I just found that the file format "rar" is not known to vbulletin! Kind of surprising. So, I'll do it the old fashioned way....

Summary: Alpha Lipoic Acid, Acetyl-L-Carnitine, L-Carnosine

1- Accelerates nerve regeneration.
2- Improves nerve conduction.
3- Acts to preserve normal enteric peptide balance.
4- Restores mitochondrial function.
5- Improves cognition.
6- Synergizes with fatty acids.
7- Acts against glycation (Lewy bodies).



1: Endocr Res. 1997 Feb-May;23(1-2):27-36.

Acetyl-L-carnitine effects on nerve conduction and glycemic regulation in
experimental diabetes.

Soneru IL, Khan T, Orfalian Z, Abraira C.

Extended Care & Geriatrics Service (181C), Hines VA Hospital, Illinois 60141,
USA.

Acetyl-L-Carnitine (ALC), an activator of carnitine, can accelerate nerve
regeneration after experimental surgical injury in rats. In this study, we
examined the ability of ALC to improve nerve conduction velocity and its effect
on intravenous glucose tolerance test in streptozotocin-induced diabetic rats.
Diabetic (blood glucose > 200 mg%) and normal animals were treated
intraperitoneally for four weeks with ALC, 50 mg/Kg/d and 150 mg/Kg/d. Nerve
conduction velocity was measured by direct exposure of sural nerve. Two-hour
IVGTT was studied by measuring plasma glucose, insulin and free fatty acids
after intravenous injection of glucose, 1.75 gm/Kg/body weight in animals
treated either with ALC 150 md/Kg/d or saline alone. Six weeks of STZ-induced
diabetes resulted in impairment of nerve conduction velocity in animals injected
with saline (16.05 +/- 1.09 m/s), as compared to saline-treated normals who did
not receive streptozotocin (31.0 +/- 0.84 m/s, p<0.0005). Diabetic animals
treated with ALC, 150 mg/Kg/d, preserved near normal nerve conduction (27.10 +/-
1.42 m/s), compared with the saline-treated diabetic animals (p < 0.0005), but
diabetic animals treated with ALC, 50 mg/Kg/d, had a non-significant increase in
nerve conduction (23.68 +/- 1.6). ALC treatment had no effect on fasting or
post-intravenous plasma glucose in normal or diabetic rats, although it
moderately reduced baseline and 40 minute insulin levels (p < 0.02) in normal
rats as compared with their saline-treated counterparts. ALC treatment lowered
baseline free fatty acids in normal (p < 0.04) and diabetic (p < 0.03) animals,
and the 60 minute levels in the normal group only (p < 0.003). CONCLUSION: ALC
at a dose of 150 mg/Kg/d given for one month, produced near normalization of
nerve conduction velocity in streptozotocin-induced diabetes with no adverse
effects on glucose, insulin or free fatty acid levels.

PMID: 9187536 [PubMed - indexed for MEDLINE]



1: Metabolism. 1995 May;44(5):677-80.

Acetyl-L-carnitine corrects the altered peripheral nerve function of
experimental diabetes.

Lowitt S, Malone JI, Salem AF, Korthals J, Benford S.

Department of Pediatrics, University of South Florida, Tampa, USA.

Acetyl-L-carnitine (ALC) has been shown to facilitate the repair of transected
sciatic nerves. The effect of ALC (50 mg/kg/d) on the diminished nerve
conduction velocity (NCV) of rats with streptozotocin (STZ)-induced
hyperglycemia of 3 weeks' duration was evaluated. The aldose reductase
inhibitor, sorbinil, which is reported to normalize the impaired NCV associated
with experimental diabetes, was used as a positive control. Aldose reductase
inhibitors are thought to have an effect by decreasing peripheral nerve sorbitol
content and increasing nerve myo-inositol. Treatment of STZ-diabetic rats with
either ALC or sorbinil resulted in normal NCV. Sorbinil treatment was associated
with normalized sciatic nerve sorbitol and myo-inositol; ALC treatment did not
reduce the elevated sorbitol levels, but sciatic nerve myo-inositol content was
no different from nondiabetic levels. Both ALC and sorbinil treatment of
STZ-diabetic rats were associated with a reduction in the elevated
malondialdehyde (MDA) content of diabetic sciatic nerve, indicating reduced
lipid peroxidation. The beneficial effects of sorbinil and ALC on the altered
peripheral nerve function associated with diabetes were similar, but their
effects on the polyol pathway (frequently implicated in the pathogenesis of
peripheral neuropathy) were different.

