Western countries are in the privileged situation of food surplus. The future snack is always just the next snack bar or supermarket away. However, the eating behavior that is most common in modern societies, three meals plus snacks a day, is not the rule from an evolutionary perspective. In evolution, food-rich periods were always followed by food-poor times - there were simply no permanent surpluses.
The consequences of the status quo, thanks to fast food, range from cardiovascular diseases to diabetes and various types of cancer. Science has gained useful insights from this context. Data from current and past studies in animal models and humans suggest that Fasting can improve health indicators and counteract disease.
How to fast?
Humans fast by consuming no to minimal amounts of food or calorie-containing beverages for periods of time that typically range from 12 hours to a few weeks. This principle is by no means new. Fasting rituals are part of most human populations and cultures, including Buddhism, Christianity, Hinduism, Judaism and Islam. Traditionally, people fast here at certain time intervals or on certain days of the week. The consequences of this behavior, apart from the favor of the gods, remained largely speculative for centuries. Only in the 20th In the 19th century, researchers delved into the molecular basis of fasting.
But not all fasting is the same. First and foremost, it must be differentiated from starvation. Starvation means chronic nutritional insufficiency, which is sometimes incorrectly used as a substitute for the word fasting, but is more likely an extreme form of fasting that can lead to degeneration and death. A look across the Aegean Sea provides insight into this sad state of affairs.
In addition to a healthy diet, fasting can be another important building block for a long life.
Calorie restriction
There are roughly two principles when it comes to fasting. On the one hand, there is the so-called calorie reduction (caloric restriction). This means a permanent reduction in daily calorie intake by 10-50% without causing malnutrition. In humans, there is research that a 15% calorie reduction per day is most effective against age-related mortality. Bryan Johnson – tech CEO with the desire to stop aging – relies on a calorie reduction of around 24% in “Blueprint”.
Did you know? The vast majority of fasting methods that exist today do not have their origins in science. Either they came from religious customs, such as Ramadan, or were set for convenience. The popular 16/8 model tries to accommodate a society with three meals by simply skipping one meal. Which fasting periods are ideal for individuals is still being researched.
Okinawa and the diet of 100-year-olds
At this point we take a short trip to Okinawa, Japan - one of the world's five Blue Zones. The long-lived population of Japan's southernmost province is one of the most studied links between calorie restriction and improved healthspan. The residents of Okinawa know how to combine above-average exercise with below-average food intake like no other population. However, as local families moved to Brazil, they adapted to the Western lifestyle, which influenced both their diet and physical activity. The Consequences were weight gain and a decrease in life expectancy by a whopping 17 years.
There are also a few things that you have to consider when reducing calories. A long-term reduction will sooner or later lead to weight loss. This can be desirable for overweight people, but the collective of people of normal weight are naturally also affected by aging. Depending on your initial weight, additional weight reduction can have a negative effect.
Intermittent fasting
In addition to calorie restriction, there is a second well-known fasting principle: time restriction = Time restricted eating (TRE). The best-known form is probably intermittent fasting, also called intermittent fasting or short-term fasting. This is the name for a form of nutrition in which you constantly, switch between fasting and normal food intake at a certain rhythm. This form of fasting has become increasingly popular in recent years. Probably for one simple reason: it's easy to use. You don't have to change your eating habits, just limit the time you eat.
Accordingly, in contrast to calorie reduction, there is no significant weight loss. The average across studies was approximately 3-5%. Nevertheless, intermittent fasting is a sensible start. The most popular model is probably the 16/8 principle. Here you eat within eight hours and then follow a 16-hour fasting period. The eating time window can be divided depending on personal needs or working hours - but should remain constant.
This type of fasting has led to a number of beneficial effects on healthspan in studies on mouse models of minimizing the risk of developing age-associated diseases . These include neurodegeneration, cardiovascular diseases and cancer. In similar animal studies periodic fasting was able to attenuate the harmful consequences of Alzheimer's, Parkinson's and Huntington's disease. In cancer treatment, parallel fasting during selected chemotherapy regimens partially helped to “starve” the tumor.
