15 Years later and we still don't know basic information about ACETYL-L-CARNITINE
M5
literature. We have had tons of small scale studies that suggest it
might be of beneficial use for life extension, but to my knowledge the
most basic piece of information is missing for this; Does
ACETYL-L-CARNITINE extend the maximum life span of mice or rats (Note!
By this I mean animals that haven't been bread to have accelerated
disease profiles).
I'm kind of amazed that this level of basic research hasn't been
conducted. From what I have seen we don't even have a maximum life
span test conducted in mice or rats bred for accelerated aging.
I have to fault the scientific community and the private sector for
this glaring oversite. Firms such as LEF (which I am a member of) and
other supplement suppliers need to fund this particular research
option. As for the scientific community, why publish zillions of small
scale studies (primarily on rats) and not do a basic piece of research?
Let get focused on what counts here. If we are to extend viable life
extension alternatives beyond Caloric Restriction, we need to make
progress in basic areas. As the founder of the Caloric Restriction
society mailing list I know all to well how easily the community gets
lost debating the nuances of small microscopic studies on supplements
and nutrients. But the reality is that the instrument we are using,
the well constructed study, is very non-informative on the scale they
typically are sited in the literature i.e. it took us 500,000 women
before we could answer the basic question is hormone replacement
therapy good or bad on average for a woman. A cohort of 50 males given
supplement X for 60 days won't tell us what we need to know about the
effect of supplement X given over a lifetime.
Steve M.
tcar...@elp.rr.com
LEF did just such a study with lipoic acid and it was null. We
really don't need more. We have more that enough human studies that
show it to be so beneficial for human health that it is probably life
extending. With the hi safety profile that's all we need to make the
decision to supplement. If your looking for certainty, or even wide
spread public, and scientific acceptance, you want have any time soon.
Here's what I have.
Thomas
Clinical trials
In '05 the search string acetyl-l-carnitine AND (clinical
trial[pt] OR randomized OR multicenter study[pt] OR placebo OR
intervention) contains no trials over one year, but shows efficacy in
AD, diabetic neuropathy, and suggest some in enhancement of energy
levels and aging
Drugs R D. 2002;3(4):223-31.
Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic
neuropathy. A
long-term, randomised, double-blind, placebo-controlled study.
De Grandis D, Minardi C.
Department of Neuroscience, Ospedale Civile, Rovigo, Italy.
ddegr...@iol.it
OBJECTIVE: To assess the efficacy and tolerability of
acetyl-L-carnitine
(levacecarnine; LAC) versus placebo in the treatment of diabetic
neuropathy,
mainly by evaluating the effects of treatment on electrophysiological
parameters
and pain symptoms. DESIGN: This was a multicentre (n = 20), randomised,
double-blind, placebo-controlled, parallel-group study. PATIENTS: 333
patients
meeting clinical and/or neurophysiological criteria for diabetic
neuropathy were
enrolled. INTERVENTIONS: Patients were randomised to treatment with LAC
or
placebo. LAC (or placebo) was started intramuscularly at a dosage of
1000 mg/day
for 10 days and continued orally at a dosage of 2000 mg/day for the
remainder of
the study (355 days). MAIN OUTCOME PARAMETERS AND RESULTS: The main
efficacy
parameter was the effect of treatment on 6- and 12-month changes from
baseline
in nerve conduction velocity (NCV) and amplitude in the sensory (ulnar,
sural
and median) and motor (median, ulnar and peroneal) nerves. The effect
of
treatment on pain was also evaluated by means of a visual analogue
scale (VAS).
