Fasting – perspective for a long life

Western countries are in the privileged situation of having a surplus of food. The next snack is always just the next fast food stand or supermarket away. However, the most common eating behavior in modern societies, three meals plus snacks a day, is not the norm from an evolutionary perspective. In evolution, periods of abundance were always followed by periods of scarcity of food - there simply were 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 on animal models and humans suggest that Fast can improve health indicators and counteract diseases.

Water fasting, FMD, short-term fasting – a guide to different forms of fasting

In addition to the two concepts of calorie and time restriction, there are a multitude of other forms of fasting. The Medical Association for Therapeutic Fasting and Nutrition is currently developing precise definitions for the various forms of fasting as part of the guidelines. For a better overview, the four most important are listed here:

• Prolonged fasting: In this form, participants are only allowed to consume liquids.A prolonged fast is one that lasts at least 4 days
• short-term fasting: Similar to prolonged fasting, but the duration is limited to 1-3 days
• water fasting: You are only allowed to drink water. The length is not fixed
• FMD (Fasting Mimicking Diet): This relatively new form of fasting was developed by the American Dr. Valter Longo. It allows you to eat certain foods, especially vegetables and healthy fats. The composition of the foods is intended to imitate fasting on a molecular level, without having to fast. In addition to an appropriate diet, fasting-imitating supplements such as spermidine, glucosamine or Berbersome discussed.

Fasting – religious hype or is there more to it?

Fasting has been part of various cultures for centuries, but it is still in its infancy in (conventional) medicine. Often labelled as “esoteric” and “ineffective”, fasting has remained a niche practiceOnly recent research results – on animals and humans – shed more light on the beneficial biochemical and molecular genetic processesthat take place in our body 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 to 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, who lived from 460-370 BC. He believed in the body's ability to heal itself if you take care of it through a proper diet and a healthy lifestyle. There are no direct recommendations for fasting in his writings, but his dietary rules 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 had to "believe" back then, we have come further today. With the help of detailed studies, we can understand the individual signaling pathways in our body that are activated when we fast.

An important protagonist is AMPK – one of the four longevity pathways. The abbreviation stands for AMP-activated protein kinaseThe ending -ase tells us that AMPK is an enzyme. You can imagine its role in the body as a kind of "sensor". AMPK measures the energy contentby 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 sensitivityThe diabetes drug metformin also works using this mechanism. It also breaks down fatty acids, which helps you lose weight.Not only does AMPK activate countless energy pathways in your cells, higher levels of AMPK also seem to anti-inflammatory effect on your body.

A final, important aspect of AMPK in the context of fasting is its ability stimulate the autophagy of cellsDuring autophagy, your cells switch to "recycling mode". Everything that is no longer needed is thrown 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.

Nowadays, the molecule spermidine and autophagy mentioned in one sentenceResearchers hope that the substance will directly activate the recycling processes in the body. The Bruneck study of the Medical University of Innsbruck has already shown a strong positive correlation between spermidine-rich diet and durability! 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 a few years ago. Certain diseases, such as Alzheimer's and cardiovascular diseases, but also cancer, are associated with altered autophagy Especially as we age, our ability to autophagy away.

Fasting also seems to have positive effects on cognitive function. This could be particularly interesting as a therapy supplement for Alzheimer's disease.

mTOR – another important sensor

The next molecule, with a complicated abbreviation. mTOR, short for mammalian target of rapamycin) is, like AMPK, an enzyme that is connected to many different processes in our body.

One task of mTOR is to assess the availability of nutrients. mTOR is particularly sensitive to two types of molecules: Sugars, in the form of glucose and proteins, in the form of amino acidsTo put it simply, our body uses mTOR to know how much amino acids and sugar are available to it. However, this is a very rough 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, such as 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 has great potential for longevity in researchMany animal studies have shown that lower mTOR levels lead to a longer life.

