http://www.eurekalert.org/pub_releas...-cav091406.php

Public release date: 19-Sep-2006

Contact: James Newton
james.newton@childrens.harvard.edu
617-355-6420
Children's Hospital Boston

Can a vitamin alleviate chronic, progressive multiple sclerosis?
Ongoing nerve-fiber damage, disability prevented in animal study

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In mice with MS-like disease, nicotinamide delayed and reduced neurologic disability as indicated by behavioral scores (1 indicating mild weakness only in the tail; 4, paralysis involving all four limbs)....

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Researchers have found a possible way to protect people with multiple sclerosis (MS) from severe long-term disability: increase nervous-system levels of a vital compound, called nicotinamide adenine dinucleotide (NAD), by giving its chemical precursor – nicotinamide, a form of vitamin B3.

Current therapies for MS mainly address the relapsing-remitting phase of the disease, but some of these have severe side effects, and most patients eventually enter a chronic progressive phase for which there is no good treatment. Using a mouse model of MS, researchers in the Neurobiology Program at Children's Hospital Boston found strong evidence that nicotinamide may protect against nerve damage in the chronic progressive phase, when the most serious disabilities occur. Their findings appear in a cover article in the September 20 Journal of Neuroscience.

MS is a neurologic disorder in which nerve fibers, or axons, are damaged through inflammation, loss of their insulating myelin coating, and degeneration. This damage disrupts nerves' ability to conduct electrical impulses to and from the brain, causing such symptoms as fatigue, difficulty walking, pain, spasticity, and emotional and cognitive changes. Current treatments mainly protect against inflammation and myelin loss, but do not completely prevent long-term axon damage.

A team led by Shinjiro Kaneko, MD, a research fellow at Children's, and senior investigator Zhigang He, PhD, also from Children's, worked with mice that had an MS-like disease called experimental autoimmune encephalitis (EAE). Through careful experiments, they showed that nicotinamide protected the animals' axons from degeneration – not only preventing axon inflammation and myelin loss, but also protecting axons that had already lost their myelin from further degradation.

Intriguingly, mice with EAE who received daily nicotinamide injections under their skin had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treatment. The greater the dose of nicotinamide, the greater the protective effect. [See accompanying figure.]

On a scale of 1 to 5 (1 indicating mild weakness only in the tail, 4 indicating paralysis involving all four limbs, and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4. All differences between treated groups and controls were statistically significant.

Mice with the greatest neurologic deficits had the lowest levels of NAD in their spinal cord, and those with the mildest deficits had the highest NAD levels. Mice that had higher levels of an enzyme that converts nicotinamide to NAD (known as Wlds mice) responded best to treatment.

Moreover, nicotinamide significantly reduced neurologic deficits even when treatment was delayed until 10 days after the induction of EAE, raising hope that it will also be effective in the later stages of MS. "The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," says Kaneko.

In other experiments, the researchers demonstrated that nicotinamide works by increasing levels of NAD in the spinal cord and that NAD levels decrease when axons degenerate. Finally, they showed that giving NAD directly also prevented axon degeneration.

NAD is used extensively by cells to produce energy through the breakdown of carbohydrates. Its chemical precursor, nicotinamide, has several characteristics that make it a promising therapeutic agent: it readily crosses the blood-brain barrier, is inexpensive and available in any drugstore, and its close relative, vitamin B3, is already used clinically to treat pellagra (vitamin B3 deficiency), high cholesterol, and other disorders. Although nicotinamide is thought to have few side effects, the doses used in mice would translate to much higher human doses than are normally used clinically, so would need to be tested for safety.

"We hope that our work will initiate a clinical trial, and that nicotinamide could be used in real patients," Kaneko says. "In the early phase of MS, anti-inflammatory drugs may work, but long-term you need to protect against axonal damage."

