вход по аккаунту



код для вставкиСкачать
A Role for Multivitamins in Infection?
illions of Americans take multivitamin and mineral
supplements hoping to promote good health, but
few studies have documented the benefits (1). The strongest evidence supports use of folate supplements to reduce
birth defects; less compelling but suggestive evidence supports multivitamin use for prevention of chronic disease,
especially coronary disease and cancer. Despite fortification
of the U.S. food supply with folate, homocysteine levels
could be further reduced with optimal intake of folate,
vitamin B6, and vitamin B12. Moreover, although many
elderly adults produce insufficient gastric acid to liberate
vitamin B12 from food, causing subclinical insufficiency,
acid is not required to absorb vitamin B12 from supplements. A recent randomized trial among postangioplasty
patients showed that homocysteine-lowering vitamin therapy reduced major adverse outcomes by one third compared with placebo (2).
Ames and Wakimoto (3) have summarized several
lines of evidence suggesting that insufficient micronutrient
intake may increase cancer risk. Giovannucci and colleagues (4) found that folate intake was related to reduced
risk for colon cancer, but the association was largely limited to persons who had taken folate supplements of adequate dosage (400 ␮g/d) for 15 years or more. This finding
underscores the difficulties in designing trials to test these
hypotheses, particularly in well-nourished populations.
This finding and other evidence provide a reasonable rationale for widespread use of multivitamins as further data
What about infectious diseases? Supplementation with
multivitamins and minerals has enhanced markers of cellular immunity (5). However, evidence linking multivitamin supplements to occurrence of clinical infectious disease has been found only in the elderly and in persons in
developing countries, groups vulnerable to nutritional inadequacy.
In this issue, Barringer and colleagues (6) report that a
daily multivitamin and mineral supplement significantly
reduced self-reported infection-related illnesses and infection-related absenteeism from work among healthy persons
45 years of age or older. In subgroup analyses, persons with
diabetes, who were also more likely to be undernourished,
had the largest benefit in both infection-related outcomes;
this accounted for most of the overall observed effect. No
significant difference in benefit was noted between individuals younger or older than 65 years of age.
While contributing to our understanding of the important question of supplementation, Barringer and colleagues’ trial has several limitations. The small size (130
participants) led to imbalances between the two treatment
groups at baseline. Specifically, the experimental group was
somewhat better nourished and more educated than the
placebo group. Secondary multivariate analyses would have
430 4 March 2003 Annals of Internal Medicine Volume 138 • Number 5
Downloaded From: by a Queens Univ Belfast User on 10/25/2017
addressed this concern, but potential confounding by other
unmeasured variables cannot be excluded. The small sample size also limited the statistical power to examine possible effects among elderly persons. A second limitation,
which the authors noted, is that most participants correctly
guessed their randomized assignment. Thus, despite the
investigators’ efforts, the trial was not truly blinded. This is
of particular concern given the subjective nature of reporting of the study outcomes. However, the finding of no
difference between the two groups on physical and mental
subscales— even more subjective assessments—suggests
that the lack of blinding did not play a major role in the
resulting effects of supplementation on infection.
Three other trials have examined the effect of multivitamin supplements on infection among healthy individuals, all elderly, in developed countries. Supplementation
included vitamins and minerals in amounts typical of those
found in commercially available regimens. Studies from
France (110 participants) (7) and the Netherlands (652
participants) (8) found no beneficial effects. In the third
study (9), which was from Canada and involved 96 participants, supplementation significantly improved immune
responses and reduced patient-reported infections.
A major difference among these trials lies in the nutritional status of the study participants, as defined by dietary
intake and biochemical markers. Those in the French and
Dutch studies had apparently adequate micronutrient status, whereas a larger proportion of participants in the Canadian study had low blood vitamin concentrations. This
factor may explain the difference in effect across the three
trials and supports the findings of the trial by Barringer
and colleagues, in which most of the effect was observed
among diabetic persons, a nutritionally vulnerable group.
Several studies have examined supplementation with
individual nutrients. In one (10), daily use of 200 mg of
vitamin E improved indexes of cell-mediated immunity
and nonsignificantly reduced incidence of infections
among elderly Americans. However, this finding was not
confirmed in a Dutch trial (8) that found apparently increased infection severity with daily use of vitamin E. Several randomized trials found little if any evidence for clinically significant benefits of vitamin C supplementation on
the risk for common cold (11).
