Skip Navigation
American College of Physicians Logo
  • Subscribe
  • Submit a Manuscript
  • Sign In
    Sign in below to access your subscription for full content
    INDIVIDUAL SIGN IN
    Sign In|Set Up Account
    You will be directed to acponline.org to register and create your Annals account
    INSTITUTIONAL SIGN IN
    Open Athens|Shibboleth|Log In
    Annals of Internal Medicine
    SUBSCRIBE
    Subscribe to Annals of Internal Medicine.
    You will be directed to acponline.org to complete your purchase.
Annals of Internal Medicine Logo Menu
  • Latest
  • Issues
  • Channels
  • CME/MOC
  • In the Clinic
  • Journal Club
  • Web Exclusives
  • Author Info
Advanced Search
  • ‹ PREV ARTICLE
  • This Issue
  • NEXT ARTICLE ›
Articles |4 March 2003

Effect of a Multivitamin and Mineral Supplement on Infection and Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Trial Free

Thomas A. Barringer, MD; Julienne K. Kirk, PharmD; Amy C. Santaniello, PharmD; Kristie Long Foley, PhD; Robert Michielutte, PhD

Thomas A. Barringer, MD
From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Julienne K. Kirk, PharmD
From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Amy C. Santaniello, PharmD
From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Kristie Long Foley, PhD
From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Robert Michielutte, PhD
From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Article, Author, and Disclosure Information
Author, Article, and Disclosure Information
  • From University of North Carolina School of Medicine at Carolinas Medical Center, Charlotte, and Wake Forest University School of Medicine, Winston-Salem, North Carolina.

    Acknowledgments: The authors thank Dave Reboussin, PhD, for his assistance in the statistical analysis. Dr. Barringer thanks Geraldine D. Anastasio, PharmD, his original co-investigator who initiated the research project, for her enthusiasm and encouragement to continue the study in her absence.

    Grant Support: By the Charlotte-Mecklenburg Health Services Foundation, an independent, charitable foundation that supports medical education and research within the Carolinas HealthCare System.

    Potential Financial Conflicts of Interest: None disclosed.

    Requests for Single Reprints: Thomas A. Barringer, MD, Department of Family Practice, Carolinas Medical Center, CMC-MP Building, 1350 South Kings Drive, Charlotte, NC 28207; e-mail, tbarringer@carolinas.org.

    Current Author Addresses: Dr. Barringer: Department of Family Practice, Carolinas Medical Center, CMC-MP Building, 1350 South Kings Drive, Charlotte, NC 28207.

    Drs. Kirk and Michielutte: Department of Family Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.

    Dr. Santaniello: 8918 Waltham Forest Court, Waxhaw, NC 28173.

    Dr. Foley: Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.

    Author Contributions: Conception and design: T.A. Barringer, J.K. Kirk.

    Analysis and interpretation of the data: T.A. Barringer, J.K. Kirk, K.L. Foley, R. Michielutte.

    Drafting of the article: T.A. Barringer, J.K. Kirk, A.C. Santaniello, K.L. Foley.

    Critical revision of the article for important intellectual content: T.A. Barringer, J.K. Kirk, K.L. Foley, R. Michielutte.

    Final approval of the article: T.A. Barringer, J.K. Kirk, A.C. Santaniello, R. Michielutte.

    Provision of study materials or patients: T.A. Barringer, J.K. Kirk, A.C. Santaniello.

    Statistical expertise: T.A. Barringer, K.L. Foley, R. Michielutte.

    Obtaining of funding: T.A. Barringer.

    Administrative, technical, or logistic support: T.A. Barringer, J.K. Kirk.

    Collection and assembly of data: T.A. Barringer, J.K. Kirk, A.C. Santaniello.

×
  • ‹ PREV ARTICLE
  • This Issue
  • NEXT ARTICLE ›
Jump To
  • Full Article
  • FULL ARTICLE
  • FULL ARTICLE
    • Abstract
    • Editors’ Notes
    • Methods
    • Results
    • Discussion
      1. References
  • Figures
  • Tables
  • Supplements
  • Audio/Video
  • Summary for Patients
  • Clinical Slide Sets
  • CME / MOC
  • Comments
  • Twitter Link
  • Facebook Link
  • Email Link
More
  • LinkedIn Link

Abstract

Background:

Use of multivitamin and mineral supplements is common among U.S. adults, yet few well-designed trials have assessed the reputed benefits.

Objective:

To determine the effect of a daily multivitamin and mineral supplement on infection and well-being.

Design:

Randomized, double-blind, placebo-controlled trial.

Setting:

Primary care clinics at two medical centers in North Carolina.

Participants:

130 community-dwelling adults stratified by age (45 to 64 years or 65 years) and presence of type 2 diabetes mellitus.

Intervention:

Multivitamin and mineral supplement or placebo taken daily for 1 year.

Measurements:

Incidence of participant-reported symptoms of infection, incidence of infection-associated absenteeism, and scores on the physical and mental health subscales of the Medical Outcomes Study 12-Item Short Form.

