Nicotinamide, a form of vitamin B3, lowered levels of a protein called phosphorylated tau that leads to the development of tangles, one of two brain lesions associated with Alzheimer's disease. The vitamin also strengthened scaffolding along which information travels in brain cells, helping to keep neurons alive and further preventing symptoms in mice genetically wired to develop Alzheimer's.
"Nicotinamide has a very robust effect on neurons," said Kim Green, UCI scientist and lead author of the study. "Nicotinamide prevents loss of cognition in mice with Alzheimer's disease, and the beauty of it is we already are moving forward with a clinical trial."
The study appears online Nov. 5 in the Journal of Neuroscience.
Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions.
Nicotinamide belongs to a class of compounds called HDAC inhibitors, which have been shown to protect the central nervous system in rodent models of Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. Clinical trials are underway to learn whether HDAC inhibitors help ALS and Huntington's patients.
In the nicotinamide study, Green and his colleague, Frank LaFerla, added the vitamin to drinking water fed to mice. They tested the rodents' short-term and long-term memory over time using water-maze and object-recognition tasks and found that treated Alzheimer's mice performed at the same level as normal mice, while untreated Alzheimer's mice experienced memory loss.
The nicotinamide, in fact, slightly enhanced cognitive abilities in normal mice. "This suggests that not only is it good for Alzheimer's disease, but if normal people take it, some aspects of their memory might improve," said LaFerla, UCI neurobiology and behavior professor.
Scientists also found that the nicotinamide-treated animals had dramatically lower levels of the tau protein that leads to the Alzheimer's tangle lesion. The vitamin did not affect levels of the protein beta amyloid, which clumps in the brain to form plaques, the second type of Alzheimer's lesion.
Nicotinamide, they found, led to an increase in proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. When this scaffolding breaks down, the brain cells can die. Neuronal death leads to dementia experienced by Alzheimer's patients.
"Microtubules are like highways inside cells. What we're doing with nicotinamide is making a wider, more stable highway," Green said. "In Alzheimer's disease, this highway breaks down. We are preventing that from happening.
Abstract of original article:
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability
A general dose of 1,000 milligrams taken three times a day is recommended - this dose is actually the "human equivalent" of the amount given to the mice who recovered from the symptoms of Alzheimer's in the study mentioned above.
All B Vitamins are not the same. Another study showed B vitamins were inneffective which included supplementation with folic acid and vitamins B6 and B12 for 18 months in 409 individuals with mild to moderate Alzheimer's disease. "Participants were randomly assigned to two groups of unequal size; to increase enrollment, 60 percent were treated with high-dose supplements and the remaining 40 percent treated with identical dosages of placebo. A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Cognitive abilities were measured via testing with the Alzheimer Disease Assessment Scale (ADAS-cog).
The researchers found that the ADAS-cog score did not differ significantly between treatment groups, but that symptoms of depression were more common in the high-dose supplement group.
"Our study does not support the treatment of individuals with mild to moderate Alzheimer's disease and normal vitamin levels with B vitamin supplements," the authors conclude." This study did not include vitamin B3m only B6 and B12.
Vitamin B3 (Niacin)
Vitamin B3 is one of 8 B vitamins. It is also known as niacin (nicotinic acid) and has 2 other forms, niacinamide (nicotinamide) and inositol hexanicotinate, which have different effects from niacin.
All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body metabolize fats and protein. B complex vitamins are necessary for healthy skin, hair, eyes, and liver. They also help the nervous system function properly.
Niacin also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Niacin is effective in improving circulation and reducing cholesterol levels in the blood.
All the B vitamins are water-soluble, meaning that the body does not store them.
You can meet all of your body's needs for B3 through diet; it is rare for anyone in the developed world to have a B3 deficiency. In the United States, alcoholism is the prime cause of vitamin B3 deficiency.
Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also results in burning in the mouth and a swollen, bright red tongue.
Very high doses of B3 (available by prescription) have been shown to prevent or improve symptoms of the following conditions. However, taken at high doses niacin can be toxic, so you should take doses higher than the Recommended Daily Allowance only under your doctor's supervision. Researchers are trying to determine if inositol hexanicotinate has similar benefits without serious side effects, but so far results are preliminary.
Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.
High doses (50 mg or more) of niacin can cause side effects. The most common side effect is called "niacin flush," which is a burning, tingling sensation in the face and chest, and red or "flushed" skin. Taking an aspirin 30 minutes prior to the niacin may help reduce this symptom.
At the very high doses used to lower cholesterol and treat other conditions, liver damage and stomach ulcers can occur. Your health care provider will periodically check your liver function through a blood test.
People with a history of liver disease or stomach ulcers should not take niacin supplements. Those with diabetes or gallbladder disease should do so only under the close supervision of their doctor.
Niacin should not be used if you have gout.
Taking any one of the B complex vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, it is generally important to take a B complex vitamin with any single B vitamin.
If you are currently taking any of the following medications, you should not use niacin without first talking to your health care provider.
Antibiotics, Tetracycline -- Niacin should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. (All vitamin B complex supplements act in this way and should therefore be taken at different times from tetracycline.)
Aspirin -- Taking aspirin before taking niacin may reduce flushing associated with this vitamin, but should only be done under your doctor's supervision.
Anticoagulants (blood thinners) -- Niacin may make the effects of these medications stronger, increasing the risk of bleeding.
Blood Pressure Medications, Alpha-blockers -- Niacin can make the effects of medications taken to lower blood pressure stronger, leading to the risk of low blood pressure.
Cholesterol-lowering Medications -- Niacin binds bile-acid sequestrants (cholesterol-lowering medications such as colestipol, colesevelam, and cholestyramine) and may decrease their effectiveness. For this reason, niacin and these medications should be taken at different times of the day.
Recent scientific evidence suggests that taking niacin with simvastatin (a drug that belongs to a class of cholesterol-lowering medications known as HMG-CoA reductase inhibitors, or statins), appears to slow down the progression of heart disease. However, the combination may also increase the likelihood for serious side effects, such as muscle inflammation or liver damage.
Diabetes Medications -- Niacin may increase blood glucose (sugar) levels. People taking insulin, metformin, glyburide, glipizide, or other medications used to treat high blood sugar levels should monitor their blood sugar levels closely when taking niacin supplements.
Isoniazid (INH) -- INH, a medication used to treat tuberculosis, may lower levels of niacin in the body and cause a deficiency.
Nicotine Patches -- Using nicotine patches with niacin may worsen or increase the risk of flushing associated with niacin.
Inositol hexaniacinate; Niacin; Niacinamide; Nicotinamide; Nicotinic acid
So, maybe I am grasping at straws, but adding a Niacin Supplement seems like it couldn't hurt, and may help. Once again, as with the Pomegranate Juice mentioned in another post, there is some evidence in the research of a recovery, and clearance of the tau protein clumps - at least if you happen to be a genetically-altered mouse. The jury is still out for us human-folk. I am not going to sit around and wait for the verdict. This morning I washed my 1000 mg of B3 down with a nice cold glass of Pomegranate Juice. Something seems to be working. I feel good.
Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME. Medical Disclaimer.
Comments and questions are welcome.