September 21, 2006
Vitamin B3 Form Slows Multiple Sclerosis In Mice
Nicotinamide (aka niacinamide as distinct from niacin) is the form of vitamin B3 that does not cause flushing in your skin. Nicotinamide injected into mice provided protection to nerve cells from a mouse disease that is very similar to multiple sclerosis.
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.
This is great news because nicotinamide has very low toxicity, is cheap, and is easy to administer. Just taking large doses in pills might be enough to greatly slow the progress of MS.
The highest nicotinamide doses provided the biggest benefit.
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.
Perhaps nicotinamide works by boosting energy output so that damaged nerve cells can repair themselves faster and thereby avoid too much accumulated damage.
As much as I like high technology I even more like low tech solutions that can be put into practice immediately.
If you are wondering about dosing: The doses were 125 mg per kg and 500 mg per kg. A kilogram is 2.2 pounds. I have no idea whether the human doses would need to scale by those ratios.
Cholesterol lowering statin drugs also reduce the damage caused by MS.
CHAPEL HILL - Scientists from the University of North Carolina at Chapel Hill have established how statins -- cholesterol-lowering drugs -- inhibit inflammation and nerve cell damage caused by multiple sclerosis.
Preliminary research has shown that multiple sclerosis (MS) patients taking statins with their standard drug regimen develop less nerve cell damage over time than MS patients on standard therapy. Understanding the precise mechanisms by which statins fight multiple sclerosis is an important step toward approving the commonly used drugs for MS treatment, said Dr. Silva Markovic-Plese, associate professor of neurology, immunology and microbiology in the UNC School of Medicine.
In tests performed on blood samples from people with relapse-remitting MS, statins shut down several inflammatory processes. The statins inhibited the formation of immune-system cells called lymphocytes and monocytes, which cause inflammation by attacking the body's nerve cells.
"When we compared the effects of statins to well-understood MS therapies such as interferon, an anti-inflammatory, statins were equal if not stronger in some aspects," Markovic-Plese said. The researchers also examined blood samples from healthy people.
People suffering from MS ought to consider taking one of the statin drugs such as Crestor (Rosuvastatin), Lipitor (Atorvastatin), Zocor (Simvastatin), Mevacor (Lovastatin), Pravachol (Pravastatin), or Lescol (Fluvastatin).
Nicotinamide is more commonly known as niacin. It's used (along with other drugs, such as statins) in megadoses to reduce bad cholesterol and increase good (HDL). The dose limit is due to intense flushing and burning sensations in the skin (akin to hot flashes, I am told). You can build up to higher doses as your body becomes accustomed to it.
I am on slow-release niacin, and can tolerate about 2 grams/day. This is far below the dose level in this study. I have to wonder how the animals felt, getting such enormous amounts.
Nicotinamide is not niacin. Nicotinamide is niacinamide. It has an extra amide group added.
Thanks for the helpful link.
When you buy niacin you get nicotinic acid. That causes the flushing (skin turning red and feeling hot and perhaps even a drop in blood pressure) since it causes histamine to be released from mast cells into the blood.
When you buy niacinamide you get nicotinamide.
Yes, people sometimes use niacin to refer to both. But in vitamin bottles niacin always means nicotinic acid. They want to make clear which will cause flushing and which won't.
I believe only the nicotinic acid form substantially lowers cholesterol. People take the nicotinic acid form in time release tablets in order to avoid the flushing.
As much as I like high technology I even more like low tech solutions that can be put into practice immediately.
This remark reminded me that one of the competitors for the Methuselah Mouse Prize plans to test lifelong low-dose aspirin to determine its effects on mice over a lifetime and to see what effect it has on their healthy lifespan.
Niacinamide is the form of Niacin that is present in the brain, so it does not have to be converted in the body before it goes to the brain, reducing a step in the process where something can go wrong. However, since it is a large molecule, it still has to compete with Thiamine, Riboflabin and other large molecules to cross the blood brain barrier. This is solved by taking Pyrodoxine, Vitamin B6, which is a small molecule and selectively transports niacinamide across the blood brain barrier. So, if taking niacinamide for any brain-related reason, Pyrodoxine can assist its effectiveness. Also, it is recommended that significant amounts of Vitamin C assist in its metabolism. I take 5 grams of C a day.
I learned this nearly 30 years ago from a British doctor in Birmmingham, AL and continue to take 3 grams a day of niacinamide. For me, it is to relieve the discomfort of my alcoholism recovery and the depression that ensued, and is still present without the niacinamide. (Using it, I remain active, not depressed and very effective). I take no prescription drugs at the age of 69.
