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1.  The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study 
Studies utilizing beta-hydroxy-beta-methylbutyrate (HMB) supplementation in trained populations are limited. No long-term studies utilizing HMB free acid (HMB-FA) have been conducted. Therefore, we investigated the effects of 12 weeks of HMB-FA supplementation on skeletal muscle hypertrophy, body composition, strength, and power in trained individuals. We also determined the effects of HMB-FA on muscle damage and performance during an overreaching cycle.
A three-phase double-blind, placebo- and diet-controlled randomized intervention study was conducted. Phase 1 was an 8-week-periodized resistance-training program; Phase 2 was a 2-week overreaching cycle; and Phase 3 was a 2-week taper. Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of HMB-FA; and assessment of these, as well as cortisol, testosterone, and creatine kinase (CK) was performed at weeks 9 and 10 of the overreaching cycle.
HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1 ± 18.4 vs. 25.3 ± 22.0 kg, p < 0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W, p < 0.001); and increased lean body mass gain (7.4 ± 4.2 vs. 2.1 ± 6.1 kg, p < 0.001) in HMB-FA- and placebo-supplemented groups, respectively. During the overreaching cycle, HMB-FA attenuated increases in CK (−6 ± 91 vs. 277 ± 229 IU/l, p < 0.001) and cortisol (−0.2 ± 2.9 vs. 4.5 ± 1.7 μg/dl, p < 0.003) in the HMB-FA- and placebo-supplemented groups, respectively.
These results suggest that HMB-FA enhances hypertrophy, strength, and power following chronic resistance training, and prevents decrements in performance following the overreaching.
Electronic supplementary material
The online version of this article (doi:10.1007/s00421-014-2854-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4019830  PMID: 24599749
Leucine metabolite; Resistance training; Overreaching; Recovery; Sports supplements
2.  Comparative absorption of curcumin formulations 
Nutrition Journal  2014;13:11.
The potential health benefits of curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination. The purpose of this study was the comparative measurement of the increases in levels of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and the metabolite tetrahydrocurcumin after oral administration of three different curcumin formulations in comparison to unformulated standard.
The relative absorption of a curcumin phytosome formulation (CP), a formulation with volatile oils of turmeric rhizome (CTR) and a formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants (CHC) in comparison to a standardized curcumin mixture (CS) was investigated in a randomized, double-blind, crossover human study in healthy volunteers. Samples were analyzed by HPLC-MS/MS.
Total curcuminoids appearance in the blood was 1.3-fold higher for CTR and 7.9-fold higher for CP in comparison to unformulated CS. CHC showed a 45.9-fold higher absorption over CS and significantly improved absorption over CP (5.8-fold) and CTR (34.9-fold, all p < 0.001).
A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants significantly increases curcuminoid appearance in the blood in comparison to unformulated standard curcumin CS, CTR and CP.
PMCID: PMC3918227  PMID: 24461029
Curcumin; Absorption; Bioavailability
9.  Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men 
Currently, there is a lack of studies examining the effects of adenosine-5′-triphosphate (ATP) supplementation utilizing a long-term, periodized resistance-training program (RT) in resistance-trained populations. Therefore, we investigated the effects of 12 weeks of 400 mg per day of oral ATP on muscular adaptations in trained individuals. We also sought to determine the effects of ATP on muscle protein breakdown, cortisol, and performance during an overreaching cycle.
The study was a 3-phase randomized, double-blind, and placebo- and diet-controlled intervention. Phase 1 was a periodized resistance-training program. Phase 2 consisted of a two week overreaching cycle in which volume and frequency were increased followed by a 2-week taper (Phase 3). Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of ATP; assessment performance variables also occurred at the end of weeks 9 and 10, corresponding to the mid and endpoints of the overreaching cycle.
There were time (p < 0.001), and group x time effects for increased total body strength (+55.3 ± 6.0 kg ATP vs. + 22.4 ± 7.1 kg placebo, p < 0.001); increased vertical jump power (+ 796 ± 75 ATP vs. 614 ± 52 watts placebo, p < 0.001); and greater ultrasound determined muscle thickness (+4.9 ± 1.0 ATP vs. (2.5 ± 0.6 mm placebo, p < 0.02) with ATP supplementation. During the overreaching cycle, there were group x time effects for strength and power, which decreased to a greater extent in the placebo group. Protein breakdown was also lower in the ATP group.