Results:

More participants receiving placebo reported an infectious illness over the study year than did participants receiving multivitamin and mineral supplements (73% vs. 43%; P < 0.001). Infection-related absenteeism was also higher in the placebo group than in the treatment group (57% vs. 21%; P < 0.001). Participants with type 2 diabetes mellitus (n = 51) accounted for this finding. Among diabetic participants receiving placebo, 93% reported an infection compared with 17% of those receiving supplements (P < 0.001). Medical Outcomes Study 12-Item Short Form scores did not differ between the treatment and placebo groups.

Conclusions:

A multivitamin and mineral supplement reduced the incidence of participant-reported infection and related absenteeism in a sample of participants with type 2 diabetes mellitus and a high prevalence of subclinical micronutrient deficiency. A larger clinical trial is needed to determine whether these findings can be replicated not only in diabetic persons but also in any population with a high rate of suboptimal nutrition or potential underlying disease impairment.

Editors’ Notes

Context

  • Forty percent of U.S. adults use vitamin and mineral supplements, yet evidence of the health benefits of these supplements is lacking. The purported benefits of supplements relate to the immune system.

Contribution

  • In this randomized, controlled trial, participants taking multivitamin and mineral supplements reported fewer infections and days absent from work than participants taking placebo. The results were largely due to striking benefits in participants with type 2 diabetes mellitus.

Implications

  • Multivitamin and mineral supplements appear to reduce infections in people with type 2 diabetes mellitus, a group at risk for micronutrient deficiency.

The Editors
The U.S. Centers for Disease Control and Prevention estimates that 40% of U.S. adults use supplements regularly and spend $1.3 to $1.7 billion on them annually. About half of these persons take a combination vitamin and mineral product (1). Despite this extensive use, however, little evidence supports the purported health benefits (2).
Most of the research on vitamin and mineral supplementation has been related to its effects on immunity and infectious disease. Various degrees of malnutrition, even of individual micronutrients, are known to markedly impair immune function (3). The extent to which subtle deficiencies of various micronutrients contribute to clinically significant infections is unclear. Several studies indicate that vitamin supplementation may improve various immunologic factors (4-6). However, other trials demonstrated impaired immunologic response in participants who consumed larger than recommended quantities of certain nutrient supplements (7-10).
Healthy, community-dwelling elderly persons, who have been shown to have impaired markers of immune function and a high prevalence of subclinical micronutrient deficiency (5, 11-13), have made up the study samples in the only known randomized, controlled trials of the effect of a multivitamin and mineral supplement on clinically apparent infection in persons not obviously malnourished or seriously immunocompromised (11, 14). Of interest, these two trials reached opposite conclusions about a protective benefit. Our study was designed to assess the effect of a standard multivitamin and mineral supplement on participant-reported infection. We also used a validated quality-of-life instrument to assess the subjective effect of supplementation on physical and emotional well-being.

Methods

Study Design

We conducted a randomized, double-blind, placebo-controlled trial in two academic primary care clinics. Study participants were recruited by announcements made in the primary care clinics, at senior group meetings in the community, and to employees in the medical facilities where the study was conducted. Participants had to be 45 years of age or older and willing to be randomly assigned to the treatment or placebo group. Persons were excluded if they were currently using immunosuppressive drugs or anticoagulants; had used vitamin or mineral supplements (except calcium) in the past month; had a history of kidney stones; had malignant disease, renal insufficiency, hepatic impairment, dementia, or uncontrolled hypertension; abused alcohol or drugs; or were pregnant or lactating.

Study Sample

A total of 158 persons were enrolled and provided written informed consent. The institutional review boards of Carolinas Medical Center, Charlotte, and Wake Forest Medical Center, Winston-Salem, North Carolina, approved the study. After stratification by age (45 to 64 years or 65 years) and diabetes status (type 2 diabetes mellitus only), a computer-generated list was used to randomly assigned participants to the treatment group (n = 78) or the placebo group (n = 80). Participants were stratified by age and diabetes because increasing age and presence of diabetes may decrease immune function and increase the likelihood of subclinical micronutrient deficiencies and susceptibility to infection. The Figure illustrates the flow of participants through the study.
Figure.

Flow of participants through the study.

Intervention

Participants in the treatment group received a daily oral tablet that contained amounts of vitamins and minerals very similar to those found in most commercially available multivitamin and mineral supplements. Table 1 lists the exact ingredients of each tablet. Participants in the placebo group received a daily oral tablet containing calcium, 120 mg; magnesium, 100 mg; and vitamin B2 (riboflavin), 3.4 mg. These ingredients were chosen so that the tablet would look and smell as similar as possible to the complete multivitamin and mineral supplement and would cause similar changes in the color of participants' urine. Tishcon Corp. (Westbury, New York) prepared the supplement and placebo pills specifically for this study. All participants were required to take the tablets daily for 1 year.

