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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:1800-1805, July 2004

Nutritional Epidemiology

The Validity of Questionnaire-Based Micronutrient Intake Estimates Is Increased by Including Dietary Supplement Use in Swedish Men1

Maria Messerer2, Sven-Erik Johansson* and Alicja Wolk

Division of Nutritional Epidemiology, the National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden and * Department of Family Medicine, Karolinska Institutet, Stockholm, Sweden

2To whom correspondence should be addressed. E-mail: Maria.Messerer{at}imm.ki.se.


   ABSTRACT
TOP
 ABSTRACT
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
Although many validation studies of FFQ have been reported, only a few addressed the effect of inclusion of dietary supplement use on the validity of micronutrient estimates. The purpose of the present study was to assess reproducibility and validity of a self-administered FFQ, intended to measure total nutrient intake from diet and from dietary supplements, in a random population-based sample of 248 middle-aged and elderly men (40–74 y old) in central Sweden. Fourteen 24-h recall interviews were used as the reference method. Participants were telephoned about once a month for 1 y, covering every day of the week, twice in random order. Spearman correlation coefficients increased 13% (from 0.49 to 0.62), between FFQ-based micronutrient estimates and the fourteen 24-h recall interviews (reference method) when supplement use was included. Correct classification into highest quintiles was also improved by 14% (from 37 to 51%). There were no differences in mean intraclass correlation coefficients for 1-y reproducibility between total micronutrient intake and micronutrients from foods only. The increase in the validity of micronutrient estimates due to inclusion of supplements in nutrient intake assessment has important implications for sample size in epidemiologic studies. Because a dramatic increase in dietary supplement use has occurred in recent decades in many countries, the issue of including supplements in dietary assessment should be of highest priority in nutritional epidemiologic studies of chronic diseases.

KEY WORDS: • dietary assessment • dietary supplements • reproducibility • validity • men

To investigate the relation between diet, dietary supplements, and chronic diseases is a challenge and generates a great deal of public interest. Epidemiologic studies play an important role in understanding the relation between dietary factors and many chronic diseases. However, data from cohort studies and clinical trials of dietary supplements are inconclusive (1–4) and whether there is a metabolic need for dietary supplementation continues to be discussed (5,6).

Numerous studies on dietary assessment have been performed in various countries and populations to measure nutrient intake (7). However, most FFQs estimate intake of minerals and vitamins from foods only, leaving out information on the use of dietary supplements, whereas in fact the total intake of minerals and vitamins is what might be of importance (8). Failure to include dietary supplements leads to errors in nutrient estimates, notably misclassification of individuals with regard to their total intake, and rankings of intake that bear little or no relation to blood concentrations of those nutrients (9). Hence, there is a need for methods to assess with adequate accuracy the total long-term dietary intake including supplements (10,11).

A population-based prospective cohort of Swedish men (COSM)3 including >48,000 subjects living in central Sweden was established during the autumn of 1997. The present study was conducted to evaluate the validity and the reproducibility of the self-administered FFQ used in the COSM. The FFQ was intended to measure total nutrient intake, including dietary supplements in middle-aged and elderly men.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
    Subjects. For the present methodological study, we invited 790 men (aged 40–74 y) from central Sweden, who had been randomly selected from the Swedish population register. Among them, 466 subjects completed the first FFQ (FFQ1); 327 of these men also completed FFQ2. The respondents to FFQ1 were telephoned by a research dietician who performed the first 24-h recall interview. The dietician informed the participants about the validation study and asked about further participation. Those who agreed to participate were telephoned about once a month for 1 y, covering every day of the week twice in a random order. In the validation study we included 255 men who participated in fourteen 24-h dietary recall interviews. We excluded 7 subjects who reported extreme energy intake estimates (2.5 SD below or above the mean for log-transformed energy intake; cut points were 194 and 962 kJ). Thus, the final analyses included 248 men.

