20 replies to this topic

[Lufega]

I'm reposting this from my regimen thread to get more exposure. NDM already mentioned lithium, valproate and ashwagandha. Thanks!

Following an electromyography, I was diagnosed with axonal polyneuropathy. There are basically less axons innervating my muscles and other areas. This finally explains the weakess and fatigue I suffer from. The problem is exclusively peripheral as a cranial MRI shows no problems. There seems to be nothing wrong with acetylcholine production like I thought previously but there is still a strong autonomic affect. The receptors and myelin sheaths are also fine. I just seem to be loosing my nerves! lol

In order to halt the progression, I know I have to find the cause. This will probably take time though. So, in the meanwhile, what does research say about substances that can induce nerve/axon regrowth?

Some of the causes the Doc. mentioned are B12 def, Mercury, cadmium & lead poisoning, H. pylori (and possibly Lyme disease), but there's a whole bunch of other causes. I wouldn't be surprised if there's a viral etiology as well. EBV??

IP6 comes to mind to chelate Mercury, cadmium & lead.

[Lufega]

Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats.
Ozay R, Bekar A, Kocaeli H, Karli N, Filiz G, Ulus IH.

Department of Neurosurgery, Uludağ University School of Medicine, 16059, Görükle, Bursa, Turkey.

BACKGROUND: Citicoline has been shown to have beneficial effects in a variety of CNS injury models. The aim of this study was to test the effects of citicoline on nerve regeneration and scarring in a rat model of peripheral nerve surgery. METHODS: Seventy adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve section and epineural suturing. Rats were assigned to the control or experiment groups to receive a topical application of 0.4 mL of saline or 0.4 mL (100 micromol/L) of citicoline, respectively. Macroscopic, histological, functional, and electromyographic assessments of nerves were performed 4 to 12 weeks after surgery. RESULTS: In the control versus citicoline-treated rats, SFI was -90 +/- 1 versus -84 +/- 1 (P < .001), -76 +/- 4 versus -61 +/- 3 (P < .001), and -66 +/- 2 versus -46 +/- 3 (P < .001) at 4, 8, and 12 weeks after surgery, respectively. At 12 weeks after surgery, axon count and diameter were 16400 +/- 600 number/mm(2) and 5.47 +/- 0.25 microm versus 22250 +/- 660 number/mm(2) (P < .001) and 6.65 +/- 0.28 microm (P < .01) in the control and citicoline-treated groups, respectively. In citicoline-treated rats, histomorphological axonal organization score at the repair site was (3.4 +/- 0.1) significantly better than that in controls (2.6 +/- 0.3) (P < .001). Peripheral nerve regeneration evaluated by EMG at 12 weeks after surgery showed significantly better results in the citicoline group (P < .05). Nerves treated with citicoline demonstrated reduced scarring at the repair site (P < .001). CONCLUSION: Our results demonstrate that citicoline promotes regeneration of peripheral nerves subjected to immediate section suturing type surgery and reduces postoperative scarring.

Thanks Rwac!

[Lufega]

Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation - A morphological study.
Wilson AD, Hart A, Wiberg M, Terenghi G.

Peripheral nerve injury frequently results in functional morbidity since standard management fails to adequately address many of the neurobiological hurdles to optimal regeneration. Neuronal survival and regeneration are neurotrophin dependent and require increased aerobic capacity. Acetyl-l-carnitine (ALCAR) facilitates this need and prevents neuronal loss. ALCAR is clinically safe and is shown here to significantly improve nerve regeneration and target organ reinnervation. Two groups of five rats underwent sciatic nerve division followed by immediate repair. One group received parenteral ALCAR (50mg/kg/day) from time of operation until termination at 12 weeks. A 'sham treatment' group received normal saline. A third group was left unoperated and did not receive any treatment. A segment of nerve was harvested between 5mm proximal and 10mm distal to the repair in operated groups, and at the corresponding level in the unoperated group. Mean axonal count in normal, non-axotomised nerve was 14,720 (SD 2378). That of the saline group (17,217 SD 1808) was not significantly different from normal nerve (P=0.0985). Mean number of myelinated axons in the ALCAR group (24,460 SD 3750) was significantly greater than both sham group (P<0.01) and normal nerve (P=0.0012). Mean myelin thickness in the saline treated group (0.408mum SD 0.067mum) was less than normal nerve (0.770mum SD 0.143mum) (P<0.001). Mean myelin thickness in the ALCAR group (0.627mum SD 0.052mum) was greater than the sham (saline) group (P<0.01) and not statistically different from normal nerve (P=0.07). ALCAR increased dermal PGP9.5 staining by 210% compared to sham treatment (P<0.0001) and significantly reduced the mean percentage weight loss in gastrocnemius muscle (ALCAR group 0.203% vs. 0.312% in sham group P=0.015). ALCAR not only increases the number of regenerating nerve fibres but also morphologically improves the quality of regeneration and target organ reinnervation. Adjuvant ALCAR treatment may improve both sensory and motor outcomes and merits further investigation.