Our results suggest oral ATP supplementation may enhance muscular adaptations following 12-weeks of resistance training, and prevent decrements in performance following overreaching. No statistically or clinically significant changes in blood chemistry or hematology were observed.
Trial registration NCT01508338
PMCID: PMC3849389  PMID: 24330670
Adenosine triphosphate; Exercise performance; Power; Strength; Muscle hypertrophy; Sports nutrition
10.  The effects of 8 weeks of whey or rice protein supplementation on body composition and exercise performance 
Nutrition Journal  2013;12:86.
Consumption of moderate amounts of animal-derived protein has been shown to differently influence skeletal muscle hypertrophy during resistance training when compared with nitrogenous and isoenergetic amounts of plant-based protein administered in small to moderate doses. Therefore, the purpose of the study was to determine if the post-exercise consumption of rice protein isolate could increase recovery and elicit adequate changes in body composition compared to equally dosed whey protein isolate if given in large, isocaloric doses.
24 college-aged, resistance trained males were recruited for this study. Subjects were randomly and equally divided into two groups, either consuming 48 g of rice or whey protein isolate (isocaloric and isonitrogenous) on training days. Subjects trained 3 days per week for 8 weeks as a part of a daily undulating periodized resistance-training program. The rice and whey protein supplements were consumed immediately following exercise. Ratings of perceived recovery, soreness, and readiness to train were recorded prior to and following the first training session. Ultrasonography determined muscle thickness, dual emission x-ray absorptiometry determined body composition, and bench press and leg press for upper and lower body strength were recorded during weeks 0, 4, and 8. An ANOVA model was used to measure group, time, and group by time interactions. If any main effects were observed, a Tukey post-hoc was employed to locate where differences occurred.
No detectable differences were present in psychometric scores of perceived recovery, soreness, or readiness to train (p > 0.05). Significant time effects were observed in which lean body mass, muscle mass, strength and power all increased and fat mass decreased; however, no condition by time interactions were observed (p > 0.05).
Both whey and rice protein isolate administration post resistance exercise improved indices of body composition and exercise performance; however, there were no differences between the two groups.
PMCID: PMC3698202  PMID: 23782948
Protein Quality; Leucine; Whey; Rice
11.  Predicting Body Composition in College Students Using the Womersley and Durnin Body Mass Index Equation 
Asian Journal of Sports Medicine  2013;4(2):153-157.
When assessing fitness levels, body composition is usually measured. The purpose of this study was to determine the overall efficacy of a body mass index (BMI) equation for predicting body composition with respect to college aged participants.
Body composition was measured using dual-energy x-ray absorptiometry (DXA) and was estimated using the Womersley and Durnin BMI prediction equation.
There was no significant (P=0.8) percent body fat (%BF) difference between the BMI prediction equation and DXA (BMI Predicted=25 (10) [min=6; max=52] %BF vs DXA=25 (6) [min=10; max=45] %BF). In addition, a significant correlation was found between the two approaches (r=0.791, P=0.001). However, both the standard error of estimate (6.32 %BF) and total error (6.63 %BF) were outside acceptable ranges for prediction equations.
The Womersley and Durnin equation for estimating %BF was not found to be a good estimate. Therefore, although the BMI predicted %BF has been previously found to predict skinfold estimated %BF, it does not appear valid in estimating %BF from DXA.
PMCID: PMC3690736  PMID: 23802058
Body Fat; Percent Fat; Fat Mass
12.  International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB) 
Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.
PMCID: PMC3568064  PMID: 23374455
15.  Blood Flow Restriction: How Does It Work? 
PMCID: PMC3463864  PMID: 23060816
16.  The Estimation of the Fat Free Mass Index in Athletes 
Asian Journal of Sports Medicine  2012;3(3):200-203.
The purpose of this investigation was to compare a practical measurement of fat free mass index (FFMI) from bioelectrical impedance analysis (BIA) to the dual energy X-ray absorptiometry (DEXA) value in collegiate athletes.
Thirty-three male baseball players and 16 female gymnasts volunteered to participate in this study during their respective pre-season. Subjects visited the laboratory once and had their measurements taken in the following order: weight, height, DEXA, and Omron HBF-500.