    Assessment of diet and dietary supplement use. The self-administered, semiquantitative FFQ was designed to classify individuals according to levels of average daily intake of selected nutrients from food and dietary supplements. Participants were asked to report their frequency of use of 88 food items over the past year. There were 9 possible frequency categories in increasing order from never or almost never to ≥3 times per day and 3 possible portion sizes, i.e., small, medium, and large; the medium portion was specified using commonly used units (e.g., slice, gram, or decilitre). Furthermore, there were open-ended questions about the quantity of some food items eaten daily by most Swedes, e.g., milk, bread, coffee, and cheese. The questionnaire also included questions about use of dietary supplements. The participants were asked to indicate if dietary supplements were used regularly, occasionally, or never. Those who were regularly or occasionally using dietary supplements were asked to specify further what kind of predefined supplement, i.e., multivitamins, vitamin C, vitamin E, vitamin A, ß-carotene, selenium, magnesium, iron, zinc, calcium, and fish oil [eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)] and how much (number of tablets or capsules/wk) they took. Furthermore, there was 1 open-ended question in which the participants could indicate the use of supplements other than those that were prespecified in the questionnaire. A brief questionnaire regarding smoking history, physical activity level, weight, and height was answered by the participants. We computed the BMI (kg/m2) as a measure of relative weight.

The nutrient calculations were carried out using nutrient composition values from the Swedish National Food Administration data (12). The intake of nutrients was computed by multiplying the frequency of consumption of each food item by the nutrient content of the specified portions.

A database was created, containing information on all dietary supplements. Information about the products sold at pharmacies was obtained from the Medical Product Agency of Sweden. For products that were sold at health food stores, information was obtained by correspondence with companies distributing or producing dietary supplements. Using the information available in the database, the mean daily intake of vitamins and minerals from dietary supplements was calculated for the participants.

    Statistics. Means and SD were calculated for nutrient intakes from both FFQs and from the fourteen 24-h recall interviews. Intraclass correlation (ICC) was used to measure the reproducibility between the first and the second FFQ. Because the distributions of nutrient intake among subjects were skewed to the high values also after log transformation, we decided to calculate the ICC based on ranks (13). Further, the ICC was calculated in 2 different ways, i.e., based on nutrients from foods only, and from foods and dietary supplements together. To test validity, nutrient estimates based on the questionnaire were compared with a mean total intake (food and dietary supplements) based on fourteen 24-h recall interviews. We calculated Pearson rank correlations (after log transforming the nutrients) and Spearman rank correlations and results for these 2 tests were similar. However, because some variables were not normally distributed even after log transformation, we decided to show Spearman rank correlations to evaluate validity of the FFQ. Analyses of the validity and reproducibility of total micronutrient intakes were based on nonusers and users of dietary supplements.

Energy adjustment of nutrients was preformed by using the residual method (7). We used an approximate mean energy intake of 478 kJ/d when the nutrients were energy-adjusted (the mean value in the study group based on fourteen 24-h interviews was 497 kJ). When calculating correlation coefficients for total nutrient intake including vitamins and minerals from dietary supplements, all nutrients from foods were first energy-adjusted and then reported supplements were added before calculating the correlation coefficients.

An attenuation coefficient based on fourteen 24-h recall interviews was used to correct the day-to-day variation within and between subjects in the reference method. This was done by using the methods of Beaton et al. (14) and Liu et al. (15). We corrected the validity coefficients for random error in the estimates on the basis of the 2 questionnaires (reproducibility coefficients).

To measure the degree of misclassification, subjects were categorized by nutrient intake into quintiles. For both FFQs and 24-h recalls, separate quintile cut points were established from their respective distributions of nutrient intake. As reference values, we used total nutrient intake, i.e., nutrients from diet and dietary supplements reported in fourteen 24-h recall interviews. The proportions of correctly categorized subjects in the same or adjacent quintiles were calculated.

The study was approved by the Ethics Committee at Karolinska Institutet.


