Calorie restriction with overeating can harm the body

An American research group has discovered some immunological peculiarities of fasting. They were able to identify a fasting-induced switch in leukocyte migration.

Corticosterone leads to increase in CXCR4 chemokine receptor

The researchers had mice fast for up to 24 hours before providing them with food again. They were able to show that fasting during the active phase could trigger the rapid return of monocytes from the blood to the bone marrow. The re-entry of monocytes was controlled by the release of corticosterone. The released corticosterone was accompanied by an increase in the CXCR4 chemokine receptor. This regulatory mechanism occurs depending on the hypothalamic-pituitary-adrenal (HPA) axis.1

Pro-inflammatory monocytes in the blood after renewed food intake

The research group was able to observe a special feature of fasting: The diet had a modulating effect on the lifespan of monocytes as well as their adaptation to external stress factors. Under nutrient deprivation, the bone marrow represents a safe haven for monocytes, but feeding the experimental animals again was accompanied by the mobilisation of chronologically older and transcriptionally different monocytes. The cells, which had previously been hiding in the bone marrow due to nutrient deficiency, re-entered the bloodstream within a few hours. This led to an increase in monocytes and a resulting increased level of inflammation. The research group concluded that the reintroduction of food can lead to a flood of monocytes in the blood that can become problematic. Instead of protecting against infection, the altered monocytes had pro-inflammatory properties. This was accompanied by a decrease in the organism's resistance to infections.1

Fasting advantages for the body

A few years earlier, various research groups had already looked at the immunological advantages and disadvantages of fasting. It was known that fasting could reduce autoimmune processes in the body. At that time, it was observed in scientific studies that fasting cycles with renewed food intake could promote the activation of haematopoietic stem cells and the regeneration of immune cells. In addition, they were said to modulate the gut microbiome and improve autoimmunity in mice. Caloric restriction followed by caloric re-introduction had even promoted T-cell-dependent killing of cancer cells.2

Dangerous water fasting damages the gut and reduces immune response

In 2019, the research group led by Nagai et al. showed that multiple and frequent cycles of water-only fasting attenuated the normal immune response of mice to oral immunisation. This was due in part to apoptotic-induced loss of a large proportion of germinal centres and IgA+ B cells in Peyer's Patches (PPs). Even then, it was known that fasting could down-regulate CXCL13-CXCR5 signalling in naïve B cells of PPs and CCL2-CCR2 signalling in bone marrow monocytes. It was also known that refeeding could restore both signalling pathways and result in a major change in cell composition. Water-only fasting cycles resulted in increased gut leakage and a change in the gut microbiome.

48-hour water-only fasting was found to be associated with reduced mobilisation of monocytes following listeria infection (listeriosis) or wound healing. The researchers already concluded in 2019 that a complete nutrient deficiency could impair the immune system.2-6 We now know thanks to the study by the research team led by Janssen H. et al. that not only the complete nutrient deficiency during water fasting, but also the renewed nutrient intake after 24 hours of calorie restriction can harm the body.1

Sources:
  1. Janssen H. et al. (2023) Monocytes re-enter the bone marrow during fasting and alter the host response to infection, Immunity (2023).
  2. Buono R. et al. (2019). When Fasting Gets Tough, the Tough Immune Cells Get Going-or Die. Cell. 2019 Aug 22;178(5):1038-1040. 
  3. Rangan P. et al. (2019). Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology. Cell Rep. 26, 2704–2719.
  4. Nagai M. et al. (2019). Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses. Cell 178, this issue, 1072–1087.
  5. Jordan S. et al. (2019). Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool. Cell 178, this issue, 1102–1114.
  6. Collins N. et al. (2019). The Bone Marrow Protects and Optimizes Immunological Memory during Dietary Restriction. Cell 178, this issue, 1088–1101.