Vitamins

Definition

Vitamins are micronutrients found in many foods, which are essential to proper bodily function. They act as enzymes or coenzymes, and when they are not consumed in adequate amounts, result in a deficiency syndrome. Some vitamins can be produced either by the body, or by bacteria normally resident in the intestines, but some intake from either foods or supplements is still essential. Some vitamins, when taken in large quantities, may have uses other than prevention of the deficiency syndrome.

Description

Vitamins are usually divided into two groups, the oil soluable vitamins, D, E, A and K, and the watwer soluable vitamins C and the B complex.

Vitamin A is an umbrella term for a group of related compounds, all of which can produce the same effects. Although retinol, which is chemically and alcohol, and retinal, an aldehyde, have direct action, there are a number of compounds called provitamin A carotenoids, which can be converted by the body into retinol. Retinol and retinal are called preformed vitamin A and are normally ingested in the form of animal products, paerticularly milk and liver. The provitamin compounds are most commonly found in vegetables, including carrots, peppers, tomatoes, peas and many others, however although there are many caotenoid compounds, only about 10% of the known carotenoids can be effectively converted into retinol. Beta-carotene, alpha-carotene, and beta-cryptoxanthin can all be converted into retinol, but with different degrees of efficiency, with beta-carotene being the best.

Although vitamin A would seem to be readily available, either as part of a normal diet or in the form of supplements, a deficiency has been reported both in developing nations and among low income familes in Canada. While vitamin A deficiency is relatively rare in the United States, it can be associated with other conditions, such as iron deficiency which leads to inadequate ability to store the vitamin, alcoholism, or diseases of the pancreas, liver or intestines. Chronic diarrhea may also lead to vitamin A deficiency. On occasion, vitamin A deficiency is observed among people following a vegan diet, but this can be easily remedied by eating more vitamin A rich vegetables.

The best known symptom of vitamin A deficiency is night blindness, a condition in which the ability of the eyes to adapt to low lighting is reduced. Vitamin A deficiency has also been linked to immune system impairment, particularly in the lining of the lungs, resulting in increased susceptibility to pneumonia . While some data would seem to indicate thsat vitamin A may prevent some forms of cancer , a 1996 study comparing male smokers who received vitamin A supplements with a placebo control found an 18% higher rate of lung cancer among patients in the study group.

While vitamin A is essential to the diet, it also has potential for toxicity, even in relatively modest excess (see Precautions. According to the United States National Library of Medicine, forms of vitamin A have been found useful in acute promyelocytic leukemia and improves median survival in this disease. There have been reports that vitamin A may be useful for control or prevention of cataracts and breast cancer , but the results and inconclusive. Other established uses for forms of vitamin A include treatment of acne and supportive therapy in measels and malaria.

Vitamin B₁, thiamine is found in whole grains, meat, particularly pork and liver, in nuts, beans and potatoes. It is a water soluable vitamin, which is essential for carbohydrate metabolism and nerve conduction, since it is essential for the production of actylcholine, the primary neurohormone of the parasympathetic nervous system. The deficiency syndrome associated with thiamine is Beri-Beri, and is most often seen in areas where milled rice is the major food source, since milling removes most of the outer, vitamin containing layer. A 2007 report from the Thailand Ministry of Health described an outbreak of the syndrome among fisherman who subsisted on only fish ans rice for a period of 2 months. While the earliest symptoms are known to be tiredness and irritability, followed by peripheral nerve pain , the report describes one advanced case: leg edema scrotal edema or ascites, dyspnea, chest discomfort, chest pain, extremity numbness, or extremity weakness. The other cases were similar, and 2 crewmembers died as a result of heart failure caused by the vitamin deficiency. Wernicke-Korsakoff syndrome, also called Korsakoff psychosis; Alcoholic encephalopathy, and Wernicke's disease is also related to thiamine deficiency, but is caused by inhibition of thiamine utilization by heavy alcohol use, so that it may appear even in the presence of adequate thiamine intake. The initial symptoms are double vision and eye movement problems, later evolving into memory loss , which can be severe, and ultimately hallucinations. While alcohol withdrawal and thiamine supplementation may repaier the muscle weakness, brain function does not usually recover. Untreated, Wernicke-Korsakoff syndrome leads to death .