   RESULTS
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
The 248 men included in analyses were 60.8 ± 9.8 y old with a BMI of 26.8 ± 3.2 kg/m2. Among them, 18% were smokers and in the first questionnaire, 40.7% reported use of dietary supplements either regularly or occasionally. The mean age of the initial 466 participants in the study was 57.7 ± 10.0 y and 42.3% reported regular or occasional use of dietary supplements.

In the 24-h dietary recall interviews, 50.8% reported use of dietary supplements. Use of multivitamins was reported by 33.0% and vitamin C products by 22.0%, in at least 1 recall. Corresponding use of B vitamins and vitamin E were 10.5 and 3.6%, respectively. Use of selenium, iron, and magnesium as single supplements was reported by 6.0, 3.6, and 2.0%, respectively. Fish oil intake was reported by 6.9%. The remaining supplements were reported by <2% (vitamin A, ß-carotene, calcium, and zinc).

According to the FFQ1, multivitamins and vitamin C products were also the most popular dietary supplements; either regular or occasional use of these products was reported by 21.8 and 24.2%, respectively. Furthermore, selenium supplements were used by 8.5%, fish oil by 7.8%, and vitamin E as well as iron (as single supplements) by 4.8% of the participants. Use of the remaining supplements was reported by <2% (vitamin A, vitamin B, ß-carotene, calcium, magnesium, and zinc).

We compared the means for daily nutrient intakes from fourteen 24-h recall interviews and from FFQ1 and FFQ2 for the 248 men included in the validation analysis (Table 1). The energy intake estimated by the first and the second FFQ (1 y apart) was within 8% of the intake assessed by 14 repeated 24-h recalls. Intake of most nutrients measured by the FFQs was generally similar to those estimated by diet recalls.


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  		TABLE 1 Daily intakes of energy and nutrients by Swedish men based on fourteen 24-h recall interviews and FFQs1

 
To evaluate reproducibility, we computed correlations for daily nutrient intakes assessed by the 2 FFQs (Table 1) spaced 1 y apart. The comparison between the 2 questionnaires indicate a high degree of reproducibility, ranging from r = 0.54 (EPA) to r = 0.85 (alcohol). Correlations for macronutrients were 0.70 and for 14 micronutrients with and without dietary supplements, 0.61 and 0.60, respectively.

Validity evaluated by Spearman rank correlation coefficients between the FFQ1 and the total intake of nutrients (food and supplements) for the fourteen 24-h recall interviews is shown in Table 2. Spearman rank correlations for deattenuated and energy-adjusted macronutrients ranged from 0.44 (protein) to 0.81 (alcohol) with a mean of 0.65. Further, Spearman rank correlations for deattenuated and energy-adjusted dietary micronutrients and for total micronutrients including supplements were between 0.38 (iron) and 0.81 (vitamin C), with a mean of 0.62. Corresponding numbers for micronutrients without supplements ranged between 0.25 (iron) and 0.77 (calcium), with a mean of 0.49. The correlations increased in most cases when dietary supplements were included.


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  		TABLE 2 Validity of nutrient estimates based on the FFQ in comparison to total intake of nutrients by Swedish men from fourteen 24-h recall interviews1

 
Classification of micronutrient intake using quintiles from the questionnaire by nutrient intake using quintiles from fourteen 24-h recall interviews (total intake) is shown in Table 3. For micronutrients, the proportions of correctly classified subjects were 51 and 37% overall, with and without supplements, respectively. We observed only small misclassification of subjects from the lowest quintile of nutrient intake measured by recall interviews to the highest quintile of intake measured by the questionnaire. When we considered micronutrients of food items only, 9% were grossly misclassified. After inclusion of micronutrients from supplements, 6% were grossly misclassified. When {alpha}-tocopherol from supplements was omitted, only 22% were correctly classified in the highest quintile, whereas 63% were classified correctly when supplement sources were included.


