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 Histidine-Containing Dipeptides

Reprinted with permission from www.benbest.com/nutrceut/carnosine.html .

Beta-alanine residueImidazolering

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

% buffering capacity from dipeptides 30.6 24.7 6.7

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.

Buffering capacity = Microequivalent of H+ per g muscle dry weight to lower the pH from 7.1 to 6.5

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

Reprinted from Everaert I, et al. Amino Acids. 2011;40(4):1221-1229.a P .004

8

7

6

5

4

3

2

1

0

Mu

scle

Car

no

sin

e C

on

ten

t, m

M

Soleus Gastrocnemius Tibialis Anterior

a

a

a

Women

Men

Men have higher carnosine levels than women

Effects of an Omnivorous vs Vegetarian Diet on Muscle Carnosine Levels

Reprinted from Everaert I, et al. Amino Acids. 2011;40(4):1221-1229. a P < .05; b P < .10

8

7

6

5

4

3

2

1

0

Mu

scle

Car

no

sin

e C

on

ten

t, m

M

Soleus Gastrocnemius Tibialis Anterior

a

Vegetarians

Omnivores

a

b

Omnivores have higher carnosine levels than vegetarians

Effects of Exercise Type on Muscle Carnosine Levels

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

AthleteCarnosine levels,

µmol/g

Sprinters 4.93 0.76b

Rowers 5.04 0.72b

Marathoners 2.80 0.74

Untrained 3.75 0.86

UntrainedBodybuilders

a

60

Car

no

sin

e, m

mo

L/k

g D

W

50

40

30

20

10

0

Bodybuilders have higher carnosine levels in the vastus lateralis than

untrained individuals1

Sprinters and rowers have higher carnosine levels than marathon

runners and untrained individuals2

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% beta-alanine by weight

Estimated beta-alanine intake for young adult males is 200 to 750 mg/day

MeatCarnosine 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.

Plasma Beta-alanine Concentrations After Ingestion

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.

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

1,000

Mea

n B

eta-

alan

ine

Co

nc,

µm

ol/L

750

500

250

0

0 1 2 3 4 5 6

Time After Ingestion, hours

Effects of Beta-alanine Supplementation on Muscle Carnosine Levels

Effect of Different Beta-alanine Dosing Regimens on Muscle Carnosine Levels

Abbreviation: SE, standard error.Harris RC, et al. Amino Acids. 2006;30(3):279-289.

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

Protocols I, II, and III effectively increased muscle

carnosine concentrations compared with placebo (IV)

Mean (SE) Carnosine, µmol/L

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

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.

80

60

40

20

0 A B C D E F G H I J K L M N O P Q R S T U

Individual Subjects

Car

no

sin

e C

on

c, µ

mo

l/kg

DM

1210

86420–9 –6 –3 0 3 6 9 12

a a

Soleus

Beta-alaninePlacebo

Ca

rno

sin

e C

on

ten

t, m

M

1210

86420

–6 –3 0 3 6 9 12

Supplementation

Tibialis Anterior

A

B

C Gastrocnemius

a

1210

86420

–6 –3 0 3 6 9 12Time, weeks

Supplementation

Supplementation

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

–9

–9

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

Reprinted from Hill CA, et al. Amino Acids. 2007;32(2):225-233.

100

50

0

100

50

0

51.6± 3.1

58.8± 3.4

63.1± 5.3

b-Ala

Placebo

55.1± 2.8

56.2± 2.8

54.9± 3.9

0 w 4 w 10 w4 w 10 wD from 0 w

1.1± 1.1

1.7± 1.5

7.3± 1.3P < .01

8.6± 3.1P < .05

15

10

5

0

15

10

5

0

D T

WD

, kJ

Tota

l W

ork

Do

ne,

kJ

Increase in Total Work Done (TWD) followed an increase in muscle carnosine levels– 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 order1. 110 minutes at 50% to 90% of maximal lactate steady state (MLSS)2. 10-minute time trial (maximal effort)3. 5-minute period at 50% MLSS4. 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

Van Thienen R, et al. Med Sci Sports Exerc. 2009;41(4):898-903.

Mean and peak power output in the sprint test were significantly increased by 5.0% and 11.4%, respectively, by beta-alanine

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

Pretest Posttest Pretest Posttest600

700

800

900

1000

1100

1200

717 711

10951070

693 727

993

1105

Po

we

r O

utp

ut,

W

Placebo

-Ala

Mean Peak

1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10

350

330

310

290

270

250

Po

we

r O

utp

ut,

W

-AlaPlacebo

Pretest Posttest

+11.4%

+5.0%

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 mg4 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

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.

2

1

0 0

50

100

150

200

Placebo b-Ala Placebo b-Ala

PW

CF

T,

wat

ts

VT,

L/m

in

P < .001

P < .001

P < .001

P < .001

12.6% ↑13.9% ↑

Effects of Beta-alanine Supplementation on VO2max and Time to Exhaustion

Abbreviations: TTE, time to exhaustion; VO2max, maximal oxygen uptake.Reprinted from Stout JR, et al. Amino Acids. 2007;32(3):381-386.

2

1

0 0

500

1000

1500

2000

Placebo b-Ala Placebo b-Ala

TT

E,

seco

nd

s

VO

2m

ax,

L/m

in

P < .05

3

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):357-363.2Walter AA, et al. J Strength Cond Res. 2010;24(5):1199-1207.

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

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.

a Significantly greater than placebo, P = .004, 2 = 0.17 (large)b Significantly greater than placebo, P = .011, 2 = 0.13 (medium)

250

200

150

100

50

0Placebo BA Cr CrBA

PW

CF

T ,W

a b

PWCFT increased after beta-alanine

supplementation and creatine + beta-alanine

supplementation

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 A, et al. J Appl Physiol. 2010;109(4):1096-1101.2Derave 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 JR, et al. Nutr Res. 2008;28(1):31-35.2Hoffman 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– Body mass– Whole body strength– Isokinetic force production– Muscular endurance – Body composition

1Goto K, et al. J Strength Cond Res. 2011;25(2):398-405.2Kendrick IP, et al. Amino Acids. 2008;34(4):547-554.

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

Average weekly training volume forsquat exercise:

creatine + beta-alanine increased training volume (effect size >1.47)

Average weekly training volume forbench press exercise:

creatine + beta-alanine increased training volume (effect size = 0.78)

a P < .05Abbreviations: 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.

12,000

10,000

8,000

6,000

4,000

2,000

0

8,000

7,000

6,000

5,000

4,000

3,000

2,000

1,000

0P CA C

a a

P CA C

kg kg

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

a 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.

PWCFT increased 28.6% after beta-alanine supplementation

100

90

80

70

60

50

40

30

20

10

0

PRE

POST

PW

CF

T

Beta-alanine Placebo

a

Beta-alanine: Safety

General Safety Profile of Beta-alanine Toxicology studies in animals (up to 90 days) have shown no beta-alanine-

related 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 high-intensity 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