Download Beta-alanine Supplementation

Beta-alanine
Presentation Topics
 General information and metabolism of beta-alanine
 Beta-alanine and muscle carnosine levels
 Beta-alanine and exercise performance
 Beta-alanine and aging
 Safety of beta-alanine
Beta-alanine: Introduction
 Pushing through fatigue is a common challenge for athletes
– Decline in muscle pH is a major contributor to fatigue
 Beta-alanine, via its role in synthesis of carnosine, can improve
muscle cell buffering capacity
– Carnosine is a dipeptide composed of beta-alanine and histidine
 Beta-alanine supplementation is often used by athletes to
enhance workout capacity and delay fatigue
Background on Beta-alanine,
Muscle Carnosine Levels and Muscle Function
Beta-alanine: What Is It?
 Beta-alanine is an amino acid structurally similar to L-alanine
 Not used in the synthesis of larger body proteins
– No transfer-RNA (tRNA) for beta-alanine
 A key role for beta-alanine is synthesis of the dipeptide carnosine
– Carnosine has been shown to improve the buffering capacity of muscle
tissue
– Carnosine is synthesized in the body from beta-alanine and histidine via
carnosine synthase
• Beta-alanine is rate-limiting
– Degradation of carnosine occurs via plasma carnosinase
 99% of the body’s carnosine is located within skeletal muscles
Derave W, et al. Sports Med. 2010;40(3):247-263.
Structures of Carnosine and Related HistidineContaining Dipeptides
Imidazole
ring
Reprinted with permission from www.benbest.com/nutrceut/carnosine.html .
Beta-alanine residue
Functions of Carnosine
 Carnosine functions as a pH buffer in muscles
– The imidazole ring of histidine has pKa = 6.1
– When bound to beta-alanine, the pKa increases to 6.8
– Ideal buffers are within the physiologic range of myocytes (pH 6.5 to 7.1)
• As such, carnosine is an ideal buffer for muscle tissue
– This was the first function of carnosine to be identified
 Additional functions of carnosine
–
–
–
–
–
Antioxidant
Anti-glycation
Metal chelation (divalent cations such as zinc, copper, ferrous iron)
Activator of carbonic anhydrase
Angiotensin-converting enzyme (ACE) inhibition
Abbreviation: pKa, acid dissociation constant.
Derave W, et al. Sports Med. 2010;40(3):247-263.
Muscle Carnosine Levels and Exercise
 The rate of adenosine triphosphate (ATP) hydrolysis is high during
high-intensity exercise
– Aerobic metabolism (mitochondria) cannot keep up with the demand for ATP
– Dependent on glycolysis (anaerobic pathway) for the difference
• Leads to accumulation of lactate
 When a molecule of ATP is hydrolyzed, a hydrogen proton (H+) is
released
– H+ accumulate faster than muscle clearance rates at higher exercise intensity
• Results in decreased intramuscular pH that is probably at least one
contributor to fatigue
• This, not lactate, is the real cause of “lactic acidosis” of exercise
 Carnosine’s buffering activity slows muscle pH decline
– Additional histidine-related compounds also contribute (eg, anserine and
balenine [ophidine]) to varying degrees, depending on species
Robergs RA, et al. Am J Physiol Regul Integr Comp Physiol. 2004;287(3):R502-R516.
Carnosine and Histidine-Related Compounds (HRC):
Concentrations in the Muscles of Different Species
 Whales, as deep divers, are heavily dependent on anaerobic
metabolism and have high content of HRC in muscle tissue
(68.5 µmol/g wet muscle; 20 to 80 µmol/g balenine)
Thoroughbred Horse
Greyhound Dog
Human
Carnosine (µmol/g dry weight)
108.3  15.9
33.0  19.1
16.0  7.2
Anserine (µmol/g dry weight)
Not detected
48.6  18.4
Not detected
Total buffering capacity
117.7  8.5
105.2  9.1
79.5  8.0
Buffering capacity from dipeptides
36.0  5.3
26.0  10.1
5.3  2.4
30.6
24.7
6.7
% buffering capacity from dipeptides
Buffering capacity = Microequivalent of H+ per g muscle dry weight to lower the pH from 7.1 to 6.5
Suyama M, et al. J Tokyo Univ Fish. 1977;63:189-196; Castellini MA, et al. J Comp Physiol. 1981;143B:191-198; Abe H, Okuma E. Nippon Shokuhin Kagaku
Kogaku Kaishi. 1995;42:827-834; Okuma E, Abe H. Comp Biochem Physiol. 1992;102A:37-41; Harris RC, et al. Comp Biochem Physiol. 1990;97A:249-251.