[Lufega]

Effects of N-acetyl-cysteine on the survival and regeneration of sural sensory neurons in adult rats.
Welin D, Novikova LN, Wiberg M, Kellerth JO, Novikov LN.

Department of Integrative Medical Biology, Section of Anatomy, Umeå University, SE-901 87 Umeå, Sweden.

Microsurgical reconstruction of injured peripheral nerves often results in limited functional recovery. One contributing factor is the retrograde neuronal degeneration of sensory neurons in the dorsal root ganglia (DRG) and of motor neurons in the spinal cord. The present study investigates the neuroprotective and growth-promoting effects of N-acetyl-cysteine (NAC) on sensory DRG neurons and spinal motoneurons after sciatic axotomy and nerve grafting in adult rats. Sciatic axotomy and nerve grafting were performed at 1 week after sural DRG neurons and motoneurons were retrogradely labeled with the fluorescent tracer Fast Blue. To assess the efficacy of axonal regeneration, a second fluorescent dye Fluoro-Ruby was applied distal to the graft at 12 weeks after nerve repair. At 8-13 weeks after axotomy, only 52-56% of the sural sensory neurons remained in the lumbar DRG, while the majority of motoneurons survived the sciatic nerve injury. Nerve grafting alone or continuous intrathecal NAC treatment (2.4 mg/day) improved survival of sural DRG neurons. Combined treatment with nerve graft and NAC had significant additive effect on neuronal survival and also increased the number of sensory neurons regenerating across the graft. However, NAC treatment neither affected the number of regenerating motoneurons nor the number of myelinated axons in the nerve graft or in the distal nerve stump. The present results demonstrate that NAC provides a highly significant effect of neuroprotection in an animal nerve injury model and that combination with nerve grafting further attenuates retrograde cell death and promotes regeneration of sensory neurons.

[rwac]

Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons

RM Lindsay
Sandoz Institute for Medical Research, London, England.

Largely on the basis of studies with nerve growth factor (NGF), it is now widely accepted that development of the peripheral nervous system of vertebrates is dependent in part on the interaction of immature sensory and autonomic neurons with specific survival factors that are derived from peripheral target fields. I have found, in marked contrast to an absolute requirement for NGF during development, that adult rat dorsal root ganglion sensory neurons are not dependent on NGF or other survival factors for long-term (3-4 weeks) maintenance in vitro. When dissociated and enriched, at least 70-80% of adult DRG neurons survived and extended long processes either in the absence of exogenously added NGF or upon the removal of any possible source of endogenous NGF or other neurotrophic activity (i.e., nonneuronal cells, in chemically defined culture medium, in the presence of an excess of anti-NGF antibodies, or when cultured as single neurons in microwells). Although not required for survival or expression of a range of complex morphologies, both NGF and brain-derived neurotrophic factor (BDNF) were found to stimulate the regeneration of axons from adult DRG neurons.

http://www.jneurosci...stract/8/7/2394


Doesn't lion's mane boost NGF ?

http://findarticles....9/ai_114820665/

Edited by rwac, 01 December 2009 - 03:36 AM.

[Lufega]

[Axonal growth inhibition by chondroitin sulfate proteoglycans in the central nervous system]
[Article in Spanish]

Díaz-Martínez NE, Velasco I.

Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.

Chondroitin sulphate proteoglycans (CSPG) are components of the extracellular matrix, consisting of peptides chemically attached covalently to chains of glycosaminoglycans. There are 4 families of CSPG including lecticans, which are found mainly in the central nervous system (CNS) of vertebrates. In vitro studies have shown a negative effect of these proteoglycans on axonal growth, mediated by depolymerization of actin filaments in the neuronal cytoskeleton. In some neurodegenerative diseases, and especially after traumatic injuries of adult CNS, there are increased levels of CSPG expression. Axonal growth inhibition by CSPG has been observed also in vivo, and therefore a strategy aimed to counteract the inhibition of axonal growth might lead to new therapies designed to restore neural circuits. There is compelling in vivo evidence that CSPG degradation by Chondroitinase ABC allows both axonal growth and functional recovery in models of injury in the mammalian CNS. These data suggest that manipulation of the response to damage could result in effective ways to promote recovery of nerve functions in neurological disorders that affect humans, such as spinal cord lesions or Parkinson disease.