Table 1. Supplement Formulation

Table 1. Supplement Formulation

Data Collection

Baseline measurements included sociodemographic characteristics, clinical data, nutritional status, level of stress, health behaviors, and quality of life. All sociodemographic data were dichotomized and included age (45 to 64 years or 65 years), sex, ethnicity (black or white), and years of education (less than high school or high school graduate and beyond). Clinical data included body mass index (normal, <25 kg/m2; overweight, 25 to 29.9 kg/m2; obese, 30 kg/m2). Hemoglobin A1c level was measured among participants with diabetes. We also assessed history of vitamin use in the year before the study, previous influenza immunization, and whether the participant had had at least one infection in the previous year.
Nutritional status was assessed with a 3-day food diary that participants kept at baseline and at 6 months. At randomization, participants were given detailed written and verbal instructions on how to fill out the food diary, and the study nutritionist reviewed each completed diary with the participant. Analysis was performed by using Nutritionist V, version 2.0 (First DataBank, Inc., San Bruno, California). Nutrient deficiency, for the purpose of this study, was defined as intake below the 33rd percentile of the recommended daily allowance (RDA) for zinc; selenium; iron; folic acid; or vitamins A, C, E, or B6. Selection was based on research indicating that even moderate deficiencies of these individual nutrients can impair markers of immune function (3-6, 15-17). Our choice of the 33rd percentile was somewhat arbitrary. There is no standard cut-point for micronutrient deficiency as it relates to impairment of immune function because the role of each micronutrient depends on many other factors, such as age, chronic disease, other nutrient deficiencies, and bioavailability. Because many variables are unique to each individual and sample, previous studies demonstrating an immune function benefit from supplementation have defined deficiency post hoc (11, 16).
Stress, which has been shown to influence susceptibility to minor infection (18, 19), was measured by using a 10-item scale that assessed perceived stress during the previous month (20). Each question was measured on a scale of 0 to 4 points, yielding a possible range of 0 to 40 points. For health behaviors, we included smoking status (current, past, or never) and measures of routine physical and recreational exercise (very or moderately active vs. inactive), using items from the National Health and Nutrition Examination Survey II.
The primary end point of our study was incidence of participant-reported infection. Infection data were obtained from symptom checklist diaries recorded daily by the study participants. Detailed instructions on keeping the diaries were given to each participant at the start of the study, and participants were encouraged to call with any questions if they became uncertain. Each participant brought his or her diary to every quarterly study visit, and all aspects of the recorded data were reviewed with participants for clarity, accuracy, and completeness. Using this record of illness, the study physician then assigned a specific diagnosis and duration. Standard criteria were used to diagnose common adult infectious illnesses (upper respiratory tract infection, lower respiratory tract infection, influenza-like syndrome, gastrointestinal infection, and urinary tract infection). Symptom checklist records that fit into the above categories prompted further detailed interview by the physician to confirm or exclude other infectious and noninfectious entities (for example, allergic rhinitis and medication-induced diarrhea).
Infection incidence was determined by using both continuous and categorical variables. First, we calculated the mean number of total symptomatic days due to infection per year. Because many study participants (n = 54) reported no infection and the data were therefore considerably skewed, the dichotomous variable of infection versus no infection proved more meaningful. We also assessed the significance of infections by ascertaining absentee days, that is, days of infection-related illness that resulted in missed work or inability to perform planned activities.
The secondary end point, quality of life, was assessed at baseline and at 12 months. Proxy measures of physical and mental health were obtained by using the Medical Outcomes Study 12-Item Short Form (SF-12) (21). We computed total scores using weighted-item response categories similar to those used to score the 36-Item Short-Form Health Survey (22). Adverse effects, adherence, and any substantial change in medical status were assessed at the quarterly visits.

Statistical Analysis

Descriptive statistics for baseline covariates were assessed by using frequencies for dichotomous variables and medians and interquartile ranges for continuous variables. Chi-square tests and t-tests were used to evaluate the differences between the treatment and placebo groups across all categorical and continuous baseline covariates, respectively. These analyses were conducted for all 158 participants recruited to the study and for the 130 participants who followed the protocol for the entire study year.
Twenty-eight participants withdrew from the study between collection of the baseline data and initial evaluation of the study end points. Because no data were available on the study end points for these participants, we evaluated the effect of attrition using worst-case and best-case scenarios. First, we assumed all participants who withdrew had an infection and analyzed the data using an intention-to-treat analysis. We then repeated the analysis assuming that all participants who withdrew did not have an infection. Neither of these assumptions affected the directionality or statistical significance of our results. Thus, we proceeded with our analysis using the total number of participants who completed the trial (n = 130). All analyses were conducted by using Stata 7.0 (Stata Corp., College Station, Texas).
For our primary outcomes, we calculated the absolute and relative risk for infection and infection-associated absenteeism for all persons who completed the 12-month trial (n = 130), according to study group, age, and diabetes status. A MantelHaenszel test of homogeneity was performed to test for differences between the age and diabetes subgroups. We also conducted univariate and multivariate analyses using ordinary least-squares regression to evaluate the effect of the supplement on physical and mental quality of life while controlling for age, diabetes status, nutritional deficiency, and physical activity.

