Author: BalanceGenics Anti-aging Research Team (How100.com)
In recent years, the claim that fasting for 16 hours triggers autophagy has gone viral on the internet. The argument states that if the human body goes without food for 16 hours, two functions are activated: one is the depletion of liver glycogen, leading the body to start digesting fat, and the other function is called "autophagy."
Regarding the claim that the human body initiates autophagy after fasting for 16 hours, many amateurs may wonder: will the body really consume itself if you haven't eaten for less than a day? What exactly is this autophagic response?
Analysis
Having an empty stomach or restricting calorie intake for a prolonged period indeed can promote the body's autophagic response. However, there isn't a clear answer as to how long fasting must last to trigger the body's autophagic response.
What is the Nobel Prize-winning autophagic response?
The term "autophagy" originates from Greek, where "auto-" means "self" and "phagy" comes from "phagein," meaning "to eat." So, autophagy does refer to "self-devouring," which is quite accurate.
However, this is a concept in cell biology that began in the 1960s when researchers observed that cells could envelop certain parts of themselves, deliver them to acidic lysosomal compartments for degradation, and then recycle the degraded products. It's akin to dismantling unnecessary LEGO pieces to be used for assembling other new structures.
Japanese scientist Yoshinori Ohsumi made significant contributions to the field of autophagy. He established his laboratory in 1988, focusing on protein degradation in yeast cells. He found that starving yeast cells would initiate autophagic responses, digesting unnecessary parts to sustain essential physiological functions and survive. This is somewhat reminiscent of the ancient Western story of the Good Samaritan, making a personal sacrifice to sustain the life of another in a time of dire need. It's a desperate measure taken out of necessity.
Source: Nobelprize.org
Ohsumi later identified a set of genes crucial for autophagic responses, revealing that autophagy is a complex process strictly regulated by cells and is a result of natural evolution. Moreover, not only in yeast but also in human cells, almost identical autophagic responses exist.
Thanks to Ohsumi and other scientists researching autophagy, we now know that autophagy controls cells, degrading and recycling their own components to provide energy or bring new materials for cellular metabolism.
More importantly, autophagic responses are closely related to our health – they can eliminate intracellular bacteria and viruses, facilitate normal embryonic development, and combat cellular aging by clearing damaged cellular contents. Disruption of autophagic function may lead to diseases such as Parkinson's and diabetes.
Source: tanpaku.org
Over 50 years after the concept of autophagy was proposed, Ohsumi made us realize its significant roles in physiology and medicine. It was for this reason that in 2016, the Nobel Committee awarded him the Nobel Prize in Physiology or Medicine for "discoveries of mechanisms for autophagy."
Does fasting for 16 hours really trigger autophagic responses?
In Ohsumi's research, starving yeast cells could initiate their autophagic responses. But in the human body, does fasting for 16 hours indeed trigger autophagic responses, as the viral internet information claims? This question is quite complex.
According to the Cleveland Clinic, in animal studies, fasting for 24 to 48 hours consecutively can generally initiate autophagic responses. In the human body, it's confirmed that having an empty stomach or restricting calorie intake for a prolonged period can indeed promote autophagic responses. However, due to the lack of data, there isn't a definite answer to how long one must fast to induce autophagic responses.
It's also worth noting that there are some human studies. In a 2018 review article on autophagy, 35 studies were listed, with only three from human subjects. The time required to initiate autophagic responses varied among these studies, with the shortest being 36 to 72 hours and the longest requiring calorie restriction for 3 to 15 years. As for the claimed 16 hours of fasting on the internet, there isn't a clear source or basis for it.
Additionally, in animal models, it's confirmed that autophagic responses can clear damaged cellular components, clean up erroneous proteins, or eliminate invading pathogens, which is beneficial for health. Therefore, the medical community is also developing drugs targeting autophagy to utilize it in disease treatment.
Can fasting for 16 hours really aid weight loss?
Interestingly, the 16-hour fasting mentioned in the internet message is related to another hot research topic. This involves the concept of "intermittent fasting" proposed in recent years, which refers to concentrating daily eating within a short period and fasting for the remaining time. The most common form of "intermittent fasting" is 8:16, where eating is restricted to an 8-hour window (e.g., from 9 AM to 5 PM), leaving 16 hours without food.