PMID: 7752919 [PubMed - indexed for MEDLINE]


1: Int J Clin Pharmacol Res. 1992;12(5-6):225-30.

Peptide alterations in autonomic diabetic neuropathy prevented by
acetyl-L-carnitine.

Gorio A, Di Giulio AM, Tenconi B, Donadoni L, Germani E, Bertelli A, Mantegazza
P, Maccari F, Ramacci MT.

Department of Medical Pharmacology, Faculty of Medicine, University of Milan,
Italy.

Autonomic neuropathy and gastrointestinal problems are among the most common
complications of diabetes. In this report it is shown that a possible
correlation between the two disorders might exist, since diabetes causes a
profound alteration of the peptidergic innervation of the gut. It is reported
that 14 weeks after diabetes induction with alloxan the levels of substance P
and methionine-enkephalin are markedly reduced throughout the intestine, while
vasoactive intestinal polypeptide content is dramatically increased. Therefore
the enteric innervation of diabetic animals is completely disorganized, with
some systems undergoing atrophy and others undergoing hypertrophy. Treatment of
diabetic animals with acetyl-L-carnitine prevents the onset of the marked
peptide changes described above. The results suggest a potential for
acetyl-L-carnitine in the treatment of autonomic neuropathies.

PMID: 1284498 [PubMed - indexed for MEDLINE]



1: Brain Res. 2002 Apr 5;932(1-2):70-8.

L-carnitine accelerates the in vitro regeneration of neural network from adult
murine brain cells.

Athanassakis I, Zarifi I, Evangeliou A, Vassiliadis S.

Department of Biology, University of Crete, P.O. Box 2208, 714-09 Heraklion,
Crete, Greece. athan@biology.uoc.gr

The development, growth and regeneration of nerve cells remain an unresolved
issue. The up-to-date reported brain repair mechanisms are numerous and evidence
suggests that, apart from the required trophism, tropism, microenvironment and
specificity of the brain, a plethora of chemical, physiological and
immunological compounds can contribute to such events. Among these compounds, we
concentrated our interest on L-carnitine (L-Cn), which regulates the
beta-oxidation of long chain fatty acids necessary for brain development,
myelinization and growth. In contrast to fetal brain cells that grow easily in
culture, adult brain cells show limited neurogenesis. Here, using adult brain
cells from experimental mice, we show that although L-Cn does not improve their
proliferative activity in short-term cultures, it accelerates the growth and
differentiation of neurons, astrocytes, oligodendrocytes and ependymal cells
from neurospheres in long-term cultures. Thus, the formation of a confluent
neural network requires a 2-month period in culture. These observations provide
new insights for in vivo use of L-Cn to support brain cell development in cases
of injury or brain degenerative diseases.

PMID: 11911863 [PubMed - indexed for MEDLINE]


1: Ann N Y Acad Sci. 2004 Nov;1033:108-16.

Delaying the mitochondrial decay of aging with acetylcarnitine.

Ames BN, Liu J.

Nutritional Genomics Center, Children's Hospital Oakland Research Institute,
Oakland, CA 94609, USA. bames@chori.org

Oxidative mitochondrial decay is a major contributor to aging. Some of this
decay can be reversed in old rats by feeding them normal mitochondrial
metabolites, acetylcarnitine (ALC) and lipoic acid (LA), at high levels. Feeding
the substrate ALC with LA, a mitochondrial antioxidant, restores the velocity of
the reaction (K(m)) for ALC transferase and mitochondrial function. The
principle appears to be that, with age, increased oxidative damage to protein
causes a deformation of structure of key enzymes with a consequent lessening of
affinity (K(m)) for the enzyme substrate. The effect of age on the
enzyme-binding affinity can be mimicked by reacting it with malondialdehyde (a
lipid peroxidation product that increases with age). In old rats (vs. young
rats), mitochondrial membrane potential, cardiolipin level, respiratory control
ratio, and cellular O(2) uptake are lower; oxidants/O(2), neuron RNA oxidation,
and mutagenic aldehydes from lipid peroxidation are higher. Ambulatory activity
and cognition decline with age. Feeding old rats ALC with LA for a few weeks
restores mitochondrial function; lowers oxidants, neuron RNA oxidation, and
mutagenic aldehydes; and increases rat ambulatory activity and cognition (as
assayed with the Skinner box and Morris water maze). A recent meta-analysis of
21 double-blind clinical trials of ALC in the treatment of mild cognitive
impairment and mild Alzheimer's disease showed significant efficacy vs. placebo.
A meta-analysis of 4 clinical trials of LA for treatment of neuropathic deficits
in diabetes showed significant efficacy vs. placebo.

