Milk, Fruit and Vegetable, and Total Antioxidant Intakes in Relation to Mortality Rates

Cohort Studies in Women and Men

Karl Michaëlsson; Alicja Wolk; Håkan Melhus; Liisa Byberg

Disclosures

Am J Epidemiol. 2017;185(5):345-361. 

In This Article

Results

Characteristics of the study population by baseline date and sex are presented in Tables 1–3. Approximately 9% of the women reported milk consumption of ≥3 glasses/day in 1987–1990 ( Table 1 ), whereas in 1997 only 2% reported such intake ( Table 2 ). Men had on average higher consumption of milk; 15% drank ≥3 glasses/day in 1997 ( Table 3 ). Average reported consumption of fruits and vegetables among women was 3.5 servings/day (standard deviation (SD), 2.0) at baseline and 5.3 servings/day (SD, 3.0) at the follow-up examination. Men reported an average consumption of 4.1 servings/day (SD, 2.5). Intake of fruits and vegetables did not vary by milk intake in either women or men.

During a mean follow-up period of 23 years (maximum 29 years), 22,391 women (total time at risk = 1,434,171 person-years) died. From January 1, 1998, onward, 10,314 women (581,785 person-years) and 15,478 men (687,688 person-years) died during a mean follow-up period of 15 years (maximum 17 years). Death rates increased in both sexes with increasing milk consumption (Figure 1A), and death rates decreased with higher consumption of fruit and vegetables (Figure 1B), as well as with higher ORACs (Figure 1C), although a threshold seemed to be discerned (>5 servings of fruit/vegetables per day and 15,000 μmol ORAC/day). In men, higher death rates started to be observed after only 3 or more glasses of milk per day (Figure 1A). In women, death rates were already increased at 1–2 glasses of milk per day.

Figure 1.

Sex-specific multivariable-adjusted spline curves illustrating the relationship of milk intake (A), fruit and vegetable intake (B), and oxygen radical absorbance capacity (ORAC; μmol/day) (C) with hazard ratios for death from all causes by the use of time-updated information in the whole Swedish Mammography Cohort (SMC; baseline 1987–1990) (solid line), in the SMC after administration of the second food frequency questionnaire (baseline 1997) (short-dashed line), and in the Cohort of Swedish Men (baseline 1998) (long-dashed line). The shaded areas illustrate 95% confidence intervals. One glass of milk corresponds to 200 mL. Covariates were age, body mass index (weight (kg)/height (m)2), height, energy intake, alcohol intake, intakes of yogurt, cheese, and red and processed meat, education, marital status (living alone vs. not), physical activity (metabolic equivalent-hours/day), smoking habits (never, former, or current smoker and, for baseline 1997, also pack-years of smoking), ever use of antioxidant-containing supplements, and weighted Charlson's comorbidity index. Associations with milk intake were further adjusted for intake of fruit and vegetables, and associations with fruit and vegetable intake and ORAC were adjusted for intake of milk.

In further analyses, we combined milk intake with fruit and vegetable consumption, as well as with ORACs. In Table 4 , we present age-adjusted rates and numbers of deaths by each combination category. The rate of mortality was highest among persons consuming less than 1 serving of fruit and vegetables per day (or in the lowest quartile of ORAC) combined with a high consumption of milk, in both men and women. In contrast, the lowest age-adjusted mortality rates were found in women and men who reported high consumption of fruits and vegetables or had high ORACs combined with low intake of milk.