A 2006 report from George Washington University indicated that thiamine supplementation might be of some use in control of type 2 diabetes ansd atherosclerosis , but this has not been confirmed.

vitamin B₂, riboflavin is found in meat, milk, cheese, eggs, leafy green vegetables, peas and beans. The vitamin is so common that a pure vitamin deficiency is almost never seen, but only as part of general malnutrition . Symptoms of the deficiency syndrome include sore throat, swelling of mucous membranes, mouth or lip sores, anemia , and skin disorders. There is some, very limited, evidence that riboflavin may be useful in migraine prophylaxis.

Vitamin B₃, niacin has also been called Vitamin P and nicotinic acid. It is found in dairy, poultry, meats, fish, nuts and eggs. The deficiency state is pellagra, and is marked by scaly skin sores, diarrhea, inflamed mucous membranes, mental confusion, and delusions. Beyond its vitamin applications, niacin has been recognized as a treatment for high cholesterol , but its use is limited by the frequency of adverse effects. A review, published in 2007, described new formulations that may minimize or eliminate the side effects, but success has been limited.

Vitamin B₅, pantothenic acid derives its name from “pan” meaning “from everywhere”, and is found in some quantity in virtually all food, but especially in eggs, fish, dairy products and meat. Because pantothenic acid is so prevalent in nature, a true vitamin deficiency is never seen except as part of the most severe malnutrition, and the dificiency syndrome has not been fully established. Even so, pantothenic acid is recognized as an essential nutrient because it is required for formation of coenzyme A (CoA), a molecule that is essential to the metabolism of carbohydrates , proteins, and fats, as well as for the synthesis of hormones and cholesterol. Claijms have been made that pantothenic acid can prevent hair from turning grey, lower cholesterol, relieve aerthritis, and prevent post-surgical sore throat, but none of these reports have been well documented.

Vitamin B₆, pyridoxine beans, nuts, legumes, eggs, meats, fish, whole grains, and dweficiency is extremely rare, although processing of foods does reduce the B6 content. The deficiency syndrome is similar to pellegra, and includes rash, glossitis, and cracks at the corners of the mouth. Pyridoxine deficiency can also cause cause depression , confusion, abnormal brain waves, and seizures.

Vitamin B₇, biotin has also been called cadaverine and vitamin H. There is no established deficiency state because biotin deficiency has only been seen in cases of complete malnutrition, but it is recognized as an essential component of several enzyme systems. Metabolic problems including very low blood sugars between meals, high blood ammonia, or acidic blood (acidosis) can occur. Recent studies suggest that biotin is also necessary for processes on the genetic level in cells. Like pantothenic acid, biotin is found in almost all foods.

Vitamin B9, folic acid has also been called vitamin M, and is found in leafy green vegetables, but the amount is greatly reduced if these vegetables are stored at room temperature or cooked. The Merck Manual notes that the bioavailability of folates is greater in supplements ans enriched foods than in fodstuffs as commonly consumed.

Folate deficiency is common, and may result from inadequate intake, malabsorption, or the effects of drugs, most notably methotrexate which is used to treat cancer and rheumatoid arthritis , and trimethoprim/sulfamethoxazole, an antibacterial combination, and metformin, which is used to treat diabetes type 2. Renal dialysis increases the excretion of folates. The deficiency syndrome is a megaloblastic anemia, in which red cells are released before they are mature, and so lack adequate oxygen carrying capacity. The appearance of these cells is identical to the anemia caused by vitamin B₁₂, and so tests are required to determine which supplements are required for treatment. Other symptoms of folate deficiency are diarrhea, depression, and confusion.

Vitamin B₁₂, cyanocobalamine is found only in foods of animal origen, eggs, milk, fish and meat. Vegans are advised to supplement their diets to maintain adequate cobalamine levels. Since the body is capable of storing B12, observed deficiency is rare, and is most often seen in elderly persons.

Vitamin B₁₂ deficiency can result in a megaloblastic anemia which is superficially indistinguishable from that caused by folate deficiency. A number of other uses have been studied, but some of the reports are based on epidemiologic data showing that patients with specific pathologic conditions have low B12 levels—this does not indicate that the diseases are secondary to B₁₂ deficiency. For example, it had been observed that persons with Alzheimer's Disease had low B₁₂ levels, suggesting that there might be an association, but a 2008 Swedish study was unable to show any relationship between the two. While B₁₂ defieicncies may produce some mental confusion, this was overshadowed by the deterioration caused by Alzheimer's. Similarly, low folate levels have been linked to depression, and folate injections have been given to improve the general sense of well-being, but a 2007 review from Harvard Medical School concludes that the evidence for this use is still speculative. The National Library of Medicine has reported that folate supplements are of doubtful, is any, value in sleep disorders , lung cancer and stroke .

