Ah, yes i can see your point and tend to agree.
Thank you for you time, I much aprechiate it.
Curious
--
"Age is a very high price to pay for maturity."
-Tom Stoppard
You're not fooling anyone, you know.
-- David Wright :: alphabeta at prodigy.net
These are my opinions only, but they're almost always correct.
"If you can't say something nice, then sit next to me."
-- Alice Roosevelt Longworth
>Paul Antonik Wakfer wrote:
>> beni wrote:
>> > hi guys!
>> > Is there any new finding about the meaning of overriding the
>> > carnosinase?
>>
>> AFAIK, there never has been a study on the pharmacology of "swamping"
>> the carnosinase enzyme (taking such a large dosage of carnosine that
>> much of it gets transported by the bloodstream to cells before it can
>> all be hydrolyzed by the serum carnosinase enzyme).
>> While seeming to be reasonable, this approach to delivering intact
>> carnosine to cells is pure theory, dosages to achieve it are mostly
>> guesswork and any consequences of it, either positive or negative, are
>> purely speculative.
>>
>> --Paul Wakfer
>>
>> MoreLife for the rational - http://morelife.org
>> Reality based tools for more life in quantity and quality
>> The Self-Sovereign Individual Project - http://selfsip.org
>> Rational freedom by self-sovereignty & social contracting
>
Curious wrote:
> Olafur Pall Olafsson wrote:
> > So I will have to look at other ways to get it.
>
> Hm, do you take whey potein for life extension purposes? Whey has
> arround 350mg Histidine in a 29g/1oz (120 Calories) Serving if I am not
> mistaken.
>
> Regards
> Curious
> --
> "I don't wanna die, there's no future in it!"
> -Curly Howard
Still kicking!
Wait... Wait... Ok - I just wanted to make sure that last hill sprint
didn't fibulate my heart.
Yep! Still kicking! Whoo hoo! Another reprieve!
Seriously though, I can attest that if you take enough carnosine in one
dose (preferably on an empty stomach) you will indeed overwhelm the
carnosinase in your body and therefore get the benefits from it... At
least with regards to preventing soreness from lactic acidosis. I
would assume that the other benefits (anti-glycation, cross link
breaking, increased O2 transport, cytotoxicity to neoplastic cells,
etc.) are active during that period as well.
Yes, I know it's anecdotal. But given the grueling nature of my
cardio/endurance workout (110 hard flights of stairs. REAL stairs now,
no step machines...) by all rights I should be shuffling out of bed the
next morning like an octogenarian from muscle soreness. It's like I
almost did nothing at all...
Carnosine is a dipeptide composed of the amino acids beta-alanine and
histidine and is synthetized in muscles and cells of the central
nervous system by the enzyme carnosine synthetase. It's synthesis in
humans is limited by the availability of beta-alanine. This appears to
be caused by the low concentrations of beta-alanine in muscles and
plasma relative to it's hith Michaelis constant towards carnosine
synthetase. Histidine on the other hand is much more abundant in
muscles and plasma and has a much lower Michaelis constant towards
carnosine synthetase than beta-alanine, and is therefore not rate
limiting for the synthesis of Carnosine under normal circumstances.
Consequently beta-alanine has been effectively used to stimulate
carnosine synthesis in humans in doses up to 6.4g daily distributed
throughout the day. To avoid symptoms of flushing it is advisable to
start with low doses and take beta-alanine in a distributed fashion.
BTW beta-alanine is already available at a reasonable price at
1fast400.com: http://www.1fast400.com/?products_id=2318
J Neurochem. 1985 May;44(5):1459-64. Related Articles, Links
Carnosine synthesis in olfactory tissue during ontogeny: effect of
exogenous beta-alanine.
Margolis FL, Grillo M, Kawano T, Farbman AI.
Carnosine has now been demonstrated by chemical analysis to be
present in rat olfactory mucosa on day 16 of gestation. The tissue
content of this dipeptide then increases progressively during fetal and
postnatal life. Radioactive carnosine can be isolated from cultured
embryonic rat olfactory mucosa incubated with [14C]beta-alanine as
early as 13-14 days of gestation. The amount of incorporation also
increases progressively with the initial age of the explant and with
time in culture indicating in vitro maturation of the carnosine
synthesis capability of olfactory tissue. To test whether the level of
beta-alanine was limiting the synthesis of carnosine, we evaluated the
effect of elevated beta-alanine levels on tissue carnosine content.
Exogenous beta-alanine caused an increase in the tissue content of
carnosine at several ages in vivo and in vitro. In adult animals this
increase was observed in olfactory bulb, olfactory mucosa, and skeletal
muscle. However, there was no associated alteration in carnosine
synthetase activity. In addition, the different half-lives of carnosine
in olfactory tissue and muscle seemed unaltered, arguing against any
effect on degradative enzymes. Thus, tissue carnosine levels are
regulated, at least in part, by substrate availability. The early
appearance of carnosine synthetic capacity during prenatal development
indicates that this enzyme activity should be a valuable aid in
studying early events in olfactory neuron maturation.
PMID: 3921664 [PubMed - indexed for MEDLINE]
Equine Vet J Suppl. 1999 Jul;30:499-504. Related Articles, Links
Influence of oral beta-alanine and L-histidine supplementation on
the carnosine content of the gluteus medius.
Dunnett M, Harris RC.
Department of Veterinary Basic Sciences, Royal Veterinary College,
Hatfield, Hertfordshire, UK.
The aim of this work was to test the hypothesis that in vivo
carnosine biosynthesis is dependent upon endogenous beta-alanine
availability, by studying the effect of sustained dietary beta-alanine
supplementation in the horse on the carnosine concentration in types I,
IIA and IIB skeletal muscle fibres. The diets of 6 Thoroughbred horses
were supplemented 3 times/day with beta-alanine (100 mg/kg bwt) and
L-histidine (12.5 mg/kg bwt) for a period of 30 days. Percutaneous
biopsies of the m. gluteus medius from a depth of 6 cm were taken on
the days immediately before and after the supplementation period.
