We examined the micronutrient intakes of breast cancer survivors enrolled in the WHEL Study and found that dietary supplements contributed a substantial portion of the total intake for most micronutrients that were examined among those women who reported using them. The mean intake was higher in supplement users as compared to non-users for nearly every micronutrient. For such micronutrients as retinol, folate, vitamin D, and vitamin E; dietary supplement use contributed a significant proportion of the total intake. Our findings corroborate earlier findings that dietary supplements can improve dietary quality for certain micronutrients. One study reported that over half of the participants reported micronutrient intakes below the RDA level from food alone, but after accounting for supplements, less than 17% were classified as having micronutrient inadequacies (25
). In addition, Burnett-Hartman (26
) found that supplement use, either in the form of multivitamins or single-micronutrient supplements, was observed to be associated with adequate intakes of minerals. Additionally, vitamin E and folate are among the micronutrients for which intakes were commonly increased through supplement use in our study and in early studies (25
). Overall, the previous studies in addition to the present analysis have indicated that supplement users are more likely than non-users to have adequate intakes of micronutrients.
We examined whether micronutrient intake was associated with all-cause mortality and found that for most micronutrients examined in this study, there was not a statistically significant association. Although our analytic approach differed, our findings were in accordance with the previous studies (10
). Others have typically used the group with the lowest intake as the reference group and examined the risk according to increases in micronutrient intakes, while we have defined our reference group as those who have intakes between the levels of the RDA and UL and compared the risk for mortality to those with levels below the RDA. We found that those with micronutrient intakes below the RDA had an equivalent risk for mortality as those above the RDA. In the unadjusted regression model, those women who had vitamin B-12 intakes below the RDA had a reduced risk of all-cause mortality; however, the effect was no longer statistically significant after controlling for the covariates. Low vitamin B-12 intakes may be a reflection of a diet that consists of more plant-based foods and fewer animal products. Dietary recommendations for the prevention of chronic diseases include avoiding red meat and whole-fat dairy product, both of which are sources of vitamin B-12. Prudent dietary patterns, such as this, have been shown previously to reduce the risk of all-cause mortality among breast cancer survivors (27
Although the term ‘mega-dose’ does not have a standardized or accepted definition, some investigators have hypothesized that a very high intake (mega-dose) of certain micronutrients could improve overall survival of cancer patients (28
). The proposed mechanisms are uncertain but micronutrients which are known to have antioxidant properties (such as vitamins C and E, beta carotene, selenium, and zinc) may reduce the free radicals in the body and lower chronic disease risk (30
). For the purpose of comparison, we evaluated the group who has exceeded the upper limit for these micronutrients and did not find any evidence to support this hypothesis. Those who exceeded the upper limit did not have any lower risk of death than those with adequate micronutrient intakes. Further studies are needed to examine the question of whether high intakes of micronutrients could benefit or harm breast cancer patients. Previous studies have shown mixed results (32
) and this was study was not specifically designed for answering the question regarding the effect of excessive or mega-dose intakes.
Certain limitations of this study need to be acknowledged. The participants of the present study are not a representative sample of women with a breast cancer diagnosis since they have previously agreed to participate in a dietary intervention. These women reported healthier dietary patterns than the general population, such as a higher fruit and vegetable intake and lower fat intake. Changes in dietary patterns following diagnosis, which included dietary supplements, may limit the representation of those with micronutrient inadequacies and therefore limit our ability to show their impact on survival. Further, the micronutrient intakes are based on self-reported data, using methodologies with well-known limitations for accuracy.
Given that the WHEL study had a large sample and a long follow-up period; the study had adequate power to address the research question. The study had extensive dietary data as well as data for the relevant covariates such as tumor characteristics and treatment modalities, which were collected using quantifiable and validated measures. This study addressed the impact of dietary adequacy, using the dietary reference intakes, instead of categorizing the micronutrient intake according to quintiles. Because the large variance in micronutrient exposure across studies, reporting supplement use in a binary fashion or by quintile makes comparisons of results across studies more challenging. Should future studies use the dietary reference intakes as a standard method of describing exposures, then researchers could synthesize study results more easily and clinicians could provide more precise nutritional guidance to cancer patients. In conclusion, more supplement users had adequate micronutrient intakes than non-users of supplements; however, micronutrient intakes, from food and supplements, were not significantly associated with all-cause mortality in this cohort of breast cancer survivors.