This study doesn't say what effect it had on the PNS, if any. I wonder what effect Hyaluronic acid has on Axon regeneration?

Found this and several others..

Hyaluronic acid enhances peripheral nerve regeneration in vivo.
Wang KK, Nemeth IR, Seckel BR, Chakalis-Haley DP, Swann DA, Kuo JW, Bryan DJ, Cetrulo CL Jr.

Department of Plastic and Reconstructive Surgery, Lahey Clinic Medical Center, Burlington, MA 01805, USA.

Hyaluronic acid has been shown to enhance peripheral nerve regeneration in vitro. It has been proposed that, during the fibrin matrix phase of regeneration, hyaluronic acid organizes the extracellular matrix into a hydrated open lattice, thereby facilitating migration of the regenerating axons. Hyaluronic acid solutions and saline control solutions were injected into a nerve guide spanning a transected gap in the sciatic nerve of Sprague-Dawley rats (five in each group). Nerve conduction velocities were measured at 4 weeks by electromyography (EMG) before sacrifice of the animals. These studies demonstrated increased conduction velocities in the hyaluronic acid group compared with control animals (P = 0.006). After the animals were sacrificed, regenerated axon cables were quantified histologically, and axon branching was delineated by retrograde tracer analysis. In addition, the hyaluronic acid group showed an increase in myelinated axon counts at 4 weeks (P= 0.03). An increase in retrograde flow was demonstrated in the hyaluronic acid groups compared with animals receiving saline solution.

[Matt]

GOOD LUCK healing. Took me quite along time to recover fully from peripheral neuropathy from Ciprofloxacin... many many symptoms, including autonomic issues. Will try list some things tomorrow that I found helped after I did some research.

[medicineman]

Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.^[17] Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (arthritis, congestive heart failure, Parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, and neuroprotection).^{[citation needed]}

A study demonstrated that creatine is twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to cell death.^[18] A similarly promising result has been obtained in prolonging the life of transgenic mice affected by Huntington's disease. Creatine treatment lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate, and delayed the development of hyperglycemia.^[19]

Given the results in animal studies, creatine is just beginning to be explored in several multi-center clinical studies in the USA and elsewhere.^{[citation needed]}.

[medicineman]

Im not sure if it does anything for axonal regeneration, but thats all I can think of that can help any muscular symptoms as a result of neuromuscular degeneration.

[Lufega]

Thank you that medicineman. I've seen a couple of posts here about the best type of creatine. Any ideas?

[medicineman]

Im not sure about brands, but stick to creatine monohydrate, don't go for any of the other formulated BS..... And skip the loading dose, just do 3-5 grams a day. Our ancestors had plenty of creatine in the form of raw meat, and a study done on rats with moderate kidney failure showed that supplementing creatine did not worsen their condition.... Do 6 weeks, and take a week break for safety.

[DeadMeat]

Another one for your collection: the ethanolic extract of Centella asiatica(Gotu Kola).
http://www.ncbi.nlm....pubmed/16105244

Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro.
Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG.

Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland OR 97239, USA.

Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.

[Lufega]

Thanks DeadMeat. I note they used an ethanolic extract. I've used the powdered extract and they don't do anything for me. Will try the alcohol extract. I just came across these:

An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease.
Simonin Y, Charron Y, Sonderegger P, Vassalli JD, Kato AC.

Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.

Various studies suggest that proteolytic activity may be involved in a number of neurodegenerative disorders, including stroke and seizure. In this report, we examined the role of tryptic serine proteases, plasminogen activators (PAs), in the evolution of a neurodegenerative disease. Transgenic mice overexpressing an axonally secreted inhibitor of serine proteases (neuroserpin) were crossed with mice characterized by a "dying-back" motor neuron disease [progressive motor neuronopathy (pmn/pmn)]. Compared with pmn/pmn mice that showed an increase in PA activity, double mutant mice had decreased PA activity in sciatic nerves and spinal cord; their lifespan was increased by 50%, their motor behavior was stabilized, and histological analysis revealed increased numbers of myelinated axons and rescue of motoneuron number and size. This is the first report showing that a class of serine proteases (PAs) may be involved in the pathogenesis of a motor neuron disease and more specifically in axonal degeneration. Inhibiting serine proteases could offer a new strategy for delaying these disorders.
PMID: 17035547 [PubMed - indexed for MEDLINE]

This ties in with my alpha-1-antitrypsin def. Funny how everything's connected.