Among the 294 patients with impaired electrophysiological parameters at
baseline, those treated with LAC showed a statistically significant
improvement
in mean NCV and amplitude compared with placebo (p < 0.01). The
greatest changes
in NCV (at 12 months) were observed in the sensory sural nerve (7 m/sec
in the
LAC group vs +1.0 m/sec in the placebo group), sensory ulnar nerve
(+2.9 vs +0.1
m/sec, respectively) and motor peroneal nerve (+2.7 vs -0.2 m/sec),
whereas the
greatest changes in amplitude were recorded in the motor peroneal nerve
(+2.2 vs
+0.1 mV). After 12 months of treatment, mean VAS scores for pain were
significantly reduced from baseline by 39% in LAC-treated patients (p <
0.0 vs
baseline) compared with 8% in placebo recipients. LAC was well
tolerated over
the study period. CONCLUSIONS: LAC was effective and well tolerated in
improving
neurophysiological parameters and in reducing pain over a 1-year
period. LAC is,
therefore, a promising treatment option in patients with diabetic
neuropathy.
PMID: 12455197.................................
Acetyl-L-carnitine for dementia.
Cochrane Database Syst Rev. 2003;(2):CD003158. Review.
PMID: 12804452 ALC not efficacious for AD
Meta-analysis of double blind randomized controlled clinical trials of
acetyl-L-carnitine versus placebo in the treatment of mild cognitive
impairment and mild Alzheimer's disease.
Int Clin Psychopharmacol. 2003 Mar;18(2):61-71.
PMID: 12598816 ALC is efficacious for AD the related articles button
shows ample, but moderate corroboration.
Alzheimer's disease vs acetyl-L-carnitine
This is from Medscape
April 14, 2004 - Carnitine is more active than testosterone for
improving symptoms of male aging such as sexual dysfunction, depressed
mood, and fatigue, according to the results of a randomized study
published in the April issue of Urology.
"Testosterone increases the tissue carnitine concentration," write G.
Cavallini, from the Società Italiana di Studi di Medicina della
Riproduzione in Bologna, Italy. "@Propionyl-L-carnitine and
acetyl-L-carnitine proved active for diseases typical of aging."
In this trial, 120 patients were randomized to receive testosterone
undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus
acetyl-L-carnitine 2 g/day, or placebo for six months. Mean age was 66
years (range, 60-74 years).
Compared with baseline, testosterone and carnitines significantly
improved the peak systolic velocity, end-diastolic velocity, and
resistive index of cavernosal penile arteries, as well as nocturnal
penile tumescence (NPT), International Index of Erectile Function
score, Depression Melancholia Scale score, and fatigue scale score.
Compared with testosterone, carnitines were significantly more active
in improving NPT and International Index of Erectile Function score.
Testosterone, but not carnitines, significantly increased the prostate
volume and free and total testosterone levels and significantly lowered
serum luteinizing hormone. Prostate-specific antigen (PSA) and
prolactin did not change significantly in any group.
No symptoms or physiological markers improved in the placebo group.
Adverse effects were negligible in all groups.
Carnitines and testosterone were effective for as long as they were
administered, with reversal to baseline values when treatment was
stopped. Six months after testosterone suspension, prostate volume
remained significantly greater than baseline.
"Testosterone and, especially, carnitines proved to be active drugs for
the therapy of symptoms associated with male aging," the authors write.
"At least one side effect of testosterone administration (i.e. prostate
enlargement) will be avoided by carnitine administration."
Two of the authors are patent inventors for use of carnitines in
treating symptoms of male aging.
Urology. 2004;63:641-646
Learning Objectives
Upon completion of this activity, participants will be able to:
Describe the possible mechanisms of androgen replacement and carnitine
in improving symptoms of male aging.
Evaluate the efficacy of these two therapies in treating symptoms of
male aging.
Clinical Context
Both testosterone and carnitine metabolism have been implicated in
contributing to the symptoms of sexual dysfunction, depressed mood, and
fatigue in older men. A decline of testosterone's effects in the
hypothalamic dopaminergic system, striated skeletal muscle, and corpus
cavernosum may explain why older men suffer from the symptoms described
above.
Both male and female sex hormones increase L-carnitine levels, in vivo
carnitine-acetyl-transferase activity, and the activities of
mitochondrial carnitine palmitoil-transferases. Carnitines act as an
antioxidant by promoting activity in the Krebs cycle, while also
decreasing apoptosis via a reduction in ceramide levels along with
insulin-like growth factor.
