Consultant PharmacistForum

Vitamin E and Zinc: Putting the Hype in Perspective

Here we'll review the properties of vitamin E and zinc, including their mechanisms of action, dietary sources, the consequences of inadequate intake, and the outlook for future expanded use in clinical practice.

Vitamin E: The Next 'Wonder Drug'?

Function and physiology. Vitamin E acts as an antioxidant. It binds to lipid membranes of cells and interrupts oxidative breakdown by free radicals in the cell, thereby protecting cell membrane fatty acids from oxidative damage. As a second-line defense against free radicals, vitamin E has a synergetic relationship with selenium. Selenium enhances vitamin E, reducing its requirements, and vitamin E does the same for selenium. Hence, vitamin E and selenium work together as antioxidants to protect cell membranes from oxidative damage.

Vitamin E is absorbed (with the aid of bile) through the small intestine, then transported by blood plasma lipoproteins into the circulation and carried to target organs, where it is stored. Vitamin E is stored primarily in the adrenal and pituitary glands, adipose tissue, and liver. High concentrations are also found in the testes.

Vitamin E deficiency. Severe vitamin E deficiency is rare because the vitamin is available in many foods, easily stored, and readily reused by the body.² When deficiency does occur, the cause is usually fat malabsorption, as seen in celiac disease and cystic fibrosis. Individuals at risk for vitamin E deficiency include those with chronic liver disease or inherited red blood cell disorders, hemodialysis patients, premature and low birthweight infants, and the elderly. Symptoms of vitamin E deficiency include peripheral neuropathy and ataxia.

Sources and requirements. The primary dietary sources of vitamin E are the vegetable oils-corn, safflower, sunflower, and cottonseed. Other sources include nuts and whole grains. Since these food sources are also high in polyunsaturated fats, the recommended daily allowance of vitamin E is only 10 mg for men and 8 mg for women.

Novel clinical uses. A great deal of attention is currently focused on the potential for use of vitamin E in treatment of dementia, as well as mild cognitive impairments. Antioxidants have been implicated in processes related to aging, selective neuronal damage, and atherosclerosis, all of which ultimately affect cognitive functioning.

It is thought that free radical oxidative processes cause neuronal death, thereby contributing to the loss of cognitive function in dementia. There is mounting evidence that oxidative stress may be associated with the onset and progression of Alzheimer's disease (AD). Vitamin E is being promoted to enhance mental function and delay cognitive loss. It interacts with the cell membranes and traps free radicals, resulting in interference with the chain reaction that damages cells.³ It also inhibits lipid peroxidation and reduces cell death associated with beta-amyloid protein. It is soluble in the central nervous system and thus remains localized in the lipid membrane, where it prevents and suppresses lipid peroxidation. Vitamin E's ability to fend off lipid peroxidation is the basis of the free-radical hypothesis of neuronal degeneration in AD.⁴ While the use of vitamin E has shown benefit in delaying the progression of dementia and cognitive decline in limited studies, the biological significance of this apparent benefit needs further exploration.

The structure of vitamin E allows it to inhibit lipid peroxidation, thus preventing low-density lipoprotein (LDL) cholesterol from becoming oxidized.⁵ LDL cholesterol is known to build up in artery walls and cause arteriosclerosis. Consequently, an increase in vitamin E supplementation is thought to prevent or delay the development of arteriosclerosis.

A recent study was conducted by Jain et al.⁶ to determine the effect of vitamin E supplementation on platelet hyperaggregability in patients with type 1 diabetes. The researchers found that dietary supplementation with 100 international units (IU) of vitamin E daily significantly lowers platelet hyperaggregability, as well as lipid peroxidation products such as LDL. These findings indicate that vitamin E may be effective in decreasing diabetes patients' risk of developing arteriosclerosis and thrombotic disease.

Although not validated by current studies, several sources indicate that vitamin E holds potential for treatment of intermittent claudication. This condition is usually treated with anticoagulants. However, as mentioned above, vitamin E has been found to decrease platelet aggregability, thereby thinning the blood and decreasing the pain associated with intermittent claudication.