Reprinted from Abe H. Biochemistry (Moscow). 2000;65(7):757-765.
Factors That Influence Muscle Carnosine Levels
 Diet
– Omnivores generally have higher levels than vegetarians
 Muscle fiber type
– Fast twitch, glycolytic fibers have higher levels than slow twitch fibers
 Gender
– Males generally have higher levels than females
 Exercise type
– Those who exercise anaerobically tend to have higher levels than endurance
athletes
• Unknown whether training is the cause or whether there is an issue of
predisposition to a given exercise based on proportions of existing types
of muscle fiber
 Age
– Weak negative correlation between age and carnosine levels
– Could be explained by other factors that also correlate with age
Everaert I, et al. Amino Acids. 2011;40(4):1221-1229; Derave W, et al. Sports Med. 2010;40(3):247-263.
Differences Between Men and Women in Muscle
Carnosine Content
Men have higher carnosine
levels than women
Muscle Carnosine Content, mM
8
7
6
Men
Women
a
5
a
4
a
3
2
1
0
Soleus
Reprinted from Everaert I, et al. Amino Acids. 2011;40(4):1221-1229.
a P  .004
Gastrocnemius
Tibialis Anterior
Effects of an Omnivorous vs Vegetarian Diet on
Muscle Carnosine Levels
Omnivores have higher carnosine
levels than vegetarians
Muscle Carnosine Content, mM
8
7
Omnivores
b
Vegetarians
6
a
5
4
a
3
2
1
0
Soleus
Reprinted from Everaert I, et al. Amino Acids. 2011;40(4):1221-1229.
a P < .05; b P < .10
Gastrocnemius
Tibialis Anterior
Effects of Exercise Type on Muscle Carnosine Levels
Bodybuilders have higher carnosine
levels in the vastus lateralis than
untrained individuals1
Carnosine, mmoL/kg DW
60
50
a
40
Sprinters and rowers have higher
carnosine levels than marathon
runners and untrained individuals2
Athlete
Carnosine levels,
µmol/g
Sprinters
4.93  0.76b
Rowers
5.04  0.72b
Marathoners
2.80  0.74
Untrained
3.75  0.86
30
20
10
0
Bodybuilders
Untrained
Abbreviation; DW, dry weight.
1Reprinted from Tallon MJ, et al. J Strength Cond Res. 2005;19(4):725-729.
2Adapted from Parkhouse WS, et al. J Appl Physiol. 1985;58(1):14-17.
a P  .001; b P < .01
Beta-alanine: Pathway Toward Muscle Carnosine
 Humans can derive beta-alanine from 2 different sources
– Major source is diet via carnosine and anserine in flesh foods
– Some endogenous synthesis from breakdown of pyrimidine
nucleotides
 Carnosine is absorbed intact from intestine
– Hydrolysis to amino acids occurs in plasma in humans because
carnosinase is absent from intestine and muscle
 Beta-alanine and histidine are taken up by muscle tissue
 Carnosine is reformed in muscle cell by carnosine
synthase
Dietary Intake of Carnosine
 3 main sources of carnosine in
the US diet
– Beef
– Pork
– Chicken
 Some meats are a significant
source of anserine as well
 Carnosine is roughly 32% betaalanine by weight
 Estimated beta-alanine intake
for young adult males is 200 to
750 mg/day
Meat
Carnosine Content,
mg/100 g
Beef, topside, rump
333
Pork, loin & shoulder
466
Lamb, leg
190
Chicken, breast
400
Chicken, leg
124
Chan KM, Decker EA. Crit Rev Food Sci Nutr. 1994;34(4):403-426; Hill CA, et al. Amino Acids. 2007;32(2):225-233.