One drug that achieves this is rapamycin. It comes from the family of immunosuppressants - that is, it suppresses our immune system - and is used in organ transplants. The idea of ​​using rapamycin as a “longevity drug”, already exists and is used by, among others, Peter Attia However, we currently know too little about the effects on the different mTOR groups. Too low levels, such as those achieved by high doses of rapamycin, can due to the immunosuppressive effect, more harm than goodHere, or so it seems, one can find a natural middle way through fasting.

Did you know? Some studies have provided evidence that secondary plant substances such as resveratrol can downregulate mTORResveratrol 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: A fundamental building block for the longevity effects of fasting

The term sirtuins refers to a group of proteins, of which mammals, according to current research, possess seven different ones (SIRT1-SIRT7).

SIRT1 plays an important role in fasting. Calorie restriction activates SIRT1 and thus its potentially health-promoting propertiesSirtuins 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.

Currently, intensive research is being carried out on sirtuins, because they show great potential in animal studies to extend life and health spanSIRT1 in particular seems to be a promising candidate.

However, the connections are complicated by the complex biochemical mechanisms. One example is the way sirtuins work. A quick warning, it will be very detailed again, but then you will have made the excursion into the physiology behind fasting:

Sirtuins have what is known as enzymatic deacetylase activity. This means that they can split acetyl groups (= a chemical structure consisting of one oxygen, two carbon atoms and three hydrogen atoms) from one molecule and transfer them to another. One place where this happens is on the histones. You find these in the nuclei of your cells.

So what does that mean for us? Imagine histones like the string around a present. Sirtuins can loosen this packaging cord with the help of their enzyme activity and thus expose the DNA underneathYour “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 act particularly on the genes that promote a longer life. The catch is that sirtuins need a partner, namely NAD+.

With the NAD test from MoleQlar you can determine your intracellular NAD levels.

Sirtuins and NAD+ – you need both

NAD stands for Nicotinamide adenine dinucleotide and the + describes the active form of the molecule.

Back to the sirtuins: They need NAD+ as a partner to do their job. Unfortunately, as we age, our NAD+ levels continue to decline. Our body therefore has less and 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 integrated NAD boosters into his supplement plan, is the renowned aging researcher Dr. David Sinclair.

Did you know? Besides fasting, there is another way to activate SIRT1 in your body. resveratrol, a secondary plant substance found in red wine, among other things, can also contribute to a longer life, according to Prof. Sinclair's research on the activation of SIRT1. The Harvard researcher himself takes 1 gram of resveratrol and NAD booster for breakfast.

In addition to resveratrol, there are other molecules that can activate SIRT1. This includes glucosamineThis substance occurs naturally in our bodies – primarily in synovial fluid and cartilage. For this reason, glucosamine has been studied in the treatment of knee pain – with mixed results. However, in animal studies, glucosamine has shown life-prolonging effects, which is why further studies will followOne of the suspected mechanisms is the activation of SIRT1 and the resulting increase in 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) ways in which fasting can contribute to a healthier and longer life. The question remains: which type of fasting is the best?

This question can hardly be answered in general terms. 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 similar effects, but to a lesser extent.

Now, not everyone wants to go several days without eating. That is completely understandable, because a longer fasting episode cannot always be reconciled with our everyday tasksThe 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 also works molecularly

Reap the benefits of fasting without actually fasting? That sounds almost too good to be true. By carefully researching the molecular signaling pathways, we can now “trick” our bodies in a certain way. and pretend to him that we are fasting. This procedure is also called mock fasting and is used by Valter Longo researched.

With the help of glucosamine For example, SIRT1 can be activated. Supporting this spermidine, because spermidine is not only a potent autophagy promoter, studies have shown it has a positive effect on your heart health and has an anti-inflammatory effect. This is particularly important because SIRT1 is less likely to be activated in an inflammatory environment. berberine is a useful addition due to its positive influence on carbohydrate metabolism and insulin sensitivity.

Disclaimer: Please note: You can take both spermidine and glucosamine during a real fast. You should be careful with Berbersome. If you don't eat any carbohydrates, taking Berbersome in addition to your usual diet can lead to dangerous hypoglycemia. It is always advisable to fast under medical supervision.