Heparinised blood samples were collected at hourly intervals on the
first and last days of supplementation, and on every sixth day during
the supplementation period, 2 h after each ration. Individual muscle
fibres were dissected from freeze-dried biopsies, weighed and
characterised histochemically. beta-alanine, histidine and carnosine
concentrations were measured in plasma. The areas under the plasma
concentration-time curves (AUC) for beta-alanine and histidine were
calculated as indicators of the doses absorbed. Carnosine
concentrations were measured in types I, IIA and IIB muscle fibres.
There was an adaptive response to sustained beta-alanine administration
resulting in mean +/- s.d. beta-alanine AUC increasing significantly
from 1130 +/- 612 mumol/l h (Day 1) to 2490 +/- 1416 mumol/l h (Day 30)
(P < 0.05). This was probably due to increased beta-amino acid
transport across the gastrointestinal lumen. There was no consistent
increase in histidine AUC between Days 1 and 30, (mean +/- s.d. values
being 757 +/- 447 mumol/l h Day 1[ and 1162 +/- 1084 mumol/l h Day 30[
P > 0.05[). Type IIA fibre carnosine concentrations increased from
59.9-102.6 to 76.2-112.2 mmol/kg dry weight (dw). Increases were
statistically significant in 2 of the 6 horses (P < 0.05 in both
instances). Type IIB fibre carnosine concentrations increased from
101.3-131.2 to 114.3-153.3 mmol/kg dw. Increases were statistically
significant in 5 of the 6 horses (P < 0.05 in 3 horses, P < 0.01 in 1
horse, P < 0.005 in 1 horse). Changes in muscle carnosine concentration
appeared to be influenced by beta-alanine bioavailability. Individual
increases in muscle carnosine concentration were significantly
correlated with individual changes in beta-alanine AUC (r2 = 0.973, P <
0.005). Increased muscle carnosine concentrations lead to increased
intramuscular hydrogen ion (H+) buffering capacity.
PMID: 10659307 [PubMed - indexed for MEDLINE]
Amino Acids. 2006 May;30(3):279-89. Epub 2006 Mar 24. Related
Articles, Links
Click here to read
The absorption of orally supplied beta-alanine and its effect on
muscle carnosine synthesis in human vastus lateralis.
Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ,
Fallowfield JL, Hill CA, Sale C, Wise JA.
School of Sports, Exercise and Health Sciences, University College
Chichester, Chichester, U.K..
beta-Alanine in blood-plasma when administered as A) histidine
dipeptides (equivalent to 40 mg . kg(-1) bwt of beta-alanine) in
chicken broth, or B) 10, C) 20 and D) 40 mg . kg(-1) bwt beta-alanine
(CarnoSyntrade mark, NAI, USA), peaked at 428 +/- SE 66, 47 +/- 13, 374
+/- 68 and 833 +/- 43 microM. Concentrations regained baseline at 2 h.
Carnosine was not detected in plasma with A) although traces of this
and anserine were found in urine. Loss of beta-alanine in urine with B)
to D) was <5%. Plasma taurine was increased by beta-alanine ingestion
but this did not result in any increased loss via urine.
Pharmacodynamics were further investigated with 3 x B) per day given
for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1)
beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine
(isomolar to II) for 4 w resulted in significant increases in muscle
carnosine estimated at 42.1, 64.2 and 65.8%.
PMID: 16554972 [PubMed - in process]
Quotes from the full text article:
"In human vastus lateralis muscle carnosine ranges from 10.5 +/- SDind
7.6mmol x kg(-1) dry muscle (dm) in type I and 23.2 +/- SDind 17.8mmol
x kg(-1) dm in type II fibres (Harris et al., 1998), where SDind is the
estimated standard deviation in fibre content within an individual."
"In human vastus lateralis muscle the most frequently cited range for
the carnosine content is 17.5 +/- 4.8 mmol x kg(-1) dm in females to
21.3 +/- 4.2 mmol x kg(-1) dm in males (Mannion et al., 1992)."
"Carnosine is synthesized in muscle and cells of the CNS (Bakardjiev
and Bauer, 1984) although other cell types express a dipeptide
transporter enabling the molecule to be taken up intact (Hoffmann et
al., 1996; Dieck et al., 1999)."
"As the concentration of histidine in muscle (and plasma) is high
relative to its Km with muscle carnosine synthetase (CS) (Horinishi et
al., 1978), in contrast to the low concentration of b-alanine in muscle
which exhibits a much higher Km with CS (Skaper et al., 1978), it was
concluded that b-alanine was probably limiting to carnosine synthesis
in equine muscle."
"Subjects were staff and students of University College Chichester,
non-smokers and had not taken any dietary supplements 4 to 6 weeks
prior to the start of the relevant study. None of the subjects
recruited to the various studies were vegetarians."
The study was divided into three parts, the last of which examined the
effects of beta-alanine supplementation on muscle Carnosine content.
Below are some quotes relating to the third part of the study:
"Study 3: The effect of 4 weeks dietary supplementation with
beta-alanine or carnosine on the muscle carnosine content
The main study was preceded by an investigation of 16 male subjects
(19.4 +/- SD 1.6 yrs; 79.5 +/- SD 9.3 kg) to assess the effects of
repeated administration of b-alanine on blood biochemistry and
haematology."
"Venous blood samples were taken at St. Richard's Hospital,
Chichester, at the start and end of the 4 weeks supplementation with 4
doses per day of 800mg of b-alanine (n=8) or a matching placebo (n=8).
Both treatments were provided as 2 x 400mg contained in gelatin
capsules. Subjects were instructed to take the 4 doses at approximately
9 am, 12am, 3 pm and 6pm."
"Subjects ingested b-alanine daily using one of two regimens (I and II,
both n=5), L-carnosine (III, n=5) or placebo (IV, n=6) for 4 weeks:
I) 800mg of b-alanine was given 4 times per day (approximately 9 am,
12am, 3pm and 6pm) to give an average daily dose of 3.2 g and total 4
week dose of 89.6g.