Role of the Funding Source

The funding source had no role in the design, conduct, or reporting of the study.

Results

Participant Characteristics

Table 2 summarizes the characteristics of the study participants. The treatment group was more physically active and better nourished than the placebo group but was similar with respect to baseline covariates. The overall sample was predominately female, white, and between the ages of 45 and 64 years. Approximately 10% of participants had not finished high school. Two thirds of the sample were overweight or obese, and approximately 30% had type 2 diabetes mellitus. Approximately 18% of the total sample were classified as nutritionally deficient. Slightly more than half of the participants in both the placebo and treatment groups remembered having had at least one infection in the previous year.

Table 2. Baseline Demographic Characteristics and Clinical, Stress, Health Behavior, and Quality-of-Life Data according to Study Group

Table 2. Baseline Demographic Characteristics and Clinical, Stress, Health Behavior, and Quality-of-Life Data according to Study Group
Twenty-eight persons did not complete the trial (15 in the treatment group vs. 13 in the placebo group). Participants who withdrew were more likely to be 45 to 64 years of age and nondiabetic at baseline, but no other differences were noted (Figure). The most commonly reported reason for withdrawal was the inconvenience of keeping a daily diary or attending quarterly physician visits. One serious adverse event, a cardiac arrest, occurred during the trial; the affected participant was successfully resuscitated and continued in the study.

Infection Outcomes

No infections requiring hospitalization occurred during the study period. Forty-two percent of participants had upper respiratory tract infections, 19% had influenza-like syndromes, 12% had gastrointestinal infections, 7% had lower respiratory tract infections, and fewer than 2% had urinary tract infections or miscellaneous infections. Twenty percent of persons experienced more than one type of infection over the study year.
Seventy-three percent of the placebo group experienced one or more infection-related illnesses versus 43% of the treatment group (P < 0.001). Similarly, 57% of the placebo group reported illness-related absenteeism versus 21% of the treatment group (Table 3). Analysis within the age and diabetes subgroups showed that the differential effect of vitamin supplementation on infection was found primarily among participants with diabetes. Ninety-three percent of diabetic participants in the placebo group experienced an infectious illness versus only 17% of diabetic participants in the treatment group (relative risk, 0.18 [95% CI, 0.07 to 0.44]). Similarly, 89% of diabetic participants in the placebo group reported one or more absentee days compared with 0% of diabetic participants in the treatment group. Participants without diabetes did not differ by study group.

Table 3. Effect of a Multivitamin and Mineral Supplement on Infection Incidence and Infection-Related Absenteeism according to Diabetes Status and Age

Table 3. Effect of a Multivitamin and Mineral Supplement on Infection Incidence and Infection-Related Absenteeism according to Diabetes Status and Age
We did not find an effect of age on infection. However, the lack of a statistically significant effect among participants older than 65 years of age does not allow us to draw any meaningful conclusions because only 33 participants were in this age group. Participants younger than 65 years of age experienced an apparent reduction in infection because of vitamin supplementation (78% in the placebo group vs. 43% in the treatment group); however, the difference in outcome between the two age groups was not statistically significant (P > 0.2) (Table 3). At baseline, diabetic participants were more likely than nondiabetic participants to be deficient in one or more micronutrients (33% vs. 19%; P = 0.06) (Table 4).

Table 4. Nutritional Deficiency among Subgroups of Diabetes Status and Age

Table 4. Nutritional Deficiency among Subgroups of Diabetes Status and Age

Treatment Effects on Quality of Life

The quality-of-life scores in our study were similar to those in persons who reported minor medical problems in a validation study of the SF-12 (21). In multivariate analyses, vitamin supplementation had no effect on physical or mental health scores (difference, 1.02 [CI, 2.22 to 4.2] and 0.98 [CI, 1.97 to 3.94], respectively). No additional analyses of quality of life were conducted within the age and diabetes subgroups because treatment had no main effect on outcome.