Vitamin C also called ascorbic acid, is required for prevention of scurvy. Symptoms of scurvy include include loss of appetite, diarrhea, shortness of breath, weakness, and fever, followed by irritability, depression, leg pain, pseudoparalysis, swelling over long bones of the body, anemia, paleness, poor wound healing, corkscrew hair, dry eyes, skin thickening (hyperkeratosis), and bleeding (particularly gum bleeding, bleeding behind the eyes causing prominence…, bleeding at the joints of the ribs and sternum causing discoloration under the skin of the chest,,, skin bruising, or blood in the urine or stool).

Because vitamin C is acidic and has a high margin of safety, it has been used to acidify urine for the prevention of urinary tract infections, however reports of other uses, which include cold prevention, asthma prevention, and cancer prevention and treatment have been inconclusive at best.

Vitamin D is an oil soluable vitamin which, unlike other vitamins, can be synthesized by the human body. The vitamin can be produced by the skin during exposure to ultraviolet-B (UVB) rays in sunlight. Even so, diatary intake is necessary, paerticulaerly among the elderly, obese, and people who routinely use high levels of sun protection including sunscreens. There is also an inherited condition, familial hypo-phosphatemia which causes impaired transport and utilization of phsophate and vitamin D , which can be effectively treated with vitamin supplementation. Also, inadequate secretions drom the parathyroid gland or surgical removal of the parathyroid, can result in inadequate vitamin D utilization.

The classic vitamin D deficiency syndrome is rickets, seen among children, and marked by skeletal deformities as a result of failure of calcium utilization. In adults, the deficiency syndrome is marked by weakness both of muscles and bones. While the role of vitamin D in prevention or treatment of many bone and muscle disorders has been demonstrated, it has also been hypothesized that it may be useful in other conditions, although as of 2008, the evidence is inconclusive. There is an epidemiologic association between high vitamin D levels and a low incidence of multiple sclerosis , but further study is needed before a cause and effect relationship can be drawn. Similarly, vitamin D levels seem to have an inverse relationship to vitamin D levels, and it has been noted that blood pressure may rise in the winter, when there is less sun exposure, and decline during warmer months. This too requires additional study.

Vitamin E, tocopherols is a fat soluable vitamin with a rich history. The vitamin was discovered in 1922, when it was found to be essential for reproduction in rats. This led to the name “the antisterility vitamin”, and led to the belief that vitamin E was not only essential for reproduction, but had aphrodisiac properties. In fact, vitamin E, while essential for reproduction in rats, has no comparable effect in humans. The vitamin is well established as an antioxidant, and plays a role in maintaining the integrity of the cell membranes of red blood cells and in vitamin K utilization, but its value beyond that has not been confirmed by well designed studies. Vitamin E apparently inhibits platelet aggregation and causes some degree of vasodilation, which would lower blood pressure ansd reduce the risk of heart attacks and strokes, but clear documentation of the ability of vitamin E to prevent or treat cancer, heart disease , dementia, liver disease, and stroke has not been achieved.

In November, 2004, the American Heart Association stated that high amounts of vitamin E can be harmful. Taking 400 IU per day, or higher, may increase the risk of death, however the interpretation of the studies on which this conclusion is based has been questioned. A 2006 report indicated that higher vitamin E levels within the normal range were associated with lowered all-cause mortality as compared with a control group. A 2005 report from Harvard Medical School found vitamin E to be neither beneficial nor harmful in the course of their women's health study. The researchers concluded that 600 IU of natural source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.

Vitamin K refers to a group of chemically similar compounds which affect blood coagulation. Vitamin K1 (phytonadione) is the natural form of vitamin K, which is found in plants, and provides the primary source of vitamin K. Vitamin K2 compounds (menaquinones) are made by bacteria in the intestine, while vitamin K3 is a water soluable derivative which is useful in treating vitamin K deficiencies caused by problems in fat absorption. Vitamin K is found in green leafy vegetables, cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Cooking does not remove significant amounts of vitamin K from these foods.

Vitamin K functions in blood clotting, and to some extent in bone formation. The deficiency syndrome is marked by excess bleeding and osteoporosis .