The potential benefits of regular vitamin supplementation are likely to be higher in developing countries,
where micronutrient deficiencies are more common. Infectious diseases remain major causes of mortality and morbidity in many of these countries. For example, approximately 40 million people were living with HIV and AIDS
as of the end of 2001, a year that had seen 5 million new
infections. Lower respiratory tract diseases cause more than
4 million deaths per year, and deaths from diarrhea number almost 3 million (12). Most of the evidence on the role
A Role for Multivitamins in Infection?
lowering therapy with folic acid, vitamin B(12), and vitamin B(6) on clinical
outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA. 2002;288:973-9. [PMID: 12190367]
3. Ames BN, Wakimoto P. Are vitamin and mineral deficiencies a major cancer
risk? Nat Rev Cancer. 2002;2:694-704. [PMID: 12209158]
4. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA,
et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health
Study. Ann Intern Med. 1998;129:517-24. [PMID: 9758570]
5. Chandra RK. Nutrition, immunity and infection: from basic knowledge of
dietary manipulation of immune responses to practical application of ameliorating suffering and improving survival. Proc Natl Acad Sci U S A. 1996;93:
14304-7. [PMID: 8962043]
6. Barringer TA, Kirk JK, Santaniello AC, Foley KL, Michielutte R. Effect of a
multivitamin and mineral supplement on infection and quality of life. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:365-71.
7. Chavance M, Herbeth B, Lemoine A, Zhu BP. Does multivitamin supplementation prevent infections in healthy elderly subjects? A controlled trial. Int J
Vitam Nutr Res. 1993;63:11-6. [PMID: 8320052]
8. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitaminmineral supplementation on acute respiratory tract infections in elderly persons: a
randomized controlled trial. JAMA. 2002;288:715-21. [PMID: 12169075]
9. Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet. 1992;340:1124-7.
[PMID: 1359211]
10. Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, et
al. Vitamin E supplementation and in vivo immune response in healthy elderly
subjects. A randomized controlled trial. JAMA. 1997;277:1380-6. [PMID: 9134944]
11. Spiers PS. On the prevention of the common cold: no help from vitamin C.
Epidemiology. 2002;13:4-5. [PMID: 11805579]
12. The World Health Report 1999. Geneva: World Health Organization; 1999
13. Villamor E, Fawzi WW. Vitamin A supplementation: implications for morbidity and mortality in children. J Infect Dis. 2000;182 Suppl 1:S122-33. [PMID:
14. Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, et al.
Prevention of diarrhea and pneumonia by zinc supplementation in children in
developing countries: pooled analysis of randomized controlled trials. Zinc Investigators’ Collaborative Group. J Pediatr. 1999;135:689-97. [PMID: 10586170]
15. Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJ, McGrath N, Mwakagile D, et al. Randomised trial of effects of vitamin supplements on pregnancy
outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet.
1998;351:1477-82. [PMID: 9605804]
1. Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults:
clinical applications. JAMA. 2002;287:3127-9. [PMID: 12069676]
2. Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-
© 2003 American College of Physicians–American Society of Internal
of supplements in these settings involves individual nutrients, notably vitamin A and zinc supplementation among
children. The beneficial effects of periodic vitamin A supplementation on child health and survival are well documented, especially in specific clinical situations, including
among patients with measles, diarrhea, and HIV infection
(13). In many clinical trials, daily zinc supplementation in
children significantly reduced incidence of diarrhea and
pneumonia (14). A daily supplement of vitamins B, C, and
E improved immunologic factors among HIV-infected
persons, but the clinical significance of these findings is yet
to be confirmed (15); the same supplement significantly
reduced fetal loss and other adverse outcomes of pregnancy.
Vitamin supplements are inexpensive and might improve health status in settings where infections are major
public health problems. In developed countries, infections
pose important economic burdens. The potential impact of
supplements merits further rigorous study, especially
among diabetic persons and other vulnerable populations.
Wafaie Fawzi, MBBS, DrPH
Meir J. Stampfer, MD, DrPH
Harvard School of Public Health
Boston, MA 02115
Corresponding Author: Wafaie Fawzi, MBBS, DrPH, Department of
Nutrition, Harvard School of Public Health, 655 Huntington Avenue,
Building II, Room 329A, Boston, MA 02115.
Current author addresses are available at
Ann Intern Med. 2003;138:430-431.
Downloaded From: by a Queens Univ Belfast User on 10/25/2017
4 March 2003 Annals of Internal Medicine Volume 138 • Number 5 431
Current Author Addresses: Dr. Fawzi: Department of Nutrition, Har-
vard School of Public Health, 655 Huntington Avenue, Building II,
Room 329A, Boston, MA 02115.
Dr. Stampfer: Department of Epidemiology, Harvard School of Public
Health, 677 Huntington Avenue, Kresge Building, Room 904, Boston,
MA 02115.
Annals of Internal Medicine Volume • Number
Downloaded From: by a Queens Univ Belfast User on 10/25/2017
Без категории
Размер файла
66 Кб
138, 4819, 200303040, 00014, 0003
Пожаловаться на содержимое документа