Vitamin E has been used in several cancer prevention studies. It has been thought to play a role in protecting against mutations of carcinogenic substances. An analysis by the National Cancer institute (NCI) and National Public Health Institute of Finland demonstrated that long-term use of a moderate dose of vitamin E supplements substantially reduced prostate cancer incidence and deaths in male smokers.⁷

According to Meydani and Beharka, studies of vitamin E's potential anticancer benefits have yielded conflicting results.² However, a 1998 Harvard Health Letter discusses a Finnish research study indicating that 50 IUs of vitamin E daily decreases the risk for development of prostate cancer.⁸ This same study indicated that vitamin E supplementation helps to keep latent tumors from becoming advanced.

A study conducted by Mezetti et al. reviewed vitamin E intake as a risk factor for breast cancer.⁹ Their results indicate that increased vitamin E intake, along with lifestyle modifications such as decreased alcohol intake and increased exercise, may help to prevent one-third of breast cancer cases per year. Though this study is not conclusive about vitamin E and its effect on carcinogenesis, the results suggest the vitamin's potential benefits.

NCI has also published a study suggesting a potential role for vitamin E in reducing the risk of lung cancer.¹⁰

Vitamin E is thought to protect the cells of the immune system against oxidative damage. In a review of the literature, Meydani and Beharka found several studies that investigated the benefits of vitamin E against infectious diseases in laboratory mice.² Results of these studies indicate reduced mortality in animals infected with Eschericia coli, Diplococcus pneumoniae type 1, Eimeria tenella, Histomas melacardis or Treponema hydysenteriae that received vitamin E supplementation. In HIV-infected mice, studies indicate vitamin E supplementation significantly restored cell proliferation.² The immunostimulatory effect of vitamin E in animals indicates its potential for improving function of the immune response in humans, though the effect on humans needs to be investigated.

Other potential uses. Vitamin E is thought to have many beneficial effects when used as a supplement. Scientific data are not present to support all claims for uses of vitamin E. However, several sources indicate benefits of vitamin E such as wound healing and reduction of scar formation, treatment of Parkinson's disease, treatment of Alzheimer's disease, reduced need for insulin in diabetes, prevention of cataracts, fertility enhancement, and treatment of rheumatoid arthritis.¹

Zinc: An Essential Trace Metal

Zinc is absorbed in the duodenum and proximal jejunum. Absorption by the intestines involves pyridoxine, or vitamin B-6. Zinc is essential to nucleic acid metabolism and protein synthesis, and it also has a role in collagen formation and glycolysis, as well as oxidative phosphorylation. Zinc is also an essential component of several enzymes, such as alcohol dehydrogenase, alkaline phosphatase, carbonic anhydrase, and retinene reductase.

Function. Zinc has been found to stimulate taste, smell, and mood, and is also important in maintaining normal skin hydration and promoting wound healing. Zinc activates areas of the brain that receive and process information from taste and smell sensors. Insufficient zinc has been linked to anorexia, which responds well to zinc replacement treatment. In vesicles of the brain's hippocampus, zinc interacts with other chemicals to send messages to the sensory brain center-thus the claims of enhanced memory and thinking skills with use of zinc. Low levels of zinc have been found in mood disorder patients. For healthy skin, an adequate zinc level is essential. Zinc is used as a drying agent and astringent, as a natural sunscreen, and as an anti-inflammatory agent for soothing skin and skin tissue. Acne, cold sores, burns, poison ivy, sunburn, blisters, and gum disease have shown improvement when treated with zinc.

Dietary sources. Food sources of zinc include seafood (particularly oysters and clams), meat, liver, eggs, milk, and whole grain cereals. The recommended daily allowance is 12-15 mg, 25-50 mg if a zinc deficiency is present. Studies show that many adults get less than 10 mg of zinc per day. Typically, women average less than 8.1 mg per day. Zinc is excreted through the gastrointestinal tract and sweat. Biliary and pancreatic loses may account for up to 25% of daily losses.