The authors of the current study sought to determine if the direct
administration of carnitine could improve symptoms of male aging to a
similar degree as androgen treatment. They also wanted to establish the
safety of carnitine administration.
Study Highlights
Patients eligible for participation were men older than 60 years with
symptoms of decreased libido and erectile quality, depressed mood and
ability to concentrate, irritability, and fatigue. Patients with a free
~testosterone level less than 6 pg/mL were also included.
Patients had to be generally healthy to participate in the study. Those
with a history of obstructive urinary symptoms, alcohol or cigarette
use, or cardiovascular disease were excluded.
Subjects were randomized to receive 1 of 3 treatments: testosterone
undecanoate 160 mg/day, propionyl-L-carnitine 2 g/day plus
acetyl-L-carnitine 2 g/day, or placebo. All treatments were
administered for 6 months.
Participants were followed for PSA levels and prostate volume,
measurements of penile blood flow, NPT, and serum levels of
testosterone, luteinizing hormone (LH), and prolactin. They were also
assessed for sexual function, mood, and fatigue. All of these
evaluations were performed at baseline, at 3 and 6 months after
initiation of treatment, and 6 months after cessation of treatment.
Although treatment was administered by blinded personnel, the authors
did not comment whether subjects' assessment was completed in a
similarly blinded manner.
150 patients were randomized into the study, and 130 completed the
study protocol. The authors did not perform an intent-to-treat analysis
of their data.
Baseline values for all study groups were similar. Mean age of subjects
was 64 years.
The testosterone group exhibited an increase in prostate volume as
measured by ultrasonography at 3 and 6 months. The authors mention in
their discussion that this increase prompted cessation of the study
protocol at 6 months. Prostate volume in the testosterone group had
decreased 6 months after cessation of treatment but had not returned to
baseline levels.
Carnitine administration had no effect on prostate volume.
Neither testosterone nor carnitine treatment changed PSA levels.
Both carnitine and testosterone treatment improved penile blood flow at
3 and 6 months compared with placebo. There was no difference between
the carnitine and testosterone groups in this outcome.
NPT was improved to a similar degree in both active treatment groups at
3 months compared with placebo, and this improvement was stable at 6
months.
Testosterone therapy caused an increase in serum testosterone levels
and a decrease in LH levels at 3 months that remained stable at 6
months. Prolactin was unaffected by testosterone treatment. Carnitine
did not significantly change any hormonal levels measured.
Testosterone improved erectile dysfunction and sexual desire scores at
3 months, but it did not improve scores for orgasm or general sexual
well-being at any point.
Carnitine improved erectile dysfunction, sexual desire, orgasm, and
general sexual well-being scores at 3 months, and these values either
remained stable or improved slightly at 6 months.
Carnitine was superior to testosterone in the 3- and 6-month erectile
function domain, the 6-month orgasm domain, and the 6-month general
sexual well-being domain.
Both carnitine and testosterone improved depression scores compared
with placebo, but carnitine was superior to testosterone in this
variable.
Fatigue was improved to a similar degree in both active treatment
groups compared with placebo.
Adverse events were similar among all treatment groups.
Pearls for Practice
Both testosterone and carnitine can affect symptoms of male aging
through multiple biochemical pathways in different tissues.
Carnitine appears to improve symptoms of male aging to a similar or
better degree than testosterone without causing an increase in prostate
volume
Prostate cancer vs carnitine
XXXX
Am Heart J 2000 Feb;139(2 Pt 3):S120-3 Three-year survival of patients
with heart failure caused by dilated cardiomyopathy and L-carnitine
administration. Rizos I. University of Athens Medical School,
Greece. We examined the efficacy of long-term L-carnitine
administration for the treatment of heart failure caused by dilated
cardiomyopathy in adult patients. To accomplish this, we studied 80
patients with moderate to severe heart failure (New York Heart
Association classification III to IV) caused by dilated cardiomyopathy.
