Shielding the Brain and Nerves
In animal and test-tube studies, Methylcobalamin has been shown to protect nerve cells against a wide variety of hostile environmental situations, including lack of vital cellular fuel, thiamine deficiency (which normally causes degeneration of the nervous system), oxygen starvation, and exposure to toxins like methylmercury, botulin, or nitroprusside, and the excitotoxic nerotransmitter glutamate. And the cyanocobalamin form of B12 in your multivitamin? When tested directly, it's usually been found that regular B12 supplements don't provide the neuroprotective and neuroregenerative benefits of Methylcobalamin.

Paralyzing Viruses
Several groups of scientists have investigated the use of Methylcobalamin in Bell's palsy, and they have uniformly found that Methylcobalamin speeds the recovery of normal nerve function. In two separate human trials, patients were given either prednisone alone (a steroid anti-inflammatory drug commonly used to treat Bell's palsy), Methylcobalamin alone, or the drug and the coenzyme together. Both trials found that the time required for complete recovery was significantly shorter for people who took Methylcobalamin (whether in combination with prednisone, or even by itself) than for those who took the steroid drug alone.

Multiple Sclerosis (MS)
In a pilot trial, six people with degenerating MS received 60 milligrams of Methylcobalamin a day. The scientists compared the changes which took place in the patients' nerve function over the course of up to two years before the trial began, to the changes which happened during the six months in which the patients took Methylcobalamin. They found that there was a significant improvement in nerve function while patients took Methylcobalamin. Before Methylcobalamin, about one fifth of all measurements of nerve function suggested that the nerves were degenerating. While the patients were supplementing with Methylcobalamin, however, only half as many nerve measurements showed signs of degeneration. And while, in the time before the trial began, just 4% of the nerve measurements suggested that the nerve in question had improved, it was found that 18%, or four-and-a-half times as many nerve readings, showed signs of improvement while patients were taking Methylcobalamin.

Lou Gehrig's Disease
In a randomized, double-blind, controlled trial, 24 patients with Amyotrophic Lateral Sclerosis (ALS), better known as Lou Gehrig's disease, took megadoses of Methylcobalamin through intramuscular injection for just under a month at one of two doses (25 milligrams or 500 micrograms a day). While no results were seen in the lower dose, patients who took the higher dose of Methylcobalamin experienced increases in measurements of their nerves' ability to trigger responses in the muscles. Two patients' gaits were also noted to improve in the higher-dose group.

Alzheimer's Disease
Two trials have between them found that giving Methylcobalamin to people with Alzheimer's disease or related dementias (like Pick's disease) leads patients to have better interaction with other people and with the world around them, while improving mood and relieving neurological symptoms. The evaluation by the patients' familes and physicians was also improved. The findings in these trials on intellectual functioning were inconsistent: some scales showed improvements, but others did not. Both of these trials, however, used relatively low doses of Methylcobalamin.

A Good Guess: Parkinson's Disease
There's good reason to believe that Parkinson's disease is caused and/or accelerated by "excitotoxicity" resulting from overstimulation by the neurotransmitter glutamate. Drugs which lower glutamate levels, or which "tune down" its receptor, improve many of the symptoms of the disease, while drugs which stimulate the receptor make them worse.

So if Methylcobalamin protects neurons from the toxicity of glutamate, might it provide support for people with Parkinson's disease? Unfortunately, no clinical trials have yet been run to test this idea. But granted how safe Methylcobalamin supplements have proven to be, and its clear benefits in other neurodegenerative diseases, this essential coenzyme holds out hope as a potential way to prevent, and perhaps even to treat, this debilitating disease.

Caramelized Nerves
A string of clinical trials have reported that Methylcobalamin improves nerve function in people with diabetic neuropathy as demonstrated by things like improvements in the ability to detect gentle vibration, reduced tingling, numbness, and pain in the extremities, less feelings of "heaviness" in the legs, and the restoration of neurons' ability to efficiently transmit a signal and to properly regulate the heartbeat. Trials which have looked at the overall improvement of patients' neuropathic symptoms and signs have also reported remarkably positive results.

Eyes Under Pressure
In a controlled study, 14 patients with normal-tension glaucoma were treated with Methylcobalamin, and their progress was compared with that of 22 other normal-tension glaucoma patients who did not take Methylcobalamin supplements. While 59% of the people not taking Methylcobalamin experienced worsening sight, 86% of patients taking Methylcobalamin experienced no loss of function.