Current and potential uses. Zinc is a natural insect repellent. It can be found in hundreds of products, including vitamins, cosmetics, pet foods, paints, fertilizers, tires, batteries, ointments, shampoos, soaps, and pharmaceuticals. In architecture, zinc is used for roofs or facades, on counters, and on bar tops. It is primarily used as a coating on iron and steel to protect against corrosion, and, when combined with copper, it makes brass.

In medicine, zinc has also received attention in wound care. It has been used as adjunct therapy to systemic antibiotics, local treatments, and other nutritional supplements for the prevention and management of pressure ulcers.¹¹

Because zinc is a cofactor for metalloproteinases, including collagenases that are involved in the breakdown of connective tissue collagen, it has been studied for wound healing.¹² Recent studies (in rats) have demonstrated the benefits of zinc in wound healing. Products containing zinc were noted to lower wound infection rates and appeared to hold some potential for promoting the growth of granulation tissue and epithelium in burn victims.

Zinc-containing products, especially ones that include silver, demonstrate significant antimicrobial activity. It appears that zinc may have a potential role in wound debridement. It may also affect the concentrations of some cytokines and have a bacteriostatic effect.

Zinc deficiency. Zinc deficiency is clinically characterized by the development of a moist eczematous dermatitis most apparent in the nasolabial fold and around orifices. Other presenting signs and symptoms may include hypogeusia, alopecia, diarrhea, rash, apathy, and depression. Clinical zinc deficiency occurs most frequently in the setting of abnormal losses, such as in Crohn's disease, malabsorption states, and fistula losses; or from prolonged inadequate intake, such as with zinc-free parenteral nutrition.

A Final Note

There is, however, sufficient data to support at least some claims regarding preventative uses of vitamin E (e.g., encouraging the use of 200-300 IUs supplementation daily to prevent a variety of diseases). In addition, zinc has already gained fame as an ingredient of throat lozenges and for the treatment of the common cold, and it shows some promise as an aid to wound healing.

Phyllis M. Parks-Veal, BS, PharmD
Consultants & Lecturers in
Pharmacology & Therapeutics
Milledgeville, Georgia

A Multicultural Approach to Providing Pharmacy Services

This ongoing shift in the composition of the U.S. population presents a challenge for pharmacists seeking to improve their interactions with ethnically diverse colleagues and patients. In the area of drug therapy, the challenge will be to provide services in an appropriate psychosocial context.

To date, U.S. health care providers have often undertaken a "generic" approach to members of various ethnic groups, and this has sometimes led to strained relations with patients and noncompliance with drug therapy. This article will provide insights on ethnic factors that influence drug metabolism and response; lifestyle practices and health care attitudes common among selected ethnic subgroups; and how pharmacists can better serve ethnically diverse patient populations through adherence to the tenets of "cultural competence."

It is important to note that the observations presented in this article regarding health practices and views toward western-style health care common among various ethnic subgroups are based on interviews of patients representing each subgroup. It is also important to note that within broad ethnic groups, there can be major differences between various subgroups. For example, Central American Hispanics can differ greatly from Barcelonoan Hispanics; among Asian Americans, there are many differences between the Japanese, Chinese, Korean, Vietnamese, Thai, and Filipino cultures. Therefore, each patient, regardless of ethnicity, must be treated as an individual.

Ethnicity and Drug Metabolism

Debrisoquine is an antihypertensive agent that exhibits polymorphism in its oxidative metabolism. Drugs metabolized through this pathway include amitriptyline, imipramine, clomipramine, nortriptyline, chlorpromazine, perphenazine, haloperidol, labetalol, metaprolol, timolol, and propranolol.

