Sage Advice Blog

The Placebo Effect and Cancer-Related Fatigue

March 23, 2018

Alex Speers ND, MS


Fatigue is considered the most common cancer-related side effect, with some studies reporting fatigue being present in 75-99% of patients with cancer. Unlike some cancer treatment-related side effects such as nausea, cognitive impairment, hair loss, or appetite changes, fatigue is unique in that it tends to last longer, often lingering for months to years after treatment ends.


Studies on the subject estimate that 19-38% of cancer survivors experience significant fatigue after treatment. One study of 763 breast cancer survivors found that 5-10 years post-treatment, 34% of the women still reported fatigue. Unfortunately, we still do not fully understand the mechanisms underlying cancer-related fatigue and as a result, there are no reliable treatment options. A recent study, published this past February in Scientific Reports, investigated whether this common, difficult-to-treat side effect could be improved by giving patients what most would consider “nothing”: a placebo.


The study included 74 cancer survivors who had completed treatment 6 months to 10 years prior to enrollment in the study and who reported at least moderate fatigue. Researchers randomized patients into one of two groups: a “treatment as usual” group, who were asked to continue whatever treatments they were currently doing, or a placebo group. The placebo group was given a package of pills clearly labeled “placebos” and instructed to take 2 placebo pills, twice per day, for 21 days. This type of study is called an open-label study, which means that the patients were fully aware of what they are taking, which in this case was a pill containing no active ingredients.


At the end of 21 days, each patient met with a research investigator, who did not know the patient’s assigned treatment group, and completed two fatigue questionnaires. Researchers found that compared to the treatment as usual group, the placebo group reported a 29% improvement in fatigue severity and a 39% improvement in fatigue-disrupted quality of life, both of which were statistically significant. This completed the first phase of the study.


Next, after a 7-day waiting period, those in the treatment as usual group were asked to take the placebo pills for the next 21 days. At the end of the second phase of the study (day 49), both groups of patients met again with a research investigator to complete fatigue questionnaires. Similar to the findings on day 21, researchers found that the treatment as usual group experienced a significant reduction in fatigue severity and fatigue-disrupted quality of life after 21 days of taking placebos. Interestingly, the original placebo group, who had stopped taking the placebo pills on day 21, showed no decline in their fatigue scores, maintaining the improvements seen at the end of the first phase of the study.


While these results may initially be surprising, it is worth noting that several recently published open-label placebo trials have found significant symptom improvement for conditions such as IBS, acute migraines, chronic low back pain, allergic rhinitis, and depression. As a naturopathic physician, these results raise interesting questions regarding the nature of healing, the role of the physician in the healing process, and the value of transparency in the prescribing of medications. While it's difficult to imagine placebo ever being used as a treatment in clinical practice, this research is interesting in that it could help us to gain a deeper understanding of the body's ability to heal itself and eventually, lead to more reliable methods to harness that ability.


Hoenemeyer TW, Kaptchuk TJ, Mehta TS, Fontaine KR. Open-label placebo treatment for cancer-related fatigue: a randomized-controlled clinical trial. Sci Rep. 2018;8(1):2784.


LaVoy E, Fagundes C, Dantzer R. Exercise, inflammation and fatigue in cancer survivors. Exerc Immunol Rev. 2016;22:82-93.


DISCLAIMER: These statements have not been evaluated by the Food and Drug Administration. There are no financial ties to any supplement companies, pharmaceutical companies, or to any of the products mentioned in this post. This post is not meant to treat, cure, prevent, or diagnose conditions or diseases and is meant for educational purposes. As always, please consult your doctor before trying any new treatments or supplements.

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