There are two main forms: nicotinic acid, known medically as niacin, and nicotinamide which is known medically as niacinamide. The term vitamin B-3 refers to these two and to the nicotinamide adenine dinucleotide system, NAD and NADH. NADH is the reduced form and more active than NAD. The term vitamin B-3 deficiency means a deficiency of niacin, or of niacinamide, or of nicotinamide adenine dinucleotide (NAD) or its reduced derivative NADH. No-flush niacin is inositol niacinate. It does not cause any flushing, but there is some question whether it is as effective as niacin.
Niacin is not toxic to the liver. The notion that it is, is based upon a few observations, some of which were dead wrong. Between 1940 and 1950 when the toxicity of niacin and niacinamide was studied, the LD-50 on animals was determined. The LD 50 is the amount of compound that will kill one-half of the population of animals used to test toxicity. If 100 mice are given the drug and half die that dose is the LD50; for niacin it is very high, about 4.5 grams per kilogram. This is equivalent to 225 grams (nearly half a pound) for a 110 pound female and 360 grams for a 176 pound male, or approximately 100 times as much as is normally recommended. At autopsy the animals showed elevated fatty acids in the liver.
Using the electron microscope the Mayo Clinic examined the livers of a series of their patients on niacin being treated for high blood cholesterol, and they found no evidence of pathology. This was first reported by Dr. William Parsons Jr1 (www.cholesterolnodiet.com). Dr. Parsons points out that increase in the liver function tests, unless they are very substantial i.e. over threefold, do not indicate liver pathology. There are many compounds that elevate liver enzymes including all the statins. In most patients with elevated liver function tests the values become normal in a few days even if the niacin is not discontinued. We advise all doctors that they should stop the niacin for at least five days before doing the test. With real liver pathology they will not be normal in five days, but when they are elevated with niacin they are normal within these five days
There are a few side effects which may be a nuisance, but these are not toxic reactions. Apart from a very few subjects who are allergic to the pills, either the active component or some of the fillers, most of these reactions are dose related. People must not take niacin unless they are informed of the possible side effects, both positive and negative.
1 Parsons Jr WB: The Effect of Nicotinic Acid on the Liver. Evidence Favoring Functional Alteration of Enzymatic Reactions Without Hepatocellular Damage. In Niacin in Vascular Disorders and Hyperlipemia. Ed R Altshul. CC Thomas, Springfield, Ill. 1964.
Negative Side Effects
All side effects are dose related. They occur very infrequently at the smaller dose levels and become more common with higher doses. If one wanted to enrich food with 100 milligrams niacinamide daily, it would not even be noticed by the average consumer. Smaller amounts are now being added to flour and this eradicated pellagra, the classical deficiency disease.
Niacin Flush or Vasodilatation
Niacin usually causes a flush a few minutes after it is taken. A few people will flush with 25 milligrams, more with 50, and most with 100 milligrams. The flush begins in the forehead and works its way down the body, rarely affecting the toes. The higher the initial dose, the greater is the initial flush, but if any dose causes a maximum flush, a larger dose taken later will not cause any greater flush. The capillaries are dilated and the blood flow through the organs is increased. There is an internal increase in blood flow as well as in the skin that may last up to several hours. Patients must be warned this will happen. If not, they may be very surprised and even shocked. Patients can be started on lower doses until they have adjusted to the lower intensity flush; then the dose may be increased gradually.
Each time the niacin is taken the flush is repeated, but to a much lesser degree and in most cases after a week or so it is almost all gone or is a minor nuisance at worst. However, some people do not tolerate the flush and they will have to discontinue the niacin. If the niacin routine is interrupted for several days and then resumed the same sequence of flushing will occur, but the initial flush will usually not be as strong as the original one was. The intensity of the flush is minimized by taking the pills after meals and by taking them regularly three times daily. I have been taking it for fifty years and at the maximum have very minor flushes. It is a dry flush, not like the wet menopausal flush, or the flush suffered by male hormone blockers used in treating prostate cancer.
Niacinamide does not cause flushing, except in about 1 percent of the subjects in whom it will cause a very unpleasant flush, and for these people it can not be used. Probably they convert the niacinamide too rapidly into niacin.
Vasodilatation is sometimes very helpful. Many patients, particularly arthritics, have reported that they feel much better when their joints are warmed up by the flush, and some will stop taking niacin for a few days in order to once more experience the flush, but for most people the sensation is not pleasant. It is tolerable if the patient knows what to expect and is properly prepared for it by the physician. Bill Parsons wrote that only physicians who KNOW niacin should use it.
Non flush and slow release preparations, which are also no-flush, are available. The best known no-flush product is inositol hexaniacinate, which is an ester of inositol, a vitamin, and niacin.
Other uncommon side effects are increased gastric acidity, probably because niacin does stimulate secretion of gastric juice, and increased brown pigmentation of certain areas of the skin, usually the flexor surfaces; this is not acanthosis nigricans, a very serious condition, even though it has been erroneously labeled as such. This is never a problem for patients if they are told the truth, but is a problem for some doctors who are not familiar with it. Acanthosis nigricans is a very serious, almost cancer-like condition. Parsons correctly called the increased skin pigmentation a skin change which resembles acanthosis nigricans. The similarity is only in color, not in pathology. The browning effect of niacin on a very few subjects is entirely different. It is transient, usually lasting only a few months, and when it clears the skin is perfectly normal; like an old tan, it washes off if the skin is rubbed when moist. It never recurs even with continued use. I think it is due to the deposition of melanin-containing indoles from tyrosine and adrenalin. It occurs most commonly in schizophrenic patients and is part of the healing process.
