An important study, published in Cell Metabolism by a research group from University of California San Diego, La Jolla (Division of Gastroenterology) and performed in mice (very similar to humans in terms of metabolic and immune-related responses), showed how a recurring short period of fasting is able to reduce inflammation, boost fat body weight loss and trigger a new metabolic pattern that can last over time.
Understanding which signals should be sent to the body through food may become one of the most effective tools to tackle the epidemic levels of obesity currently affecting industrialized countries.
Most of these signals are already known (the importance of breakfast and of balancing carbs and protein in each meal, the role of chewing and so on). Their role can be even more powerful, if we take into account when and where these messengers come into play.
The abovementioned study rigorously describes the effects of diet and short fasting on all possible levels (from changes in gene expression, inflammatory cytokines and adipokines production, to modifications in the microbiome); even though it is based on a mammalian species different from humans, we should not forget that in the past few years most of the research done in mice translated successfully into men (Chaix a et al, Cell Metab. 2014 Dec 2; 20(6): 991-1005. doi: 10.1016/j.cmet.2014.11.001).
In either case, the study of signals produced by short (around 15 hours) fasting as opposed to prolonged fasting (which always generates offsetting fattening effects) has produced significant amounts of high-quality scientific articles, which are now “forcing” anyone interested in the discussion to talk about real data, not just speculations.
How the topic has been investigated
When designing the experimental plan, researchers have recreated several different eating and fasting conditions and have involved both obese and slim subjects. Classic diets, diets high in fat, sugar or fructose have been analysed, while time-restricted eating moments have been defined, that is, active periods of the day when it was allowed to eat (during the night in mice, during the day in humans).
Both ad libitum intake diets (without limits, except those set by hunger) and normocaloric diets (those sufficient to keep the participants of the study in good health) have been evaluated.
In addition, researchers focused on food intake intervals of 9 hours (the following 15 hours as brief fasting), 12 hours (while fasting in the following 12 hours) and 15 hours (and short fasting in the next 9 hours). On average, 15 hours short fasting resulted to be the most effective one, while the 12 hours fasting interval produced intermediate results; 9 hours of fasting never led to significant effects.
Strict experimental checkpoints made possible to study these dietary combinations for long periods of time. Altogether, the different experimental combinations identified substantial differences between subjects free to eat whatever, but only for 9 hours when active and awake (followed by 15 hours of fasting), compared to those control subjects, who could eat anytime during the 24 hours.
Short fasting produced the following results:
- Reduction in body fat accumulation in obese/overweight as well as slim people.
- Protection against the development of diet-related hepatic steatosis, and reduction in transaminases levels.
- Decrease in fat mass-related inflammation (in particular, cytokines such as TNF-alpha and IL-1- beta were found to be reduced), thus limiting all those warning signals (such as those triggered by BAFF) able to cause fat accumulation.
- Improvement of glucose tolerance and reduction of insulin resistance; in particular, it was possible to ameliorate the glucose intolerance produced by fattening diets (thus becoming a new effective tool for diabetes).
- Definition of a strong metabolic memory (via documented gene activation mechanisms) in the person, which is not altered by the presence of two freedom days (for instance, the weekend). While having a free diet for extended periods of time leads to body fat accumulation, the free time-limited intake of food triggers a durable activation of the metabolism, which is maintained even if two days of complete freedom are included in the scheme.
The abovementioned conclusions are just a few of those drawn in the study by Chaix but are enough to show how a diet based upon food intake restricted over 9 hours is the only option available to produce a global action against a number of metabolic problems affecting nowadays the industrialized world.
The clinical application of such dietary planning should be carefully modulated, but it offers an innovative starting point for a novel nutritional treatment, much different to what has been known up to now.
The interesting study by Hatori, recently published in Methods in Enzymology, goes towards the same direction by explaining that the scientific understanding around the circadian rhythm and of its impact on metabolism, genome, microbiome and enzymatic activity is only now reaching an acceptable level, while opening future avenues of understanding and innovation.
In presence of a total metabolic and hormonal dysfunction consequent to highly fatty uncontrolled diets, Hatori demonstrated that a time-restricted dietary plan (eating only during active hours, followed by a short fasting in the following period of time) helps restoring the primitive metabolic structure while preventing obesity and many other metabolic conditions, even when the actual food choice and intake is completely wrong for that person (Hatori M et al, Methods Enzymol. 2015; 552:145-61. doi: 10.1016 / bs.mie.2014.10.027. Epub 2014 Dec 27).
Continuity with the past and innovation
For years, our practice in Milan has been successfully applying some of these interesting ideas through specific therapeutic programs, individually designed by applying fundamental food education basics.
Everyone studying these signals is already putting into practice something very similar to our plans. The typical suggestions are to eat a very rich breakfast, a decent lunch and a very light dinner. If instead of a light dinner one skipped that meal until next morning’s breakfast, he/she would reach the amount of time of short fasting (15-16 hours).
Now it is all down to perfecting (scientifically) something that has already been used by many nutritionists, who exploit food signals to modify metabolism.
Being aware of how time can impact, understanding where certain molecules are active and creating an enlarged but yet detailed vision of what happens biologically does help a lot to master the whole story.
In a previous article on FSP27, we have described the action of a protein that is widely known both for its lipogenic action at liver level (the organ designated to fat reception and management) and its lipolytic function at adipose tissue level (from where both patient and nutritionist are interested in mobilizing fat away) during the first 15 hours of short fasting.
FSP27 is involved in the formation of lipid droplets within the cells, where it acts as a lipid vector without determining fat accumulation or mobilization by itself. As signal protein, it simply abides by the metabolic status of the cell in relation to the specific time and type of cell involved.
Experts not well-prepared on the topic tend to consider FSP27 merely for its downregulating action on lipid metabolism.
The fact that the immediate consumption of fat is reduced during short fasting is linked to the phase of metabolic resetting of cellular energy supply management, which stops for a few hours any uncontrolled fat consumption. For example, in the early stages of fasting the adipose tissue exploits FSP27 action to mobilize fat reserves, which will reach all body tissues (primarily muscles) as a form of energy support.
Therefore, those cells expressing FSP27 are not those where actually fat will be burned, but rather those that start the weight loss process described in Chaix’s studies.
It is important to read carefully when and where a protein comes into business and how these details are correlated with the effect produced by the molecule.
The study by Vilà-Brau on FSP27 describes really well such paradoxical effect similarly to what done in Chaix’s article, in which time is defined as the main determinant between the lipogenic and the fat mobilizing action.
It is important to understand the diversity in timing of a molecule’s action if we want to embrace a change in the interpretation of metabolic events. In order to change the way we interpret metabolism, we should start focusing primarily on the reaction timing of a molecule.
A calorie is not just a calorie; an adipokine is no longer just an adipokine. It all depends on when and where a specific molecule is expressed.
From theory to practice
In order to lose weight, one should eat during active hours and fast for 15 hours after having satisfied his/her hunger, since both behaviours do produce the same effect in the same amount of time.
Probably, we should aim at taking a step further in the evolutionary interpretation of our relationship with food, in order to get a better understanding of which signals are the most effective and beneficial for health, to translate the experimental knowledge into clinic.
This does not mean that everyone should follow some sort of protocol, but being aware of this means that we can master an effective and innovative tool potentially applicable today to every patient willing to accentuate lipolysis.
A new exciting period of innovative studies and knowledge growth is currently opening, supported by the same reasons that make our daily research steps continuously attractive.