Reprinted from Cattlemen’s Beef Board and National Cattlemen’s Beef Association. Beef Facts: Antioxidant Properties and Meat. Available at:
http://www.beef.org/uDocs/ACF2E.pdf. Accessed: February 20, 2011.
Beta-alanine Supplementation
 Beta-alanine is the rate-limiting compound for carnosine synthesis
– Histidine, an essential amino acid, is present in skeletal muscles in large
concentrations (larger than the Km for carnosine synthase)
 The potential for increasing intramuscular carnosine stores over
time with beta-alanine supplementation has been explored in a
number of studies
– Similar level of interest as creatine supplementation
– Evaluated effects on carnosine stores in various muscles and fiber types
– Evaluated effects on different types of exercise
 Doses of beta-alanine supplementation typically range from
2.4 to 6.4 g/day
– Often given in multiple divided doses over the course of the day for better
absorption
Abbreviation: Km, Michaelis-Menten dissociation constant.
Mean Beta-alanine Conc, µmol/L
Plasma Beta-alanine Concentrations After Ingestion
1,000
Supplementation with beta-alanine increases
peak beta-alanine levels in the blood much
faster than does ingesting the equivalent
amount of beta-alanine in the form of
chicken broth
750
500
250
0
0
1
2
3
4
5
6
Time After Ingestion, hours
Beta-alanine (40 mg/kg body weight )
Chicken broth with ~40 mg/kg beta-alanine as carnosine and anserine
Reprinted from Harris RC, et al. Amino Acids. 2006;30(3):279-289.
Effects of Beta-alanine Supplementation on
Muscle Carnosine Levels
Effect of Different Beta-alanine Dosing Regimens on
Muscle Carnosine Levels
 Study of 21 physically active, meat eating male subjects
 4 beta-alanine supplementation protocols for 28 days
 Muscle biopsies taken from vastus lateralis muscle
I.
800 mg beta-alanine 4 times/day
II. 8 daily doses ≤ 800 mg/dose; daily dose increased from 4 g/day week 1 to
6.4 g/day week 4
III. L-carnosine from chicken broth, 8 daily doses ≤ 2,000 mg carnosine per dose;
daily dose increased from 10 g/d week 1 to 16 g/day week 4
IV. Placebo (maltodextrin) capsules
Mean (SE) Carnosine, µmol/L
Protocols I, II, and III
effectively increased muscle
carnosine concentrations
compared with placebo (IV)
Abbreviation: SE, standard error.
Harris RC, et al. Amino Acids. 2006;30(3):279-289.
Treatment
Pre
4 Weeks
I
19.58 (1.66)
27.38 (1.33)
II
24.23 (2.36)
35.27 (2.76)
III
23.15 (2.27)
39.52 (7.58)
IV
23.63 (2.43)
25.49 (2.03)
More Results on Increases in Muscle Carnosine
Concentrations With Beta-alanine Supplementation
80
Carnosine Content, mM
Carnosine Conc, µmol/kg DM
Protocols I, II, and III
effectively increased muscle
carnosine concentrations in
individual subjects1
Elevated carnosine persisted in 15 untrained
subjects supplemented for 6 weeks with 4.8 g/day
followed by 9 weeks of no supplementation2
60
40
20
0
ABCDE
FGHIJ
KLMNO PQRSTU
Individual Subjects
Abbreviation; DM, dry mass.
a P < .05 from placebo.
1Reprinted from Harris RC, et al. Amino Acids. 2006;30(3):279-289.
2Reprinted from Baguet A, et al. J Appl Physiol. 2009;106(3):837-842.