Also, in the mid-60s, I was one of two ministers who set up the Psychedelic Informatin Center in Boston, to deal with students who were taking psychedelics. a new drug came on the market which seemed like LSD, except that the high lasted for 3 days, not 12 or so hours, and almost always resulted in a bad trip. We were called and took people to the emergency room, whre they were given the antagonist of the day, thorozine. If it was the new drug, then called STP, they died, and so the medidal profession began to say that the problem was that LSD was fatal, which was wrong. However, something had to be done, and we in our group took things into our own hands and began to use mega-dose of niacinamide! It worked. The high was aborted within a half hour without side-effects, such as death.
Miacinamide, which is involved in the serotonin processes in the brain, is extremely important in many ways. Its use with multiple sclerosis should be explored further. There is no history that I can find of bad reactions to niacinamide, other possible extremely fetid bowel movements in the beginning of use. It should not be taken orally if one has stomanh uclers, of course.
This is very welcome news.
Maybe sharing my experiences may help someone.
Since first reading about this, I have been taking between four and six 250mg tablets of Nictotinamide daily. If I take them on an empty stomach they give me indigestion, but a bit of indigestion is nothing and besides, it's avoidable.
I have had MS since 2001, and it's teetering between the secondary progressive and relapsing-remitting. My last big relapse was in March this year (2006) and I have slowly improved a little since. I can walk a short distance unaided, my speech was affected a bit but now it's ok, my clonus isn't so bad. All in all, I don't function all that well, but still well enough to be able to cope with it all fairly happily. Sorry to go on about my symptoms, but I reckon that painting a good picture might be useful to other people with ms.
Anyway, three days ago I had my first relapse in 8 months. It turned out that it only lasted two or three days, and though it was pretty severe - the spasticity in my legs was such that I could barely bend them at all, now, three days later it's all passed and I am back to where I was before. In fact, I'm a tiny bit better. Anyway, I'm only boring you with all of this because I have a feeling that the Nictotinamide may have helped and caused this relapse to last only three days, instead of the week long relapse which preceeded it, and for the disability that it created to disappear as soon as the relapse disappeared, instead of the six months which the previous relapse took to reverse.
So, I would recommend anyone with MS to get some high strength nictotinamide tablets and take lots of them.
One thing that interested me is that the psychedelic Rev. Jack Zylman says that nicotinamide is a large molecule and that proxidine, or B6 helps it across the blood brain barrier. Well, on the Boston Children's hospital's site, they say that the advantaes to Nicotinamide are that it 'readily crosses the blood-brain barrier, is inexpensive and (is) available in any drugstore'. Well, this is the case, no? 100 grams of pyroxidine daily might not be essential? You see, I did take it for a week, but it made my piss smell really horrible - like the inside of a very very old burned out electric gadget. Dreadful. I'm now taking a smaller amount of pyroxidine. I'll put up with the smell of vitamin b6 if you really think it'll help, but I'd rather not.
Is it a small molecule or a large one?
Well, well, well. Good luck everyone!
High doses of B6 run the risk of damaging your kidneys. It is a diuretic. Be careful.
Thankyou Randall. I might just avoid the B6 and stick to the B3.
Also, it's interesting, and a bit of a shame, to note that the mice built up a resistance to the NAD, or rather the NAD levels dropped as their disease progressed: http://www.ninds.nih.gov/news_and_events/news_articles/news_article_MS_B3.htm
So perhaps it's only worth consuming lots and lots of pills at the onset of a relapse...
My guess is the niacinamide is good to take all the time.
I would also guess MS patients will benefit from plenty of vitamin D. MS is more common at higher latitudes and one theory to explain this is that vitamin D deficiency increases the odds of auto-immune disease. Whether Vit D will help once diagnosed with MS is hard to say though.
Also, an anti-inflammatory diet (high in omega 3 fatty acids and berries) might help too.
ginger has anti-inflamatory effect.
Hope this topic isn't entirely dead yet:)
I have RR MS for about 3-4 years now, just had my liver checked which was fine, haven't had any shoops in a long time and now i'm thinking about doing LSD for the first time. This weekend actually so my question is: is it relatively safe or should I just stay away from it?
Thanks in advance
Thanks for the article, but where can I find and read the original document. Also, has niacin therapies ever been applied clinically?
I am sooo confused. A neurologist reccommended vitamin B3 for MS. He said that it is a natural acting chemical in my body so the more the better. He suggested taking an extremely high amount. He said, "It can't hurt, so you might as well." I asked my family doctor to prescribe me the B3. She gave me a script for niacin 500mg. The side effect do not look nice and I have had several family members try to take this and were unable to handle them. I tried to read through the previous posts and the links but that has just confused me even more. Did my doctor prescribe the wrong thing? Should I go back to her and ask her for the nictotinamide? Thanks!
Other articles at the Journal of Neuroscience suggest that this has been replicated - has it?
I wonder if MS is sufficiently similar to Chronic Fatigue Syndrome for this to be meaningful to CFS patients?