Figures 2 and 3 depict the multivariable-adjusted hazard ratios for mortality by milk and fruit/vegetable intake or ORAC, using the group with the lowest intake of milk (<1 glass/day) and the highest intake of fruit and vegetables (≥5 servings/day) or ORAC (highest quartile) as the reference. Hazard ratios for mortality tended to increase with higher milk consumption in every category of fruit and vegetable intake or ORAC, although the estimates were attenuated with increasing consumption of fruits and vegetables or ORAC. The pattern was clearer with time-updated information as compared with a single exposure assessment. Accordingly, in time-updated analysis of the SMC, a high intake of milk (≥3 glasses/day) with a concomitant low intake of fruit and vegetables (<1 serving/day) conferred a multivariable-adjusted hazard ratio of 2.79 (95% confidence interval (CI): 2.42, 3.21), and with a combined high intake of fruit and vegetables, the hazard ratio was 1.60 (95% CI: 1.40, 1.82). In women with a single exposure assessment, the corresponding estimates were 1.81 (95% CI: 1.03, 3.20) and 1.10 (95% CI: 0.88, 1.38), respectively. The same comparisons in men revealed a hazard ratio of 1.31 (95% CI: 1.14, 1.51) for high consumers of milk with a low fruit and vegetable intake and a hazard ratio of 1.07 (95% CI: 0.97, 1.18) for high consumers of milk who also consumed 5 or more servings of fruits and vegetables per day. If we used ORAC intake instead of fruit and vegetable intake as the effect-measure modifier, the estimates remained essentially unaltered. The relative excess risk of interaction estimate of 0.37 (95% CI: 0.01, 1.27) in the time-updated analysis of women indicated a modest additive interaction. No significant interaction was discovered among men (data not shown).

Figure 2.

Adjusted hazard ratios (HRs) and 95% confidence intervals (in parentheses) for all-cause mortality according to combined intakes of milk and fruit and vegetables, using persons with the lowest milk intake and the highest fruit and vegetable intake as the reference group. A) HRs based on time-updated information on the whole Swedish Mammography Cohort (SMC) (women, baseline 1987–1990); B) HRs based on the SMC after administration of the second food frequency questionnaire (women, baseline 1997); C) HRs based on the Cohort of Swedish Men (men, baseline 1997). The shading corresponds to the value of the HR; the darker the shading, the larger the HR. One glass of milk corresponds to 200 mL. Covariates were age, body mass index (weight (kg)/height (m)2), height, energy intake, alcohol intake, intakes of yogurt, cheese, and red and processed meat, education, marital status (living alone vs. not), physical activity (metabolic equivalent-hours/day), smoking habits (never, former, or current smoker and, for baseline 1997, also pack-years of smoking), ever use of antioxidant-containing supplements, and weighted Charlson's comorbidity index.

Figure 3.

Adjusted hazard ratios (HRs) and 95% confidence intervals (in parentheses) for all-cause mortality according to combined daily intake of milk and oxygen radical absorbance capacity (ORAC; μmol/day), using persons with the lowest intake of milk and the highest quartile of ORAC as the reference group. A) HRs based on the Swedish Mammography Cohort after administration of the second food frequency questionnaire (women, baseline 1997); B) HRs based on the Cohort of Swedish Men (men, baseline 1997). The shading corresponds to the value of the HR; the darker the shading, the larger the HR. One glass of milk corresponds to 200 mL. Covariates were age, body mass index (weight (kg)/height (m)2), height, energy intake, alcohol intake, intakes of yogurt, cheese, and red and processed meat, education, marital status (living alone vs. not), physical activity (metabolic equivalent-hours/day), smoking habits (never, former, or current smoker and pack-years of smoking), ever use of antioxidant-containing supplements, and weighted Charlson's comorbidity index.

Hazard ratios were not attenuated in women after additional adjustment, including adjustment for vitamin and mineral nutrients common in milk, although they were somewhat attenuated in men (see Web Table 1, available at http://aje.oxfordjournals.org/). The total number of cardiovascular disease or cancer deaths was less than half that of the number of deaths from any cause (Web Tables 2 and 3). Nevertheless, for cardiovascular mortality (Web Table 4 ), the hazard ratios remained similar to estimates of all-cause mortality, whereas hazard ratios for cancer mortality were lower (Web Table 5). Exclusion of the first 2 years of follow-up (Web Table 6; 2%–5% of all deaths were excluded, depending on the analysis), persons with a body mass index greater than 35 (Web Table 7; 2% of all deaths were excluded), and current smokers (Web Table 8; 24%–29% of all deaths were excluded) gave estimates similar to those seen in the total cohort.

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