Vitamins

Vitamin A

Vitamin A deficiency is uncommon except with prolonged starvation. Toxicity may occur with intake above the RDA of 800 to 1000 µg retinol equivalents (> 2700 to 3300 IU); the symptoms of toxicity (liver, skin, mucous membrane, and mental changes) are nonspecific and difficult to recognize.

A diet rich in fruits and vegetables, which contain carotenoids (including -carotene), is highly recommended for everyone. -Carotene is often called pro-vitamin A but does not have the toxicity of regular vitamin A. Supplementation with -carotene alone, however, is not recommended, because high intake can turn the skin yellow-orange, and there is some concern that it may increase the risk of cancer.

Vitamin D

For the elderly, daily vitamin D intake of up to 600 to 800 IU (RDA = 200 IU [5 µg]) may strengthen bones and protect against some cancers (eg, prostate cancer). Higher intakes are not recommended because the resulting hypercalcemia rapidly increases the toxicity.

Dietary sources of vitamin D include fortified dairy products (8 oz of fortified milk contains 100 IU). Vitamin D is also produced by exposure to moderate direct sunlight, although such exposure can have photoaging and carcinogenic effects on the skin. Synthetic forms of vitamin D are under study.

Vitamin E

A low-fat diet may be deficient in vitamin E, which is found primarily in vegetable oils and the products made from these oils (eg, margarine, mayonnaise). Vitamin E is a common supplement. When taken in doses exceeding the RDA (ie, > 8 to 10 IU), the antioxidant effects of vitamin E may lower the risk of cardiovascular disease, peripheral vascular disease, and certain eye diseases. This high dose also acts as an anticoagulant, which may lower the risk of myocardial infarction. Whether the high dose increases the risk of bleeding remains unclear. Vitamin E improves cellular immune function, which potentially lowers the risk of infection. Its hypothetical protective effect against certain neurologic diseases (eg, Parkinson's disease, Alzheimer's disease) is under study.

The long-term consequences of high-dose supplementation are unknown. Vitamin E has very low toxicity at intakes < 800 IU, but vitamin E can affect coagulation in patients taking warfarin. Daily supplemental doses > 800 IU generally are not recommended. Vitamin E complex, which contains various subtypes of vitamin E, may be more beneficial than -tocopherol alone.

Thiamine

(Vitamin B₁)

Thiamine deficiency usually occurs with deficiency of the other B vitamins. Symptoms of deficiency, which are vague, include anorexia, weight loss, confusion, apathy, and weakness. Isolated thiamine deficiency can lead to beriberi, causing heart failure and peripheral nerve damage. Deficiency is very rare in developed countries but can occur with psychiatric eating disorders. Thiamine supplementation (100 mg daily) is recommended for persons with chronic alcoholism to prevent Wernicke's encephalopathy and psychosis (Korsakoff's syndrome).

Riboflavin

(Vitamin B₂)

Riboflavin deficiency generally occurs with other B-vitamin deficiencies and can manifest as inflammation of the mouth and tongue or cracking of the lips. The possible role of riboflavin in preventing migraine headaches is under study.

Pyridoxine

(Vitamin B₆)

Several drugs can affect pyridoxine function (see Table 60-1). Pyridoxine deficiency usually occurs with other water-soluble B-vitamin deficiencies. Pyridoxine may play a minor role, compared with folic acid, in causing an elevated homocysteine level in the blood and an increased risk of vascular disease. Supplementation does not lessen symptoms of carpal tunnel syndrome, contrary to some health food advertisers' claims. High intake of pyridoxine (ie, > 100 mg daily [RDA = 1.5 to 1.7 mg daily]) may increase toxicity or decrease efficacy of many drugs used to treat Parkinson's disease and seizures and can cause sensory neuropathy in the lower extremities.

Vitamin B₁₂

In younger adults, vitamin B₁₂ deficiency is usually due to loss of intrinsic factor secretion needed to absorb the vitamin in the distal ileum. In the elderly, however, more common causes of vitamin B₁₂ deficiency are decreased gastric acid production (hypochlorhydria--occurring in up to 15% of persons > 65) and Helicobacter pylori infection of the stomach. Thus, the Schilling test, which is used to measure intrinsic factor in younger adults, usually is not used to detect vitamin B₁₂ deficiency in the elderly.

Vitamin B₁₂ deficiency causes hematologic and neurologic signs and symptoms. Hematologic signs include anemia with macrocytosis and megaloblastic changes noted as hypersegmented polymorphonuclear leukocytes. Neurologic damage is independent of the hematologic changes and results in nonspecific paresthesias (eg, numbness) of the extremities, abnormal position and vibration sense, difficulty walking (ie, gait ataxia from degeneration of the posterolateral columns of the spinal cord), and mental confusion, each of which can occur in many other age-related diseases. However, vitamin B₁₂ deficiency only rarely causes symptoms similar to the slowly progressive mental changes typical of Alzheimer's disease. Although vitamin B₁₂ plays a role in homocysteine metabolism and arteriosclerosis, folic acid appears to play a much more significant role.

