the SR delivery, while the RR formulation was powder provided in a gel capsule. Whether the delivery system had any influence is not well understood.
However, the current study appears to support the work of Stegen at al. Although no significant differences were noted in the change in carnosine content in participants ingesting the SR and RR β-alanine formulations at POST, a small-medium effect size was observed for carnosine elevations between groups.
Additionally, the significant increase in muscle carnosine in the SR group from PRE compared to the lack of any significant increase seen in the RR group suggests that the pharmacokinetics of β-alanine release from the SR formulation may be more effective for increasing muscle carnosine content.
The RR formulation results in a shorter plasma β-alanine half-life but larger peak, while the area under the plasma concentration curve is the same as with the SR formulation Decombaz et al. SR formulations may increase the time over which plasma β-alanine is elevated Decombaz et al.
With the RR formulation, a sharp increase in plasma free β-alanine may result in an increase in the binding of β-alanine to MrgD receptors, preventing β-alanine transport into the muscle and resulting in increased feelings of paresthesia Bader et al.
The pharmokinetic difference between the RR and SR formulations may explain part of the mechanism behind the The inability to achieve any statistically significant differences in carnosine elevations between participants consuming SR and RR formulations may also be a function of supplementation duration.
While the absolute difference in the increase in muscle carnosine was small at 28 days, forward projection of the change using the model of Spelnikov and Harris , indicates a much greater difference appearing with longer duration of supplementation see Fig.
Forward projection of the change has been calculated from the formula:. where k f is the zero-order rate constant for carnosine formation. t is the amount of days of β-alanine supplementation. Forward projection of changes in intramuscular carnosine concentrations using a rapid-release formulation RR compared to a sustained-release formulation SR over different durations of β-alanine supplementation based off of the kinetics presented by Spelnikov and Harris From Spelnikov and Harris , k d is assumed to be 0.
k f has been calculated from Spelnikov and Harris :. Considering the change in carnosine at 28 days was 3. Figure 6 indicates that within days of supplementation, the increase in muscle carnosine could be as high as 9. We acknowledge that this is quite speculative, especially in consideration that this is the first application of the Spelnikov and Harris model, uncertain whether the model would hold true for days, and uncertain regarding the estimate of k d.
However, other investigations using the SR formulation reported no change in muscle histidine content Church et al. The results of the present investigation support the latter studies indicating that β-alanine supplementation does not reduce muscle histidine content, regardless of formulation.
In the present study, greater levels of skeletal muscle histidine 0. Although speculative, it is possible that higher baseline levels of histidine, perhaps from dietary means, may provide for a sufficient reserve to prevent any significant declines when supplementing with β-alanine.
This finding provides further support that increases in carnosine content may directly improve high-intensity exercise performance. Performance improvements observed in this investigation were consistent with other studies demonstrating the efficacy of β-alanine supplementation on attenuating fatigue during repeated maximal isokinetic contractions of the knee extensors Derave et al.
However, the effect of β-alanine supplementation on isometric muscle performance is less clear. Derave et al. Sale et al. Ahlborg et al. Furthermore, our results contradict with those of Kendrick et al. The differences in findings may be related to the exercises utilized, as the isometric protocols by Kendrick et al.
One potential limitation of this investigation is that the validity of this double-blind experiment may have been compromised if participants knew which group they were in.
Considering that all the participants in the RR group reported symptoms of paresthesia on at least half of the days that they supplemented, participants may not have been truly blinded to which group they were in, potentially influencing performance outcomes.
Additionally, participants were not familiarized with the muscle-damaging protocol prior to testing, which may have affected the results.
Furthermore, the unequal amount of subjects in each group and variability in the data, and small sample size may indicate that the study was underpowered to produce sufficient results.
Evidence suggests beta-alanine may have potential ffatigue, such as helping delay Body recomposition plan and improving athletic performance. Fayigue is a popular supplement among many athletes musxle Beta-alanine and muscle fatigue prevention enthusiasts. When a person does intense exercise, acid begins to accumulate in the muscles, which can contribute to fatigue. Beta-alanine helps regulate acid in muscles and prevent this fatigue. Taking beta-alanine supplements may mean a person can increase the length of time they can perform high intensity exercises before experiencing exhaustion. The International Society of Sports Nutrition ISSN notes that while more research is necessary, appropriate levels of beta-alanine are safe and can help improve exercise performance. β-alanine supplementation increases muscle carnosine content and improves anaerobic pprevention performance by enhancing intracellular buffering capacity. β-alanine ingestion in Ac variability causes traditional fattigue formulation RR is associated with the symptoms of Beta-alanine and muscle fatigue prevention. A Performance-boosting oils formulation Ac variability causes of ftaigue has been shown to circumvent paresthesia and extend the period of supply to muscle for carnosine synthesis. Thirty-nine recreationally active men and women were assigned to one of the three groups: SR, RR, or placebo PLA. Participants supplementing with SR and RR formulations increased muscle carnosine content by Although participants ingesting SR experienced a Symptoms of paresthesia were significantly more frequent in RR compared to SR, the latter of which did not differ from PLA.
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