This article reports on the nearly 3 years of follow-up data on patient
mortality. Primary results will be published in the future. After a
period of stable cardiac function up to 3 months, patients were
randomly assigned to receive either L-carnitine (2 g/d orally) or
placebo. There were no statistical differences between the 2 groups at
baseline examination in clinical and hemodynamic parameters, such as
ejection fraction, Weber classification, maximal time of
cardiopulmonary exercise test, peak VO(2) consumption, arterial and
pulmonary blood pressure, and cardiac output. After a mean of 33.7 +/-
11.8 months of follow-up (range 10 to 54 months), 70 patients were in
the study: 33 in the placebo group and 37 in the L-carnitine group. At
the time of analysis, 63 patients were alive. There were 6 deaths in
the placebo group and 1 death in the L-carnitine group. Survival
analysis with the Kaplan-Meier method showed that patients' survival
was statistically significant (P <.04) in favor of the L-carnitine
group. L-carnitine appears to possess considerable potential for the
long-term treatment of patients with heart failure attributable to
dilated cardiomyopathy. Publication Types: Clinical Trial Randomized
Controlled Trial PMID: 10650325
L-carnitine vs mortality in heart patients
Propionly-L-carnitine vs ejection fraction in heart patients
Eksp Klin Farmakol. 2003 May-Jun;66(3):32-5.
Department of Neurochemistry, Institute of Neurology, Russian Academy
of Medical
Sciences, Volokolamskoe sh. 80, Moscow, 123367 Russia.
The antioxidant properties of mildronate and a structurally
close compound
L-carnitine were studied under clinical conditions during the therapy
of
patients with acute lacunar stroke and discirculatory encephalopathy
(DEP) on
the background of diabetes mellitus, respectively. Administered in
addition to
the base course of therapy, both mildronate (in a daily dose of 500 mg)
and
L-carnitine (2 mg) increased the resistance of blood serum lipoproteins
with
respect to peroxidation. It was concluded that the drugs possess
antioxidant
activity and offer protection against lipid peroxidation. L-carnitine
acute
produced a significant hypoglycemic action and made possible an almost
twofold
(42%) decrease in the dose of hypoglycemic drugs. The administration of
L-carnitine also improved both abstract and concrete thinking and
memory
function in DEP patients. The results allowed mildronate and
L-carnitine to be
included in the complex therapy of patients with cerebrovascular
diseases.
PMID: 12924230
Acetyl-L-carnitine protects against amyloid-beta neurotoxicity: roles
of oxidative buffering and ATP levels.
Dhitavat S, Ortiz D, Shea TB, Rivera ER.
Center for Neurobiology and Neurodegeneration Research, University of
Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
Thoma...@uml.edu
Acetyl-L-carnitine (ALCAR), normally produced in mitochondria,
is a
precursor of acetyl-CoA in the tricarboxylic (TCA) cycle. Since
mitochondrial compromise and ATP depletion have been considered to
play a role in neuronal degeneration in Alzheimer's disease (AD), we
examined whether ALCAR attenuated oxidative stress and/or ATP
depletion after exposure of cells to beta-amyloid (Abeta), a
neurotoxic peptide that accumulates in AD brain. Differentiated
SH-SY-5Y human neuroblastoma cells were exposed for 2-24 h to 20
microM Abeta in the presence and absence of 50 microM ALCAR. ALCAR
attenuated oxidative stress and cell death induced by Abeta
neurotoxicity. Abeta depleted ATP levels, suggesting Abeta may induce
neurotoxicity in part by compromising neuronal energy. ALCAR prevented
ATP depletion; therefore, ALCAR may mediate its protective effect by
buffering oxidative stress and maintaining ATP levels.