II) used a more frequent dosage strategy in order to increase the dose
but not to exceed 800mg in any one dose. In week 1 subjects consumed
800, 400, 400, 400, 800, 400, 400 and 400mg at 9, 10, 11 and 12 am,
and, 3, 4, 5, and 6pm to give an average daily dose of 4 g. In week 2
the 11 am and 5 pm doses were increased to 800mg; in week the 10am and
4pm doses were similarly increased and in week 4 also the 12am and 6 pm
doses. Thus in week 4 the average daily dose was 6.4 g. The total dose
over the 4 weeks was 145.6 g.
III) subjects ingested L-carnosine using a dosing strategy identical to
II) and where each individual dose was approximately isomolar with
respect to b-alanine. Thus where 400 and 800mg of b-alanine were given
in II), 1000 and 2000mg of L-carnosine were given in III). The total
given over the 4 weeks was 364 g of L-carnosine corresponding to 143.3
g of b-alanine.
IV) subjects were given capsules containing maltodextrin to match those
of II) and at the same frequency as given also in III).
"Mild symptoms of flushing were reported in week 2 by 4 of the subjects
given b-alanine (with fewer subjects in the other weeks) and 3 subjects
in week 4 given carnosine. One subject given the placebo also recorded
mild symptoms of flushing."
"b-Alanine was below the limit of detection of 0.1-0.2mmol x kg(-1)
dm in most muscle extracts both before and following supplementation,"
"The mean carnosine content of all subjects prior to treatment was
22.69 +/- 1.11mmol x kg(-1) dm and the mean change over the 4 weeks in
the four groups was: I: +7.80 +/- 0.36 (P<0.05), II: +11.04 +/- 2.68
(P<0.05), III: +16.37 +/- 3.03 (P<0.05), IV:+1.87 +/- 1.73 (P>0.05)mmol
x kg(-1) dm (Table 3)."
"The mean percent changes in the four groups (after exclusion of
subject J from group II) were: I: +42.1%, II: +64.2%, III: +65.8%, IV:
þ9.9%."
"Transport of b-alanine into muscle cells has been shown in cultures of
embryonic chick pectoral muscle to be sodium and chloride dependent and
to show Michaelis- Menten kinetics with a Km of approximately 40 mcM
(Bakardjiev and Bauer, 1994). Prior to administration of b-alanine the
plasma concentration was <0.5 mcM in all subjects but increased to 50
to 100 mcM within 30 min of ingestion of 10 mg x kg(-1) bwt (Figs. 2
and 6). This, however, subsequently fell 60% within 30 min and 95% to
an average of 12.8 mcM within 90 min. Within this range transport of
b-alanine will be concentration dependent fluctuating between 10 and
70% of Vmax. Nonetheless, 10 mg x kg(-1) bwt must be close to the upper
practical dose if symptoms of flushing are to be avoided. Consequently
in study 3 supplementation was provided 4 (group I) or 8 (groups II and
III) times per day in order to provide a more even concentration
profile in plasma with a maximum concentration of 125 to 250% of the
assumed Km of the transporter."
"Based on the affinity of CS for its two substrates - the Km for
b-alanine is 1.0-2.3mM (Ng and Marshall 1978; Skaper et al., 1973),
and the Km for histidine is 16.8 mcM (Horinishi et al., 1978) -
compared with the relative abundance of histidine in muscle and plasma
and the very much lower concentrations of b-alanine, it is probable
that muscle carnosine synthesis is limited only by the intracellular
availability of b-alanine. Where b-alanine is in abundance then
synthesis may be further limited by the activity of CS itself."
Amino Acids. 2006 Jul 28; [Epub ahead of print] Related Articles,
Links
Click here to read
Influence of beta-alanine supplementation on skeletal muscle
carnosine concentrations and high intensity cycling capacity.
Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK,
Wise JA.
School of Sports, Exercise & Health Sciences, University of
Chichester, Chichester, U.K..
Muscle carnosine synthesis is limited by the availability of
beta-alanine. Thirteen male subjects were supplemented with
beta-alanine (CarnoSyntrade mark) for 4 wks, 8 of these for 10 wks. A
biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and
10 wks. Subjects undertook a cycle capacity test to determine total
work done (TWD) at 110% (CCT(110%)) of their maximum power (W(max)).
Twelve matched subjects received a placebo. Eleven of these completed
the CCT(110%) at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were
obtained from 5 of the 8 and one additional subject. Muscle carnosine
was significantly increased by +58.8% and +80.1% after 4 and 10 wks
beta-alanine supplementation. Carnosine, initially 1.71 times higher in
type IIa fibres, increased equally in both type I and IIa fibres. No
increase was seen in control subjects. Taurine was unchanged by 10 wks
of supplementation. 4 wks beta-alanine supplementation resulted in a
significant increase in TWD (+13.0%); with a further +3.2% increase at
10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The
increase in TWD with supplementation followed the increase in muscle
carnosine.
PMID: 16868650 [PubMed - as supplied by publisher]
Quotes from the full text article:
"Twenty-five physically active male subjects, mainly undergraduate and
postgraduate students at the University of Chichester, volunteered to
participate in the study. None of the subjects were actively involved
at the time in a structured training programme."
"None of the subjects were vegetarian and had estimated daily intakes
of b-alanine from the digestion of histidine dipeptides in meat of
250-750mg daily (estimates based on values of histidine dipeptide
contents in Abe, 2000)."
"Following a cycle performance test subjects were supplemented for 4 or
10 weeks with either b-alanine (b-Ala, n=13) or a matching placebo (P,
n=12). Allocation to treatments was randomized. b-alanine (CarnoSynTM)
was obtained from Natural Alternatives International, San Marcos, USA.
