Fasting - perspective for a long life

Western countries are in the privileged position of having a surplus of food. The future snack is always just the next snack bar or supermarket away. However, the most common eating behavior in modern societies, three meals plus snacks a day, is not the rule from an evolutionary perspective. In evolution, periods rich in food have always been followed by periods poor in food - there were simply no permanent surpluses.

Thanks to fast food, the consequences of the status quo range from cardiovascular diseases and diabetes to various forms of cancer. Science has gained useful insights from this context. Data from current and past studies on animal models and humans suggest that fasting 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 many other forms of fasting. The Medical Association for Therapeutic Fasting and Nutrition e.V. is currently working on precise definitions for the various forms of fasting as part of its 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 period of at least 4 days
• Short-term fasting: Similar to prolonged fasting, but the duration is limited to 1-3 days
• Water fasting: Here you are only allowed to drink water. The length is not specified
• FMD (Fasting Mimicking Diet): This relatively new form of fasting was developed by the American Dr. Valter Longo. It involves eating certain foods, especially vegetables and healthy fats. The combination of foods is intended to imitate fasting at a molecular level without having to fast. In addition to an appropriate diet, fasting-imitating supplements such as Spermidine, Glucosamine or Berbersome are also discussed.

Fasting - religious hype or is there more to it?

Fasting has been anchored in various cultures for centuries, but is still in its infancy in (conventional) medicine. Often labeled as "esoteric" and "ineffective", fasting has led a niche existence. Only recent research results - on animals and humans - have shed more light on the beneficial biochemical and molecular genetic processesthat 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, this in-depth 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. 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 benefits of fasting.

AMPK - the "energy sensor" of our cells

While Hippocrates still had to "believe" back then, we are already further along today. With the help of detailed studies, we can understand the individual signaling pathways in our body that are activated during fasting.

An important protagonist here 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 think of 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 energy balance of the cell. Glucose is increasingly absorbed into the cells, which increases your insulin sensitivity. This mechanism of action is also behind the diabetes drug metformin. 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 appear to have an anti-inflammatory effect 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.

Meanwhile, the molecule spermidine and autophagy are often mentioned in the same sentence . Researchers hope that the substance will directly activate the recycling processes in the body. The Bruneck study by the Medical University of Innsbruck has already established a strong positive link between a spermidine-rich diet and longevity ! Dr. David Sinclair and Bryan Johnson both rely on a corresponding dietary supplement.

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 . In particular, our capacity for autophagy decreases with age.

Fasting also appears 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 detect the availability of nutrients. MTOR is particularly sensitive to two types of molecule: sugar, in the form of glucose, and proteins, in the form of amino acids. Put simply, with the help of mTOR, our body knows how many amino acids and sugars are available to it. However, this is a very crude simplification. There are several subtypes of mTOR, the exact properties and roles of which are not yet fully understood. Excessive activation of mTOR is associated with various diseases, for example cancer.

The opposite occurs during fasting - namely an inhibition of mTOR. Due to the self-induced "stress", the cells switch to recycling (autophagy) and survival mode. For this reason, the "deactivation" 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. it suppresses our immune system - and is used in organ transplants. The idea of using rapamycin as a "longevity drug"already exists and has been proposed by Peter Attia , among others. However, we currently know too little about the effects on the various mTOR groups. Levels that are too low, such as those achieved by high doses of rapamycin, may do us more harm than gooddue to the immunosuppressive effect. Here, at least it seems, we can find a natural middle ground with fasting.

Did you know Some studies have provided evidence that secondary plant compounds such as resveratrol mTOR can downregulate . Resveratrol also interacts with sirtuins and thus appears to have great potential as a fasting mimetic.

For powder fans and capsule lovers - Trans-Resveratrol from MoleQlar is for everyone.

Sirtuins: A fundamental building block for the longevity effects of fasting

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

SIRT1 plays an important role in 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.

Currently, intensive research is being carried out on sirtuins, because they show great potential in animal studies to extend life and healthspan. SIRT1 in particular appears to be a promising candidate

However, the relationships are complicated by the complex biochemical mechanisms involved. One example is the functioning of sirtuins. Quick warning, it gets very detailed again, but then you've made the excursion into the physiology behind fasting:

Sirtuins have what is known as enzymatic deacetylase activity. This means that 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 at the histones. You can find these in the nuclei of your cells.

And where does that leave us now? Think of histones like the packaging string around a present. Sirtuins can loosen this packaging string with the help of their enzyme activity and thus expose the DNA underneath. Your "gift" can now be unwrapped and used. In this way, our body can "decide" which genes are read and which are not. Sirtuins act in particular on the genes that promote a longer life. Here's the catch. Sirtuins require a partner, namely NAD+.

You can determine your intracellular NAD level with the NAD test from MoleQlar.

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 in order to do their work. Unfortunately, as we age, our NAD+ levels continue to drop. Our body therefore has less and less energy available. One way to counteract this is to supplement the precursors of NAD+. This could possibly 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 ageing researcher Dr. David Sinclair.

Did you know In addition to fasting, there is another way to activate SIRT1 in your body. Resveratrol, a phytochemical found in red wine, among other things, can be used as a stimulant to activate SIRT1 in your body, according to research by Prof. David Sinclair. Sinclair also contribute to a longer life via the activation of SIRT1. The Harvard researcher himself takes 1 gram each of resveratrol and NAD-Booster for breakfast .

In addition to resveratrol, there are other molecules that can activate SIRT1. These include glucosamine. This substance occurs naturally in our body - primarily in the synovial fluid and cartilage. For this reason, glucosamine has been investigated in the treatment of knee pain - with mixed results. However, glucosamine has been shown to have a life-prolonging effect in animal studies, which is why further studies will follow here. 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) ways in which fasting can contribute to a healthier and longer life. The question remains as to which type of fasting is the best?

There is no general answer to this question. 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 probably need a longer fast of at least 2 days. Intermittent fasting can also achieve corresponding effects, but to a lesser extent.

Not everyone wants to go without food for several days at a time. This is completely understandable, as it is not always possible to reconcile a longer fasting episode with our everyday tasks. The side effects, such as tiredness 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 the right diet, certain supplements described as fasting mimetics can support the fasting process. Spermidine, Resveratrol and NAD-Booster are the most promising candidates here.

Fasting can also be molecular

Use the benefits of fasting without actually fasting? That sounds almost too good to be true. However, thanks to detailed research into molecular signaling pathways, we can now "trick" our body to a certain extent and pretend that we are fasting. This procedure is also known as sham fasting and has been researched by Valter Longo , among others.

With the help of glucosamine SIRT1, for example, can be activated. Supporting this spermidine, because spermidine is not only a potent autophagy promoter, studies have shown that it has a positive effect on your heart health and has an anti-inflammatory effect. This is particularly important as 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: Bitte beachte. You can take both spermidine and glucosamine during a real fast. Caution is advised with Berbersome. If you do not consume any carbohydrates, the additional intake of Berbersome can lead to dangerous hypoglycaemia. It is always advisable to fast under medical supervision.