The Squeezing Spine
Lumbar spinal stenosis is the compression of the nerves in the lower spine caused by arthritis, spinal degeneration, injury, or sometimes unfortunate genes. The squeezing of the nerves leads to pain on exertion in the lower back or buttocks, which is relieved by shifting position. In a single-blind, randomized controlled trial, 152 people with lumbar spinal stenosis were given the current standard care (physiotherapy, standard drugs, and education on managing their disease), and additionally either did or did not take Methylcobalamin. For whatever reason, the dose chosen for the trial was very low (half a milligram) compared to what has been used successfully in most trials pitting Methylcobalamin against nerve disease. At this low dose, there was no improvement in pain or in the doctors' evaluations of the appearance, sensation, or function of their nerves; however, despite the clearly inadequate dose, those people who took Methylcobalamin found themselves able to walk further distances without experiencing pains than people who were not taking it.

Let There Be Light ... And Dark
Scientific journals abound with clinical trials demonstrating that Methylcobalamin puts people back on track with their circadian rhythms, thereby improving sleep quality and enhancing mental. One major reason for this effect is that Methylcobalamin makes the part of the brain which adjusts the body's internal clock more sensitive to light. In other words, it makes the message "Wake up! It's daytime now!" come through more clearly. This, in turn, brings the body's release of the "sleep hormone" melatonin back in line with the cycle of the day. Other circadian cycles - like peaks and valleys in levels of the hormone cortisol and the changes in body temperature - are also brought back in line by Methylcobalamin.

The Question of Dose
In general, most trials in which Methylcobalamin has been used to help people with various forms of diabetic neuropathy, non-diabetic neuropathy associated with uremia, peripheral facial paralysis (including Bell's palsy and Ramsay Hunt Syndrome), normal tension glaucoma and dementia (including Pick's disease and Alzheimer's disease) have used doses ranging from1.5 to 5 milligrams. On the other hand, trials involving victims of ALS (Lou Gehrig's disease) and multiple sclerosis (MS) have used much higher doses, such as 25 milligrams per day for ALS and 60 milligrams daily for MS.

Note that in some cases only one trial has ever been performed, with only a single dose used, and the results are often preliminary; it's therefore possible that higher (or lower) doses might be more effective. Because of the well-established safety of Methylcobalamin, many nutritionally-oriented physicians are working with their patients using doses considerably higher than those used in the relevant trial. There are some cases where this has seemed especially prudent to some physicians.

For instance, the evidence suggests that Methylcobalamin is much more effective against Bell's Palsy when taken within days of the initial attack; at later times, a higher dose might be more appropriate. Likewise, the only trial of Methylcobalamin in patients with lumbar spinal stenosis used only 0.5 milligrams per day - and achieved only very minor results. It seems reasonable to speculate that a higher dose might have been more effective, granted the fact that nearly all successful trials in other neurological disorders have used minimum doses of 1.5 milligrams, and many have been higher. Discuss these issues with your doctor.

There are also several neurological disorders in which there is reason to believe that Methylcobalaminmight make a good supplement choice if your physician approves, but in which no clinical trial has been performed. These would include Parkinson's disease, tinnitus, Spinal Muscular Atrophy (SMA), and people suffering with environmental illnesses who suffer with neurological signs and symptoms. In such cases, because we don't have formal human trials to use as a guideline, your physician will have to rely all the more strongly on his or her judgement.

A range of Methylcobalamin sublingual supplements are now available, making customizing your dose more convenient and affordable than at any time in the past.

References

Jalaludin MA. Methylcobalamin treatment of Bell's palsy. Methods Find Exp Clin Pharmacol. 1995 Oct; 17(8): 539-44.

Yagi N, Ishikawa Y, Fukazawa T. The effect of steroid and CH3-vB12 on peripheral facial paralysis. Otol Fukuoaka. 1981; 74(7): 1613.

Kira J, Tobimatsu S, Goto I. Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med. 1994 Feb; 33(2): 82-6.

Kaji R, Kodama M, Imamura A, Hashida T, Kohara N, Ishizu M, Inui K, Kimura J. Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials inamyotrophic lateral sclerosis: a double-blind controlled study. Muscle Nerve. 1998 Dec; 21(12): 1775-8.

Mitsuyama Y, Kogoh H. Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment - preliminary study. Jpn J Psychiatry Neurol. 1988 Mar; 42(1): 65-71.

Yaqub BA, Siddique A, Sulimani R. Effects of methylcobalamin on diabetic neuropathy. Clin Neurol Neurosurg. 1992; 94(2): 105-11.

Takahashi K, Okawa M, Matsumoto M, et al. Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders. Psychiatry Clin Neurosci. 1999 Apr; 53(2): 211-3.

Background: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline.
Objective: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom.
Design: Cognitive function was assessed with the Mini-Mental State Examination on 3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995.
Results: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 µmol/L) or MMA (from 0.25 to 0.50 µmol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant.
Conclusions: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.