Details of the specific dosing strategies employed for both groups are
provided in Table 2. As in a previous study (Harris et al., 2006),
b-alanine was administered each day as 8 divided doses, with the dose
increasing during the first 4 weeks. 800mg b-alanine corresponds to the
amount in dipeptide form available from 100 g of whale beef, 150 g
turkey breast meat (Abe, 2000) or 100 g north-Atlantic seaprawns
(unpublished observations)."
"Carnosine increased in both fibre types (p<0.01) and to the same
extent with supplementation representing a doubling in the content in
type I fibres and a 50% increase in type IIa fibres. At this time the
mean content in IIa fibres was 1.43 +/- 0.14 times higher than that in
type I fibres (p<0.05) (Table 3)."
"TWD was significantly increased following 4 and 10 weeks of b-alanine
supplementation (+7.3 +/- 1.3 [+13.0%] and +8.6 +/- 3.1 [+16.2%] kJ,
respectively; Fig. 5) compared with no change in P (+1.1 +/- 1.1
[+2.3%] and +1.7 +/- 1.5 [+3.3%], respectively) [2-way rm-ANOVA:
p<0.015; Zp 2 =0.37; observed power=0.731]. The corresponding changes
in exercise times from the initial mean of 156.5 s were +11.8 +/- 3.2%
and +15.9 +/- 5.1%, and, +0.2 +/- 1.5% and +0.6 +/- 1.3%,
respectively."
"In agreement with a previous study (Harris et al., 2006),
supplementation was not associated with any reduction in muscle taurine
arising from increased competition between b-alanine and taurine for
transport into muscle cells (Jessen, 1994; Ramamoorthy et al., 1994)."
"As carnosine has been implicated in a number of physiological actions,
several explanations for the increase in performance are possible. The
most likely would seem to be a change in Ca2þ sensitivity, E-C
coupling (Lamont and Miller, 1992; Batrukova and Rubtsov, 1997) and
increase in intracellular buffering. Of these, we would favour the
latter."
Also, since there's been some concern that supplementation with over 1g
of carnosine daily made lead to negative health problems, is there a
limit on b-a? Is one gram of b-a converted to one gram of carnosine?
If not, does anyone know the conversion rate?
Scott Miller
>BTW beta-alanine is already available at a reasonable price at
>1fast400.com: http://www.1fast400.com/?products_id=2318
Beyond A Century has it as a new product:
http://www.easycart.net/BeyondACenturyInc./New_Products.html#0390
BETA-ALANINE is an amino acid produced in the body in limited amounts;
is found in heart, brain, and muscle tissue; and occurs in protein foods
such as chicken. Usual use is 2-4g/day, divided in 2 or more doses. 300g
powder (75-150 days) 300 grams, $12.50 Code 039.0
http://www.t-nation.com/readTopic.do?id=1196017
> ş9.9%."
> most likely would seem to be a change in Ca2ş sensitivity, E-C
I just realised that this sounds an awful lot like an advertisement for
1fast400.com. Just in case anyone is in doubt I whish to state that I
do not have any affiliations with this or any other supplement company.
This was merely provided as an example of a reasonable priced
beta-alanine product I found doing a quick search.
tomm...@gmail.com wrote:
> Is there evidence that supplementing with beta-alanine is more
> effective that supplementing with carnosine itself? In other words,
> why supplement with b-a when you can supplement with carnosine?
That's a good question. There are positives and negatives to both sides
but after examining this in more detail it appears to me that
beta-alanine does not have any benefits over carnosine except for it's
much lower cost, and possibly less risk with respect to the concern of
overriding the carnosinase enzyme, as it mainly raises carnosine levels
inside cells and is therefore less subject to serum carnosinase.
Here is a qoute from the full text of PMID: 16341596:
"Comparison of the different cell culture systems revealed not only
considerable differences in their capacity to synthesize
x-aminoacyl-amino acids (muscle cells exhibit by far the highest
activities of carnosine synthetase) but also with regard to the release
of these dipeptides into the culture medium. As expected from the high
concentrations of carnosine in skeletal muscle, carnosine was not
released into the medium of cultured muscle cells. Carnosine
synthesized by the glioma C-6 cell line also remained within the cells
whereas the dipeptides synthesized by astroglia- rich and
oligodendrocyte-enriched cultures were readily released into the
culture medium (6,8)."
This quote seems to suggests that once sythesized inside cells most of
the carnosine stays there and therefore that much of the benefits of
increased synthesis caused by beta-alanine supplementation may be
localised to the tissues carnosine is synthesized in, namely muscle
tissue and cells of the central nervous system. However in addition to
the cells that synthesize it there are some cells that cannot
synthesize carnosine but can take it up from the circulation, so
carnosine would probably be more beneficial than beta-alanine in the
circulation and in cells that cannot synthesize it but can take it up.
Therefore I do not suggest that people stop taking carnosine and
replace it with beta-alanine if they are taking it for life-extension,
I rather suggest adding beta-alanine to their regimen to get additional
benefit in the tissues that synthesize carnosine. On the other hand for
people that are solely interested in enhanced sport performance not
life-extension taking beta-alanine would be a much cheaper option and
probably just as effective as carnosine. For such people I would
suggest taking beta-alanine rather than carnosine simply because it is
much cheaper with respect to the dose needed to elevate muscle
carnosine levels.
> Also, since there's been some concern that supplementation with over 1g
> of carnosine daily made lead to negative health problems, is there a
> limit on b-a?
I must admit that I am getting less concerned about carnosine having
negative effects at doses over 1g daily although this still remains an
issue. It is possible that beta-alanine is safer in this regard since
it raises carnosine by increasing it's synthesis which is similar to
what exercise has been shown to do (PMID: 14610252 PMID: 1910085). This
might be a safer approach than taking exogenous carnosine. Also I can't
think of any negative effects from taking beta-alanine in doses
comparable to that used in the studies I posted, except for flushing
which can be avoided by reducing the dose and taking it in a more
distributed fashion. Therefore even for young people I would not
recommend against taking beta-alanine in doses as high as used in the
studies I posted.