12 A Soleus
a
10
8
6
4
2
Supplementation
0
–9
–6
–3
0
3
6
9
12
12 B Tibialis Anterior
a
10
8
6
4
Supplementation
2
0
–9
–6
–3
0
3
6
9
12
a
Beta-alanine
Placebo
12 C Gastrocnemius
10
8
6
4
Supplementation
2
0
–9
–6
–3
0
3
6
Time, weeks
9
12
Effects of Beta-alanine on Exercise
Performance
Beta-alanine Supplementation and Performance
 Some predictions can be made about the benefits of
supplementation for particular athletes
– Based on what is known about carnosine functions in muscle
– Based on what is known about beta-alanine in carnosine formation
 High-intensity, anaerobic exercise is more likely to benefit vs
submaximal work
 Beta-alanine, by itself, probably will not directly increase strength
– May improve training, indirectly benefitting strength
• Increased training capacity, higher quality of reps at heavier weights
 Individuals with low muscle carnosine levels may benefit more
from beta-alanine supplementation, including
– Elderly
– Vegetarians
 Effects of beta-alanine are not immediate, requires a period of
loading
– Timing of ingestion relative to exercise is not critical
Beta-alanine Supplementation and
Cycling Performance
Influence of Beta-alanine on High-Intensity Cycling
Capacity (Hill et al, 2007)
 25 male, physically active subjects (n = 13 beta-alanine,
n = 12 matching placebo)
 Beta-alanine supplementation for 4 weeks in all 13 subjects;
8 of these subjects supplemented for an additional 6 weeks
(10 weeks total)
– Total daily doses increased from 4 g/day in week 1 to
6.4 g/day in weeks 4 to 10
• Total daily dose was subdivided into 8 doses of no more than 800 mg
 Subjects completed a cycle performance test and muscle biopsy
before and after supplementation
Hill CA, et al. Amino Acids. 2007;32(2):225-233.
Results of Hill et al, 2007
100
7.3
± 1.3
P < .01
b-Ala
8.6
± 3.1
P < .05
 Increase in Total
Work Done (TWD)
followed an increase
in muscle carnosine
levels
15
10
5
0
100
51.6
± 3.1
58.8
± 3.4
63.1
± 5.3
0
15
Placebo
10
50
0
55.1
± 2.8
0w
56.2
± 2.8
4w
54.9
± 3.9
10 w
Reprinted from Hill CA, et al. Amino Acids. 2007;32(2):225-233.
1.7
1.1
± 1.1 ± 1.5
4 w 10 w
D from 0 w
5
0
D TWD, kJ
Total Work Done, kJ
50
– Increased carnosine
by 58.8% and 80.1%
at 4 and 10 weeks,
respectively
 Muscle carnosine
increase was similar
across both fiber
types
– Carnosine was
initially 1.7 times
higher in type IIa
fibers vs type I fibers
Effects of Beta-alanine on Sprint Performance in
Endurance Cycling (Van Thienen et al, 2009)
 21 male subjects (moderately to well-trained cyclists)
 8 weeks’ supplementation with beta-alanine or placebo
(maltodextrin) capsules
– 2 g/day weeks 1 and 2
– 3 g/day weeks 3 and 4
– 4 g/day weeks 5 to 8
 Rode cycle ergometer before and after supplementation, in order
1.
2.
3.
4.
110 minutes at 50% to 90% of maximal lactate steady state (MLSS)
10-minute time trial (maximal effort)
5-minute period at 50% MLSS
30-second sprint (maximal effort)
Van Thienen R, et al. Med Sci Sports Exerc. 2009;41(4):898-903.
Results of Van Thienen et al, 2009
Mean
Peak
350
+11.4%
1200
Power Output, W
1100
1095
1105
1070
993
1000
900
+5.0%
800
717
700
693
330
Power Output, W
Placebo
b -Ala
b -Ala
Placebo
310
290
270
711 727
250
600
Pretest
Posttest
Pretest
Posttest
Mean and peak power output in the sprint
test were significantly increased by 5.0%
and 11.4%, respectively, by beta-alanine
Van Thienen R, et al. Med Sci Sports Exerc. 2009;41(4):898-903.