Cellular Zn2+ chelators cause "dying-back" neurite degeneration associated with energy impairment.
Yang Y, Kawataki T, Fukui K, Koike T.

Molecular Neurobiology Laboratory, Division of Life Science, Graduate School of Life Science, Hokkaido University, Sapporo, Japan.

Most cellular zinc is tightly associated with metalloproteins and other Zn2+-dependent proteins, which along with cellular Zn2+ compartments may coordinately regulate cytoplasmic free Zn2+ levels in the picomolar range. Moreover, Zn2+-containing endosomes or protein complexes appear to move along axons or dendrites, suggesting a dynamic mechanism for trafficking, exchanging, or scavenging Zn2+ and/or Zn2+ protein complexes in neurons. It is therefore interesting to examine whether cellular Zn2+ levels might alter neurite integrity and dynamics. Here we show that membrane-permeable zinc chelators, including 1,10-phenanthroline, N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN), and zinquin, selectively elicit axon and dendrite degeneration but leave the cell body intact in sympathetic neurons. The process begins distally and then moves retrogradely, with a distinct "dying-back" pattern. An inactive isomer of 1,10-phenanthroline failed to cause neuite degeneration, and these chelators mediated their effects by selectively chelating Zn2+, but not other metals. Moreover, neurite degeneration was associated with a decrease in neuritic ATP levels and was caused by energy failure, because an exogenous supply of nicotinamide adenine dinucleotide (NAD) or its precursor nicotinamide suppressed the degeneration by delaying axonal ATP reduction caused by Zn2+ depletion. Blockage of autophagy by 3-methyladenine provided partial protection against degeneration of terminal axons or dendrites; there was, however, no obvious alteration in that of medial portions. Collectively, our results show that cellular Zn2+ depletion induces a "dying-back" degeneration characterized by an NAD- and autophagy-dependent process, independently of neurite elongation dynamics. 2007 Wiley-Liss, Inc.

Distal axonopathy is also called by "dying-back" degeneration. All these different names throw me off. Makes research a little more difficult.

[rwac]

http://www3.intersci...685071/abstract

Retinoic acid increases tissue and plasma contents of nerve growth factor and prevents neuropathy in diabetic mice

O. Arrieta , R. García-Navarrete , S. Zúñiga , G. Ordóñez , A. Ortiz , G. Palencia , D. Morales-Espinosa , N. Hernández-Pedro and J. Sotelo

KEYWORDS
Axonal myelinization • diabetes • nerve growth factor • nerve regeneration • peripheral neuropathy • retinoic acid

Eur J Clin Invest 2005; 35 (3): 201–207

Background Decreased production of nerve growth factor (NGF) may contribute to diabetic neuropathy; however, exogenous administration of NGF induces only a modest benefit. Retinoic acid (RA) promotes the endogenous expression of nerve growth factor and its receptor. We studied the effects of RA on diabetic neuropathy in mice with streptozotocin-induced diabetes.

Material and methods One hundred and twenty National Institutes of Health (NIH) albino mice randomly separated into three groups (A, n = 30; B, n = 30; C, n = 60). Diabetes mellitus was induced with streptozotocin in groups A and B. Animals from group A received a subcutaneous injection of 25 µl of mineral oil daily for 90 days, while those from group B received a subcutaneous injection of 20 mg kg−1 of all trans RA. Animals from group C were taken as controls. At the end of the experiment, blood glucose and NGF levels (both in serum and sciatic nerve) were measured. Two behavioural tests were conducted in a blind fashion to detect abnormalities of thermal and nociceptive thresholds.

Results Contents of NGF in healthy untreated mice were 1490 ± 190 pg mg−1 in nerve and 113 ± 67 pg mg−1 in serum; in diabetic untreated mice the values were 697 ± 219 pg mL−1 in nerve and 55 ± 41 pg mL−1 in serum; and in diabetic mice treated with RA the values were 2432 ± 80 pg mL−1 in nerve and 235 ± 133 pg mg−1 in serum (P < 0·002). Ultrastructural evidence of nerve regeneration and sensitivity tests improved in diabetic mice treated with RA as compared with nontreated diabetic mice.