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  		TABLE 3 Comparison of micronutrient estimates from the first FFQ with the mean of fourteen 24-h dietary recall interviews in Swedish men based on cross-classification of quintiles, calculated from energy-adjusted nutrient intake1

 

   DISCUSSION
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
Adding information about dietary supplement use increased by 13% overall the validity of micronutrient estimates based on a self-administered FFQ. Furthermore, correct classification of micronutrient estimates into quintiles increased by 14%. Reproducibility of total micronutrient estimates (including supplements) was the same as reproducibility of micronutrients from food only.

The strength of our validation study is the large size of our random sample from the general population and the reference method based on fourteen 24-h recall interviews, including every day of the week twice for 1 y, thus covering differences in food intake and dietary supplement use, if any, on different days of the week and seasons. Negligible changes in correlations when we adjusted for within- and between-person variability in the 24-h recall interviews (deattenuated correlation) indicate that the number of recalls was satisfactory for estimating long-term mean total nutrient intake. Nevertheless, recall interviews are not a perfect "gold standard" for assessing daily nutrient intake. The method depends on the accuracy with which subjects remember and report their intake, and errors might arise if some foods or dietary supplements are not reported. Furthermore, men who participated in all 14 interviews might be more health conscious and thus more attentive when filling in the FFQ, which may lead to higher correlations in this group between the questionnaire and the interviews. However, characteristics of the validation group were comparable to the Swedish Annual Level of Living Survey (SALLS) for mean BMI and smoking among men in the same age group (16). Nevertheless, use of dietary supplements was more common among the men who participated in the validation study. In the first FFQ, 40.7% of the participants reported regular or occasional use of dietary supplements, compared with 20.0% in SALLS. Yet in SALLS, use of dietary supplements during the last 2 wk was reported, which makes it difficult to compare our results (17). In the fourteen 24-h recall interviews in our study, 50.8% reported ever using dietary supplements. It was shown previously that 4 consecutive day weighed food records were not enough to identify all subjects who used dietary supplements (18). The 14 recalls in our study repeated at random during a year seem to capture even irregular dietary supplement users quite accurately.

The correlations for 1-y reproducibility of total micronutrient estimates were similar to correlations for micronutrients from diet only. Two previous studies reported similar results (19,20). Three-month reproducibility of a diet history questionnaire had the same results among middle-aged men (age 43–64 y) (21). However, among older men (age 65–86 y) in the same study, the mean intraclass correlation for micronutrients increased from 0.75 to 0.85 when dietary supplements were included. Mayer-Davis and co-workers (22) also observed increased correlations for vitamin A, E and C when dietary supplements were included. Among American male health professionals, the reproducibility increased from 0.55 to 0.64 for micronutrients when dietary supplements were included (23). Also among American nurses, reproducibility increased after the inclusion of micronutrients from 3 dietary supplements (vitamins A, B-6,and C) from 0.53 to 0.59 (24).

The few validation studies that report separate correlations for total micronutrient estimates and micronutrients without supplements had results similar to those reported in our study (20–23,25,26). Rimm and co-workers (23) observed an increase in the mean correlation for 14 micronutrients from 0.58 to 0.72 after inclusion of supplements in the Health Professionals’ Study. Mares-Perlman and co-workers (21) showed that inclusion of dietary supplements increased the overall correlation coefficient from 0.52 to 0.71 among older men (age 65–84 y) but did not alter the correlation coefficient among middle-aged men (age 43–64 y). In a study of women from Iowa, the validity of 12 micronutrient intakes increased from 0.37 to 0.62 when dietary supplements were included (20). An even higher increase was reported in a study comparing the validity of food frequency interviews among 4 different ethnic groups in Hawaii (22). The mean correlation increased by >25% in the different ethnic groups when dietary supplements were included. However, they included only vitamins A, C, and E as micronutrients in their analyses. Willett and co-workers (24) also showed an increased correlation from 0.41 to 0.49 among 173 nurses after inclusion of 3 dietary supplements. Furthermore, they showed a somewhat smaller increase in the correlation coefficient from 0.49 to 0.54, after inclusion of 7 micronutrients when validating an extended FFQ (26); there were 4 y between the diet records and the questionnaire. More marginal increases were seen for the correlations in the Women’s Health Trial Feasibility Study (25). The correlations increased from 0.54 to 0.57 when dietary supplements were included.

