Pulling a Fast One on Cancer

Fasting effects on immune cell regeneration can affect cancer recovery

Fasting causes a major reduction in white blood cells followed by their replenishment after refeeding. These effects of prolonged fasting can result in the reversal of chemotherapy-induced immunosuppression.

There is a report making the rounds on social media that really needs to be explained, because as usual the media hype is distorting the findings. The article in question was published in the Cell Stem Cell journal, and is Open Access. I will explain the background, what these results mean, and more importantly, what they don’t mean.

✤ Traditional chemotherapy is toxic to cells. The only reason traditional chemotherapy works is because it kills cancer cells faster than it kills normal cells. The side effects from chemo often happen because normal cells are also affected. One such side effect is the suppression of the immune system. This happens because chemo damages adult stem cells too, which impairs tissue repair and regeneration.

✤ Blood stem cells (known as hematopoietic stem cells) are responsible for replacing our blood cells; these reside in the bone marrow. In this study, scientists investigated the effect of prolonged fasting on hematopoietic stem cells.

✤ Mice used in this study were fasted for 48 hours, which the scientists defined as prolonged fasting. These mice received no food, only water. They then treated the mice with cyclophosphamide, a common chemotherapy drug. They found that cycles of prolonged fasting reduced the damage caused to hematopoietic stem cells when the mice were treated with cyclophosphamide. They also found that prolonged fasting cycles promoted the regeneration of blood cells through the protection of hematopoietic stem cells.

✤ Next, the scientists tested whether the effects of prolonged fasting were independent of the toxic side effects of chemotherapy. Could prolonged fasting alone stimulate hematopoietic stem cells to self-renew? Indeed, it could.

✤ What is the molecular mechanism for this process? A growth factor known as Insulin-like Growth Factor-1 (IGF-1) seemed to be involved. Growth factors are proteins that control the multiplication of cells. To examine this mechanism, the scientists used mice that were deficient in IGF-1. If you’re curious about how these ‘knockout mice’ are generated, I wrote an article about this here. When these IGF-1 deficient mice were treated with cyclophosphamide, they showed similar results to the prolonged fasting mice; reduced levels of hematopoietic stem cell damage. So getting rid of IGF-1 induced the same protective effects on hematopoietic stem cells.

✤ How does IGF-1 signalling protect hematopoietic stem cells? They found that the activity of an enzyme known as PKA was also reduced in these prolonged fasting/IGF-1 deficient mice. PKA controls the pathway involved in stem cell regeneration. So inhibiting IGF-1 or PKA signalling mimics the effect of prolonged fasting; it promotes the regeneration of hematopoietic stem cells, thereby reducing the immunosuppressive side effect of chemotherapy.

✤ This is really interesting data – this research has identified one of the signalling pathways in the intricate network of reactions controlling the behaviour of hematopoietic stem cells. The mechanism involves PKA and IGF-1 signalling.

What the data doesn’t show

What this doesn’t show is that fasting is magically a cure-all for cancer. There isn’t a single study that shows lowered incidence of cancer in human populations that fast regularly. The fasting that these mice underwent also did not include the feasting that goes on every night as seen with human populations either. The scientists also conducted a small Phase I clinical trial in which patients undergoing chemotherapy fasted for 72h – the results are promising; their hematopoietic stem cells were protected when compared with the non-fasting control group. But obviously more data is needed, and it is highly inadvisable to fast before undergoing chemo, without the explicit guidance of a physician.

To summarise, fasting is not a cure for cancer. If anything, fasting does “cure” everything, eventually; this pathway involves a mechanism known as ‘death’.

Original research paper and image source (Open Access)

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