Discussion

The purpose of this study was to assess the effect of a typical one-a-day multivitamin and mineral supplement on infection rate and perceived quality of life in a fairly broad sample of relatively healthy adults. We found no difference between the treatment and placebo groups in physical and mental health measures of quality of life. Furthermore, within the SF-12 instrument, the specific items of general health and energy were analyzed separately and showed no difference in treatment effects between the study groups. Thus, it seems that multivitamin and mineral supplements do not enhance health or energy level any more than does placebo.
Our trial, which was performed in a sample of middle-aged persons, demonstrated a benefit in incidence of infection. However, this benefit was almost entirely observed in participants with diabetes, for whom the magnitude was dramatic. Correction of micronutrient deficiencies would be the most biologically plausible explanation for our results. When we defined nutritional deficiency as intake below the 33rd percentile of the RDA, participants who were diabetic at baseline were more likely than nondiabetic participants to be deficient in one or more micronutrients. It remains uncertain, however, whether these small differences in nutritional status were enough to account for the dramatic difference in outcome. This uncertainty is due not only to the limitations of our study but also to inherent difficulties in defining micronutrient deficiency.
Most of the previous research on vitamin and mineral supplementation has evaluated its effect on various markers of immune function (3-10, 15, 16). A few studies have evaluated clinical outcomes, although mostly in severely compromised or malnourished persons. Research in samples of relatively healthy elderly persons, however, has shown that even mild nutrient deficiencies can impair immune response (3-6, 12, 13, 16). Such subclinical deficiencies are common in community-dwelling elderly persons and probably account for some of the impaired immunity in this population (11-13, 15-17). Whether these data can be extrapolated to other minimally compromised groups, such as middle-aged participants with stable chronic disease processes, is unknown.
Only two published trials have evaluated the effect of a multivitamin and mineral supplement on clinical infection in apparently healthy samples of community-dwelling elderly persons. Chavance and colleagues (14) found no difference in incidence of infection, but their trial was methodologically flawed. Infection data were gathered by using personal recall at 2-month intervals, and the study was too short (4 months) to exclude a treatment effect or to examine seasonal variation. In addition, persons with chronic illness or possible micronutrient deficiency were excluded.
Chandra's 12-month study (11) of 96 healthy elderly persons showed a statistically significant difference in the mean number of days with an infection-related illness (23 days vs. 48 days) in favor of the group that received the vitamin and mineral supplement. No reported results showed an effect on severity of illness (other than number of days antibiotics were taken). In addition, participants in the treatment group had statistically significant improvement in several reliable indices of immune function. Nutritional status was determined by using biochemical measurements, and deficiency in a given nutrient was defined as a blood concentration value below the fifth percentile in a previously established reference range developed by the same researcher from a similar sample. Although the study groups had equal prevalence of deficiency at baseline, the treatment group had less severe deficiencies of vitamin A, beta-carotene, vitamin B6, vitamin C, iron, and zinc. However, the author noted some statistically significant improvements in markers of immune function even among persons who were not deficient by the same criterion (12). This illustrates the important unresolved issue of how to define micronutrient deficiency. In our trial, we used the criterion of intake below the 33rd percentile of the RDA for zinc; selenium; iron; or vitamins A, C, E, or B6. These micronutrients were specifically chosen because studies have demonstrated that even minor deficiencies lead to impairment in indices of immune function (3-6, 15-17).
One of the limitations of our study was that we determined micronutrient status with a 3-day food diary, which has only a moderate correlation with more accurate and expensive methods. Nevertheless, even if the quantitation of intake were highly accurate, there remains the challenging problem of defining deficiency. The relationship between intake of a nutrient and levels of the same nutrient in serum or tissue depends on numerous bioavailability variables. Defining deficiency on the basis of response to supplementation depends on the specified response end point, numerous physiologic characteristics of the study sample, and biological interconnections and interactions among various micronutrients. All of these factors disallow a simple association between a specific nutrient deficit (however defined) and a given physiologic or clinical outcome. We believe, however, that the diabetic persons we studied had substantial preexisting micronutrient deficiencies. They were also less likely than nondiabetic participants to be white, to have a high school degree, and to have previously used vitamins and were more likely to have experienced illnesses before the trial, to be obese, and to have perceived stress. Lower socioeconomic status and poor health are strongly associated with poorer nutritional status.
Although substantial research shows that certain infections are associated with diabetes (for example, foot ulcer infections, urinary tract infections, and unusual fungal infections), little published work addresses common upper respiratory tract infections, which accounted for the largest proportion of sick days in our trial. The type and severity of impaired immunity in diabetic persons have been studied to some extent, but scant literature exists on ways in which to improve such impairment, other than possibly by improving glycemic control (23-25). Some research has suggested that antioxidant systems are impaired in diabetes, thus providing a theoretical basis for benefit from a supplement with antioxidant potential (26).
Age was the other prespecified subgroup in this trial. No effect of supplementation was noted among those 65 years of age and older. Because few elderly participants were included, however, even a large effect may have been missed, as shown by the large CI (Table 3).
Unlike most researchers performing studies of nutritional supplements, we tested the blinding of our drug intervention. Although we went to great effort to have the pills look and smell as identical as possible, most participants correctly guessed what they were taking. Nevertheless, we doubt that this partial unblinding substantially influenced the results. First, at least some differential effect of supplementation would be expected in all of the subgroups. However, in the largest subgroup (nondiabetic persons), no difference was seen between those who received vitamins and those who received placebo. Second, in the group in which treatment had the largest effect on infection rate, unblinding had no effect on the secondary outcome of interest, quality of life.
Infection type and severity could have varied by season of the year, but randomization did not differ by season, and the 12-month study duration provided equal exposure to seasonal variability for all participants. It should be reiterated that the infections prevented in this study were minor, primarily respiratory tract infections and influenza-like illnesses. Nonetheless, because such infections are very common, they account for a large share of the productive days lost in industrialized societies (27, 28).
Our findings suggest that in certain diabetic samples, perhaps those with a high prevalence of micronutrient deficiency, daily use of a multivitamin and mineral supplement can decrease infection frequency. These dramatic results warrant testing in a larger clinical trial, both for confirmation and to disentangle the effects of chronic disease status from those of other important factors, such as ethnicity and obesity, that serve as proxies for socioeconomic status and poorer nutrition. Multivitamin and mineral supplements are convenient and relatively inexpensive. If our results are confirmed in a larger trial, the widespread implementation of this preventive measure could have a substantial economic impact and could ease the burden of suffering in our society.

