Fasting Improves Recovery of Bone Marrow Stem Cells after Chemotherapy
[Note: This is a guest post by Tauseef (@CellSpell)]
Fasting is defined as either completely abstaining from or minimizing food intake for a defined period time - ranging from about 12 hours to even a few weeks. Calorie restriction, on the other hand, refers to an overall reduction in the daily calorie intake by about 20%-40% without necessarily reducing the meal intake frequency. Although calorie restriction is well-suited for weight loss and thus also reduces the risk of chronic diseases such as diabetes or heart disease, proponents of fasting claim that it has distinct health benefits which cannot be attributed to weight loss.
Scientific data for the benefits of fasting have been rather limited, but some recent studies have now shown that fasting can enhance cellular resistance to toxins and increase longevity in laboratory animals as well as humans. Fasting has also been proposed as a therapeutic approach in the setting of selected diseases such as neurodegeneration, seizures and rheumatoid arthritis.
The recent study "Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression" published in the journal Cell Stem Cell by Cheng and colleagues in 2014 investigated a novel benefit of fasting – enhancing recovery from the side effects of treatments. The researchers looked into whether fasting in a mouse model of chemotherapy would help the mice recover from the suppression of their blood cell production. Chemotherapy drugs suppress the growth of malignant cancer cells, but they unfortunately often also affect healthy stem cells and other growing cells needed to maintain our health. The bone marrow contains blood-forming hematopoietic stem cells (HSCs), which churn out billions of healthy blood cells, such as white blood cells (WBCs) and red blood cells (RBCs), every day. When these healthy stem cells are suppressed or even eliminated as a form of collateral damage during chemotherapy, patients can develop severe anemia or immune suppression.
In their study, Cheng and colleagues showed a strong protective role of multiple cycles of fasting (no food for 48 to 120 hours) in mice treated with the chemotherapy drug cyclophosphamide. The fasting was able to partially reverse the suppression of bone marrow stem cells, improve immune function and reduce the death rate of the mice. The researchers found a similar protective effect of fasting in cancer patients (no food for 72 hours) who were treated with anti-cancer drugs as a part of phase I clinical trial, although there was no control group and no details were provided about the overall fluid and calorie intake of the patients.
By utilizing a gene array to screen for the expression levels of thousands of genes, the researchers determined that the benefits of fasting were due to the reduction of insulin-like growth factor-1 (IGF-1) hormone levels in the bone marrow. Suppression of IGF-1 by fasting increased the expansion of bone marrow stem cells (HSCs) and improved the immune function during chemotherapy. Mice in which the IGF-1 gene was deleted showed a similar degree of protection as what was observed in fasting mice.
Although, the present study provides interesting new insights for how fasting can improve bone marrow function in chemotherapy, some unanswered questions need to be addressed in future studies. People who are suffering from cancer routinely lose a substantial amount of weight during the progression of their disease, and it is not clear that their physical health would be able to tolerate the additional stress of fasting. Moreover, the researchers did not provide details about the calorie restriction and potential weight loss associated with the fasting. Perhaps the benefits in the mice were not due to fasting but instead due to calorie restriction. Furthermore, the patient study only showed that 72 hours of fasting increased lymphocyte counts, but did not describe the nutritional status and any potential weight loss in the patients.
This study is one of the first studies to uncover the molecular mechanisms of how fasting can improve the recovery of bone marrow stem cell function after chemotherapy. Despite its limitations, the study also identified the IGF-1 pathway as a potential new target for treatments to enhance bone marrow stem cell recovery. The outcomes of chemotherapy might be therefore improved by pharmacologically suppressing IGF-1 without requiring fasting, but this idea would still need to be tested in humans.
- M. Tauseef (@CellSpell)
Cheng, C., Adams, G., Perin, L., Wei, M., Zhou, X., Lam, B., Da Sacco, S., Mirisola, M., Quinn, D., Dorff, T., Kopchick, J., & Longo, V. (2014). Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression Cell Stem Cell, 14 (6), 810-823 DOI: 10.1016/j.stem.2014.04.014