PMID: 12199155
Acetyle carnitine and lipoic acid
Delaying Brain Mitochondrial Decay and Aging with Mitochondrial
Antioxidants and Metabolites
Ann NY Acad Sci 2002 959: 133-166 Bruce N. Ames
Mitochondria decay with age due to the oxidation of lipids,
proteins, RNA, and DNA. Some of this decay can be reversed in aged
animals by feeding them the mitochondrial metabolites acetylcarnitine
and lipoic acid. In this review, we summarize our recent studies on the
effects of these mitochondrial metabolites and mitochondrial
antioxidants (-phenyl-N-t-butyl nitrone and N-t-butyl hydroxylamine) on
the age-associated mitochondrial decay of the brain of old rats,
neuronal cells, and human diploid fibroblast cells. In feeding studies
in old rats, these mitochondrial metabolites and antioxidants improve
the age-associated decline of ambulatory activity and memory, partially
restore mitochondrial structure and function, inhibit the
age-associated increase of oxidative damage to lipids, proteins, and
nucleic acids, elevate the levels of antioxidants, and restore the
activity and substrate binding affinity of a key mitochondrial enzyme,
carnitine acetyltrasferase. These mitochondrial metabolites and
antioxidants protect neuronal cells from neurotoxin- and
oxidant-induced toxicity and oxidative damage; delay the normal
senescence of human diploid fibroblast cells, and inhibit
oxidant-induced acceleration of senescence. These results suggest a
plausible mechanism: with age, increased oxidative damage to proteins
and lipid membranes, particularly in mitochondria, causes a deformation
of structure of enzymes, with a consequent decrease of enzyme activity
as well as substrate binding affinity for their substrates; an
increased level of substrate restores the velocity of the reaction and
restores mitochondrial function, thus delaying mitochondrial decay and
aging. This loss of activity due to coenzyme or substrate binding
appears to be true for a number of other enzymes as well, including
mitochondrial complex III and IV
Aging is characterized by a general decline in physiological
functions that affects many tissues and increases the risk of death.
The role of mitochondria in the process of the age-dependent
deterioration of tissues has become the focus of many studies with the
gradually accepted idea that mitochondrial decay is a major contributor
to aging.1-10 The age-dependent changes in mitochondria are
characterized by a high rate of generation of oxidants, a decline in
the activity of electron transport complexes, and a decrease in amount
and fatty acid composition of cardiolipin, an essential phospholipid
for normal function of mitochondria. During ATP production by oxidative
phosphorylation, electrons from NADH or succinate in the mitochondrial
matrix are transferred through the electron transport chain (complexes
I through IV) and reduce molecular oxygen to water. In this process,
about 2% of the electrons leak and reduce O2 to O·-2 radical and
H2O2. The leakage of oxidants from the electron transport chain appears
unavoidable, and mitochondria are considered the main endogenous source
for the formation of the superoxide radical. As the source of these
toxic oxidants, mitochondria are also their potential victims. Their
proximity to the oxidants they produce, combined with their exceedingly
intricate structure and the combination of continuous formation of
O·-2, as well as a limited antioxidant capacity of mitochondria, make
them vulnerable to oxidative damage. For example, mitochondria lack
catalase, the ability to synthesize GSH, the ability to transport GSSG
out of the matrix, and chelators for heavy metals, all of which act as
elements to decrease oxidant production.1-16 Mitochondrial decay is
also a contributor to acceleration of aging in the
senescence-accelerated mouse17-19 and in stress.20,21
Compared with young rats, old rats have a lower
mitochondrial potential, cardiolipin level, respiratory control ratio,
and cellular oxygen uptake and antioxidants, and have higher oxidants,
neuronal RNA oxidation, and mutagenic aldehydes from lipid
peroxidation.22-28 Heart mitochondria in old rats had significantly
lower cardiolipin content, reduced activities of cytochrome c oxidase
and adenine nucleotide translocase, and slower rates of phosphate and
pyruvate transport, palmitoylcarnitine-supported respiration, and the
exchange reactions of carnitine-carnitine and
carnitine-palmitoylcarnitine.29-34 In addition, old rats show a decline
of ambulatory activity and memory.27,35-40 Feeding old rats
acetylcarnitine and/or lipoic acid restores mitochondrial function,
lowers oxidants, inhibits oxidative damage to lipids, proteins, and
nucleic acids, enhances ambulatory activity, and improves memory, thus
reversing mitochondrial decay.22-28,31-34,36-38,41-44 Creatine, another