References

  1. Ervin RB, Wright JD, Kennedy-Stephenson J. Use of dietary supplements in the United States, 1988-94. Vital Health Stat. 1999; Jun(244):i-iii, 1-14. [PMID: 10464471]
  2. Balluz
    LS
    ,  
    Kieszak
    SM
    ,  
    Philen
    RM
    ,  
    Mulinare
    J
    .  
    Vitamin and mineral supplement use in the United States. Results from the third National Health and Nutrition Examination Survey
    Arch Fam Med
    2000
    9
    258
    62
     PubMed
    CrossRef
     PubMed
  3. Chandra
    RK
    .  
    Nutrition and the immune system: an introduction
    Am J Clin Nutr
    1997
    66
    460S
    463S
     PubMed
     PubMed
  4. Erickson
    KL
    ,  
    Medina
    EA
    ,  
    Hubbard
    NE
    .  
    Micronutrients and innate immunity
    J Infect Dis
    2000
    182
    S5
    10
     PubMed
    CrossRef
     PubMed
  5. High
    KP
    .  
    Micronutrient supplementation and immune function in the elderly
    Clin Infect Dis
    1999
    28
    717
    22
     PubMed
    CrossRef
     PubMed
  6. Chandra
    RK
    .  
    Nutrition and immunology: from the clinic to cellular biology and back again
    Proc Nutr Soc
    1999
    58
    681
    3
     PubMed
    CrossRef
     PubMed
  7. Baehner
    RL
    ,  
    Boxer
    LA
    ,  
    Allen
    JM
    ,  
    Davis
    J
    .  
    Autooxidation as a basis for altered function by polymorphonuclear leukocytes
    Blood
    1977
    50
    327
    35
     PubMed
     PubMed
  8. Bogden
    JD
    ,  
    Oleske
    JM
    ,  
    Lavenhar
    MA
    ,  
    Munves
    EM
    ,  
    Kemp
    FW
    ,  
    Bruening
    KS
    ,  
    .  
    Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly
    J Am Coll Nutr
    1990
    9
    214
    25
     PubMed
    CrossRef
     PubMed
  9. Chandra
    RK
    .  
    Excessive intake of zinc impairs immune responses
    JAMA
    1984
    252
    1443
    6
     PubMed
    CrossRef
     PubMed
  10. Prasad
    JS
    .  
    Effect of vitamin E supplementation on leukocyte function
    Am J Clin Nutr
    1980
    33
    606
    8
     PubMed
     PubMed
  11. Chandra
    RK
    .  
    Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects
    Lancet
    1992
    340
    1124
    7
     PubMed
    CrossRef
     PubMed
  12. Chandra
    R
    .  
    Nutrition and immunity in the elderly: clinical significance
    Nutr Rev
    1995
    53
    2
    S80
    5
     PubMed
    CrossRef
     PubMed
  13. High
    KP
    .  
    Nutritional strategies to boost immunity and prevent infection in elderly individuals
    Clin Infect Dis
    2001
    33
    1892
    900
     PubMed
    CrossRef
     PubMed
  14. 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
     PubMed
     PubMed
  15. Bogden
    JD
    ,  
    Bendich
    A
    ,  
    Kemp
    FW
    ,  
    Bruening
    KS
    ,  
    Shurnick
    JH
    ,  
    Denny
    T
    ,  
    .  
    Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people
    Am J Clin Nutr
    1994
    60
    437
    47
     PubMed
     PubMed
  16. Meydani
    SN
    ,  
    Meydani
    M
    ,  
    Blumberg
    JB
    ,  
    Leka
    LS
    ,  
    Siber
    G
    ,  
    Loszewski
    R
    ,  
    .  
    Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized, controlled trial
    JAMA
    1997
    277
    1380
    6
     PubMed
    CrossRef
     PubMed
  17. Chandra
    RK
    .  
    Graying of the immune system. Can nutrient supplements improve immunity in the elderly?
    JAMA
    1997
    277
    1398
    9
     PubMed
    CrossRef
     PubMed
  18. Cohen
    S
    ,  
    Tyrrell
    DA
    ,  
    Smith
    AP
    .  
    Psychological stress and susceptibility to the common cold
    N Engl J Med
    1991
    325
    606
    12
     PubMed
    CrossRef
     PubMed
  19. Glaser
    R
    ,  
    Rabin
    B
    ,  
    Chesney
    M
    ,  
    Cohen
    S
    ,  
    Natelson
    B
    .  
    Stress-induced immunomodulation: implications for infectious diseases?
    JAMA
    1999
    281
    2268
    70
     PubMed
    CrossRef
     PubMed
  20. Cohen
    S
    ,  
    Williamson
    G
    .  
    The Social Psychology of Health
    Newbury Park, CA
    Sage
    1988
    31
    67
  21. Ware
    J
    Jr
    ,  
    Kosinski
    M
    ,  
    Keller
    SD
    .  
    A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity
    Med Care
    1996
    34
    220
    33
     PubMed
    CrossRef
     PubMed
  22. Ware
    JE
    Jr
    ,  
    Sherbourne
    CD
    .  
    The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection
    Med Care
    1992
    30
    473
    83
     PubMed
    CrossRef
     PubMed
  23. Gallacher
    SJ
    ,  
    Thomson
    G
    ,  
    Fraser
    WD
    ,  
    Fisher
    BM
    ,  
    Gemmell
    CG
    ,  
    MacCuish
    AC
    .  
    Neutrophil bactericidal function in diabetes mellitus: evidence for association with blood glucose control
    Diabet Med
    1995
    12
    916
    20
     PubMed
    CrossRef
     PubMed
  24. Rassias
    AJ
    ,  
    Marrin
    CA
    ,  
    Arruda
    J
    ,  
    Whalen
    PK
    ,  
    Beach
    M
    ,  
    Yeager
    MP
    .  
    Insulin infusion improves neutrophil function in diabetic cardiac surgery patients
    Anesth Analg
    1999
    88
    1011
    6
     PubMed
    CrossRef
     PubMed
  25. McMahon
    MM
    ,  
    Bistrian
    BR
    .  
    Host defenses and susceptibility to infection in patients with diabetes mellitus
    Infect Dis Clin North Am
    1995
    9
    1
    9
     PubMed
     PubMed
  26. Muchov
    J
    ,  
    Liptkov
    A
    ,  
    Orszghov
    Z
    ,  
    Garaiov
    I
    ,  
    Tison
    P
    ,  
    Crsky
    J
    ,  
    .  
    Antioxidant systems in polymorphonuclear leucocytes of Type 2 diabetes mellitus
    Diabet Med
    1999
    16
    74
    8
     PubMed
    CrossRef
     PubMed
  27. Keech
    M
    ,  
    Scott
    AF
    ,  
    Ryan
    PJ
    .  
    The impact of influenza and influenza-like illness on productivity and healthcare resource utilization in a working population
    Occup Med (Lond)
    1998
    48
    85
    90
     PubMed
    CrossRef
     PubMed
  28. Smith
    AP
    .  
    Respiratory virus infections and performance
    Philos Trans R Soc Lond B Biol Sci
    1990
    327
    519
    28
     PubMed
    CrossRef
     PubMed
Figure.