Vitamin K deficiency is rare, although it may be seen in cases of malnutrition. More often it is associated with malabsorption syndromes or surgical procedures which limit the ability to absorb vitamins such as biliary obstruction, celiac disease or sprue, ulcerative colitis, regional enteritis, cystic fibrosis, short bowel syndrome or intestinal resection. In addition, some drugs affect the absorption of vitamin K, or destroy the intestinal flora which produce a portion of vitamin K. Coumadin, an anti-coagulant (blood thinner) which is routinely used after heart attacks or vardiovasular surgery to reduce the risks of blood clotting that might result in heart attacks or strokes acts by inhibiting vitamin K, while antibiotics may destroy the intestinal bacteria which produce the vitamin. Persons taking anticoagulant drugs are advised to maintain a constant diet in order to achieve steady vitamin K levels. For those people taking coumadin or other blood thinners as well as multivitamin preparations, it is important to check the vitamin K content of the vitamins. Some preparations do not include vitamin K, and a change of brands may alter the required dose of anti-coagulant.

Recommended dosage

The following are the recommended daily intakes for healthy persons over the age of 51, and are based on estimated needs of 97–98% of healthy people. Note that in this group, gender differences may be based

QUESTIONS TO ASK YOUR PHARMACIST

• What is best dosage form for me?
• Does the brand matter or can I buy generic vitamin supplements?
• Does the chemical form in which the vitamins are provided have any side effects profiles?
• Are there possible interactions with my OTC and prescription medical drugs?

largely on body size and are not absolute. Because many vitamins are available in different chemical forms, with different potencies, it is adviseable to check the form and RDA labeling on commercial products, and to discuss actual needs with a nutritionist , physician or pharmacist. In some cases, vitamins may be labeled in terms of activity units instead of by weight.

• Folate: 400 micrograms
• Niacin: women 14 mg, men 16 mg
• Riboflavin: women 1.1 mg, men 1.3 mg
• Thiamin: women 1.1 mg, men 1.2 mg
• Vitamin A: women 700 micrograms, men 900n micrograms
• Vitamin B6: woman 1.5 mg, men 1.7 mg
• Vitamin B12: 2.4 micrograms
• Vitamin C: women 75 mg, men 90 mg
• Vitamin D: 400 units, higher doses are recommended for people over the age of 70
• Vitamin E: 15 mg
• Vitamin K: women 90 micrograms, men 120 micrograms

Precautions

While vitamins are inherently safe in normal doses, some have toxic effects when taken in overdose.

Niacin causes severe facial flushing.

Vitamin A causes a severe hypervitaminosis syndrome which includes peeling of the skin, headache, enlargement of the liver and spleen and bone thickening. The recommended safe limit for vitamin A is 3,000 micrograms/day.

KEY TERMS

Anemia —a condition in which the blood is deficient in red blood cells, in hemoglobin, or in total volume

Atherosclerosis —presence of plaque in the inside of the arteries

Dyspnea —difficulty breathing

Edema —An excess accumulation of fluid in a tissue causing swelling

Glossitis —Inflammation of the tongue

Malnutrition —Inadequate nutrition caused by either inadequate intakwe of one or more nutrients, or failure to absorb or process the nutrients

Megaloblastic anemia —An anemia in which immature red blood cells appear in the peripheral blood

Provitamin —A chemical which can be converted into a vitamin in the body

Sternum —The breastbone

Syndrome —A collection of symptoms and signs that occur together

Type 2 diabetes —Maturity onset diabetes, a condition in which the body produces insulin, but does not use it properly

Vegan —A person who eats only vegetable products

Folate can cause peripheral neuropathy marked by a feeling of numbness. The recommended maximum daily dose is 1,000 micrograms/day

Vitamin D can cause elevated serum calcium, loss of appetite, kidney failure and abnormal bone growth. The maximu recommended daily dose is 2,000 units.

Vitamin E may cause abnormal bleeding. The maximum daily dose is 1,000 milligrams.

Side effects

When taken in normal nutritional doses, vitamins have no adverse effects.

Interactions

Vitamins do not have clinically significant interactions in nutritional doses. There may, however, be purposeful interactions when used with drugs whose mechanism of action is intended to couhteract the vitamins, such as the folate antagonists used in cancer therapy, or the anticoagulant coumadin which prevents blood clotting by inhibting vitamin K. These should be discussed with the prescriber.