> Is one gram of b-a converted to one gram of carnosine?
> If not, does anyone know the conversion rate?
Carnosine is approximately 40% beta-alanine by weight therefore if all
of it were taken up intact and used to synthesize carnosine 400mg of
beta-alanine would be needed to synthesize 1g of carnosine. The quotes
from the third study I posted in my previous post (PMID: 16554972) make
it clear that taking 6,4g of beta-alanine divided throughout the day is
about equally effective in raising muscle carnosine levels in humans as
is taking 16g of carnosine. So it is easy to see by comparing the
prices of beta-alanine from e.g. Beyond A Century or 1fast400 to prices
of carnosine how much cheaper beta-alanine is, with respect to raising
carnosine levels in those tissues where it is synthesized.
I just looked at the full text of that study (PMID: 15234195) which I
do not remember having done before. According to this quote from the
full text article histidine is only slightly better at protecting
against crosslinking of glyceraldehyde 3-phosphate (G3P) than carnosine
is. Note however that this only applies to situations where histidine
and carnosine are abundant (at a ratio of 20 to 1 to G3P):
"Interestingly, the anti-crosslinking activity of histidine was greater
than that of carnosine (P < 0.005) (Fig. 3). Histidine exhibited 60%
and carnosine 50% protection against glyceraldehyde-induced
crosslinking (protective agent to glycating agent RATIO = 20:1;
GLYCERALDEHYDE = 1.0 mM)."
What is very interesting is that histidine appears to act as an
effective anti-glycative agent at much lower concentrations than
carnosine does. You need a 10 to 1 ratio of carnosine to G3P to prevent
crosslinking but histidine is effective at a 1 to 1 ratio to G3P. See
this quote from the full text:
"Carnosine is a dipeptide that contains a ß-alanine, whose carboxyl
group is amide-linked to histidine (Fig. 1). Hence, our immediate
interest was in testing the two amino acids separately. Our data
suggest that histidine is a representative anti-crosslinking agent.
Foremost, histidine exhibited greater anti-crosslinking activity than
carnosine (Fig. 3). Additionally, histidine was effective at preventing
crosslinking even at 1:1 ratios of histidine to crosslinking agent
(Fig. 4). Previously we showed that a 10:1 ratio of carnosine to
glyceraldehyde 3-phosphate is necessary to prevent protein crosslinking
(Seidler, 2000)."
All this simply means that histidine is very potent at protecting
against G3P induced crosslinking. However G3P is not the only or even
the most important crosslinking agent in humans so this does not
necessarily mean that overall histidine is a better antiglycative agent
than carnosine. It only is with respect to glycation of G3P. Also
carnosine has been shown to reverse glycation in it's early stages
(PMID: 16112643) while I have seen no evidence that histidine does so.
Still this suggests that taking a little histidine (but not so high
that you get allergic symptoms from it's conversion to histamine) might
be a good idea as it will probably be effective against this type of
crosslinks in the body.
> you also posted this abstract on May 2005,
> http://groups.google.com/group/sci.life-extension/browse_frm/thread/53d6484fae747d31/ae36203e41cbddf0?lnk=gst&q=histidine+carnosine&rnum=5#ae36203e41cbddf0.
> what does all this information indicate if anti-crosslinking activity
> is your primary aim?
It indicates that all these chemicals (carnosine, beta-alanine and
histidine) would be of benefit as a supplement if you want to prevent
crosslinking but none of them is necessarily superior since they all
have their costs and benefits. I for one will try to obtain some
beta-alanine and perhaps some histidine too to complement the 500mg of
carnosine I take daily. This may be difficult though since here in
Iceland amino acids, with a few exceptions, are not allowed
individually, only in combination with other amino acids or protein. As
I except beta-alanine is not an exception to this rule, I will probably
not be able to purchase beta-alanine from 1fast400 or Beyond A Century.
Beta7 (Beta-Alanine)
We've heard it before: this supplement or that supplement stands to be
the next creatine.
Only it never does pan out to be the next creatine. Worse, whatever it
was that initially prompted such lofty comparisons usually gets dumped
to the back of history's medicine cabinet, forgotten and eventually
discarded.
But this time, this time, I think we've got it.
In many ways, Biotest's BETA-7 is reminiscent of creatine in that it
allows you to do more work, and all things being equal, more work means
more muscle. Like creatine, it works for just about everybody, and
there's usually no guesswork involved: you know it's working; the
results are concrete.
What's more, BETA-7 also works for endurance athletes. Soon, no one,
professional or amateur, strength athlete or endurance athlete, will
dream of training or competing without it.
Like creatine, it's found naturally in the body, and by giving the body
more of this substance, it allows the body to do more work.
Sweet, elegant, if I do say so myself.
The active ingredient in BETA-7 is called beta-alanine.
The trouble is, up until now, there's been a fly in the ointment
concerning the proposed use of conventional beta-alanine:
If you take it once a day, it's not very effective.
If you take it twice a day, it's not very effective.
If you take it three times a day... you guessed it, it's not very
effective.
In fact, ordinary, run of the mill beta-alanine must be taken 4 to 8
times a day for it to work effectively, but Biotest bludgeoned that
problem to smithereens with a cool drug-delivery technique, making
BETA-7 a time released beta-alanine (more on that later).
Beta-alanine already has a list of research studies behind it that
might soon match that of creatine's in length and scope, but in order
to help you understand this exciting new supplement better, we've
interviewed Dr. Jeff Stout, one of the world's foremost experts on
beta-alanine.
Prepare to learn and prepare to be blown away.
TC: First of all, Jeff, what is BETA-7 and what does it do?
JS: Beta-alanine is a non-essential amino acid found naturally in both
the body and in foods such as chicken or whale meat... not that many of
us eat whale, of course.
When beta-alanine is ingested, it enters the blood stream and is taken
up by muscle cells. It then becomes what I call the "rate limiting
substrate" to carnosine synthesis. Now, carnosine is a dipeptide
found primarily in fast-twitch muscle whose primary function, as far as
you and I are concerned, is buffering hydrogen ions (H+).