1 2 3 4 5 6 7 8 9 10
1 2 3 4 5 6 7 8 9 10
Pretest
Posttest
Mean power output in the time trial
was not significantly altered; the
beta-alanine group had more
consistent improvements in power
on a minute-by-minute basis
Effects of Beta-alanine on Neuromuscular Fatigue
and Ventilatory Threshold in Women
 22 normal-weight women (ages 26 to 29 years) were subjects in a
4 week beta-alanine supplementation trial
 Dose of beta-alanine or placebo (maltodextrin) was 800 mg
4 times/day for the first week, and 1,600 mg 4 times per day for
the remaining 3 weeks
 Subjects performed a graded exercise test (cycle ergometer)
before and after the supplementation period
 2 key variables of interest
– Ventilatory threshold (VT): point at which pulmonary ventilation increases
disproportionately to oxygen consumption
– Physical working capacity at neuromuscular fatigue threshold (PWCFT): the
highest power output that results in a nonsignificant (P < .05) increase in
muscle activation of the vastus lateralis over time
Stout JR, et al. Amino Acids. 2007;32(3):381-386.
Effects of Beta-alanine Supplementation on
Ventilatory Threshold and Physical Working Capacity
P < .001
P < .001
VT, L/min
2
P < .001
13.9% ↑
12.6% ↑
150
100
1
50
0
0
Placebo
b-Ala
Placebo
Abbreviations: PWCFT, physical working capacity at neuromuscular fatigue threshold; VT, ventilatory threshold.
Reprinted from Stout JR, et al. Amino Acids. 2007;32(3):381-386.
b-Ala
PWCFT, watts
P < .001
200
Effects of Beta-alanine Supplementation on
VO2max and Time to Exhaustion
3
2000
1500
VO2max, L/min
2
1000
1
500
0
0
Placebo
b-Ala
Abbreviations: TTE, time to exhaustion; VO2max, maximal oxygen uptake.
Reprinted from Stout JR, et al. Amino Acids. 2007;32(3):381-386.
Placebo
b-Ala
TTE, seconds
P < .05
Beta-alanine and High-Intensity Interval Training
 Two 6-week high-intensity interval training (HIIT) studies were
conducted1,2
– Both studies showed positive physiologic adaptations to HIIT
• Delay in muscular fatigue in male subjects as measured by
electromyographic fatigue measures after cycle ergometer use1
• Increased ventilatory threshold in women after graded exercise tests on
a Corival cycle ergometer2
– However, neither showed an additive benefit of beta-alanine (6 g/day split
into 4 daily doses along with dextrose)
1Smith
AE, et al. Eur J Appl Physiol. 2009;105(3):357-363.
AA, et al. J Strength Cond Res. 2010;24(5):1199-1207.
2Walter
Study of Beta-alanine + Creatine on PWCFT
 51 young adult men (mean age = 24 years, mean body weight =
82 kg) studied for 28 days
 Treatments were
–
–
–
–
–
Placebo: 34 g dextrose
Cr: 5.25 g creatine monohydrate plus 34 g dextrose
BA: 1.6 g beta-alanine plus 34 g dextrose
CrBA: 5.25 g creatine monohydrate plus 1.6 g beta-alanine plus 34 g dextrose
Treatments were given 4 times/day for 6 consecutive days, then 2 times/day
for the remaining 22 days
 Measures of PWCFT at beginning and end of supplementation
Abbreviations: PWCFT, physical working capacity at neuromuscular fatigue threshold.
Stout JR, et al. J Strength Cond Res. 2006;20(4):928-931.
Effects of Supplementation on Physical Working
Capacity
250
a
b
PWCFT ,W
200
PWCFT increased after
beta-alanine
supplementation and
creatine + beta-alanine
supplementation
150
100
50
0
Placebo
BA
Cr
CrBA
greater than placebo, P = .004, 2 = 0.17 (large)
b Significantly greater than placebo, P = .011, 2 = 0.13 (medium)
a Significantly
Abbreviations: BA, beta-alanine; Cr, creatine monohydrate; CrBA, creatine monohydrate plus beta-alanine; PWCFT, physical working capacity at neuromuscular
fatigue threshold; 2, effect size.
Reprinted from Stout JR, et al. J Strength Cond Res. 2006;20(4):928-931.