Water fasting, FMD, short-term fasting - a guide to different forms of fasting
In addition to the two concepts, calorie and time restriction, there are a wealth of other forms of fasting. The Medical Association for Therapeutic Fasting and Nutrition e.v is currently developing precise definitions for the various forms of fasting as part of the guidelines. For a better overview, the four most important ones are listed here:
- Prolonged fasting: In this form, participants are only allowed to consume liquids. Prolonged fasting is defined as a fast lasting at least 4 days
- Short-term fasting: Similar to prolonged fasting, but the duration is limited to 1-3 days
- Water fasting: Here you can only consume water. The length is not fixed
- FMD (Fasting Mimicking Diet): This fairly new form of fasting was developed by the American Dr. Designed by Valter Longo. You can eat some foods, especially vegetables and healthy fats. The composition of the food is intended to molecularly imitate fasting without having to fast. In addition to an appropriate diet, fasting-mimicking supplements such as Spermidine, Glucosamine are also recommended or Berbersome discussed.
Fasting – religious hype or is there more behind it?
Although fasting has been anchored in various cultures for centuries, it is still very much in its infancy in (conventional) medicine. Often labeled as “esoteric” and “ineffective”, fasting had a niche existence. Only recent research results - on animals and humans - are shedding more light on the beneficial biochemical and molecular genetic processes that take place in our bodies during fasting. We want to go into this in more detail here. Don't be put off by the many abbreviations and complicated names. In the end, the deeper knowledge will help you evaluate different fasting methods for you and your longevity.
Did you know? The tradition of fasting can be traced back to the Greek philosopher and physician Hippocrates. He lived from 460-370 BC. He believed in the body's ability to heal itself if you take care of your body through proper nutrition and a healthy lifestyle. There are no direct recommendations for fasting in his writings, but his dietary instructions were very similar to modern fasting.
Hippocrates already knew about the health-promoting effects of fasting.
AMPK – the “energy sensor” of our cells
While Hippocrates still had to “believe” back then, we have come a long way today. With the help of detailed examinations, we can understand the individual signaling pathways in our body that are activated when fasting.
An important protagonist is AMPK – one of the four longevity pathways. The abbreviation stands for AMP-activated protein kinase. The ending -ase tells us that AMPK is an enzyme. You can imagine its role in the body as a kind of “sensor”. AMPK measures energy content by measuring the ratio between AMP (adenosine monophosphate) and ATP (adenosine triphosphate). Fasting or intensive exercise activates AMPK.
What follows is a series of changes in the cell's energy balance. Glucose is increasingly absorbed into the cells, which increases your insulin sensitivity. The diabetes drug metformin also hides behind this mechanism of action. Fatty acids are also broken down, which helps you lose weight. Not only does AMPK activate countless energy pathways in your cells, higher levels of AMPK also appear to have anti-inflammatory effects on your body.
A final, important aspect of AMPK, in the context of fasting, is its ability to stimulate cell autophagy. During autophagy, your cells switch into “recycling mode”. Everything that is no longer needed comes out. What sounds like a molecular form of “spring cleaning” is actually an important process for cells to stay healthy for as long as possible.
Now the molecule spermidine and autophagy are often mentioned in the same sentence. Researchers expect the substance to directly activate the recycling processes in the body. The Bruneck study at the Medical University of Innsbruck has already established a strong positive connection between a spermidine-rich diet and longevity! Dr. David Sinclair and Bryan Johnson both rely on appropriate nutritional supplements.
Did you know? The recycling of old cell components is more important than was assumed just a few years ago. Certain diseases, such as Alzheimer's and cardiovascular diseases, but also cancer, are associated with altered autophagy . Especially with age, our ability for autophagy decreases.
Fasting also appears to have positive effects on cognitive function. This could be particularly exciting as a treatment supplement for Alzheimer's disease.
mTOR – another important sensor
The next molecule, with a complicated abbreviation. mTOR, short for mammalian target of rapamycin), like AMPK, is an enzyme that is connected to many different processes in our body.
One task of mTOR is to record the availability of nutrients. moTOR is particularly sensitive to two types of molecules: Sugar, in the form of glucose, and proteins, in the form of amino acids. To put it simply, our body uses mTOR to know how much amino acids and sugar are available to it. But this is a very gross simplification. There are several subtypes of mTOR, whose exact properties and roles are not yet fully understood. Excessive activation of mTOR is associated with various diseases, for example cancer.
When fasting, the opposite occurs - namely an inhibition of mTOR. Due to the self-induced “stress”, the cells switch to recycling (autophagy) and survival mode. For this reason, the “defusing” of mTOR is considered to have great potential for longevity in research. Many animal studies have already shown that lower mTOR levels lead to a longer life.