The BIA device investigated was not a valid estimate of FFMI when compared to the DEXA. The TE was 0.93 kg/ m2 for males and 0.78 kg/ m2 for females. There were also significant mean differences between the BIA prediction and the DEXA value for males (BIA=20.6 kg/m2 vs. DEXA=21.1 kg/m2, P=0.007) and females (BIA=16.2 kg/m2 vs. DEXA=17.5 kg/m2, P=0.001).
The BIA device investigated in this study did not provide a valid estimate of FFMI in male and female collegiate athletes. Although there was a general tendency for the BIA to underestimate FFMI compared to DEXA, 98% of the estimates were within plus or minus 2 kg/ m2. Therefore, while slightly biased, BIA may provide a reasonable (± 2 kg/ m2) estimate of nutritional status for practitioners who are unable able to afford more expensive equipment.
PMCID: PMC3445648  PMID: 23012640
Body Mass Index; Body Fat; Sports; Fat Free Mass; Dual Energy X-ray Absorptiometry; DEXA Scan
17.  Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats 
To determine the effects of 16 wk. of beta-hydroxy-beta-methylbutyrate (HMB) administration on age-related changes in functionality and diffusion tensor imaging (DTI) determined myofiber dimensions.
Twelve young (44 wk.), 6 middle-aged (60 wk.), 10 old (86 wk.), and 5 very old (102 wk.) male Fisher-344 rat's body composition and grip strength were assessed at baseline. Following, 6 young, 6 middle-aged, 5 old and 5 very old rats were sacrificed for baseline myofiber dimensions and gene transcript factor expression in the soleus (SOL) and gastrocnemius (GAS). The remaining 6 young and 5 old rats were given HMB for 16 wk. and then sacrificed.
Fat mass increased in the middle-aged control condition (+49%) but not the middle-aged HMB condition. In addition, fat mass declined (-56%) in the old HMB condition but not the old control condition. Normalized strength declined and maintained respectively in the control and HMB conditions from 44 to 60 wk. and increased (+23%) (p < 0.05) from 86 to 102 wk. in only the HMB condition. Declines occurred in myofiber size in all muscles from 44 to 102 wk. in the control condition(-10 to -15%), but not HMB condition. Atrogin-1 mRNA expression in the SOL and GAS muscles was greater in the 102-wk control condition than all other conditions: SOL (+45%) and GAS (+100%). This elevation was blunted by HMB in the 102 wk. old SOL. There was a condition effect in the SOL for myogenin, which significantly increased (+40%) only in the 102-wk. HMB group relative to the 44-wk. group.
HMB may blunt age-related losses of strength and myofiber dimensions, possibly through attenuating the rise in protein breakdown.
PMCID: PMC3356228  PMID: 22512917
Beta-hydroxy-beta-methylbutyrate; Aging; Fat-free mass; Strength; Sarcopenia
18.  Quality protein intake is inversely related with abdominal fat 
Dietary protein intake and specifically the quality of the protein in the diet has become an area of recent interest. This study determined the relationship between the amount of quality protein, carbohydrate, and dietary fat consumed and the amount of times the ~10 g essential amino acid (EAA) threshold was reached at a meal, with percent central abdominal fat (CAF). Quality protein was defined as the ratio of EAA to total dietary protein. Quality protein consumed in a 24-hour period and the amount of times reaching the EAA threshold per day was inversely related to percent CAF, but not for carbohydrate or dietary fat. In conclusion, moderate to strong correlations between variables indicate that quality and distribution of protein may play an important role in regulating CAF, which is a strong independent marker for disease and mortality.
PMCID: PMC3284412  PMID: 22284338
19.  Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage 
While chronic β-Hydroxy β-Methylbutyrate (HMB) supplementation (≥ 2 wk) lowers exercise induced muscle damage, its acute or timing effects have not been examined. The purpose of this study was to investigate the acute and timing effects of oral HMB supplementation on serum creatine kinase (CK), lactate dehydrogenase (LDH), muscle soreness, and maximal voluntary contraction (MVC).
