Vitamin flushing effect

The conservation and flushing effects observed in vitamin B6 metabolism can be simulated by binding relationships. 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The effects of most vitamin B overdoses have not been documented, although large dosages of pyridoxine have been reported to cause peripheral neuropathies. Ataxia and numbness of the hands and feet and impairment of the senses of pain, touch, and temperature may result. Excessive niacin intake may result in flushing, pruritus, and gastrointestinal disturbances. These symptoms are due to niacin s ability to cause the release of histamine. Large dosages of niacin can result in hepatic toxicity. 

Adverse effects of niacin are most commonly seen when this vitamin is used at pharmacological doses above I g/day in the treatment of dyslipidemia. Notable adverse effects include flushing due to vasodilatation dermatological effects including dry skin pruritus and hyperkeratosis gastrointestinal effects including peptic ulcer,. stomach pain, nausea. and diarrhea elevations in serum uric acid and glucose and hepatotoxicity. ... 

Exposed skin should be washed promptly with soap and water. Dermal application of vitamin E oil preparations may be used for both prophylaxis and treatment of paresthesia. Eor contact with eyes, flush immediately and for an extended period with generous amounts of clean water or saline. Gastric lavage is indicated if patient has ingested a large amount of pyrethroid and can be treated soon after exposure. For ingestion of smaller amounts or if treatment has been delayed, activated charcoal and catharsis are indicated. Seizures can be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenytoin or phenobarbital may be helpful for recurrent seizures. No specific antidotes for pyre-throid-induced neurotoxic effects have been approved for use in humans. Spontaneous recovery usually occurs with mild or moderate intoxication. 

An understanding of basic definitions about safety and toxicity is crucial. First, all compounds, no matter how salutary, can be ingested in some manner or in some quantity that will cause toxicity. Toxicity is the capacity of a substance to produce some adverse effect or harm. Even essential components such as water and vitamins can be consumed at toxic levels. Too much pure water can cause renal shutdown excessive vitamins can cause minor problems such as flushing or nausea or major problems such as liver damage, teratogenicity, and death. The 1538 Paracelsus motto, Only the dose makes the poison, operates for food components (Jones, 1992). 

Nicotinic acid (niacin) was first shown to lower serum cholesterol levels over 40 years ago (1955). This activity is not related to its vitamin functions (nicotinamide does not share its action). At daily doses of 3 g niacin s hypocholesterolemic effects are about equivalent to clofibrate. In addition to lowering triglycerides, it can also raise HDL levels. Unfortunately, at these high doses nicotinic acid can produce intense flushes and itching, resulting in poor patient compliance. Circumventing the problem with potential pro-drugs such as nicotinyl alcohol, fructose tetranicotinate, and others were not very successful. 

Calcitonin therapy requires the concomitant oral administration of elemental calcium (500 mg/day). Clinical studies have shown that the combination of intranasal calcitonin salmon (200 lU/day), oral calcium supplementation (>1,000 mg/day of elemental calcium), and vitamin D (400 lU/day) has decreased the rate of new fractures by more than 75% and has improved vertebral BMD by as much as 3% annually (3). Calcitonin prevents the abnormal bone turnover characteristic of Paget s disease of the bone and has antiresorptive activity. In the presence of calcitonin, the osteoclast brush borders disappear, and the osteoclasts move away from the bone surface undergoing remodeling (36). Side effects are significantly more pronounced when calcitonin-salmon Is administered by injection and can include nausea, vomiting, anorexia, and flushing. Because calcitonin-salmon Is protein in nature, the possibility of a systemic allergic reaction should be considered. 

Another treatment for cholesterol is niacin. The use of niacin predates the statins. Niacin is also known as nicotinic acid or vitamin B3. The name, niacin comes from nicotinic ac id and vitamin and was coined to avoid confusion and so that people would not think that the vitamin contained nicotine or that tobacco products contained vitamins. Niacin inhibits lipoprotein synthesis by preventing the secretion of very low density lipoprotein from the liver. Very low density lipoprotein is a precursor of low density lipoproteins (LDL). However there are several adverse side effects with niacin including flushing, warm skin, itching rash, constipation, nausea, hearthum, and problems with liver function. Because of these side effects, niacin is often used in a controlled release form [17] and even in this form is unsuitable for many patients. 

In the case of a 43-year-old man, treated for 4 weeks with a total of 130 mg vitamin D3, a hypercalcaemic crisis developed following intensive exposure to the sun and he succumbed 5 weeks later from acute cardiac failure (44 -). This patient also showed other side effects of hypervitaminosis D, including anorexia, weight loss, polydipsia, polyuria, scaling and flush of the skin, exudative dermatitis, dryness of the mucous membranes, jaundice, constipation, tiredness and mental disorientation. At autopsy massive deposits of calcium salts were observed in the lungs and in the skin. 

The vitamin is safe to at least 10 x RDA. However, high doses can produce side effects including flushing, hives and GI discomfort and even liver toxicity. High doses of nicotinamide are generally better tolerated than high doses of nicotinic acid. 

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