mitochondrial metabolite, shows neuroprotective effects in a transgenic
mouse model of Huntington's disease. Creatine may exert these
neuroprotective effects by increasing phosphocreatine levels or by
stabilizing the mitochondrial permeability transition.45 Clinical
trials in old people with creatine showed that creatine improves
exercise performance, has a beneficial effect on reducing muscle
fatigue,46-49 and increases the anaerobic power and work capacity of
both young and old sedentary persons during maximal pedaling tasks
The glutamate receptors mediate excitatory
neurotransmission in the brain and are important in memory acquisition
and learning and implicated in some neurodegenerative disorders.66-68
This receptor family is classified in three groups: the
N-methyl-d-aspartate (NMDA),
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate,
and metabotropic receptors. Excessive activation of the NMDA receptor
leads to a large influx of calcium into neurons and subsequent
generation of oxidants and oxidative stress by the stimulation of
phospholipase A2.20,69,70 Increased intracellular calcium may cause
mitochondrial dysfunction, which can result in localized oxidant
formation within mitochondria and an inability to handle free
calcium.66,71 Intact mitochondrial function appears to be essential
for neuronal resistance to excitotoxic insults. It is believed that the
reduced levels of ATP that accompany abnormal mitochondrial function
are insufficient to drive the ion pumps that maintain neuronal membrane
polarization. With depolarization of the neuronal membrane, the
magnesium that normally blocks the NMDA receptor ion channel is
extruded, and ambient extracellular levels of glutamate may become
lethal via NMDA receptor mechanism. On the basis of this mechanism, it
seems likely that compounds such as lipoic acid, which could enhance
mitochondrial function, scavenge free radicals, or increase the levels
of the antioxidants glutathione (GSH) and ascorbate, might be useful
neuroprotective agents. Lipoic acid appears to have an antiapoptotic
effect because it prevents the cells from glutamate-induced toxicity.
Figure 3 shows the dose-dependent protective effect of lipoic acid on
cell viability in HT22 cells. Lipoic acid displayed its protective
effect from 10 µM up to 1 mM under the conditions studied. Figure 4
shows the protective effect of lipoic acid on cell death induced by
glutamate, evaluated by trypan blue exclusion assay, confirming the
results of the viability assay by MTT Figure 9 shows that all forms
of lipoic acid, including the natural form R-, the unnatural form S-,
and R,S-lipoic acid as well as its reduced form, dihydrolipoic acid,
have similar protective effects whether in a short-term (24 h) or a
long-term (72 h) treatment.76,77 This result is similar to that
obtained by Wolz and Krieglstein in primary cultures of neurons from
chick embryo telencephalons and also an in vivo study in rats using
subcutaneous injection,57,58 but different from that in an ex vivo
study with isolated rat hepatocytes. (This is the famous Ames study
showing R form better than S form in the full text it also says that
the racemic mixture signigicantly protected the cell line but not as
well as the R. It did not say what the difference was.)
It has been suggested that ALCAR has antioxidant activity, which
is unexpected from its structure, and could be due to mitochondrial
improvements or metal chelation. Tesco et al.119 showed that ALCAR
protects human diploid fibroblasts from xanthine oxidase-induced
damage. Di Giacomo et al.120 showed that ALCAR inhibits lipid
peroxidation and xanthine oxidase activity in rat skeletal muscle. Kaur
et al.121 found that ALCAR reduces lipid peroxidation and lipofuscin
concentration in aged rat brain. ALCAR was also shown to inhibit
oxidant-induced DNA single-strand breaks.122 Schinetti et al.123 and
Geremia et al.124 demonstrated in vitro that ALCAR might possesses a
direct antioxidant activity. Related compounds, such as l-propionyl
carnitine and l-carnitine have been shown to have antioxidant activity
by chelating metals.125 They inhibit the age-associated increase in
lipid peroxidation126 or toxin-induced lipid peroxidation,127 elevate
antioxidants in aged rats,126 and reduce oxidant-induced DNA
single-strand breaks.122 An antioxidant role of l-propionyl carnitine
has also been implicated in ischemia-reperfusion injury.128
Arduino129,130 has suggested that carnitine and its acyl esters have a
primary antioxidant activity (inhibiting free radical generation,
scavenging the initiating free radicals, and terminating the radical
propagation reactions), and also work as secondary antioxidants
(repairing oxidized polyunsaturated fatty acids esterified in membrane
phospholipids).