Comparisons of extreme quintiles of dietary exposures are often used to examine risk of disease (23). It is also a way of looking at the agreement between a test instrument and a "gold standard" (27). The omission of dietary supplements impairs our ability to classify subjects correctly with regard to both their nutrient intake and their actual nutrient status.

Few validation studies present their data as cross-classification and the percentage of agreement for food and total nutrient intake (21,23,26). In one of the previous studies, the median value for percentage of similar classification into the 2 lowest quintiles was 70% when considering nutrients from food alone, and 80% when considering nutrients from food and supplements (21). In that study, the ability to correctly classify respondents into the 2 highest quintiles also increased substantially for several micronutrients when dietary supplements were included. Similar results were shown in a study among male health professionals (23). Willett and co-workers (26) also presented their data as cross-classification into quintiles in total nutrient intake and nutrients from food only. Subjects in the lowest quintiles had similar results, although only with ~6%; in the higher quintiles, the data were the opposite. Their questionnaire assessed diet 4 y in the past.

Improvement of the validity of micronutrient estimates has implications for the required sample size in epidemiologic studies. McKeown-Eyssen and Tibshirani (28) showed that if the correlation between the true exposure and its surrogate measure is 0.5, the sample size needed in a case-control study has to be 4.2 times larger than that needed if the true exposure would be used. An increased correlation from 0.49 to 0.62 (as in our study) reduces the study sample required by approximately one third, i.e., it reduces the adjustment factor from 4.2 to 2.6. Reducing measurement error in micronutrient estimates also has implications for the observed odds ratio; it will be closer to the true value.

Although a large proportion of participants reported use of dietary supplements in our study, most participants used multivitamins with low doses of vitamins and minerals. It is only for vitamin C, EPA, and DHA that the mean daily intake increased substantially when supplements were taken into account. Rimm and co-workers (23) reported that the mean absolute daily nutrient intake among male health professionals estimated from two 1-wk diet records for vitamin B-6 with and without supplements was 6.0 and 2.3 g, respectively. Corresponding intake for the participants in our study was 2.6 and 1.9 g, respectively. This example shows that the intake of vitamin B-6 as well as other micronutrients from supplements is quite low among participants in our study, compared with the previously mentioned study. In addition, the range of exposure does not increase substantially for most of micronutrients in our study even after inclusion of dietary supplements because in Sweden, most multivitamins are low-dose supplements with vitamin and mineral contents that do not exceed the dietary recommended daily doses.

Because previous studies showed that it is common in most industrialized countries to use dietary supplements (17,29–31), it is important to assess their intake when measuring food intake. Use of a variable representing total nutritional exposure seems to make most sense in studies on the etiologic relationship between exposure and outcome (9). Not having information about intake of a specific micronutrient from dietary supplements may lead to a gross misclassification of a subject using supplements (especially high dose supplements) into the lowest quintile, whereas this subject belongs in the highest quintile. Such drastic misclassifications may distort observed associations between specific micronutrients and disease.


   ACKNOWLEDGMENTS
 
The authors thank Rino Bellocco at the Department of Epidemiology and Biostatistics, Karolinska Institutet, for his statistical advice.


   FOOTNOTES
 
1 Supported by a research grant from the Swedish Cancer Society. Back

3 Abbreviations used: COSM, cohort of Swedish men; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ICC, intraclass correlation; SALLS, Swedish Annual Level of Living Survey. Back

Manuscript received 22 January 2004. Initial review completed 22 February 2004. Revision accepted 12 April 2004.


   LITERATURE CITED
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

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