Beta-alanine Supplementation:
Sprinting and Rowing
Beta-alanine, Rowing, and Sprinting
 Study of 18 elite Belgian rowers1
– 7-week beta-alanine supplementation (5 g/day) or placebo
– Muscle carnosine, 2,000-m ergometer test before and after
supplementation
– Beta-alanine group was 4.3 seconds faster, placebo group 0.3 seconds
slower (P = .07)
– Muscle carnosine elevation was positively correlated with performance
enhancement
 Study of 15 trained sprinters2
– 4-week beta-alanine supplementation (4.8 g/day) or placebo
– Increase in knee extension torque during 4th and 5th bout with beta-alanine
showed tendency for decreased fatigue
– 400 m sprint time or isometric endurance was not affected
1Baguet
2Derave
A, et al. J Appl Physiol. 2010;109(4):1096-1101.
W, et al. J Appl Physiol. 2007;103(5):1736-1743.
Beta-alanine, Rowing, and Sprinting
 Study of 19 physically active college men
– Beta-alanine supplementation (4 g/day for 1 week and 6 g/day for 4 weeks)
or placebo (rice flour)
– Subjects did a pre- and post-test of 2 sets of 5 × 5-second sprints with
45-second recovery, separated by 2 minutes of active recovery between sets
• Also measured horizontal power during sprint
– Beta-alanine supplementation had no effects on horizontal power or sprint
performance
Sweeney KM, et al. J Strength Cond Res. 2010;24(1):79-87.
Beta-alanine, Beta-alanine + Creatine, and
Resistance Training
Summary of Weight Training Studies on Beta-alanine
 Supplementation of 4.5 g beta-alanine/day for 30-days increased
bench press training volume (but not squat or combined squat
and bench press) and decreased subjective feelings of fatigue in
college football players during training camp1
 In experienced, weight-training men, 4.8 g beta-alanine/day for
30 days increased number of squat repetitions performed and
training volume in the squat exercise2
– No changes in hormonal profiles noted
1Hoffman
2Hoffman
JR, et al. Nutr Res. 2008;28(1):31-35.
J, et al. Int J Sports Med. 2008;29(12):952-958.
Summary of Weight Training Studies on Beta-alanine
 A chicken breast meat extract drink (2 g combined carnosine and
anserine) fed twice per day for 30 days blunted exercise-induced
increases in epinephrine, norepinephrine, and growth hormone
compared with placebo1
 In a study of 26 Vietnamese sports science students,2 10 weeks of
beta-alanine supplementation (6.4 g/day) taken with a resistance
training program did not increase
–
–
–
–
–
1Goto
Body mass
Whole body strength
Isokinetic force production
Muscular endurance
Body composition
K, et al. J Strength Cond Res. 2011;25(2):398-405.
IP, et al. Amino Acids. 2008;34(4):547-554.
2Kendrick
Effect of Creatine Plus Beta-alanine on Weight
Training Performance
 Study of 33 male strength/power athletes over a 10-week
resistance training program
– Athletes from college football team with at least 2 years of resistance
training experience
 3 study groups:
– CA: 10.5 g/day creatine monohydrate plus 3.2 g/day beta-alanine
– C: 10.5 g/day creatine monohydrate only
– P: 10.5 g/day dextrose
 Both CA and C increased 1-RM for bench press and squat
– Creatine probably drove these results
 The CA group decreased % body fat and increased lean body mass
more than P group
Hoffman J, et al. Int J Sport Nutr Exerc Metab. 2006;16(4):430-446.
Results From Hoffman et al, 2006, Focused on
Training Volume
12,000
8,000
a
a
7,000
10,000
6,000
5,000
kg
kg
8,000
6,000
4,000
3,000
4,000
2,000
2,000
0
1,000
P
CA
C
Average weekly training volume for
squat exercise:
creatine + beta-alanine increased
training volume (effect size >1.47)
a
0
P
CA
C
Average weekly training volume for
bench press exercise:
creatine + beta-alanine increased
training volume (effect size = 0.78)
P < .05
Abbreviations: C, creatine monohydrate; CA, creatine monohydrate plus beta-alanine; P, placebo.
Reprinted from Hoffman J, et al. Int J Sport Nutr Exerc Metab. 2006;16(4):430-446.