PMID: 15591008 [PubMed - indexed for MEDLINE]


1: Diabetologia. 1998 Apr;41(4):390-9.

Effects of alpha-lipoic acid on neurovascular function in diabetic rats:
interaction with essential fatty acids.

Cameron NE, Cotter MA, Horrobin DH, Tritschler HJ.

Department of Biomedical Sciences, University of Aberdeen, Scotland, UK.

Elevated oxidative stress and impaired n-6 essential fatty acid metabolism
contribute to defective nerve conduction velocity (NCV) and perfusion in
diabetic rats, which may be corrected by free radical scavenger and
gamma-linolenic acid (GLA) treatments. Alpha-lipoic acid (LPA) has antioxidant
actions and both LPA racemate (racLPA) and GLA treatments produced benefits in
clinical neuropathy trials. The aims were to study LPA action on neurovascular
function in diabetic rats and to investigate potential interactions for
co-treatment with GLA and other essential fatty acids. After 6 weeks of
diabetes, 2 weeks of racLPA treatment corrected 20% sciatic motor and 14%
saphenous sensory NCV deficits. The ED50 for motor NCV restoration was
approximately 38 mg kg(-1) day(-1). racLPA also corrected a 49% diabetic deficit
in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in
correcting NCV and blood flow deficits. Treatment of diabetic rats with low
doses (20 mg kg(-1) day(-1)) of racLPA and GLA, while having modest effects on
their own, showed evidence of marked synergistic action in joint treatment,
completely correcting motor NCV and blood flow deficits. This was also noted for
the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA
(ED50 9.3 mg kg(-1) day(-1), containing 3.5 mg LPA). NCV effects also showed
marked synergism when racLPA:GLA ratios were varied over a 1:3-3:1 range. In
contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid,
showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug
combinations and compounds with an order of magnitude increase in efficacy
against experimental diabetic neuropathy and are worthy of consideration for
clinical trials.

PMID: 9562342 [PubMed - indexed for MEDLINE]


1: Laryngoscope. 2002 Nov;112(11):2076-80.

Lipoic acid in the treatment of smell dysfunction following viral infection of
the upper respiratory tract.

Hummel T, Heilmann S, Huttenbriuk KB.

Department of Otorhinolaryngology, University of Dresden Medical School,
Germany. thummel@rcs.urz.tu-dresden.de

OBJECTIVES/HYPOTHESIS: The study aimed to investigate the potential therapeutic
effects of alpha-lipoic acid in olfactory loss following infections of the upper
respiratory tract. Possible mechanisms of actions include the release of nerve
growth factor and antioxidative effects, both of which may be helpful in the
regeneration of olfactory receptor neurons. STUDY DESIGN: Unblinded, prospective
clinical trial. METHODS: A total of 23 patients participated (13 women, 10 men;
mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range,
4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic
acid was used orally at a dose of 600 mg/day; it was prescribed for an average
period of 4.5 months. Olfactory function was assessed using olfactory tests for
phenyl ethyl alcohol odor threshold, odor discrimination, and odor
identification. RESULTS: Seven patients (30%) showed no change in olfactory
function. Two patients (9%) exhibited a moderate decrease in olfactory function;
in contrast, six patients (26%) showed moderate and eight patients (35%)
remarkable increase in olfactory function. Two of the 4 patients with functional
anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall,
this resulted in a significant improvement in olfactory function following
treatment (P =.002). At the end of treatment parosmias were less frequent (22%)
than at the beginning of therapy (48%). Interestingly, recovery of olfactory
function appeared to be more pronounced in younger patients than in patients
above the age of 60 years (P =.018). CONCLUSIONS: The results indicate that
alpha-lipoic acid may be helpful in patients with olfactory loss after upper
respiratory tract infection. However, to judge the true potential of this
treatment, the outcome of double-blind, placebo-controlled studies in large
groups of patients must be awaited, especially when considering the relatively
high rate of spontaneous recovery in olfactory loss after upper respiratory
tract infection.

