Negative side effects associated with niacin are the flush already described, nausea and occasionally vomiting, headache, excessive release of histamine, an effect on blood sugar tolerance, skin lesions, and liver problems.37
Nausea and Vomiting—Both niacinamide and niacin will cause nausea and vomiting if the dose is too high, but a few days are required before this side effect occurs. The first reaction is mild nausea. Later, it is more pronounced and, if the dose is not reduced, it will lead to vomiting. Excessive vomiting can cause dehydration and may be one of the factors in the etiology of liver disease when it does occur. Children may not know how to describe nausea and will simply lose their appetite. When nausea is present, the dose must be reduced, but this may lower the dose below its therapeutic level. If niacin causes nausea, one can change to niacinamide or from niacinamide to niacin, or subnauseant levels of both may be required (for example, 1,500 mg of niacin, plus 1,500 mg of niacinamide provides 3,000 mg of total vitamin B3). If neither form can be tolerated, one of the esters, such as Linodil or HexaNiacin, may be used. The nauseant effect can also be reduced or eliminated by using antihistamines and antinauseants. Tranquilizers have antihistamine properties and are also anti-nauseant and are helpful in controlling nausea.
Nausea induced by excessive vitamin B3 is nearly always gone within 24–48 hours after use is discontinued. This is the best way of determining whether the nausea is coming from the vitamin or from some physical illness. When vomiting has developed, it may require two days to clear. Adequate fluid intake, small amounts every hour, will prevent dehydration.
Headache—Headache is a rare side effect, especially of niacin, and it is probably related to the histamine-releasing properties of niacin. It is never severe, being usually a mild, prolonged tension headache that can be controlled by mild analgesics. Very rarely, the vitamin B3 has to be changed to a different form, such as niacinamide or inositol hexaniacinate.
Excessive Secretion of Stomach Acid—A few patients have experienced excessive secretion of gastric juices, perhaps because the histamine released by the niacin overstimulated gastric secretion.
Effect on Sugar Tolerance—Very soon after I (A. H.) began to study the clinical and physiological properties of vitamin B3, I found that it altered the sugar tolerance curves of a few people. When it did have an effect, it decreased sugar tolerance. It is necessary to discontinue the niacin for at least five days before doing a glucose tolerance test. There is no residual effect. Diabetics may be treated with niacin and, in most cases, it has no effect on insulin requirements. These changes are usually small and require minor dosage adjustments. Niacinamide has no effect on either glucose tolerance tests or on insulin requirements.
Skin Lesions—A very small proportion of patients, particularly schizophrenics, develop a dark pigmentation of skin when they are first treated with niacin, although niacinamide has no effect. The pigmentation comes on after several months, especially on some joint surfaces. There are no symptoms (itching or rashes) associated with it. This is not acanthosis nigricans (hyperpigmentation of the skin).
Liver Problems—Rarely, vitamin B3 will cause jaundice. In working with niacin for the past fifty years, I (A. H.) can recall fewer than five patients who developed jaundice. All recovered and one went back onto niacin with no recurrences. Many of the patients were alcoholics, who are more prone to jaundice. None died and some, it was discovered, were jaundiced from tranquilizers—when they were discontinued and the niacin retained, the jaundice cleared.
Many years ago, after the cholesterol-lowering effect of niacin was confirmed, some physicians became concerned because liver function tests showed dysfunction even though no jaundice was present. They took liver biopsies on a number of patients who had used 3,000 mg of niacin per day for one year. Histological examination with electron microscope revealed no evidence of liver dysfunction. Since then, many have noted that if the test is done while patients are taking niacin, the SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) will be elevated. It is my policy to ignore these findings unless there is clinical evidence of liver dysfunction. No liver function test is valid unless the patient has been off niacin for 5–7 days; if there is no jaundice, the tests will then be normal. Apparently, liver function tests remain normal if the dose of niacin is built up slowly.
It is likely that niacin interferes with the mechanics of the liver function test or else niacin has some effect in the liver that tends to exaggerate these effects. Thus, niacin increases bilirubin levels because it competes with bilirubin at the hepatic uptake level. It induces hyperbilirubinemia in patients with Gilbert’s syndrome. It might be a good idea to do routine bilirubin values before starting niacin to determine whether Gilbert’s syndrome patients are more apt to show abnormal liver function tests on niacin.
4
Vitamin C (Ascorbic Acid)
The six-carbon vitamin C molecule (ascorbic acid, C6H8O6) probably was present in the primordial soup in which life developed on Earth, along with vitamin B3 (niacin) and perhaps other vitamins. Smaller than the simplest sugar, vitamin C preceded life by a long time, so it would be surprising if it were dangerous, for life developed and accommodated to molecules already present in the fluid. About 450 million years ago, aquatic vertebrates developed and flourished for about 100 million years, then land animals (reptiles, birds, and mammals) evolved. Fish and amphibians made ascorbic acid in their kidneys; birds are in transition from earlier forms, which used their kidneys, to later forms, which used both kidney and liver, and finally to more recent forms which use only the liver, as do most mammals.
But about 25 million years ago, our ancestors lost the ability to make ascorbic acid. Ascorbic acid resembles glucose in structure, but it is much more reactive chemically. When animals make ascorbic acid, they start from glucose. This series of reactions requires the enzyme gulonolactone oxidase, and humans and a few other species of animals lack this enzyme and so cannot make ascorbic acid. The gene that controlled its formation vanished.
Our earliest ancestors lived on diets rich in ascorbic acid. Uncooked foods in general, and especially fruits, are high in vitamin C. So are the nonmuscle organs of prey animals. The loss of ascorbic acid synthesis did not destroy the individual because there was enough ascorbate in food to maintain life. Enough advantage was gained, by the release of energy that had been required to make ascorbic acid to instead be available for other biochemical processes, that this loss of a gene became an evolutionary advantage. But once the ability to make ascorbic acid was lost, it could not be regained. Later, humans paid an enormous price in disease and death from having to live with mild to severe deficiency of ascorbic acid. As our ancestors ranged farther and farther from ascorbic acid–rich foods, the price became still more costly. The stage before death is scurvy, a major scourge of humankind. For example, far more sailors have died from scurvy than from hurricanes, shipwreck, or cannon fire. Along with humans, guinea pigs and fruit-eating bats have also become totally dependent on external sources of ascorbic acid. Even children know that their pet guinea pigs need vitamin C–rich foods or they will get sick … from scurvy. Our other domesticated animals, especially cats and dogs, appear to be following in our footsteps. Some purebred puppies suffer from hip dysplasia, an indication of canine scurvy.
Classic, really obvious scurvy is seldom seen in industrialized nations. It usually is first seen as a sallow, muddy complexion in a person who suffers loss of energy, fatigue, and intermittent joint pains. Gums become sore and bleed. There are frequent nosebleeds and skin hemorrhages. Eventually, the skin becomes dingy and brown. Teeth loosen, old healed scars