Beta-alanine Supplementation and the
Elderly
Effect of Beta-alanine on Neuromuscular Fatigue in
Elderly Subjects
 90-day study of 26 subjects (9 males, 17 females), 55 to 92 years
of age
– Subjects from independent living communities in Florida
 Supplemented with either beta-alanine or microcrystalline
cellulose placebo (800 mg TID in each case) for duration of study
 No training protocol
 PWCFT was measured in these subjects before and after
supplementation
Abbreviations: PWCFT, physical working capacity at neuromuscular fatigue threshold; TID, three times per day.
Stout JR, et al. J Int Soc Sports Nutr. 2008;5:21.
Effects of Supplementation on Physical Working
Capacity
PWCFT increased 28.6% after
beta-alanine supplementation
100
a
90
PRE
80
POST
PWCFT
70
60
50
40
30
20
10
0
a
Beta-alanine
P < .05.
Abbreviations: PWCFT, physical working capacity at neuromuscular fatigue threshold.
Reprinted from Stout JR, et al. J Int Soc Sports Nutr. 2008;5:21.
Placebo
Beta-alanine: Safety
General Safety Profile of Beta-alanine
 Toxicology studies in animals (up to 90 days) have shown no beta-alaninerelated adverse effects up to 1,000 mg/kg/day
 No clinically significant adverse effects of beta-alanine have been
observed in any human trials with beta-alanine; the longest
supplementation trial ~10 weeks with up to 6.4 g/day
– Caveat: These studies generally have not measured biochemical laboratory
panel values, but there have been no reports of illness or injury associated
with beta-alanine in these studies
 Hypothetical interactions with taurine (absorbed by same intestinal
transporter as beta-alanine)
– Taurine is a nonessential amino acid
– Theoretical risk typically comes from studies of cultured cells depleted of
taurine and incubated with beta-alanine
– No evidence of taurine depletion with beta-alanine supplementation
observed
 Side effects
– Main side effect is mild-to-moderate paresthesia (typically a tingling
sensation in hands, upper trunk, head, and face)
• Like the hand or foot “falling asleep”
Beta-alanine and Paresthesia
 Paresthesia has not been observed with feeding of carnosine from
chicken broth
 With beta-alanine ingestion, paresthesia usually occurs within
½ hour of ingestion
 Symptoms typically last < 1 hour, often < ½ hour
 Paresthesia is generally absent or very mild at doses of up to
800 mg at one time (reason for divided dosing in previous studies)
– Symptoms present, but mild, at 1.6 g/day and increase with larger doses
 Not everyone feels the paresthesia
 Symptoms are largely related to the rapidity and/or magnitude of
the rise in plasma beta-alanine
– Timed-release pills may help to slow absorption of beta-alanine, reducing
overall amount of paresthesia
 No long-lasting effects have been observed
Why Does Beta-alanine Cause Paresthesia in Some
Individuals?
 The cause is not clearly known, but it appears that beta-alanine
can function as a neurotransmitter
 Beta-alanine is a structural analog of gamma-aminobutyric acid
(GABA) and glycine, the major inhibitory neurotransmitters in the
brain
– Beta-alanine can react with their receptors
 A G-protein coupled receptor (TGR7) from the MrgD family has
been identified in the sensory neurons of the dorsal root ganglia
– Beta-alanine appears to interact with this receptor
– Beta-alanine may modulate the pain sensation through this receptor
 Beta-alanine may be a ligand for other potential receptors in the
brain as well
Beta-alanine: Overall Summary
 Beta-alanine is the rate-limiting amino acid for synthesis of carnosine in
muscles
 Carnosine plays several important roles in muscle, the most recognized is a
muscle pH buffer during intense exercise
– Decline in muscle pH is a contributing factor to fatigue
 Beta-alanine supplementation consistently elevates muscle carnosine
– At least 28 days’ supplementation needed to boost muscle carnosine levels
 Beta-alanine supplementation can improve performance in certain highintensity exercise types in doses ranging from 2.4 to 6.4 g/day
– Especially cycling
 Beta-alanine, with or without creatine, may help boost workout capacity in
strength athletes
 There are no known safety concerns with beta-alanine supplementation up to
6.4 g/day
– Paresthesia is a common short-term side effect, but can be minimized with divided
doses or extended-release preparations
– Taking beta-alanine with food may reduce paresthesia by slowing absorption