5-Day Fast Improves Longevity Biomarkers in Humans

A recent study in Clinical and Translational Medicine followed people who went 5 days without eating and found improvements both immediately afterwards and up to 98 days later.

Fasting for longevity

Fasting is a practice in which an individual abstains from food and calories for a given length of time. There have been many preclinical studies suggesting the anti-aging effects of fasting, such as reducing cancer and extending lifespan [1-3]. Many, although not all, studies in humans also suggest benefits. It is believed these benefits are largely due to longevity-related pathways such as loss of excess fat, reduced oxidative stress, reduced inflammation, and increased autophagy [1-3].

However, it is unclear what fasting regimen (duration, frequency, etc.) is ideal, and long-term studies are still lacking. It also remains controversial whether fasting is beneficial in normal-weight individuals or only in people who are overweight [4]. A clinical trial in which 45 normal-weight individuals fasted for 5 days was recently conducted at Shanghai University [5].

Is it safe to fast for 5 days?

Participants were monitored closely by the study team to ensure their safety. Additionally, they were also permitted water with salt and mineral supplements. On the sixth, seventh, and eighth days, participants began eating 30%, 60%, and 100% of their recommended daily caloric intake, respectively, before returning to their previously unrestricted diets.

Various safety measures showed that 5 days without food was well-tolerated by the participants, including measures of liver function, kidney function, electrolyte levels, and blood cell counts. Uric acid levels increased during the fasting window, suggesting that fasting may not be appropriate for gout patients or those with impaired kidney function. Hunger levels increased approximately 4-fold on a 20-point scale, but measurements of depression and anxiety remained constant throughout the fast, and no other adverse events were reported to the study team.

Benefits of the extended fast

Many positive effects were seen initially from the 5-day fast. Participants lost an average of 4.6 kg (10.1 lbs) and 9.9 cm (3.9 inches) of waist circumference by the end of their fast. Systolic and diastolic blood pressures were reduced by approximately 10 and 20 mmHg, respectively. Insulin levels were reduced by 64% and IGF-1 by 27%. T3, a thyroid hormone negatively associated with longevity, decreased by over half. Treg cells, which reduce inflammation, were increased throughout fasting.

Many of these benefits lasted well beyond the fasting period, but only waist circumference and Treg cell populations remained improved by day 98 of the study. Insulin levels had returned to baseline after the participants’ three days of slowly reintroducing food (day 8). Diastolic blood pressure, IGF-1, and T3 returned to baseline between days 8 and 38. Body weight and systolic blood pressure returned to baseline between days 38 and 98.

The authors also investigated many glucose metabolism and ketogenic pathways, all of which showed improvements but returned to normal (except lactic acid) by day 38. Lipid levels increased dramatically as the body began burning fat for energy, but they returned to baseline shortly after the fasting period concluded. Of particular note, the well-characterized anti-aging “ketone body” ß-hydroxybutyrate increased by 51-fold by day 5 of fasting and returned to normal by day 8.

In summary, the present study suggests that 5-day water-only fasting reduces metabolic-syndrome and aging biomarkers. Water-only fasting upregulates Tregs to prevent or treat inflammation-related diseases, as well as potentially promote anti-aging by decreasing T3, insulin, IGF-1, and significantly increasing ß-hydroxybutyrate. The results of the present study are very promising as 5-day water-only fasting has many critical beneficial effects without toxicity.

Conclusion

This study adds to the body of literature showing similar benefits to other studies that have investigated caloric restriction and other fasting methods in humans. Beneficial ketone bodies increased much more dramatically in this study of extended fasting than what is typically seen during intermittent fasting, caloric restriction, and other fasting mimetics. Interestingly, whether participants were over or under 45 years of age did not influence most of the results reported in the study. This may be a hint that fasting can be beneficial across a wide range of ages.

Unfortunately, this study had no experimental comparisons or non-fasting control groups. All outcomes were assessed relative to the participants’ pre-fasting levels, but how this method might have compared to other strategies would have been particularly beneficial to see. We cannot say from this study whether a 5-day fast was beneficial relative to a regular healthy diet, caloric restriction, or a different fasting pattern, for example. It also should be noted the study population was exclusively Chinese. This provides interesting data to compare to studies with other participant backgrounds, but it potentially limits our ability to assume that its findings apply to other populations.

Finally, the intervention used in this study is quite difficult to achieve. Beyond self-control and determination, it also requires special attention to electrolyte maintenance and a re-feeding strategy. While 5 days without eating is much more feasible than might be assumed by people who are unfamiliar with fasting, it is still very difficult for inexperienced fasters. The authors themselves state how the study was conducted in a specialized clinic and that extended fasting should be guided by a clinical team.

If you are interested in learning more about fasting, check out our summary article “What is fasting and how does it work?“

Literature

[1] Fontana, L. and Partridge, L. Promoting health and longevity through diet: from model organisms to humans. Cell (2015). https://doi.org/10.1016/j.cell.2015.02.020

[2] Longo, V.D. and Mattson M.P. Fasting: molecular mechanisms and clinical applications. Cell Metab. (2014). https://doi.org/10.1016/j.cmet.2013.12.008

[3] Nencioni, A. et al. Fasting and cancer: molecular mechanisms and clinical application. Nat Rev Cancer (2018). https://doi.org/10.1038/s41568-018-0061-0

[4] Harvie, M. and Howell, A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence. Behavioral Sciences (2017). https://doi.org/10.3390/bs7010004

[5] Jiang, Y., et al. Five-day water-only fasting decreased metabolic-syndrome risk factors and increased anti-aging biomarkers without toxicity in a clinical trial of normal-weight individuals. Clinical and Translational Medicine (2021). https://doi.org/10.1002/ctm2.502