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The research was funded by the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 347-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

http://www.southcoasttoday.com/daily...6/02health.htm

A possible advance in fight against multiple sclerosis
By LEE BOWMAN , Scripps Howard News Service

Researchers working with mice report that it may be possible to protect people with multiple sclerosis from long-term nerve damage by boosting levels of a vitamin derivative in the nervous system.
MS is a neurological disorder in which nerve fibers are damaged by inflammation thought to be triggered by the immune system's mistakenly attacking them.
Damage to nerve fibers and to their fatty insulating tissues, disrupts nerves' ability to conduct electrical impulses to and from the brain. This produces the symptoms of MS that include fatigue, difficulty in walking, pain, spasticity and emotional and cognitive changes.
Currently, MS treatments mainly protect against inflammation and loss of fatty insulating tissues, but don't completely prevent long-term scarring and breaking of the nerve fibers, for which there is no good treatment. And some of the drugs given to treat the early phases of the disease have severe side effects.
Researchers at Children's Hospital Boston, the pediatric teaching hospital for Harvard Medical School, worked with mice that had an MS-like disease.
The experiments, described Wednesday in the Journal of Neuroscience, showed that nicotinamide— a form of vitamin B3, or niacin — not only protected the animals' nerve fibers from degeneration and fatty insulating tissues loss, it also protected nerve fibers that have already lost insulation from degrading further.
"We hope our work will initiate a clinical trial, and that nicotinamide could be used in real patients," said Dr. Shinjiro Kaneko, a research fellow at Children's who led the study. "In the early phase of MS, anti-inflammatory drugs may work, but long-term, you need to protect against axonal (nerve fiber) damage."
On a scale of 1 to 5 (with 1 being only mild weakness in the tail; 4, paralysis in all four limbs, and 5, death from the disease), mice receiving the highest doses of daily nicotinamide injections under the skin had scores of 1 or 2, while mice not getting the vitamin had scores of 3 or 4.
Nicotinamide significantly reduced neurological symptoms even when treatment was delayed for 10 days after the onset of disease in the mice, raising hopes that it can be effective in the later stages of MS in people.
"The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage," said Kaneko.
Kaneko noted that since vitamin B3 is already used medically to treat high cholesterol and other disorders, it should have few side effects in humans being treated for MS. But he noted that the doses used in the mice would translate to much higher doses than typically given to people, so new tests for safety would be needed before there could be any tests to evaluate the drug's effectiveness.

Date of Publication: September 19, 2006 on Page

http://www.pdrhealth.com/drug_info/n...nic_0183.shtml

http://www.patient.co.uk/showdoc/30003248/

Description of Nicotinamide

Hey! I'm ready to order large quantities of this stuff, anybody else? The only thing is, I don't know how much to take. I don't want to take too much and distroy my liver, but I don't want to take so little that it doesn't do much good.

Anybody taking this form of B3 (Nicotinamide), and if so how much? I hate to jump the gun, but it is an available supplement, so I might as well try it, 'cause I'm getting old waiting for a cure.

Wadda ya think?

Sounds promising but so did many other studies using mice. Somehow they don't seem to translate well to humans??? Maybe we should try to grow tails!!!

Keeping fingers crossed anyway!!

Yep, you're probably right, Judy. We have the healthiest
un-healthy Mice in the world.

On the other hand, it's a vitamin and it's cheap.

I tried some niacin yesterday (I forgot about the flush). I felt totally sick from it and I had the worst stomach cramps, just these waves of very acute pain that doubled me over until it passed. My skin was red as a tomato all over, from head to toe. Not sure why I got so sick or if I should try to find one that doesn't flush the person.

I asked over at the new Vitamin forum here if anyone has any info on B3 that they could share about doses, side fx, etc. Hopefully one of the local gurus there might be able to help us to understand more fully effects of taking B3.

I thought the B vitamins weren't very risky. Then again I never expected to be sick yesterday either. I swear it felt like I was having contractions.

You don't want Niacin. Just get the "Nicotinamide" part of B3, it's the non flush part of Niacin. That's what I learned, anyway.

Here is some niacin/nicotinamide info for you.