One drug that achieves this is rapamycin. It comes from the family of immunosuppressors - i.e. suppresses our immune system - and is used in organ transplants. The idea of using rapamycin as a “longevity drug” already exists and is being discussed by, among others, Peter Attia proposed. However, we currently know too little about the effects on the different mTOR groups. Levels that are too low, such as those achieved by high doses of rapamycin, can do us more harm than good due to the immune-suppressing effect. Here, at least it seems, you can find a natural middle ground with fasting.
Did you know? Some studies provided evidence that secondary plant substances such as Resveratrol Can downregulate mTOR. Resveratrol also interacts with sirtuins and therefore appears to have great potential as a fasting mimetic.
For powder fans and capsule lovers - Trans-Resveratrol from MoleQlar is there for everyone.
Sirtuins: An elementary building block for the longevity effects of fasting
The term sirtuins summarizes a group of proteins of which, according to current research, mammals have seven different ones (SIRT1-SIRT7).
SIRT1 plays an important role during fasting. Calorie restriction activates SIRT1 and thus its potentially health-promoting properties. Sirtuins can promote cell health and increase their resistance to “stressors”. SIRT1 also activates AMPK in the liver. As mentioned above, AMPK plays an important role in energy balance.
Sirtuins are currently being intensively researched, because in animal studies they show great potential for extending life and health span. SIRT1 in particular seems to be a promising candidate.
However, the connections are complicated by the complex, biochemical mechanisms. One example is how sirtuins work. Short warning, it will be very detailed again, but then you have made the excursion into the physiology behind fasting:
Sirtuins have a so-called enzymatic deacetylase activity. This means they can split off acetyl groups (=a chemical structure consisting of one oxygen, two carbon and three hydrogen atoms) from one molecule and transfer them to another. One place where this happens is on the histones. You can find these in the nuclei of your cells.
And what does that bring us now? Imagine histones like the wrapping string around a gift. Sirtuins can use their enzyme activity to loosen this packaging cord and thus expose the DNA underneath. Your “gift” can now be unpacked and used. In this way, our body can “decide” which genes are currently being read and which are not. Sirtuins work particularly on the genes that promote longer life. The catch to the whole thing. Sirtuins need a partner, namely NAD+.
Use MoleQlar's NAD test to determine your intracellular NAD levels.
Sirtuins and NAD+ – both are needed
NAD stands for Nicotinamide Adenine Dinucleotide and the + describes the active form of the molecule.
Back to the sirtuins: These need NAD+ as a partner to do their job. Unfortunately, as we age, our NAD+ levels continue to decline. Our body therefore has increasingly less energy available. One way to counteract this is to supplement the precursors of NAD+. This can potentially increase the effects of fasting. One of the leading researchers on this front who also fasts and has incorporated NAD boosters into his supplement plan is renowned aging researcher Dr. David Sinclair
Did you know? In addition to fasting, there is another way to activate SIRT1 in your body. Resveratrol, a secondary plant substance found in red wine, among other things, can, according to the research work of Prof. Sinclair also contribute to a longer life through activation of SIRT1. The Harvard researcher takes 1 gram of resveratrol and NAD booster for breakfast every day.
In addition to resveratrol, there are other molecules that can activate SIRT1. This includes Glucosamine. This substance occurs naturally in our bodies - primarily in the synovial fluid and cartilage. For this reason, glucosamine has been studied in the treatment of knee pain - with mixed results. In animal studies, glucosamine was able to show life-extending effects, which is why further studies will follow. One of the suspected mechanisms is the activation of SIRT1 and the resulting increased autophagy of cells. Glucosamine also blocks a step in carbohydrate metabolism, which also stimulates recycling in our cells.
FMD – fasting benefits without having to fast?
After this excursion into the biochemical background, you may have a better understanding of the (molecular) pathways through which fasting can contribute to a healthier and longer life. The question still remains as to which type of fasting is the best?
This question can hardly be answered in such a general way. However, the following rule of thumb can be derived from the studies: If you want to achieve the health-promoting effects of mTOR, AMPK and SIRT1, you will probably need a longer fast of at least 2 days. Intermittent fasting can also achieve corresponding effects, but to a lesser extent.