So without beta-alanine, carnosine doesn't get produced, and you don't
have the buffering of hydrogen ions.
TC: Why is buffering so important? What I want to know is this: Will it
make me hyoooge?
JS: Well, we need carnosine to buffer H+. If we buffer H+, the pH
levels in our muscles don't drop so low that our muscles start burning
and force us to quit. If we don't buffer, the acid levels in the muscle
get very, very, high, and we have to cut our sets off prematurely.
And, if you're cutting your sets prematurely, you're not growing.
Increasing muscle carnosine levels allows you to do more reps and more
sets in a given workout. It means more sets at a higher intensity with
less fatigue. That, my friend, means more growth and more strength.
There's a theory, of course, that we're limited not only by genetics,
but also how hard we can train to get huge. If fact, one of the many
actions of anabolic steroids is the ability to train harder which
results in much greater muscle and strength gains.
It's also interesting that steroids can significantly increase the
muscle's ability to delay fatigue by increasing creatine and CARNOSINE
synthesis! So, delaying fatigue, and thus increasing training volume
and intensity is extremely important to growth.
TC: So why can't you just take sodium bicarbonate? Isn't that a buffer,
too?
JS: Sodium bicarb (i.e. baking soda) will increase your blood pH if you
take enough of it. This may indirectly help consume the build-up of H+
because the higher extracellular (blood) pH may act like a magnet and
pull the H+ out before they cause muscle fatigue.
However, this doesn't always work or guarantee exercise performance
enhancement, and it often ends up giving you a stomachache. Also, you
need to ingest the right amounts (it varies from person to person) at
least 45 minutes before every workout or competition for the chance it
might work.
However, with beta-alanine supplementation you can increase carnosine
inside the muscle cell, thus preventing the build up of H+ inside the
muscle. That makes it 10 times more effective, without the stomachache!
It's really pretty cool.
TC: Okay, so why can't a person just take a lot of carnosine?
JS: Good question! First of all, carnosine is not absorbed effectively
in humans. Only a small amount remains intact, but it's that nominal
quantity where you encounter the real problems. The intact carnosine is
hydrolyzed into histidine and beta-alanine, which is then taken up by
skeletal muscle and synthesized back into carnosine.
Because of the initial hydrolysis, the ingested carnosine can't be
taken up into muscle intact. As such, the only value you gain by
ingesting expensive carnosine is the beta-alanine that's formed, since
it's the beta-alanine that can "remake" carnosine in muscle.
So it's much more logical and much more efficient and much less
expensive to take beta-alanine directly.
TC: Is there any research supporting the effects of Beta-alanine?
JS: You bet! There have been studies showing significant increases in
anaerobic threshold, training capacity, effects of training, muscular
strength, muscular endurance, lean body mass, and even a significant
drop in body fat percentage.
I've personally been involved in a few of these studies.
TC: Tell us about the study that's going to appear in the International
Journal of Sports Nutrition?
JS: Dr. Hoffman and his colleagues assembled a highly trained group of
33 college football players and split them into three groups: a
creatine group who took five grams twice daily; a creatine and
beta-alanine group who took the same amount of creatine plus a total of
3.2 g of beta-alanine daily; and a placebo group, who took nothing.
Prior to and following the 10-week study, the researchers measured the
athletes' body composition, body weight, one-rep maxes in the bench
press and squat, and had them keep a log of their training. All were
placed on a weight training program that included all the usual
suspects: bench presses, squats, deadlifts, power cleans, incline
presses and flyes, rows, etc.
Here's what they found: when you combine creatine and beta-alanine,
your training volume goes up and you get stronger. The athletes were
able to knock out more reps with the same weights, and although this
was the case with the other groups, it happened to a greater and more
significant extent in the creatine plus beta-alanine group. The one-rep
bench and squat max was significantly higher than that seen in the
placebo group.
The most impressive results of beta-alanine, at least in this study,
were its effects on lean mass gains and fat loss, effects not seen in
either of the two other groups.
Only in the creatine plus beta-alanine group did the investigators
record a significant increase in lean mass, with percentage of fat
dropping roughly 1.2%.
Oh, by the way, they were not on a restricted caloric diet. They ate
whatever they wanted and still lost fat!
This adds promise to a supplement that, until this study, could only be
viewed as a performance enhancer. Fat loss is also a benefit you just
don't get from creatine alone.
TC: Fat loss? Why would there be a reduction in body fat?
JS: We were stumped on this one, too. When we analyzed the diet of the
creatine vs. creatine + beta-alanine groups, we found no difference in
total calories or protein content in their diet.
However, the creatine and beta-alanine group had a much higher training
volume for every workout for the 10 weeks. The only thing we can think
of is that the creatine and beta-alanine group burned more calories
(via higher training volume) per workout than the creatine group, which
led to loss in body fat.
Other mechanisms are being explored (i.e. beta-alanine may have a small
thermogenic effect). The future will tell.
TC: Forgive me for saying this, but don't the results of that study
suggest that I'd better take beta-alanine with creatine?
JS: Well the problem with the Hoffman study is that all of the benefits
could have been from beta-alanine. We don't know because there was no
group using beta-alanine only. Further, the football players were only
taking 3.2 grams per day - a very small dose for a group of big guys.
It would have been interesting to see the same study, with a
beta-alanine only group. My guess is that the results would be just as
impressive.
However, another very recent study that I'm aware of examined the
effect of training versus training plus beta-alanine supplementation on
strength and muscle hypertrophy. It was just completed.
The preliminary results were amazing! Relative to body weight, the
muscle hypertrophy (muscle cross sectional area) and strength looked
more impressive than similar studies using creatine.
Also, in a research study that I just had accepted for publication in
The Journal of Strength and Conditioning Research demonstrated that
beta-alanine was 70% more effective than creatine in delaying fatigue
and increasing physical working capacity in young men!
