By Dr. Frank Sabatino

Your body cells contain a number of parts that perform a variety of functions, including energy production, protein synthesis and cellular repair, to maintain the tapestry of homeostasis and survival. Within every cell, there is a unique recycling/repair system that depends on a microscopic organ, the lysosome, that has a highly acidic internal environment containing approximately 60 different digestive enzymes, and maintains a form of cellular clean up and digestion. 

Similar to our larger digestive system, the lysosome also has a protective membrane around it, a barrier that controls the release of its enzymes, confining and controlling their action to protect healthy cells from being completely destroyed. However, all cells have a natural life span, and every day millions of cells are being born while millions of cells are being destroyed and eliminated in a process called apoptosis or programmed cell death. So when a cell has outlived its programmed lifespan, and is slated for death, the membrane of the lysosome breaks down, flooding the cell with enzymes that promote the destruction of the cell and the recycling/elimination of its damaged parts. 

Over the past 50 years, remarkable research discovered and highlighted the structure and genetic machinery of a process of cell renewal and repair that involves the lysosome and exists in the cells of all living things except bacteria.(1,2,3,4,5) This process is called autophagy because it involves the sequestering of damaged cell parts, proteins and even microbes, accumulated during daily function, wear and tear, into structures called autophagosomes that are transported to the lysosome for recycling, breakdown  and elimination. The word also refers to the idea of “self-eating” and is a lysosomal degradation pathway of self-digestion. Crucial roles for autophagy have been established in nutrient and energy homeostasis, stress adaptation, tumor suppression, innate and adaptive immunity, metabolism, the regulation of inflammation, and aging. (6,7)

The process of water-only fasting inspires a unique survival challenge to the  profound wisdom and intelligence of your body as it  balances energy needs with food availability. 

This increase in autophagy is one of the most profound and significant effects of water only fasting. And when the natural process of autophagy is enhanced during fasting,  it allows the body to maintain and protect healthy, functional body cells while digesting, dissolving and utilizing the parts of worn out and damaged cells, including non-essential extraneous growths like tumors, cysts and stones, for its energy needs. Autophagy can rapidly provide fuel for energy, building blocks for the renewal of cellular components, and is therefore essential for the cellular response to fasting. 

Several hormone and enzyme changes that occur in fasting are directly involved in the enhancement of constructive autophagy of fasting. The enzyme mTORC1 (the mechanistic target of the antibiotic/immunosuppressant Rapamycin) is located on the surface of lysosomes, and under typical nutrient rich conditions it senses nutrient levels,  is activated by amino acids, glucose, and growth factors, suppresses the initiation and action of autophagy, and promotes protein synthesis and the growth of cells. 

Fasting is a potent inhibitor of mTORC1 that allows autophagy to begin and proceed moving cells away from a growth mode to a state of maintenance and repair. During fasting there is also a decrease in the hormone insulin, and Insulin-like growth factor 1, in addition to the deprivation of nutrient factors (amino acids and glucose), that would typically activate mTORC1, to promote cell growth and protein synthesis. As  a result, mTORC 1 is inhibited, activating a pathway  of cellular messengers that enhance the process of autophagy diverting cells away from growth in the direction of maintenance and repair. The reduction in the activity of mTORC1 during fasting improves metabolic function, enhances fat burning, and has significant anti-aging effects. 

So that as energy is  diverted away from the procurement of food, digestion and cellular growth during water-only fasting, it is more available for cell maintenance, elimination and repair. This is one of the important reasons why fasting should be recognized as a profound resting process, and should be done with absolute rest to harbor your energy reserves for the work of cellular repair, detoxification, and healing.

The body and gut microbiota also produce the compound spermidine which mimics the anti-aging effects of calorie restriction and induces autophagy by inhibiting mTORC1. (8) Fasting triggers a natural surge in endogenous spermidine that activates autophagy after 36 hours of fasting. (9) In experiments where spermidine production is blocked, the beneficial anti-aging and anti-inflammatory effects of fasting are significantly reduced. Studies across species, including yeast, flies, mice and humans, show that the acute nutrient deprivation of fasting boosts the anti-inflammatory compound spermidine and helps cells clear and recycle damaged cell parts. A nice bonus is that the benefits of fasting-induced autophagy partially mediated by spermidine are often still pronounced in the re-feeding phase. 

Keep in mind that your body knows what belongs in it and what does not. And during a water-only fast, through the process of autophagy, it will eliminate what it needs least to support what it needs most. So for example, it needs vital organs like heart, brain, kidney, liver etc. but it does not need tumors, cysts, stones and growths. I have seen women with breasts full of fibrocystic calcium deposits that look like shrapnel on a mammogram get completely clear in 7 days of water-only fasting. I have also seen women with uterine fibroids the size of grapefruits shrink remarkably in several weeks of fasting. So in the fasting state, your body will promote this cellular alchemy and break down tumors, cysts, cancers and stones, taking from these abnormal growths whatever it can, to feed the organs that are vital to life and health. As a result, water only fasting has been shown to shrink cancers like lymphoma in work done at the True North Health Center, and a variety of abnormal growths, tumors  and cysts throughout the body.  

References

1. Levine B, Kalensky D. Development by self-digestion. molecular mechanisms and functions of autophagy. Dev Cell, 2004, 6:463-477.

2. DeDuve C, Watteux R. Functions of lysosomes. Annu Rev Physiol. 1966, 28:435-492.

3. Takeshige K, et al. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Bio. 1992, 119:301-311.

4. Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Letter, 1993, 333:169-174.

5. Kametaka S, et al. Structural and functional analyses of ApG5, a gene involved in autophagy in yeast. Gene, 1996, 178:139-143.

6. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell, 2011, 147: 728-741.

7. Mizushima N, et al. Autophagy fights disease through cellular self-digestion. Nature, 2008, 451:1069-1075.

8. Kriebs A. Spermidine controls autophagy during fasting. Nature Aging, 2024, 4:1172.

9. Hofer SJ, et al. A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity. Autophagy, 2024 Aug 30;20(12):2824-2826.