Conclusion Our findings indicate that administration of RA increases serum and nerve contents of NGF in diabetic mice and suggest a potential therapeutic role for retinoic acid in diabetic patients.

Edited by rwac, 11 December 2009 - 09:20 PM.

[kakker]

Lufega,

Good luck to you. I started experiencing a mild tingling sensation in my hands and feet in 2001 (which has never progressed). All diagnostic tests were negative. I was evaluated by one of the top neuropathy experts in the U.S. (Norman Latov), but still nothing was found. I was never officially diagnosed with anything, although I suspect I have idiopathic small fiber neuropathy (a punch biopsy is required for the diagnosis). I hope you can find the cause as my understanding is that even after extensive evaluation neuoropathy remains idiopathic about 1/3 of the time.

[rwac]

Lufega,

Good luck to you. I started experiencing a mild tingling sensation in my hands and feet in 2001 (which has never progressed). All diagnostic tests were negative. I was evaluated by one of the top neuropathy experts in the U.S. (Norman Latov), but still nothing was found. I was never officially diagnosed with anything, although I suspect I have idiopathic small fiber neuropathy (a punch biopsy is required for the diagnosis). I hope you can find the cause as my understanding is that even after extensive evaluation neuoropathy remains idiopathic about 1/3 of the time.

Have you tried the basic stuff, like Benfotiamine, Magnesium, etc ?

What's your supplement regimen like ?

[Lufega]

Lufega,

Good luck to you. I started experiencing a mild tingling sensation in my hands and feet in 2001 (which has never progressed). All diagnostic tests were negative. I was evaluated by one of the top neuropathy experts in the U.S. (Norman Latov), but still nothing was found. I was never officially diagnosed with anything, although I suspect I have idiopathic small fiber neuropathy (a punch biopsy is required for the diagnosis). I hope you can find the cause as my understanding is that even after extensive evaluation neuoropathy remains idiopathic about 1/3 of the time.

Have you tried the basic stuff, like Benfotiamine, Magnesium, etc ?

What's your supplement regimen like ?

I have. I cut back on magnesium a bit. It's a muscle relaxant and makes the muscle weakness a bit worse. Benfotiamine seemed to work, at least for my tremors, but It didn't seem to help the other parameters of the neuropathy. Plus, there's the whole cancer bit. Surpringly, I upped the dose of Butcher's broom and this seems to be helping me a lot. I posted some research in my regimen's thread showing that there is a component to the axonal degeneration that involves increased proteolytic activity from serine proteases (Elastase, trypsin, chymotrypsin). This ties in with the alpha-1- deficiency. Butcher's broom inhibits elastase rather well it appears. I think it's helping me a lot. I feel an improvement in muscle tone and volume.

Right now, I cut back on most supplements. I'm going to see a neurologist to find the cause if possible and I don't want to have variations in test results. I'm only using hyaluronic acid, NAG in the morning fasted and Butcher's broom, relora and a probiotic 3 times a day with some fish oil thrown in.

I was using horse chestnut because it inhibits hyaluronidase but I took it off my regimen. I noticed it made the skin around my face and skin sag. I can't find anything in the literature to explain why. I also saw this effect on someone else, when I suggested HC for leg venous insufficiency. The sagginess dissapears when I stop the HC. Weird.

I have an order on queue that includes antivirals (specific for EBV), Licorice root ( the autonomic portion of my neuropathy causes a pseudohypoaldosteronism, Licorice leads to pseudoHYPERaldosteronism so this should balance me out), and somethings to induce axonal generation.

I found this awsome supplement an Extract of Phaseolus Vulgaris that is used as a carb-blocker because it inhibits amylase. Research shows that it also inhibits ALL THREE serine proteases.

Edited by Lufega, 12 December 2009 - 06:24 AM.

[kakker]

Lufega,

Good luck to you. I started experiencing a mild tingling sensation in my hands and feet in 2001 (which has never progressed). All diagnostic tests were negative. I was evaluated by one of the top neuropathy experts in the U.S. (Norman Latov), but still nothing was found. I was never officially diagnosed with anything, although I suspect I have idiopathic small fiber neuropathy (a punch biopsy is required for the diagnosis). I hope you can find the cause as my understanding is that even after extensive evaluation neuoropathy remains idiopathic about 1/3 of the time.

Have you tried the basic stuff, like Benfotiamine, Magnesium, etc ?

What's your supplement regimen like ?