Flow of participants through the study.

Table 1. Supplement Formulation

Table 1. Supplement Formulation

Table 2. Baseline Demographic Characteristics and Clinical, Stress, Health Behavior, and Quality-of-Life Data according to Study Group

Table 2. Baseline Demographic Characteristics and Clinical, Stress, Health Behavior, and Quality-of-Life Data according to Study Group

Table 3. Effect of a Multivitamin and Mineral Supplement on Infection Incidence and Infection-Related Absenteeism according to Diabetes Status and Age

Table 3. Effect of a Multivitamin and Mineral Supplement on Infection Incidence and Infection-Related Absenteeism according to Diabetes Status and Age

Table 4. Nutritional Deficiency among Subgroups of Diabetes Status and Age

Table 4. Nutritional Deficiency among Subgroups of Diabetes Status and Age

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


The Effect of a Vitamin and Mineral Supplement on Infection and Self-Reported Health

This feature is available only to Registered Users

Subscribe/Learn More
Submit a Comment

0 Comments

PDF
Not Available
Citations
Citation

Barringer TA, Kirk JK, Santaniello AC, et al. Effect of a Multivitamin and Mineral Supplement on Infection and Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2003;138:365–371. doi: https://doi.org/10.7326/0003-4819-138-5-200303040-00005

Download citation file:

  • Ris (Zotero)
  • EndNote
  • BibTex
  • Medlars
  • ProCite
  • RefWorks
  • Reference Manager

© 2019

×
Permissions

Published: Ann Intern Med. 2003;138(5):365-371.

