If you’re a regular reader of this blog, you’ve probably observed that we as a group of contributors tend to be pretty critical of dietary supplements. These concerns include:
- The manufacturing quality of supplements is inconsistent, meaning consumers can’t trust that what is on the label is actually in the bottle.
- Marketing claims go well beyond proven science.
- There is little convincing evidence that most dietary supplements do anything useful or beneficial. Sometimes supplements are adulterated with actual drugs to give them the appearance of efficacy.
For the past several years there has been increasing concern that dietary supplements may not simply be useless, but that taking supplements could actually be harmful. This question is especially pertinent for those undergoing treatment for cancer. Cancer treatment can be debilitating and maintaining good dietary health can be difficult. Vitamin supplements may be viewed as a prudent way of supporting dietary intake. More generally, supplements are routinely promoted as treatments for cancer, and cancer patients may be drawn to products promoted as offering “natural” effectives. But because the mechanism of some cancer chemotherapies is to generate reactive oxygen species, there is concern that supplements such as anti-oxidants may actually reduce the effectiveness of treatment. And given the quality control standards of dietary supplements is questionable, there could be unpredictable and unanticipated interactions with chemotherapies that could have negative effects. As I have written on this topic before, there is a lot we do not understand about the effects of supplements on cancer survival. Now a new paper examines the effect of dietary supplements on survival in breast cancer patients.
What did the researchers set out to answer?
This was called the Diet, Exercise, Lifestyle and Cancer Prognosis (DELCaP) study, and the findings were published in the Journal of Clinical Oncology on December 18, 2019. The lead author is Christine Ambrosone, and the study was funded through a number of grants from government and other organizations, with no industry funding (supplement, pharmaceutical, or otherwise). Because of ongoing concerns about the effects of supplements on the effectiveness of cancer chemotherapy, the investigators set out to prospectively evaluate the relationship between the two.
What approach did they take?
This study ran concurrently with a phase 3 clinical trial (S0221) that studied different breast cancer chemotherapy treatment schedules. 80% of participants in that trial agreed to participate in the DELCaP trial, completing a baseline set of questions which asked about regular (at least 1x/week) use of supplements before beginning chemotherapy. A second survey was sent to participants about 6 months later, as chemotherapy was concluding. Among patients alive and without disease recurrent at that six-month point, patients were followed from that point until death from any cause. The median follow-up was 8.1 years.
Patients were then stratified into four categories and analyzed.
- YN – took supplements at baseline but not during chemotherapy
- YY – took supplements at baseline and during chemotherapy
- NY – no supplements at baseline but taken during chemotherapy
- NN – no supplements consumed before or during chemotherapy
What types of patients were enrolled?
A total of 1,340 patients completed questionnaire one and 1,134 completed both questionnaires. Participants were female, in their fifties, and predominantly white. Overall there were 251 recurrences and 181 deaths. Patients who experienced recurrence were more likely to be older, postmenopausal, and to have a higher BMI.
The overall prevalence of supplement use, compared to other literature reports, was low:
- Vitamin C was used by 20.5% of patients before treatment and just 12.2% during treatment.
- Vitamins E and A were taken by <10% of participants.
- Antioxidant (Vitamins C, A, E, carotenoids, coenzyme Q10) were taken by 17.5% of participants.
- In contrast, 44% of patients took multivitamins.
What did the researchers find?
- Patients who used any antioxidant both before and during treatment were at increased hazard of recurrence. The hazard ratio was 1.41, with a confidence interval of 0.98 to 2.04, meaning it wasn’t statistically significant (P=0.06). There was also a suggestion of a negative effect on the risk of death (HR=1.4, confidence intervals 0.9 to 2.18) which was also not significant. There was no relationship found between antioxidants and these outcomes if taken only before chemotherapy or only during chemotherapy.
- There were no associations found for the single antioxidants, multivitamins, and vitamin D at any point.
- Vitamin B12 both before and during treatment was associated with poorer disease free survival (HR 1.95, confidence intervals 1.15 to 2.92) and overall survival (HR 2.04, confidence intervals 1.22 to 3.40).
- Similar findings were made for iron with respect to disease free survival during treatment (HR 1.79, confidence intervals 1.20 to 2.67) and, non significantly, DFS with use before and during treatment (HR 1.91, confidence intervals 0.98 to 3.70).
- Use of omega-3 fatty acids before and during treatment were associated with poorer disease-free survival (HR 1.67, confidence intervals 1.12 to 2.49) but no effect on overall survival.
What conclusions can we draw from this study?
Dietary supplements appear to be, at best, neutral with respect to cancer survival, and there is no indication that they offer advantages or benefits to those that take them. While this was a small trial with low levels of supplement use, we have the benefit of a concurrent cancer treatment trial that ensured that all patients received standardized chemotherapy regimens. There is a strong suggestion that some dietary supplements may have a negative impact on disease-free survival and overall survival. Notably, the use of any antioxidant was associated with a 41% increase in the hazard of recurrence in this study (albeit, this was statistically non-significant.) However, there were significant negative findings with B12 and iron. The results of this study should provide additional information to cancer patients and their clinicians when discussing the potential risks and benefit of dietary supplements during the course of cancer chemotherapy.