A ‘Metabolic Switch’ May Explain Why Fasting Boosts Gut Health

Fasting for 24 hours can reverse the loss of stem cell function in the gut that accompanies aging, according to a study of mice.
Intestinal stem cells are crucial for tissue repair and regeneration, and their decline as we age means that it becomes harder to recover from gastrointestinal conditions and infections.

The researchers, who were led by a team from Massachusetts Institute of Technology (MIT) in Boston, discovered that fasting for 24 hours boosted regeneration of gut stem cells in younger and older mice. They found that fasting exerted this effect by means of a metabolic switch that causes cells to break down fatty acids instead of carbohydrates such as glucose. They also discovered a molecule that can activate the same switch – a finding that might lead to drugs that boost older people’s recovery from gastrointestinal infections or chemotherapy.

Stem cells are immature cells that have remarkable properties. For instance, they can replicate almost indefinitely and develop into virtually any type of cell in the body, forming an essential source of new cells for growth and repair in many tissues. In the gut, they maintain and repair tissue lining, which ‘renews itself’ about every 5 days.

Now published in the journal Cell Stem Cell, co-senior author Omer H. Yilmaz – an assistant professor of biology at MIT – explains that diet is known to have a “profound effect” on the ability of tissue to regenerate itself. There is also evidence that intermittent fasting can benefit health and age-related decline in tissue function.



The switch is in a pathway that is controlled by a group of molecules that regulate gene expression, called peroxisome proliferator-activated receptors (PPARs). PPARs control several pathways that trigger cells to break down fatty acids. When the scientists turned off the metabolic switch, they found that fasting no longer boosted intestinal stem cell regeneration. A final experiment showed that it was possible to “mimic” the effect of fasting on the switch with a molecule that behaves like a PPAR.

My Take:
The writing style in this paper is rather choppy, although I cleaned it up a bit.

According to recent research, the single celled epithelial lining of the entire digestive tract is replaced every 24 to 36 hours rather than every 5 days. This fact just increases the impact of this study.

Interest in intermittent fasting has grown immensely in the past year. Research around the Paleo diet and fasting practices of hunter-gatherer cultures in South America and Africa have spurred much of this interest. Atkin’s, the South Beach Diet and all ketogenic diets are an attempt to stimulate this metabolic switch.

This article suggests new drug development that will mimic PPARs. Pending research from Harvard on micro-RNA (mRNA) hopefully will show how cell nuclear supplementation might support this switch in a more natural fashion. To date, glandular extracts from heart, thyroid, thymus and the adrenals have shown the highest levels of cell receptor activity.

The Bottom Line:
I’ll continue to follow this line of research. My clinical experience with intermittent fasting is growing but is still in the early stages. Stay tuned.

Source: May 4, 2018 National Institutes of Health