Vitamin B₁₂ deficiency has four hematologic stages: negative vitamin B₁₂ balance, vitamin B₁₂ depletion, vitamin B₁₂-deficient erythropoiesis, and vitamin B₁₂ deficiency anemia. The first two stages are characterized by a serum vitamin B₁₂ level of < 350 picograms [pg]/mL (< 260 picomoles [pmol/L]) and a reduced holotranscobalamin II and transcobalamin II saturation. (The latter two tests are not commercially available.) In the third stage, hypersegmented neutrophils appear, the holotranscobalamin II and the transcobalamin II saturation fall further, and serum methylmalonic acid levels begin to increase slightly. The patient is still not anemic, and the mean corpuscular volume is often normal. By the fourth stage, all standard laboratory test results are abnormal, and the patient is anemic.

The stage at which neurologic damage occurs is not known but may predate macrocytosis and anemia. Irreversible neurologic damage and dementia can occur before hypersegmentation develops and before methylmalonic acid levels rise; therefore, screening frail elderly persons for low serum vitamin B₁₂ levels is recommended. Persons who are vegans, who are infected with HIV, who are receiving prolonged antacid therapy, or who have had stomach or small-bowel surgery or disease should be monitored for early deficiency.

The serum vitamin B₁₂ determination remains the most practical way to discover vitamin B₁₂ depletion. Diagnosis is confirmed by a serum vitamin B₁₂ level < 200 pg/mL (< 150 pmol/L). Low-normal levels--those between 200 and 350 pg/mL (150 and 260 pmol/L)--should be confirmed by demonstrating an elevated serum or urine methylmalonic acid level. Early (and reversible) vitamin B₁₂ deficiency may elevate the methylmalonic acid level before the serum vitamin level falls. The Schilling test is not as useful in the elderly because decreased vitamin B₁₂ absorption is usually not due to lack of intrinsic factor, and treatment of all vitamin B₁₂ deficiency is similar.

Because it is not known which cases will progress to anemia or neurologic injury if untreated, treatment is recommended (see Table 60-2). Oral and nasal replacement forms of vitamin B₁₂ are available, but elderly persons with symptoms or signs of deficiency should be given monthly IM injections of vitamin B₁₂. The RDA for vitamin B₁₂ is only 2.4 µg, but supplemental doses as high as 1000 to 2000 µg (daily if given orally, monthly if given by injection) may be necessary when treating deficiency.

Folic Acid

(Folate)

Deficiency of folic acid, one of the water-soluble B-vitamins, is often seen with malnutrition, alcohol abuse, or use of certain substances (see Table 60-1). Folic acid plays a major role in lowering homocysteine levels. High homocysteine levels (> 10 to 15 µmol/L) are associated with a 2- to 40-fold increased risk of coronary artery disease, cerebrovascular disease, and peripheral vascular disease. The role of folic acid in preventing or treating these diseases is being studied. The RDA is 400 µg daily for adults. Intake should not exceed 1000 µg daily; a higher intake can mask hematologic signs of vitamin B₁₂ deficiency and perhaps delay its diagnosis.

Macrocytosis and anemia may develop with prolonged deficiency.

Folic acid deficiency may also play a role in depression but does not cause a slowly progressive dementia. Measurement of serum folic acid levels is a reasonable test for deficiency unless the patient's diet has changed recently, in which case red blood cell folic acid levels should be measured.

Vitamin C

Vitamin C is found in many fresh or frozen fruits and vegetables; the RDA is 60 mg (100 mg for smokers), about the amount contained in one orange. Its antioxidant effects may be protective against certain eye diseases (eg, cataracts, macular degeneration). It also helps to reactivate vitamin E, another antioxidant. Whether vitamin C plays a role in protecting against or treating cancer or viral infections is controversial.

Persons with skin fragility, easy bruisability, or poor wound healing may benefit from increased vitamin C intake (<= 500 to 1000 mg daily). However, doses >1000 mg daily are not recommended for several reasons. First, vitamin C increases iron absorption; high levels of iron may be associated with an increased risk of cardiac disease. In addition, many people carry the hemochromatosis gene and are unaware that they do so. These people accumulate toxic levels of iron and may be harmed by vitamin C supplementation. Another concern about consuming high doses of any antioxidant is that under certain conditions, antioxidants can have the opposite effect (ie, can become a pro-oxidant) and perhaps damage cells and DNA.