Yes, I was taking LE mix and super booster, benfotiamine, curcumin, fish oil, methylcobalamin, and ALCAR/ALA for years with no noticeable improvement (or decline). The "folic acid scare" has really concerned me and I have recently backed off on everything with the exception of fish oil and vitamin D. I will reintroduce some more supplements as time progresses, but I have become much more concerned about the possibility of doing more harm than good with long-term supplementation in the absence of well-designed (and long-term) research trials on humans. Fortunately, in my case, these symptoms have always been very mild and really don't bother me much.

Edited by kakker, 12 December 2009 - 01:45 PM.

[Lufega]

Vitamin D

Vitamin D2 potentiates axon regeneration.
Chabas JF, Alluin O, Rao G, Garcia S, Lavaut MN, Risso JJ, Legre R, Magalon G, Khrestchatisky M, Marqueste T, Decherchi P, Feron F.

Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184, Université de la Méditerranée, Service de Chirurgie de la Main, Hopitaux de Marseille, Marseille, France.

To date, the use of autograft tissue remains the "gold standard" technique for repairing transected peripheral nerves. However, the recovery is suboptimal, and neuroactive molecules are required. In the current study, we focused our attention on vitamin D, an FDA-approved molecule whose neuroprotective and neurotrophic actions are increasingly recognized. We assessed the therapeutic potential of ergocalciferol--the plant-derived form of vitamin D, named vitamin D2--in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury.

Therapeutic effect of vitamin D3 in a rat diffuse axonal injury model.
Malcok UA, Sengul G, Kadioglu HH, Aydin IH.

Department of Neurosurgery, Medical School, Ataturk University, Erzurum, Turkey. umitali@atauni.edu.tr

We investigated the therapeutic effect of vitamin D3 in a rat diffuse axonal injury model. A total of 60 male Sprague-Dawley rats weighing 175-200 g were anaesthetized and subjected to head trauma using Marmarou's impact-acceleration model. The rats were then separated into two groups; one group was treated with vitamin D3 and the other with saline for up to 4 days after the head trauma. Rats from both groups were killed 1, 3 or 8 days post-injury. The brains were examined histopathologically and scored according to the level of neuronal, vascular and axonal damage. There were no significant differences between the groups after 1 or 3 days, but evaluation after 8 days revealed a significant improvement in the group treated with vitamin D3. Our data indicate that vitamin D3 has a beneficial effect in diffuse axonal injury and may be useful in the management of this condition.

1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons.
Brown J, Bianco JI, McGrath JJ, Eyles DW.

School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia.

There is an accumulation of evidence implicating a role for vitamin D(3) in the developing brain. The receptor for this seco-steroid is expressed in both neurons and glial cells, it induces nerve growth factor (NGF) and it is a potent inhibitor of mitosis and promoter of differentiation in numerous cells. We have therefore assessed the direct effect of vitamin D(3) on mitosis, neurite outgrowth, as well as NGF production as a possible mediator of those effects, in developing neurons. Using cultured embryonic hippocampal cells and explants we found the addition of vitamin D(3) significantly decreases the percentage of cultured hippocampal cells undergoing mitosis in conjunction with increases in both neurite outgrowth and NGF production. The role of vitamin D(3) during brain development warrants closer scrutiny.

[amere]

Quite an interesting collection of studies...

[Lufega]

Found other supporting studies..

Ashwagandha

Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells.


Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.

Abstract

Extension of dendrites and axons in neurons may compensate for and repair damaged neuronal circuits in the dementia brain. Our aim in the present study was to explore drugs activating neurite outgrowth and regenerating the neuronal network. We found that the methanol extract of Ashwagandha (roots of Withania somnifera; 5 microg/ml) significantly increased the percentage of cells with neurites in human neuroblastoma SK-N-SH cells. The effect of the extract was dose- and time-dependent mRNA levels of the dendritic markers MAP2 and PSD-95 by RT-PCR were found to be markedly increased by treatment with the extract, whereas those of the axonal marker Tau were not. Immunocytochemistry demonstrated the specific expression of MAP2 in neurites extended by the extract. These results suggest that the methanol extract of Ashwagandha promotes the formation of dendrites.

Withanoside IV and its active metabolite, sominone, attenuate Abeta(25-35)-induced neurodegeneration.
Kuboyama T, Tohda C, Komatsu K.

Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.

Abstract
At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 microM Abeta(25-35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone.

Neuritic regeneration and synaptic reconstruction induced by withanolide A.
Kuboyama T, Tohda C, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

Abstract
We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.

Why am I not using this stuff??

Edited by Lufega, 27 April 2010 - 04:31 PM.