Also, in another study, we demonstrated a 7% increase in anaerobic
threshold in men after supplementing only 3.2 g of beta-alanine for 28
days. However, while significant, that doesn't come close to the
women's study we just completed! In that study we also found a 13%
increase in Physical Working Capacity and 16% increase in Anaerobic
Threshold.
Anyway, I am not saying there wouldn't be a benefit with stacking
creatine and beta-alanine, but beta-alanine alone definitely promotes
greater lean body mass, strength and endurance.
TC: Speaking of endurance, what can you tell me about this study from
South Korea on Olympic caliber cyclists?
JS: Sure, in a study presented just this summer, Dr. Kim from South
Korea, examined the effects of supplementing Olympic caliber cyclist on
either beta-alanine (4.8 g per day) or placebo while training for 12
weeks.
The beta-alanine group increased their carnosine levels by 33%, thus
increasing anaerobic threshold and time to exhaustion, while the
placebo group saw no or very little change.
The placebo group changes are typical in elite athletes as very intense
training results in very small performance changes in elite athletes.
But the effect of supplementing beta-alanine is huge and could be the
difference between a medal and not finishing in the top 10.
The specific results of this study will be presented in 2007, but I
can't say anything more about it right now.
TC: I understand that some of the athletes in your studies came back to
you several weeks after the conclusion of the study and wanted to get
back on beta-alanine because their workouts now "suck" in
comparison?
JS: Ha! Yes, that's true of every study on beta-alanine I've done thus
far. Athletes came back 6 weeks later begging me for more beta-alanine
because their training "sucked!" without beta-alanine.
Just to make sure, I did the same and stopped taking beta-alanine 6
weeks ago. My subjects were right, my workouts "suck" without it!
TC: Are there any negative side effects?
JS: There's one, at least in conventional beta-alanine supplements.
Users sometimes experience a slight flushing/tingling effect with high
doses (at or greater than 1.6 grams) called paraesthesia. This is
resolved by taking 4 to 8 smaller doses several times a day.
Traditionally, you take six grams daily, in the aforementioned 4 to 8
doses, for at least two weeks to see its first effect. The reason for
taking multiple doses is to ensure a constant presence of beta-alanine,
which helps drive beta-alanine into the muscle cell, where it's
synthesized into carnosine.
HOWEVER, Biotest's BETA-7 uses the very latest in time-release
technology which will allow for a 24-hour presence of beta-alanine in
the blood from only 3 doses a day.
This will solve the problem of having to take 4 to 8 doses per days to
get the same effect and that annoying paraesthesia!! Nice!
TC: So you do need to "load" it, like creatine?
JS: Well, research so far suggest that maximal increases in carnosine
happen within 4 weeks with about 6 g per day, or 40 to 60 mg per kg of
body weight. After that, I think you could cut the dose in half to
maintain your elevated carnosine levels.
TC: Does it have this buffering effect on just slow-twitch fibers, or
fast-twitch fibers, too?
JS: Dr. Harris - the man involved in many of the early creatine
studies - recently demonstrated that after 4 weeks of beta-alanine
supplementation (6.4 g per day), subjects experienced a significant
increase (60%) in muscle carnosine levels. The percentage increase was
similar in fast and slow-twitch muscle, suggesting the increasing
carnosine in slow twitch muscle will also benefit the endurance athlete
by enhancing the H+ buffering capacity.
TC: So strength athletes and endurance athletes could benefit equally?
JS: Yes, finally a supplement that can enhance performance in ALL
athletes! Can you think of a single sport that doesn't try to deal with
delaying fatigue during training or competition? I can't.
TC: Do the effects diminish over time? Does it have to be cycled?
JS: While the research isn't there yet, it appears anecdotally, that if
you stop supplementing, your carnosine levels will return to baseline
in about 6 weeks. I would suggest taking a maintenance dose (2 to 3 g
per day) to keep carnosine levels up. I see no need to cycle.
TC: Are any groups of athletes using it now?
JS: Yes, all the ones I've consulted and as many as can get their hands
on it (NFL, College FB, etc.). Up to now, it's been hard to find a good
Beta-alanine supplement. I know that the South Korean Speed Skating
team used it prior to the last Olympics - I was invited to Italy to
watch and speak. The entire team from South Korea won 7 medals, 6 gold
and 1 silver. All in Speed skating!
TC: Is it on any banned lists?
JS: NO! Typical NCAA rules state that coaches can't give it out for
free, just as they can't give out any other amino acid or protein
supplements to student athletes. However, anyone can take it without
fear of testing positive for anything.
TC: Let's wrap this up by synopsizing the effects of BETA-7, Jeff. As I
understand it, BETA-7:
· Increases anaerobic threshold (muscular endurance)
· Increases aerobic threshold (endurance in general)
· Increases physical work capacity
· Increases lean mass
· Increases intercellular carnosine levels dramatically in both
fast-twitch and slow-twitch muscles
· Decreases body fat (possibly)
JS: It sounds like you got it all.
Biotest's BETA-7 is available right now. To add it to your supplement
arsenal and become a physical juggernaut.
References and Additional Reading
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© 1998 - 2006 Testosterone, LLC. All Rights Reserved.
Canosine is not absorbed effectively in humans. Only a small amount
A very good question. If you use Carnosine as an "exercise tonic" as I
do (I plan to add it to my daily vitamin 'stack' once I get some more
cash in), it seems you'd be better off taking carnosine ~30 minutes
before exercise.
I take 0.04 grams per kilogram. This effectively gives me protection
from (my best guess) 80% of muscle soreness from lactic acidosis.
Protection seems to last for over an hour (for endurance/stamina, I
prefer to train more instensly and for shorter time periods, so I can't
comment on more than an hour).
>
> That's a good question. There are positives and negatives to both sides
> but after examining this in more detail it appears to me that
> beta-alanine does not have any benefits over carnosine except for it's
> much lower cost, and possibly less risk with respect to the concern of
> overriding the carnosinase enzyme, as it mainly raises carnosine levels
> inside cells and is therefore less subject to serum carnosinase.