Sixteen non-resistance trained men (22 ± 2 yrs) were assigned to HMB-Pre or HMB-Post groups. In a crossover design, all subjects performed 55 maximal eccentric knee extension/flexion contractions on 2 occasions on either the right or left leg. HMB-Pre (N = 8) randomly received 3 grams of either a placebo or HMB before and a placebo after exercise. HMB-Post (N = 8) received a placebo before and either 3 grams of HMB or a placebo after exercise. Muscle damage tests were recorded before, at 8, 24, 48, and 72 hrs post exercise.
There was a reduction in MVC and an increase in soreness in the quadriceps and hamstrings following exercise (p < 0.001). Although HMB-Pre approached significance in attenuating soreness for the quadriceps (p = 0.07), there was no time × group effect. Serum indices of damage increased, peaking at 48 hrs for CK (773%) (p < 0.001) and 72 hrs for LDH (180%) (p < 0.001). While there were no time × group effects of HMB on CK and LDH, post hoc analysis revealed that only HMB-Pre showed no significant increase in LDH levels following exercise.
Our findings suggest no clear acute or timing effects of HMB supplementation. However, consuming HMB before exercise appeared to prevent increases in LDH.
PMCID: PMC2642830  PMID: 19193206
20.  Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy 
The lipid messenger phosphatidic acid (PA) plays a critical role in the stimulation of mTOR signaling. However, the mechanism by which PA stimulates mTOR is currently unknown. Therefore, the purpose of this study was to compare the effects of various PA precursors and phospholipids on their ability to stimulate mTOR signaling and its ability to augment resistance training-induced changes in body composition and performance.
In phase one, C2C12 myoblasts cells were stimulated with different phospholipids and phospholipid precursors derived from soy and egg sources. The ratio of phosphorylated p70 (P-p70-389) to total p70 was then used as readout for mTOR signaling. In phase two, resistance trained subjects (n = 28, 21 ± 3 years, 77 ± 4 kg, 176 ± 9 cm) consumed either 750 mg PA daily or placebo and each took part in an 8 week periodized resistance training program.
In phase one, soy-phosphatidylserine, soy-Lyso-PA, egg-PA, and soy-PA stimulated mTOR signaling, and the effects of soy-PA (+636%) were significantly greater than egg-PA (+221%). In phase two, PA significantly increased lean body mass (+2.4 kg), cross sectional area (+1.0 cm), and leg press strength (+51.9 kg) over placebo.
PA significantly activates mTOR and significantly improved responses in skeletal muscle hypertrophy, lean body mass, and maximal strength to resistance exercise.
PMCID: PMC4066292  PMID: 24959196
Supplementation; Skeletal muscle; Protein synthesis; Phospholipid; Ergogenic aid
21.  Oral adenosine-5’-triphosphate (ATP) administration increases blood flow following exercise in animals and humans 
Extracellular adenosine triphosphate (ATP) stimulates vasodilation by binding to endothelial ATP-selective P2Y2 receptors; a phenomenon, which is posited to be accelerated during exercise. Herein, we used a rat model to examine how different dosages of acute oral ATP administration affected the femoral blood flow response prior to, during, and after an exercise bout. In addition, we performed a single dose chronic administration pilot study in resistance trained athletes.
Animal study: Male Wistar rats were gavage-fed the body surface area, species adjusted human equivalent dose (HED) of either 100 mg (n=4), 400 mg (n=4), 1,000 mg (n=5) or 1,600 mg (n=5) of oral ATP as a disodium salt (Peak ATP®, TSI, Missoula, MT). Rats that were not gavage-fed were used as controls (CTL, n=5). Blood flow was monitored continuously: a) 60 min prior to, b) during and c) 90 min following an electrically-evoked leg-kicking exercise. Human Study: In a pilot study, 12 college-aged resistance-trained subjects were given 400 mg of ATP (Peak ATP®, TSI, Missoula, MT) daily for 12 weeks, and prior to an acute arm exercise bout at weeks 1, 4, 8, and 12. Ultrasonography-determined volumetric blood flow and vessel dilation in the brachial artery was measured at rest, at rest 30 minutes after supplementation, and then at 0, 3, and 6 minutes after the exercise.