Positive Side Effects
If a person takes niacin to normalize blood lipids and as a result of the vitamin activity feels very much better in other areas such as more energy, faster healing, etc, this is a positive side effect. There are other positive side effects that often occur. For example if the person takes niacin to deal with his arthritis and at the same time his cholesterol levels decease, this result would be a major positive side effect or, better still, side benefit. Niacin lowers C-reactive protein. This is one of the markers of inflammation. The statins also lower CRP, but in contrast to the statins, niacin is not toxic.
Clinical Use of Vitamin B-3
Niacin is also called nicotinic acid, and niacinamide is called nicotinamide.
For most conditions the two forms are interchangeable. But niacin normalizes blood lipid levels and niacinamide does not. Niacin lowers low density lipoprotein cholesterol in blood; the amount of decrease depends upon the initial level. The higher the baseline level, the greater is the percentage decrease. It also lowers triglycerides, lowers Lipo-A and most important of all it elevates high density lipoprotein cholesterol (HDL). The amount of HDL in blood is the most important single measure of cardiovascular risk. Niacin may be taken together with the statins. A combination of a statin and niacin is already available. Niacinamide has no effect on blood fats. The modern slow release or non flush forms may be used when there are side effects patients find intolerable.
Niacin was the first nutrient released by the FDA to lower cholesterol levels. This was very fortunate because this made it legal for any physician to use it for other indications as well. Another unique aspect to the history of niacin is that it was not patented, cannot be patented, and its use in orthomolecular medicine was discovered with minimum funds; it is one of the few compounds with this history. Usually the total cost of a drug from conception until it is available in every drug store has been estimated at several hundred millions of dollars. And finally, our niacin-cholesterol finding is credited as the first major assault on the vitamins-as prevention paradigm.
For all other conditions either form may be used. The decision which one to use depends upon a large number of factors such as age, the cosmetic effect of the flush, whether cardiovascular problems are present and the dose needed. Some people cannot tolerate one form and may then be given the other. If the tolerance level for both forms is very low one can use both together since the therapeutic effect is additive. If patients can not tolerate more than 1.5 grams of each daily they can take 1.5 grams of each form and the total dose becomes 3 grams and is tolerable. Many patients do well with lower doses. There is no way of determining in advance how much will be needed. Fortunately, it is so safe that one can depend upon trial and error to determine the best dose, and often patients will do that themselves.
The usual starting dose of niacin is 500 to 1000 milligrams taken immediately after meals, three times daily. If one is worried about the intensity of the flush one can start with 100 milligrams and increase it slowly. A few find this much more pleasant.
The dose of niacin seldom needs to go above 2 grams taken three times daily. It may be increased, but eventually the subjects will develop nausea and later vomiting if the dose is too high and is not decreased or stopped. The optimum dose range is very wide. The same doses are used with niacinamide but the tolerable dose range is narrower; more people develop nausea with niacinamide above 6 grams daily than with niacin. Children are more tolerant to these doses. The dose is not related to size, age or body weight. Some children will not complain of nausea. They simply lose their appetite. Vitamin B-3 must be given at least three times daily. It is water soluble and very quickly excreted, making it very safe as the levels cannot build up, but also means it has to be taken frequently and regularly.
Usually the vitamin will have to be taken forever. That is why it is so important that it is safe, tolerable and economical. The indications are both psychiatric and physical. The psychiatric indications include the schizophrenias, some schizoaffective patients, most children with learning and/or behaviour disorders, and those with early senility. The common physical indications include arthritis and high blood cholesterol.
Nature loves to use fail-safe mechanisms. We have two kidneys, two lungs and I suppose if it were mechanically possible we would also have had two hearts. In the same way, nature uses its nutrients in many ways. Another example is the fact that ascorbic acid protects against the deposition of plaque, against the development of atherosclerosis, even in the presence of high blood cholesterol. This was first reported by Linus Pauling and was of course rejected by the medical professions. One cannot patent vitamin C for this. A recent report by a group of workers1 in New Delhi showed that rabbits made hypercholesterolemic and given enough ascorbic acid did not develop atherosclerosis. My co-worker Professor R. Altschul at the University of Saskatchewan in 1955 was the first to find that niacin lowered cholesterol in rabbits. He used the niacin I gave him from the supply I had for treating schizophrenia. By combining niacin and ascorbic acid we not only make normal all the blood lipid levels but we also ensure that even if the cholesterol remains a bit too high it will cause no harm because of the ascorbic acid.
1 Das S, Ray R, Snehlata, Das N and Srivastava LM. Effect of Ascorbic Acid on Prevention of Hypercholesterolemia Induced Atherosclerosis. Molecular and Cellular Biochemistry. In Press 2005.
Niacin and Other Medications
In common with all water soluble nutrients, niacin is compatible with all foods and with medication. It reinforces the therapeutic effect of the anti psychotics so that the dose of these powerful drugs can be reduced. It reinforces the effect of the statins in lowering cholesterol and increasing high density lipoprotein cholesterol (HDL). In 2001 the University Of Washington School Of Medicine, Seattle, reported that Simvastin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels.
On November11th 2004, the Walter Reed Medical Center reported to the American Heart Association’s meeting in New Orleans results of a study they had completed. They found that giving a combination of Niaspan, an extended-release niacin preparation, with a statin, increased HDL by 23 percent in one year in a group of patients on statins alone for 4.5 years. This study marks a shift in interest from just lowering total cholesterol to increasing HDL. There is a much closer correlation between low HDL levels and cardiac episodes than with any other lipid in the blood. There is no reason why the statins and niacin cannot be combined, but if the statins are used it is wise to also add coenzyme Q10 up to 100 milligrams three times a day. The statins inhibit the formation of coenzyme Q10, a very important heart muscle enzyme necessary for heart muscle activity.