PMID: 12439184 [PubMed - indexed for MEDLINE]


1: Diabetes Care. 2006 Nov;29(11):2365-70.

Oral treatment with alpha-lipoic acid improves symptomatic diabetic
polyneuropathy: the SYDNEY 2 trial.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N,
Raz I, Novosadova M, Maus J, Samigullin R.

FRCPE, Deutsche Diabetes-Klinik, Deutsches Diabetes-Zentrum, Leibniz-Institut an
der Heinrich-Heine-Universitat, Auf'm Hennekamp 65, 40225 Dusseldorf, Germany.
dan.ziegler@ddz.uni-duesseldorf.de

OBJECTIVE: The aim of this trial was to evaluate the effects of alpha-lipoic
acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic
patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND
METHODS: In this multicenter, randomized, double-blind, placebo-controlled
trial, 181 diabetic patients in Russia and Israel received once-daily oral doses
of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800)
of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in
period. The primary outcome measure was the change from baseline of the Total
Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and
asleep numbness of the feet. Secondary end points included individual symptoms
of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score
(NIS), and patients' global assessment of efficacy. RESULTS: Mean TSS did not
differ significantly at baseline among the treatment groups and on average
decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in
ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs.
placebo). The corresponding response rates (>/=50% reduction in TSS) were 62,
50, 56, and 26%, respectively. Significant improvements favoring all three ALA
groups were also noted for stabbing and burning pain, the NSC score, and the
patients' global assessment of efficacy. The NIS was numerically reduced. Safety
analysis showed a dose-dependent increase in nausea, vomiting, and vertigo.
CONCLUSIONS: Oral treatment with ALA for 5 weeks improved neuropathic symptoms
and deficits in patients with DSP. An oral dose of 600 mg once daily appears to
provide the optimum risk-to-benefit ratio.

PMID: 17065669 [PubMed - indexed for MEDLINE]



1: Sci Aging Knowledge Environ. 2005 May 4;2005(18)e12.

Carnosine: a versatile antioxidant and antiglycating agent.

Reddy VP, Garrett MR, Perry G, Smith MA.

Department of Chemistry, University of Missouri-Rolla, Rolla, MO 65409, USA.
preddy@umr.edu

Carnosine (beta-alanyl-L-histidine) has recently attracted much attention as a
naturally occurring antioxidant and transition-metal ion sequestering agent. It
has also been shown to act as an anti-glycating agent, inhibiting the formation
of advanced glycation end products (AGEs). Through its distinctive combination
of antioxidant and antiglycating properties, carnosine is able to attenuate
cellular oxidative stress and can inhibit the intracellular formation of
reactive oxygen species and reactive nitrogen species. By controlling oxidative
stress, suppressing glycation, and chelating metal ions, carnosine is able to
reduce harmful sequelae such as DNA damage. AGEs are known contributors to the
pathology of Alzheimer's disease, and carnosine therefore merits serious
attention as a possible therapeutic agent.

Publication Types:
Review

PMID: 15872311 [PubMed - indexed for MEDLINE]



1: Ann N Y Acad Sci. 2006 May;1067:369-74.

Would carnosine or a carnivorous diet help suppress aging and associated
pathologies?

Hipkiss AR.

Centre for Experimental Therapeutics, William Harvey Research Institute, Barts'
and the London School of Medicine and Dentistry, UK. alanandjill@lineone.net

Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues.
Carnosine has the potential to suppress many of the biochemical changes (e.g.,
protein oxidation, glycation, AGE formation, and cross-linking) that accompany
aging and associated pathologies. Glycation, generation of advanced
glycosylation end-products (AGEs), and formation of protein carbonyl groups play
important roles in aging, diabetes, its secondary complications, and
neurodegenerative conditions. Due to carnosine's antiglycating activity,
reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and
low toxicity, carnosine and related structures could be effective against
age-related protein carbonyl stress. It is suggested that carnivorous diets
could be beneficial because of their carnosine content, as the dipeptide has
been shown to suppress some diabetic complications in mice. It is also suggested
that carnosine's therapeutic potential should be explored with respect to
neurodegeneration. Olfactory tissue is normally enriched in carnosine, but
olfactory dysfunction is frequently associated with neurodegeneration. Olfactory
administration of carnosine could provide a direct route to compromised tissue,
avoiding serum carnosinases.

PMID: 16804013 [PubMed - in process]