Animal Study: Rats fed 1,000 mg HED demonstrated significantly greater recovery blood flow (p < 0.01) and total blood flow AUC values (p < 0.05) compared to CTL rats. Specifically, blood flow was elevated in rats fed 1,000 mg HED versus CTL rats at 20 to 90 min post exercise when examining 10-min blood flow intervals (p < 0.05). When examining within-group differences relative to baseline values, rats fed the 1,000 mg and 1,600 mg HED exhibited the most robust increases in blood flow during exercise and into the recovery period. Human study: At weeks 1, 8, and 12, ATP supplementation significantly increased blood flow, along with significant elevations in brachial dilation.
Oral ATP administration can increase post-exercise blood flow, and may be particularly effective during exercise recovery.
PMCID: PMC4086998
22.  Effect of carbohydrate-protein supplement timing on acute exercise-induced muscle damage 
To determine if timing of a supplement would have an effect on muscle damage, function and soreness.
Twenty-seven untrained men (21 ± 3 yrs) were given a supplement before or after exercise. Subjects were randomly assigned to a pre exercise (n = 9), received carbohydrate/protein drink before exercise and placebo after, a post exercise (n = 9), received placebo before exercise and carbohydrate/protein drink after, or a control group (n = 9), received placebo before and after exercise. Subjects performed 50 eccentric quadriceps contractions on an isokinetic dynamometer. Tests for creatine kinase (CK), maximal voluntary contraction (MVC) and muscle soreness were recorded before exercise and at six, 24, 48, 72, and 96 h post exercise. Repeated measures ANOVA were used to analyze data.
There were no group by time interactions however, CK significantly increased for all groups when compared to pre exercise (101 ± 43 U/L) reaching a peak at 48 h (661 ± 1178 U/L). MVC was significantly reduced at 24 h by 31.4 ± 14.0%. Muscle soreness was also significantly increased from pre exercise peaking at 48 h.
Eccentric exercise caused significant muscle damage, loss of strength, and soreness; however timing of ingestion of carbohydrate/protein supplement had no effect.
PMCID: PMC2288590  PMID: 18284676
23.  Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review 
The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications.
PMCID: PMC2245953  PMID: 18173841
24.  Effects of 8 weeks of Xpand® 2X pre workout supplementation on skeletal muscle hypertrophy, lean body mass, and strength in resistance trained males 
Xpand® 2X is a proprietary blend comprised of branched chain amino acids, creatine monohydrate, beta-alanine (CarnoSyn®), quercetin, coenzymated B-vitamins, alanyl-glutamine (Sustamine®), and natural nitrate sources from pomegranate and beet root extracts purported to enhance the neuromuscular adaptations of resistance training. However to date, no long-term studies have been conducted with this supplement. The purpose of this study was to investigate the effects of a multi-ingredient performance supplement (MIPS) on skeletal muscle hypertrophy, lean body mass and lower body strength in resistance-trained males.
Twenty resistance-trained males (21.3 ± 1.9 years) were randomly assigned to consume a MIPS or a placebo of equal weight and volume (food-grade orange flavors and sweeteners) in a double-blind manner, 30 minutes prior to exercise. All subjects participated in an 8-week, 3-day per week, periodized, resistance-training program that was split-focused on multi-joint movements such as leg press, bench press, and bent-over rows. Ultrasonography measured muscle thickness of the quadriceps, dual-energy X-ray absorptiometry (DEXA) determined lean body mass, and strength of the bench press and leg press were determined at weeks 0, 4, and 8 of the study. Data were analyzed with a 2 × 3 repeated measures ANOVA with LSD post hoc tests utilized to locate differences.
There was a significant group-by-time interaction in which the MIPS supplementation resulted in a significant (p < 0.01) increase in strength of the bench press (18.4% vs. 9.6%) compared with placebo after 4 and 8 weeks of training. There were no significant group by time interactions between MIPS supplementation nor the placebo in leg press strength (p = .08). MIPS supplementation also resulted in a significant increase in lean body mass (7.8% vs. 3.6%) and quadriceps muscle thickness (11.8% vs. 4.5%) compared with placebo (group*time, p <0.01).
These results suggest that this MIPS can positively augment adaptations in strength, and skeletal muscle hypertrophy in resistance-trained men.
PMCID: PMC3851572  PMID: 24107586
Pre-workout; Performance; Hypertrophy; Supplementation; Sports nutrition

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