Now not everyone wants to go without food for several days at a time. This is absolutely understandable, because it is not always possible to reconcile a longer fasting episode with our everyday tasks. Side effects, such as fatigue and hunger pangs, are usually most pronounced in the first two days.
To prevent this, there is a relatively new concept. Dr. Valter Longo from the USA has postulated the FMD (Fasting mimicking diet) and describes it in detail in his book “The Longevity Diet”. The principle behind it is that the body is “tricked”. By combining different foods, especially high-quality fats such as Omega-3, hunger can be satisfied and the molecular signaling pathways of fasting can still be activated.
In addition to proper nutrition, certain supplements described as fasting mimetics can support the fasting process. Spermidine, Resveratrol and NAD boosters are the most promising candidates here.
Fasting can also be done molecularly
Reap the benefits of fasting without actually fasting? That almost sounds too good to be true. Through detailed research into the molecular signaling pathways, we can now “trick” our body in a certain way and make it believe that we are fasting. This procedure is also known as mock fasting and is being researched by, among others, Valter Longo .
With the help of glucosamine SIRT1 can be activated, for example. Supporting this Spermidine, because spermidine is not only a potent autophagy promoter, studies show it has a positive effect on your heart health and has an anti-inflammatory effect. This is particularly important because SIRT1 is more difficult to activate in an inflammatory environment. Berberine is a useful extension due to its positive influence on carbohydrate metabolism and insulin sensitivity.
Disclaimer: Please note. You can take both spermidine and glucosamine during a true fast. Be careful with Berbersome. If you don't eat any carbohydrates, taking additional berbersome can lead to dangerous hypoglycaemia. It is always advisable to fast under medical supervision.
Fasting and diabetes – why the liver plays an important role
Research is currently being carried out on many fronts in medicine. It was proven that fasting during chemo led to a better response to therapy in some breast cancer patients. But caution is advised here. The results should not be generalized and applied to all types of cancer.
Another disease where fasting therapy can be useful is in people with type 2 diabetes mellitus. Those affected can no longer adequately regulate their blood sugar levels. A suspected cause behind this disease is visceral fat, which is stored in the pancreas and liver. This fat, although not visible from the outside, is responsible for a number of “bad” signals. In contrast to our skin fat, visceral fat can release a whole armada of hormones and signaling substances. This is one of the main reasons why visceral fat makes us sick.
Little tip: Subcutaneous fat can usually be touched with two fingers (for example on the stomach or hips). The significantly more harmful visceral fat, on the other hand, is located “in the stomach” and is therefore intangible.
The problem with visceral fat is the fact that it's hard to get rid of. However, fasting can help here, especially prolonged fasting. The long absence of food causes activation of AMPK in the body. Our metabolism changes the way it uses energy – it switches from sugar to “burning fat”. This process can take between 12 and 36 hours. If we manage not to eat during this time, we force our body to burn its own fat. And here the visceral fat is used first and then the storage fat. This is probably one of the reasons why fasting can help with insulin resistance and diabetes. Perhaps fasting will be integrated into the therapy plans of those affected in the future.
Attention: If you have diabetes, please consult your doctor before fasting! Discuss with him any medications you may need to stop taking during the fast. In the worst case, if left unattended, there is a risk of life-threatening hypoglycemia!
Fluctuating blood sugar levels and insulin resistance are the precursors to diabetes mellitus . In order to live healthily for as long as possible, we must avoid excessive sugar levels damaging our vessels. A good first step is to eat as healthily as possible, with lots of legumes and healthy fats. Dr. David Sinclair and Bryan Johnson also rely on Metformin, which is available as a prescription in Germany. In recent studies, the molecule berberine has shown similar effects to metformin. And berberine, as a secondary plant substance, is available without a prescription, unlike metformin. Together with chromium and zinc, highly bioavailable berberine is contained in MoleQlar Berbersome .
The clever combination of berberine with phospholipids ensures a 10-fold increase in bioavailability compared to conventional berberine powder.
Conclusion
Fasting has been practiced for thousands of years, but only recently have studies illuminated its role in adaptive cellular responses, which reduce oxidative damage and inflammation, optimize energy metabolism, and strengthen cellular protection.
While fasting was often offered by alternative practitioners in the past, there is increasing evidence that fasting can also have medical benefits. Whether to reduce the LDL value, blood pressure or to improve insulin sensitivity, all of these factors are desirable effects that we have today often only have to be addressed with several tablets at the same time.