A previous study showed that feeding old rats ALCAR converted
the mitochondria of liver to a more youthful state, both structurally
and functionally, and increased ambulatory activity in the old rats,
but caused an increase in oxidants.22 The increased oxidants have now
been found to be a side effect of the very high dose used.
In these cognitive tests, ALCAR showed a greater effect than
lipoic acid in the spatial memory with the Morris water maze test,
while lipoic acid showed a greater effect than ALCAR in the time
discrimination task with Skinner box test. However, in both tests, the
combination of ALCAR and lipoic acid showed synergistic action. These
results demonstrate that ALCAR and lipoic acid can lesen age-associated
memory decline in aged rats, and the combination of LA and ALCAR shows
a greater effect than LA or ALCAR alone in improving memory with a
synergistic action (Of course he is trying to sell the combination)
Oxidative decay is particularly acute in
mitochondria.1-3,5-7,19 Reactive aldehyde products from lipid
peroxidation may be one of the causes of mitochondrial dysfunction
during aging. Decreased mitochondrial cardiolipin content and change of
cardiolipin composition may be one of the causes of losing
mitochondrial integrity and function.13,22,29,34 Lack of sufficient DNA
repair in mitochondria and juxtaposition to the electron transport
system adds to susceptibility and accumulation of mtDNA and other
mitochondrial macromolecular damage. Thus, feeding high levels of
several mitochondrial biochemicals, including ALCAR, LA, creatine,
phopholipids, and fatty acids, may reverse some of the decay of aging
and age-related cognitive impairment.22,25,31,32,43,45,63,140,141
Dietary restriction can prolong maximum life span, eliminate aldehyde
products of lipid peroxidation in mitochondria, increase membrane
fluidity, decrease je level, and attenuate the declines in genomic
activity (gene expression of catalase and superoxidase dismutase), and
reduce fiber loss and mitochondrial abnormality.142,143 Dietary
restriction seems to retard this deterioration of mitochondrial
respiratory function by preserving enzymatic activities and function,
thereby increasing mitochondrial complex activity and decreasing
binding affinity to substrate
Mechanistic studies using IMR-90 cells suggest that
complex III and cytochrome c are the mitochondrial components that
interact with NtBHA (In 2003, after this study the LEF studies showed
no lifespan benefit for ALA and ALCAR.)
@Alpha lipoic acid
@creatine
@mitochondria
Lifespan vs acetyl-L-carnitine
Lifespan vs alpha lipoic acid
XXXXXXXXXXXXXXXXXXXXXXXXXX
rs1...@techemail.com
lifespan study with R-ALA in non-senescence accelerated rodents. I
don't know if they were planning on testing an ALCAR/R-ALA combination.
Olafur Pall Olafsson
rs1...@techemail.com wrote:
> It was my understanding that Ames and Hagen were going to conduct a new
> lifespan study with R-ALA in non-senescence accelerated rodents.
AFAIK that study is already underway.
Michael C Price
AFAIK the dose used (of ALC and ALA) by the LEF in their "null"
study was consderably less than the dose Ames used in his positive
studies.
Cheers,
Michael C Price
----------------------------------------
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm
<tcar...@elp.rr.com> wrote in message
news:1124478117.5...@g49g2000cwa.googlegroups.com...
timo...@my-deja.com
dose-dependent. Too little apparently not much effect too much and its
toxic though this is at extrenely high doses. The induction by CR
appears to depend on low glucose levels which are known to have this
effect. Insulin signaling doen't appear to be involved.
Tim