Fasting Over Feasting

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Remember the advice to “eat frequent small meals and snacks to boost metabolism”? Perhaps that suggestion needs to be re-examined. While we should obviously eat when we’re hungry, reading that suggestion as a call to constantly be snacking is likely one of the many reasons that we have an obesity problem in this country.

Now, new research finds that fasting may be a better option for weight loss. It may also provide a whole host of other benefits.

People have been fasting (going for various periods of time without eating) for centuries. Many cultures fast for religious reasons such as during Ramadan, Lent, and Yom Kippur. Fasting is also commonly practiced for weight loss.

According to researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) and Kyoto University, fasting may boost human metabolic activity, produce antioxidants, and assist in reversing the effects of aging.

The Japanese researchers found 30 previously-unreported compounds that, when fasting, increase in quantity and produce a multitude of health benefits.

"We have been researching aging and metabolism for many years and decided to search for unknown health effects in human fasting," said Dr. Takayuki Teruya, first author of the paper and a technician in the OIST G0 Cell Unit, led by Prof. Mitsuhiro Yanagida. "Contrary to the original expectation, it turned out that fasting induced metabolic activation rather actively."

The small study on 4 individuals provides an evaluation of whole human blood, plasma, and red blood cells of subjects in a fasting state. Levels of metabolites were monitored for changes. The results uncovered 44 metabolites, which included 30 previously unknown compounds, that universally increased 1.5 to 60-fold in individuals within 58 hours of fasting.

Previous studies at the GO Cell Unit found metabolites whose quantities dropped with age. These included leucine, isoleucine, and ophthalmic acid. When individuals fast, the metabolites increase, which suggests that fasting may increase longevity. "These are very important metabolites for maintenance of muscle and antioxidant activity, respectively," said Teruya. "This result suggests the possibility of a rejuvenating effect by fasting, which was not known until now."

Our bodies use available carbohydrates for energy when needed. Without carbohydrates, the body will find alternative energy stores. This act of “energy substitution” leaves biomarkers -- metabolites called butyrates, carnitines, and branched-chain amino acids. These compounds have been shown to increase during fasting.

Fasting further seems to produce effects beyond substitution of energy. In addition to finding established fasting markers, the researchers also found an increase in compounds made by the citric acid cycle, a process wherein organisms release energy that’s been stored in chemical bonds of carbohydrates, proteins and fats. The increase indicates that, when fasting, these compounds work even harder.

Chemical compounds needed for gene expression and protein production, including purine and pyrimidine are also increased during fasting. Researchers believe fasting might reprogram which proteins cells make at what time, which impacts their function. The change may create homeostasis in cells, or modify gene expression based on environmental influences.

The production of antioxidants is increased when purine and pyrimidine are metabolized. Other antioxidants like ergothioneine and carnosine were shown to significantly increase during the 58-hour study time. Cells are protected from free radicals produced during metabolism by antioxidants. The dangerous effects of oxidation from the “pentose phosphate pathway” were mitigated during fasting, but in plasma only.

While starvation may produce a toxic oxidative environment, the researchers believe antioxidative effects may protect the body during fasting. The study provides initial evidence of antioxidants as a marker of fasting. The study also suggests that that fasting may increase production of many age-related metabolites seen in younger people, which decline in the elderly.

"Recent aging studies have shown that caloric restriction and fasting have a prolonging effect on lifespan in model animals... but the detailed mechanism has remained a mystery," said Teruya. "It might be possible to verify the anti-aging effect from various viewpoints by developing exercise programs or drugs capable of causing the metabolic reaction similar to fasting."

The research provides more information on how fasting impacts human health. The studies need to be replicated with more subjects, or evaluate how the metabolic changes might occur in other ways.

"People are interested in whether human beings can enjoy the effects of prevention of metabolic diseases and prolonging life span by fasting or caloric restriction, as with model animals," said Teruya. "Understanding the metabolic changes caused by fasting is expected to give us wisdom for maintaining health."

Clinicians should be advised that fasting is not appropriate for everyone. Individuals suffering eating disorders or at risk for eating disorders should not be encouraged to fast. Patients with IDDM should also avoid fasting due to hypoglycemia. Those with type 2 DM should speak with their doctors first about the safety of fasting and timing of medication. Fasting is also not advised for children or teens or those over the age of 75.

By Lisa Andrews, MEd, RD, LD

Takayuki Teruya, Romanas Chaleckis, Junko Takada, Mitsuhiro Yanagida, Hiroshi Kondoh. Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-018-36674-9

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