Methylcobalamin treatment of Bell's palsy.
Methods Find Exp Clin Pharmacol 1995 Oct; 17(8): 539-44.
Jalaludin MA.

Sixty patients with Bell's palsy were included in an open randomized trial. Patients were assigned into three treatment groups: steroid (group 1), methylcobalamin (group 2) and methylcobalamin + steroid (group 3). Comparison between the three groups was based on the number of days needed to attain full recovery, facial nerve scores, and improvement of concomitant symptoms. The time required for complete recovery of facial nerve function was significantly shorter ( p < 0.001) in the methylcobalamin (mean of 1.95 +/- 0.51 weeks) and methylcobalamin plus steroid groups (mean of 2.05 +/- 1.23 weeks) than in the steroid group (mean of 9.60 +/- 7.79 weeks). The facial nerve score after 1-3weeks of treatment was significantly more severe (p < 0.001) in the steroid group compared to the methylcobalamin and methylcobalamin plus steroid groups. The improvement of concomitant symptoms was better in the methylcobalamin treated groups than the group treated with steroid alone.

Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis.
Intern Med 1994 Feb; 33(2): 82-6.
Kira J, Tobimatsu S, Goto I.

Serum vitamin B12 levels and unsaturated vitamin B12 binding capacities were measured in 24 patients with multiple sclerosis (MS), 73 patients with other neurological disorders and 21 healthy subjects. There was no decrease in the vitamin B12 levels, however, a significant decrease in the unsaturated vitamin B12 binding capacities was observed in patients with MS when compared with other groups. A massive dose of methyl vitamin B12 (60 mg every day for 6 months) was administered to 6 patients with chronic progressive MS, a disease which usually had a morbid prognosis and widespread demyelination in the central nervous system. Although the motor disability did not improve clinically, the abnormalities in both the visual and brainstem auditory evoked potentials improved more frequently during the therapy than in the pre-treatment period. We therefore consider that a massive dose methyl vitamin B12 therapy may be useful as an adjunct to immunosuppressive treatment for chronic progressive MS.

Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study.
Muscle Nerve 1998 Dec; 21(12): 1775-8.
Kaji R, Kodama M, Imamura A, Hashida T, Kohara N, Ishizu M, Inui K, Kimura J.

To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh-dose and low-dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double-blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting, if a larger extended trial fulfills its promise.

Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment--preliminary study.
Jpn J Psychiatry Neurol 1988 Mar; 42(1): 65-71.
Mitsuyama Y, Kogoh H.

The vitamin B12 (VB12) parameter was studied in the serum and cerebrospinal fluid (CSF) of 14 demented patients. Eleven of these patients were in a state of dementia of the degenerative type such as Alzheimer's disease, senile dementia and Pick's disease. The serum VB12 concentration in all the patients was within normal limits, i.e. 500-1,300 pg/ml. There was no significant difference between the CSF-VB12 levels and the severity of dementia. The serum and CSF-VB12 levels of the demented patients did not show any significant elevation after the oral administration of CH3-B12, 2 mg per day. On the other hand, there was a marked elevation of both the serum and CSF-VB12 after an oral medication (2 mg per day) plus intramuscular administrations (500 micrograms per day). These results confirm that the intramuscular administration of CH3-B12 is an effective way to get a higher value of the serum and CSF-VB12 levels.

Effects of methylcobalamin on diabetic neuropathy.
Clin Neurol Neurosurg 1992; 94(2): 105-11.
Yaqub BA, Siddique A, Sulimani R.

We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy. In a double-blind study, the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy. Motor and sensory nerve conduction studies showed no statistical improvement after 4 months. The drug was easily tolerated by the patients and no side effects were encountered.

Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disorders.
Psychiatry Clin Neurosci 1999 Apr; 53(2): 211-3.
Takahashi K, Okawa M, Matsumoto M, Mishima K, Yamadera H, Sasaki M, Ishizuka Y, Yamada K, Higuchi T, Okamoto N, Furuta H, Nakagawa H, Ohta T, Kuroda K, Sugita Y, Inoue Y, Uchimura N, Nagayama H, Miike T, Kamei K.

The therapeutic effect of methylcobalamin (Met-12) on sleep-wake rhythm disorders was examined in a double-blind test. In the test group, which was given a large dosage, a higher percentage of improvement was found compared to the control group with a small dosage, although the difference was not significant. The test group inconsistently showed significant improvement in both the sleep-wake cycle parameters and in clinical symptoms. The tendency was for the results to show a beneficial effect of Met-12 on rhythm disorders. However, because the percentage of improvement was low and significant improvement was inconsistent, Met-12 might be considered to have a low therapeutic potency and possible use as a booster for other treatment methods of the disorders.