There are two distinct phenotypes observed with regard to the urinary ratio of debrisoquine to its main 4-hydroxy metabolite. Individuals deficient in their ability to oxidize the substrate are considered "poor metabolizers" (PMs). In contrast, "extensive metabolizers" (EMs) biotransform a substantial amount of the drug to its metabolite. The prevalence of the PM phenotype ranges from 2%-10%; there are very few PMs among Asian-American populations.²

Polymorphic N-acetylation was first studied when serum concentrations of isoniazid showed substantial interindividual variability. Drugs affected by this pathway include clonazepam, nitrazepam, hydralazine, procainamide, isoniazid, and caffeine. Patients are classified as "slow acetylators" (SAs) or "rapid acetylators" (RAs) according to their ability to metabolize isoniazid.

Among American and European Caucasians and African Americans, there are approximately equal numbers of SAs and RAs.² Among Japanese Americans and Canadian Eskimos, the proportion of RAs is relatively high and the proportion of SAs relatively low.²

Polymorphism of mephenytoin hydroxylation also varies according to ethnic differences. Drugs affected by this pathway include diazepam, imipramine, mephobarbital, and hexobarbital. About 2%-5% of Caucasians and 15%-20% of Japanese Americans are poor mephenytoin metabolizers²; in other ethnic subgroups (e.g., Panamanian Cuna Amerindians), this metabolic phenotype is virtually unknown.

Ethnicity and Drug Response

Antihypertensives
Monotherapy with beta blockers and ACE inhibitors has been shown to be less effective in African Americans than in Caucasian patients with hypertension.² These differences may be due to differences in renal physiology. The renin-angiotensin is more frequently suppressed relative to sodium intake and excretion in African Americans than in Caucasians.² Because beta blockers and ACE inhibitors are believed to act through lowering of plasma renin, they would be expected to be less effective in African Americans, who already have relatively lower renin levels. However, some African Americans do respond to beta blockers and ACE inhibitors.²

African Americans may respond differently to different beta blockers. For example, labetalol, unlike propranolol, is equally effective in both African-American and Caucasian hypertensives. Also, African Americans respond as well as Caucasians to beta blockers in combination with diuretics.²

Antipsychotics
African-Americans, Caucasians, and Hispanic Americans do not differ in their pharmacokinetics or dosage requirements of antipsychotic drugs. However, Asians seem to have a lower threshold than Caucasians for both the therapeutic and adverse effects of these drugs. Increased absorption,² reduced hepatic hydroxylation, and pharmacodynamic factors all play a role in dosage differences.

It has been shown that Chinese-American patients exhibit higher haloperidol plasma concentrations than Caucasians, Hispanic Americans, and African Americans.² Additionally, the haloperidol dosage required for Caucasians and African Americans is significantly greater than the dosage required to achieve comparable plasma levels in Chinese Americans.² Use of antipsychotics is generally higher in African Americans than in other ethnic groups; this is partly due to the relatively higher overall use of antipsychotics in African Americans for severe diagnoses, such as schizophrenia, than for mood and anxiety disorders.²

Being attuned to these and other significant ethnic differences in drug metabolism and drug response can help the pharmacist optimize various aspects of the pharmacotherapy process, including drug selection, dosage adjustment, compliance counseling, and monitoring for adverse effects.

Finding Common Ground

While all people share the same basic health needs, the incidence and prevalence of chronic disease varies widely among populations. Studies are just beginning to identify and examine the reasons for this cultural disparity, but a brief review of selected studies in this area can be informative.

African Americans
It is of interest to determine the effect of socioeconomic status on prevalence of disease. A study several years ago by Kingston et al. examined the relationship between wealth and income and selected racial and ethnic differences in health.³ This cross-sectional study involved a national sample of 9,744 men and women aged 51-61 participating in the 1992 Health and Retirement Survey. Compared with Caucasians, African Americans reported higher rates of hypertension, diabetes, and arthritis, while Hispanic Americans reported higher rates of hypertension and diabetes and a lower rate of heart conditions. In general, among those with chronic diseases, African Americans and Hispanic Americans reported worse functional status than Caucasians.³ This disadvantage was eliminated in every case by controlling for socioeconomic status. While socioeconomic status, including wealth, accounts for relatively little of the difference in functional status associated with chronic disease, there is a link between low socioeconomic status and reduced access to health care, which can lead to delayed disease detection and increased prevalence.