DOI: 10.7326/0003-4819-138-5-200303040-00005

©
2003 American College of Physicians
61 Citations

See Also

A Role for Multivitamins in Infection?
The Effect of a Vitamin and Mineral Supplement on Infection and Self-Reported Health
View MoreView Less

Related Articles

Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force
Annals of Internal Medicine; 159 (12): 824-834
Several simple rules predicted complications in high-risk patients with diabetes
Annals of Internal Medicine; 136 (3): 117
New Modes of Insulin Administration: Do They Have a Role in Clinical Diabetes?
Annals of Internal Medicine; 105 (1): 126-129
Diabetes and the Endocrine Pancreas: A Biochemical Approach.
Annals of Internal Medicine; 101 (2): 291
View MoreView Less

Journal Club

Review: Antioxidant vitamin or mineral supplements do not prevent age-related macular degeneration
Annals of Internal Medicine; 167 (10): JC56
Review: In age-related macular degeneration, antioxidant multivitamins and zinc supplements each decrease progression
Annals of Internal Medicine; 167 (10): JC57
Azithromycin reduced exacerbations and improved QoL in symptomatic asthma despite inhaled maintenance therapy
Annals of Internal Medicine; 167 (8): JC42
Review: CPAP improves QoL in obstructive sleep apnea; effects not as clear for mandibular advancement devices
Annals of Internal Medicine; 167 (4): JC18
View MoreView Less

Related Point of Care

Type 2 Diabetes
Annals of Internal Medicine; 162 (5): ITC1
Type 2 Diabetes
Annals of Internal Medicine; 152 (5): ITC3-1
Stable Ischemic Heart Disease
Annals of Internal Medicine; 171 (3): ITC17-ITC32
Peripheral Arterial Disease
Annals of Internal Medicine; 146 (5): ITC3-1
View MoreView Less

Related Topics

Cardiology
Coronary Risk Factors
Diabetes
Endocrine and Metabolism

Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.

PubMed Articles

The association of fish consumption and its urinary metabolites with cardiovascular risk factors: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP).
Am J Clin Nutr 2019.
Epidemiology of dietary supplement use in Serbia: Report from Novi Sad.
Complement Ther Med 2019;47():102228.
View More

Results provided by: PubMed

CME/MOC Activity Requires Users to be Registered and Logged In.
Sign in below to access your subscription for full content
INDIVIDUAL SIGN IN
Sign In|Set Up Account
You will be directed to acponline.org to register and create your Annals account
Annals of Internal Medicine
CREATE YOUR FREE ACCOUNT
Create Your Free Account|Why?
To receive access to the full text of freely available articles, alerts, and more. You will be directed to acponline.org to complete your registration.
×
The Comments Feature Requires Users to be Registered and Logged In.
Sign in below to access your subscription for full content
INDIVIDUAL SIGN IN
Sign In|Set Up Account
You will be directed to acponline.org to register and create your Annals account
Annals of Internal Medicine
CREATE YOUR FREE ACCOUNT
Create Your Free Account|Why?
To receive access to the full text of freely available articles, alerts, and more. You will be directed to acponline.org to complete your registration.
×
link to top

Content

  • Home
  • Latest
  • Issues
  • Channels
  • CME/MOC
  • In the Clinic
  • Journal Club
  • Web Exclusives

Information For

  • Author Info
  • Reviewers
  • Press
  • Readers
  • Institutions / Libraries / Agencies
  • Advertisers

Services

  • Subscribe
  • Renew
  • Alerts
  • Current Issue RSS
  • Latest RSS
  • In the Clinic RSS
  • Reprints & Permissions
  • Contact Us
  • Help
  • About Annals
  • About Mobile
  • Patient Information
  • Teaching Tools
  • Annals in the News
  • Share Your Feedback

Awards and Cover

  • Personae (Cover Photo)
  • Junior Investigator Awards
  • Poetry Prize

Other Resources

  • ACP Online
  • Career Connection
  • ACP Advocate Blog
  • ACP Journal Wise

Follow Annals On

  • Twitter Link
  • Facebook Link
acp link acp
silverchair link silverchair

Copyright © 2019 American College of Physicians. All Rights Reserved.

Print ISSN: 0003-4819 | Online ISSN: 1539-3704

Privacy Policy

|

Conditions of Use

This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy. | Accept
×

You need a subscription to this content to use this feature.

×
PDF Downloads Require Access to the Full Article.
Sign in below to access your subscription for full content
INDIVIDUAL SIGN IN
Sign In|Set Up Account
You will be directed to acponline.org to register and create your Annals account
INSTITUTIONAL SIGN IN
Open Athens|Shibboleth|Log In
Annals of Internal Medicine
PURCHASE OPTIONS
Buy This Article|Subscribe
You will be redirected to acponline.org to sign-in to Annals to complete your purchase.
CREATE YOUR FREE ACCOUNT
Create Your Free Account|Why?
To receive access to the full text of freely available articles, alerts, and more. You will be directed to acponline.org to complete your registration.
×
Access to this Free Content Requires Users to be Registered and Logged In. Please Choose One of the Following Options
Sign in below to access your subscription for full content
INDIVIDUAL SIGN IN
Sign In|Set Up Account
You will be directed to acponline.org to register and create your Annals account
Annals of Internal Medicine
CREATE YOUR FREE ACCOUNT
Create Your Free Account|Why?
To receive access to the full text of freely available articles, alerts, and more. You will be directed to acponline.org to complete your registration.
×