Basically nicotinamide has less potential for causing the dreaded flushing(which for some is very uncomfortable)

However in very high doses nicotinamide shares toxicity warnings that
are attached to niacin also.
Here is a really good monograph from Linus Pauling Institute on both:
http://lpi.oregonstate.edu/infocente...cin/index.html

Long term niacin/nicotinamide should be monitored every 3 to 6 months with a liver test at the doctor's.

I skimmed the research and it is unclear to me how much you would need.
The toxicity listed at Linus Pauling Institute would be a guideline for you.

While it is true that the B vitamins are water soluble, and hence to not build up in the body, Niacin has other effects at high dosage.

This article also discusses NAD which is in the research articles posted here.

You can use NAD as a supplement... The NOW company makes it:
http://www.nowfoods.com/?cat_id=2822
The link above explains it.

I am sorry, I cannot advise you about doses to use.
There is a warning in one of the articles that very high doses would be needed for humans...and that would necessitate physician supervision. (we are talking in the gram range here). 500mg/day of nicotinamide is not essentially harmful, but it may be too low for your purposes here.

It is interesting none the less. I found an article in Science News, on MS, this week, using a new drug (actually an old drug recycled for this purpose).
I'll post that later today in a new thread.

If you take any form of niacin in high doses you do need to get proper amounts of vitamin b6 too. Without enough vitamin b6 you can have some problems with brain chemistry.

Niacinamide-adenine dinucleotide (NAD) is an active enzyme that is required for the proper function of vital areas of the brain. In schizophrenia, there appears to be a failure to deliver enough NAD to the brain. Vitamin b3 is required for the transformation of tryptophan, an amino acid, into NAD. If there is a niacin deficiency, this necessary transformation of trypotphan into NAD is inhibited, and there is not only a NAD deficiency established, but there is also an overload of tryptophan in the brain’s chemistry. Tryptophan is considered to be one of the most toxic of amino acids. An overload of it in the brain can be very harmful, especially if it is not properly converted into NAD, because it can cause undesirable perceptual and mood changes. If there is a b3 deficiency, for whatever reason, the consequent NAD deficiency will lead to ever-increasing tryptophan overload uninterruptedly unless and until the proper levels of b3 are given.

Pyridoxine, or vitamin b6, is used in the treatment of cerebral allergies by many Orthomolecular physicians. There is clinical evidence that pyridoxine is involved in the tryptophan-niacin metabolism previously explained. Morever, b6 is a precursor to over 60 enzyme reactions, is necessary for the proper metabolism of all amino acids, and is required for the maintenance of a stable immunologic system.

Source: Brain Allergies: The Psychonutrient Connection by William H. Philpott, MD and Dwight K. Kalita, Ph.D.

Most cases of high doses of niacin I know about are recommending the nicotinic acid form.

I used to take 5 grams of nicotinic acid per day with other nutrients like b6 and the other b vitamins. My histamine levels are balanced now. I now take about 1,500 mg. of niacinamide and 200 mg. of nicotinic acid per day.

The flusihing is actually your mast and basophil cells filling up with histamine. I found references to low histamine levels (or histamine deficiency) associated with MS. There is a simple test to find out if your histamine levels are low or high. Just buy 50 mg. of nicotinic acid. If that dose (taken on an empty stomach) causes a flush then you have high histamine levels. But if it doesn't then you probably have low levels. (You can try testing again with a higher dose to make sure that some dose will cause a flush for you.) People with high histamine levels should never use nicotinic acid.

Now that my histamine levels are balanced I don't tolerate the flush as well as I used to. But I took (5 grams of) nicotinic acid for almost two years getting a flush every single morning with that first dose and didn't mind the flush at all. I honestly think that the flushing form is better for some reason; maybe something to do with the liver. Although liver enzymes will be slightly effected by high doses of nicotinic acid.

I will use amylase, a digestive enzyme for carbs, to counter the effect of the flush. Amylase lowers histamine levels.