>
You must be paying retail for carnosine! You should be able to get it
for $0.20/gram. : D
The proof is in the pudding. If taking beta-alanine will give the same
benefits as carnosine at a lower cost, I'm all for it. However, I
wonder if it is that simple, since carnosine does a lot of other things
in the body besides prevent lactic acidosis (neuroprotective,
cardioprotective, heat shock protective, anti-cellular neoplasm, etc.
etc.).
Also, one other benefit from carnosine: You only need one large dose
if you're using it for exercise. When you feel the "flush" (which is
more of a prickling sensation than a flush, sort of like a niacin flush
w/o the heat) you know it's working. I've noticed a similar sensation
from large dosages of ALC (>1gm). Avoiding the "flush" means you don't
get the benefits. A small price to pay as I don't find it
uncomfortable, it's far less intense than a niacin flush, and it's FAR
less uncomfortable than what you normally feel after running 100
flights of stairs for 40 minutes.
> In fact, ordinary, run of the mill beta-alanine must be taken 4 to 8
> times a day for it to work effectively, but Biotest bludgeoned that
> problem to smithereens with a cool drug-delivery technique, making
> BETA-7 a time released beta-alanine (more on that later).
So that's their secret: Time release capsules.
So, if you want to make it easy to keep your beta-alanine levels high,
contact someone like these folks
http://www.capsuline.com/index.php
Tell 'em you want some time release capsules (they don't list them, but
I bet they could find them) and your set.
OR... You could just take a fairly high dose with food. Tends to slow
absorption...
It's not the capsules that make it time release.
>
> OR... You could just take a fairly high dose with food. Tends to slow
> absorption...
Depending on the substance, it may decrease absorption.
AFAIK, there never has been a study on the pharmacology of "swamping"
In fact, I'm feeling better. I think I'll go for a walk!
Hm, do you take whey potein for life extension purposes? Whey has
Curious wrote:
> Olafur Pall Olafsson wrote:
> > So I will have to look at other ways to get it.
>
> Hm, do you take whey potein for life extension purposes? Whey has
> arround 350mg Histidine in a 29g/1oz (120 Calories) Serving if I am not
> mistaken.
Yes I take about 70g of cold filtrated whey protein daily. And the whey
protein I take has even more histidine than that, it has 2,0g per 100g
giving me about 1,4g of histidine daily from whey protein alone. Here
is a link to it:
http://www.trueprotein.com/store/comersus_viewItem.asp?idProduct=633
In fact I do not take it plain but order a custom mixed blend from
trueprotein.com which includes glutamine, taurine, arginine and
creatine monohydrate in addition to the whey protein. I could take more
than 70g daily but I also get plenty of protein from food and there are
reasons to suggest eating a lot of protein is not good for
life-extension.
This whey product shure sounds interresting. does it really have no real
taste? I'd like to mix it with a veggie/fruit shot which are now
available in regular shops that look fairly nice and are tasty
(switzerland only sorry) so if it is mixable i might try it...
with thanks
Curious wrote:
> Ok, so no real need to add more Histidine in your case :-).
There are reasons to think taking a little extra histidine separately
would be beneficial for me. First of all with respect to it's
antiglycative effects more would most certainly be better as long as it
does not cause any significant negative effects. With respect to the
negative effects my main concern is that it will be converted to
histamine causing allergic reactions. But I have gone through periods
of eating considerably more protein than I do now supplying me with
considerably more dietary histidine than I get now without any signs of
too much histamine, so a little bit extra might not cause me any harm.
However getting histidine through protein does not have exactly the
same effects on the body as getting it separately as an amino acid does
for the simple reason that not all the protein you ingest is completely
broken down to amino acids before being absorbed into the circulation.
So some of the histidine from the protein you ingest will probably be
taken up as small peptides which can not be converted directly to
histamine. Therefore the dose needed to cause too much conversion to
histamine might be much lower for histidine taken as an amino acid as
opposed from protein. On the other hand histidine taken separately in
amino acid form also has benefits over histidine from protein. Since it
is in it's free amino acid form it does not need to be broken down to
amino acids and therefore it's antiglycative effects will be useful
right away in the stomach upon ingestion and also in the circulation
after being absorbed.
> This whey product shure sounds interresting.
They also sell several other types of whey protein products which are
differently processed, but the reason I chose this one is because it
contains less fat and sugar than their whey protein concentrate, which
is the cheapest whey protein they carry and the one all the others are
made from. And as opposed to the other types of whey protein isolates
they sell, because of the process by which it is filtrated (cold
filtration) it retains most of the beneficial whey protein fractions,
such as lactoferrin. But for those on a budged I would suggest the whey
protein concentrate.
> does it really have no real
> taste?
The cold filtrated protein tastes pretty neutral to me plain although
it certainly has a little taste, but I prefer to have cocoa added to
it. If you chose "Chocolate" as flavor you will get dutch cocoa added
to it, no artificial crap:-)
> I'd like to mix it with a veggie/fruit shot which are now
> available in regular shops that look fairly nice and are tasty
> (switzerland only sorry) so if it is mixable i might try it...
It will probably mix easily. But in my experience, when mixing it with
water, cold filtrated protein with cocoa added mixes better than the
plain one.
Oh BTW, If you decide to order from Trueprotein be sure to use a
discount code during the end of the ordering process to get 5% off the
prices. You could use my discount code (it is: EGO693) or you could use
someones else's if you know someone that has one (everyone can get one
by contacting Trueprotein). But you should be aware that if you are a
first time customer at Trueprotein and use a discount code, an amount
of money equivalent to the amount of your first order (not including
shipping) will count towards a sum of money accociated with the
discount code. Once that sum reaches $300 (and every $300 from then)
the owner of the discount code receives 8lbs of free protein from
Trueprotein. It's a clever way to get new customers, since they do not
spend any money on advertising but rather want to use it to keep their
prices low.