Mineral oil, used as a laxative, may inhibit the absorption of oil soluable vitamins D, E, A and K.

While maintenance multi-vitamins present little risk of drug interactions , combination products which contain minerals may interact with some drugs. For example, iron, which may be present in some formulations, binds to the tetracycline antibiotics. Most of these interactions can be avoided by taking the two drugs at appropriate intervals so they are not in the digestive system at the same time.

Caregiver concerns

While routine maintenance vitamins are rarely a cause for concern, discuss the use of larger doses with a qualified professional. This is particularly true if the patient is elderly, since the vitamin needs may be higher or lower than the usual recommended dsily intakes.

Resources

BOOKS

Stanton R Vitamins: What They Do and what They Don't Do Allen & Unwin, St Leonards, NSW Australia 1999

Reynild J (ed) Martindale the Extra Pharmacopoeia 30th ed The Pharmaceutical Press London 1993

Pauling, L. Vitamin C, the Common Cold and the Flu. W.H. Freeman & Co Ltd 1977

PERIODICALS

Kirkpatrick SI, Tarasuk V Food insecurity is associated with nutrient inadequacies among Canadian adults and adolescents. J Nutr. 2008 Mar;138(3): 604-12

Albanes D, Heinonen OP, Taylor PR, et al Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst. 1996 Nov 6;88 (21): 1560-70.

Doung-ngern P, Kesornsukhon S, Kanlayanaphotporn J et al Beriberi outbreak among commercial fishermen, Thailand 2005. Southeast Asian J Trop Med Public Health. 2007 Jan;38(1): 130-5.

Arora S, Lidor A, Abularrage CJ, Weiswasser JM, et al Thiamine (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg. 2006 Sep;20(5):653-8

Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006 Jan 1;73(1):72-8

Drexel H. Nicotinic acid in the treatment of hyperlipidaemia. Fundam Clin Pharmacol. 2007 Nov;21 Suppl 2:5-6.

Gulhas N, Canpolat H, Cicek M etal Dexpanthenol pastille and benzydamine hydrochloride spray for the prevention of post-operative sore throat. Acta Anaesthesiol Scand. 2007 Feb;51(2): 239-43

Wahlin A, Fahlander K, Wahlin TB et al Vitamin B status and cognitive performance in preclinical and clinical Alzheimer's disease: data from the Kungsholmen Project. Dement Geriatr Cogn Disord. 2008;25(1):23-31

Mischoulon D, Raab MF. The role of folate in depression and dementia. J Clin Psychiatry. 2007;68 Suppl 10:28-33.

Patterson C, Feightner JW, Garcia A, et al Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ. 2008 Feb 26;178(5): 548-56

Buijsse B, Feskens EJ, Kwape et al Both alpha- and beta-carotene, but not tocopherols and vitamin C, are inversely-related to 15-year cardiovascular mortality in Dutch elderly men. J Nutr. 2008 Feb;138(2):344-50.

Munteanu A, Zingg JM, Azzi A.

Anti-atherosclerotic effects of vitamin E-myth or reality? J Cell Mol Med. 2004 Jan-Mar;8(1):59-76

Wright ME, Lawson KA, Weinstein SJ et al Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 2006 Nov;84(5):1200-7.

Lee IM, Cook NR, Gaziano JM, et al Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65

Kademian M, Bechtel M, Zirwas M. Case reports: new onset flushing due to unauthorized substitution of niacin for nicotinamide. J Drugs Dermatol. 2007 Dec;6 (12):1220-1.

OTHER

http://dietary-supplements.info.nih.gov/

http://findarticles.com/p/articles/mi_g2603/is_0005/ai_2603000575

http://www.quackwatch.org/search/webglimpse.cgi?ID=1&query=vitamin+E

http://www.musc.edu/BCMB/onlinepubs/molecularmedicinejournal/vol2002/folate_pershing.htm

http://online.factsandcomparisons.com/

http://www.hsph.harvard.edu/nutritionsource/vitamins.html HERE

http://lpi.oregonstate.edu/infocenter/vitamins.html

http://clinicaltrials.gov/search/open/intervention=vitamins

http://www.merck.com/mmpe/index.html

http://www.cfsan.fda.gov/̃dms/supplmnt.html

http://www.fda.gov/consumer/updates/vitamins111907.html

Sam Uretsky PharmD