This method has been highly successful in animal experiments, proven not only to help animals lose weight but also to improve their physical functions and even extend lifespan.
A study published in the journal Cell in 2019 found that this "mild fasting" can reduce the number of mononuclear cells in mice and humans. These cells produce various pro-inflammatory cytokines that can induce chronic inflammation. In animal disease models, mice subjected to intermittent fasting for 4 weeks indeed showed significant improvement in their condition. In January of this year, a study published in the journal Cell Metabolism found that intermittent fasting in mice helps reshape the expression of genes throughout the body, resulting in a more synchronized circadian rhythm across most tissues, indicating metabolic improvements.
Other studies have revealed that not only fasting but also timing of fasting matters. A study in fruit flies in 2021 found that only flies that started fasting in the evening and fasted until noon the next day would benefit significantly from fasting, with a noticeable extension of lifespan. Conversely, if they "ate supper" at night, even if they fasted for the same length of time and ingested the same amount of food every day, the flies would not reap the benefits of fasting.
This time-dependent fasting is believed to be related to autophagic responses. This is because animals' bodies have biological clocks, and only at night is autophagy most active. If food is ingested at night, the body will mistakenly believe it needs to remain active, thereby suppressing autophagic responses. Over time, cellular waste may not be cleared promptly, which can be detrimental to cells.
However, it's essential to note that while this theory seems plausible, it stems from animal experiments, and whether it applies to humans is still unknown with mixed research results. Intermittent fasting has moderate effectiveness for weight loss, but reducing calorie intake is the core of effective weight loss.
Conclusion
The claim that fasting can trigger autophagic responses does have some merit. However, several points need to be considered:
Firstly, fasting for 16 hours doesn't necessarily guarantee the initiation of autophagic responses in the human body. There isn't much research confirming this point. The few human studies that have confirmed fasting times required to initiate autophagic responses often extend to 2-3 days, which may not be suitable for the general population.
Secondly, autophagic responses are a normal physiological function of the human body. Even without fasting, they can be initiated through exercise or reducing calorie intake.
Thirdly, "intermittent" fasting indeed can have positive effects on the body, but the reasons are very complex, with autophagic responses being just a part of it.
Finally, it's crucial to emphasize that adopting scientific methods is necessary for achieving a healthy body. Trying to abstain from food and drink for several days solely to "initiate autophagic responses" may not be effective and could potentially harm the body.
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Reference
Bagherniya, Mohammad, et al. “The Effect of Fasting or Calorie Restriction on Autophagy Induction: A Review of the Literature.” Ageing Research Reviews, vol. 47, Nov. 2018, pp. 183–197, https://doi.org/10.1016/j.arr.2018.08.004.
Cleveland Clinic. “Autophagy: Definition, Process, Fasting & Signs.” Cleveland Clinic, 23 Aug. 2022, my.clevelandclinic.org/health/articles/24058-autophagy.
Deota, Shaunak, et al. “Diurnal Transcriptome Landscape of a Multi-Tissue Response to Time-Restricted Feeding in Mammals.” Cell Metabolism, vol. 35, no. 1, 3 Jan. 2023, pp. 150-165.e4, pubmed.ncbi.nlm.nih.gov/36599299/, https://doi.org/10.1016/j.cmet.2022.12.006.
Jordan, Stefan, et al. “Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool.” Cell, vol. 178, no. 5, Aug. 2019, pp. 1102-1114.e17, www.cell.com/cell/fulltext/S0092-8674(19)30850-5, https://doi.org/10.1016/j.cell.2019.07.050.
The Nobel Prize. “The Nobel Prize in Physiology or Medicine 2016.” NobelPrize.org, 2016, www.nobelprize.org/prizes/medicine/2016/press-release/.
Ulgherait, Matt, et al. “Circadian Autophagy Drives ITRF-Mediated Longevity.” Nature, vol. 598, no. 7880, 1 Oct. 2021, pp. 353–358, www.nature.com/articles/s41586-021-03934-0, https://doi.org/10.1038/s41586-021-03934-0.