The importance of traditional coronary artery disease risk factors in the development of coronary heart disease is well known.⁴ African Americans have a higher prevalence of such risk factors as hypertension, diabetes, obesity, cigarette smoking,⁴ and left ventricular hypertrophy. These risk factors may account for the disproportionate rate of coronary heart disease mortality in African Americans.

With regard to congestive heart failure (CHF), a recent retrospective cohort study in California revealed that African Americans had the highest rate of hospitalization for CHF. Age-adjusted CHF hospitalization rates for Caucasians, Latinos, and Asian-American women were comparable, and all were lower than the rate among African Americans. Asian-American men had the lowest rate of CHF hospitalization.⁵

With regard to diabetes, increased prevalence among minority populations such as African Americans, Native Americans, and Mexican Americans is well documented.⁶ The increased prevalence of diabetes has led to increases in microvascular complications such as blindness, end-stage kidney disease, and lower limb amputation. In people with diabetes, risk factors for cardiovascular disease include elevated fasting blood sugar, blood pressure, total cholesterol, and triglycerides, as well as obesity.

The estimated prevalence of type 2 diabetes⁹ among African-American, Hispanic-American, and American Indian/Alaska Native populations is reported to be two to six times greater than that among the non-Hispanic Caucasian U.S. population.⁷

Obesity occurs in approximately 50% of African-American women,8 and the prevalence appears to be increasing, for unknown reasons.

Hispanic Americans
In a study conducted during the period 1988-94, a national sample of 1,387 Mexican-American women and 1,404 Mexican-American men aged 25-64 was evaluated to derive an estimate of coronary heart disease mortality risk and the prevalence of five primary cardiovascular disease risk factors: elevated systolic blood pressure, elevated body mass index, cigarette smoking, elevated low-density lipoprotein cholesterol, and type II diabetes. Estimated 10-year coronary heart disease mortality was highest for U.S.-born Spanish-speaking men and women, intermediate for U.S.-born English-speaking men and women, and lowest for Mexican-born men and women. A similar pattern of higher risk among U.S.-born Spanish-speaking men and women was demonstrated for each of the five cardiovascular risk factors.⁹

Another U.S. study conducted in the late 1980s and early 1990s showed that rates of all-cause coronary heart disease and coronary heart disease mortality are approximately 20% lower among adult Hispanic Americans than among Caucasians.¹⁰

The prevalence and health burden of diabetes are greater in older Mexican Americans than in older non-Hispanic Caucasians and African Americans.¹¹

Korean Americans
In a study conducted in the late 1980s, proportional mortality ratios and age-adjusted proportional mortality ratios among Korean immigrants to New York City were calculated from data on 314 Korean-American men and 248 Korean-American women who died between during the period 1986-90.¹² Using U.S.-born Caucasians as a reference, Korean-American men had a significant excess of viral hepatitis, cancer, stroke, and external mortality causes: accidents, suicide, and homicide. They had significantly reduced proportional rates of AIDS and heart disease. Mortality patterns were similar for Korean-American women, who had significantly increased proportional rates of stroke and accident, and reduced rates of heart disease. Stomach and liver cancers were significantly elevated for both sexes, while the rate of breast cancer in females was relatively low.

Striving for Cultural Competence

As outlined in Figure 1, the process of becoming culturally competent entails transcending "cultural destructiveness," "cultural incapacity," and "cultural blindness" to achieve "cultural sensitivity," "cultural literacy," and, ultimately, "cultural openness." The culturally sensitive pharmacist is attuned and responsive to cultural differences. This sensitivity can be enhanced by hiring multicultural staff and assigning "same-culture" pharmacists and support staff to carry out patient care activities.

Culturally literate pharmacy staff members possess skills and resources that enable them to communicate effectively beyond their own ethnic group. Whenever possible, culture-specific patient information and counseling should be made available, and communication with patients, both oral and written, should occur in their native language whenever possible.

A culturally competent pharmacy staff moves easily between cultures, tailoring interventions accordingly. Culture-specific information is routinely incorporated to enable the pharmacy staff to effectively tackle a broader range of practice activities. Sensitivity, understanding, and respect for minority patients are essential to building trust-and a crucial determinant of treatment adherence.

When they're under the care of Caucasian health care providers, minority patients may be particularly sensitive to nonverbal cues and communication, especially if there is a significant language barrier.¹ Many cultures place great emphasis on facial expressions, nods of the head, or the tone of voice. To some groups, physical contact is very important.

A negative attitude toward folk medicine and healing rituals on the part of the pharmacist may be perceived by patients as a direct attack on their belief system. We must always remember that traditional, culture-based medicine is used by many ethnic groups and must be respected.

We must also keep in mind that traditional cultural beliefs and values regarding health and illness among elderly people of different ethnic minority groups may pose problems in diagnosing serious diseases because of the reluctance of such elders to submit to western health care.

The well-being, health, and quality of life of ethnic minority elderly can be improved only through greater awareness and understanding by health providers of the heterogeneity of health problems and health care in these groups, and through further well-designed research.¹³

George Taniguchi, PharmD
Consultant Pharmacist
Santa Clara, California

Corina Vera
MPH Student
Maureen Blair, RN
MPH Student
Philbert Espejo
MPH Student
Kathleen Roe, DPh
Professor, Department of Health Science
San Jose State University
San Jose, California

References

1. Levy RA, Hawks JW. Multicultural medicine and pharmacy management. Benefit Trends 1996;7:27-30.
2. Matthews HW. Racial, ethnic and gender differences in response to medicines. Drug Metabolism and Drug Interactions 1995;12:77-91.
3. Kingston RS, Smith JP. Socioeconomic status and racial and ethnic differences in functional status associated with chronic disease. Am J Public Health 1997;87:805-10.
4. Potts JL, Thomas J. Traditional coronary risk factors in African Americans. Am J Med Sci 1999;317:189-92.
5. Alexander M, Grumbach K, Remy L et al. congestive heart failure hospitalizations and survival in California; patterns according to race/ethnicity. Am Heart J 1999;137:919-27.
6. Harris MI. Diabetes in America: epidemiology and scope of the problem. Diabetes Care 1998; Suppl 3:C11-14.
7. Hosey G, Gordon S, Levine A. Type 2 diabetes in people of color. Nurse Pract Forum 1998;9:108-14.
8. Allison DB, Edlen-Nezin L, Lay-Williams G. Obesity among African American womeh: prevalence, consequences, causes and developing research. Women's Health 1997;3:243-74.
9. Cardiovascular risk factors in Mexican American adults: a transcultural analysis of NHANES III, 1988-1994. Am J Public Health 1999;89:723-30.
10. Liao Y, Cooper RS, Cao G et al. Mortality from coronary heart disese and cardiovascular disease among adult US Hispanics: findings from the National Health Interview Survey (1986-1994). J Am Coll Cardiol 1997;30:1200-5.
11. Black SA, Ray LA, Markides KS. The prevalence and health burden of self-reported diabetes in older Mexican Americans: findings from the Hispanic established populations for epidemiologic studies of the elderly. Am J Public Health 1999;89:546-52.
12. Stellman SD. Proportional mortality ratios among Korean immigrants to New York City, 1986-1990. Yonsei Medical Journal 1996;37:31-7.
13. Brooks T, Creary L. Ethnogeriatrics: unique health issues of culturally diverse elderly. In: Yoshikawa TT, Cobbs EL, Brummel-Smith K, eds. Practical ambulatory geriatrics. 2nd ed. St. Louis: Mosby-Year Book; 1998. pp 80-92.

Editor's note: Additional guidance on many of the topics discussed in this article is provided in the AMA Cultural Competence Compendium, available from the American Medical Association; 800-621-8335.