Fasting - perspective for a long life

Western countries are in the privileged position of having a food surplus. The next snack is always just a 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 food abundance were always followed by periods of food scarcity – permanent surpluses simply did not exist.

The consequences of the status quo range, thanks to fast food, 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 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 is a wealth of other forms of fasting. The Medical Society for Fasting and Nutrition e.V.Currently, precise definitions for the various forms of fasting are being developed as part of the guideline creation. For better clarity, the four most important types are listed here:

• Prolonged Fasting: In this form, participants are only allowed to consume liquids. Prolonged fasting is referred to when the duration is at least 4 days.
• Short-term Fasting: Similar to prolonged fasting, but the duration is limited to 1-3 days.
• Water Fasting: In this case, only water is allowed. The duration is not specified.
• FMD (Fasting Mimicking Diet): This relatively new form of fasting was designed by the American Dr. Valter Longo. In this method, some foods, particularly vegetables and healthy fats, are allowed. The composition of the foods is intended to molecularly imitate fasting without having to fast. In addition to a corresponding diet, fasting-mimicking supplements such as  Spermidine, Glucosamine or Berbersome are also discussed.

Fasting – religious hype or is there more behind it?

Fasting has been established in various cultures for centuries, but in (conventional) medicine, it is still quite at the beginning. Often labeled as "esoteric" and "ineffective," fasting has led a niche existence. Only recent research findings – on animals and humans – shed more light on the beneficial biochemical and molecular genetic processes that occur in our bodies during fasting.We want to go into more detail about this here. Don't let the many abbreviations and complicated names deter you. In the end, this deeper knowledge will help you assess different fasting methods for yourself 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 when one takes care of it through proper nutrition and a healthy lifestyle. Direct recommendations for fasting are not found in his writings, but his dietary guidelines were very similar to modern fasting.

Even Hippocrates knew about the health-promoting effects of fasting.

AMPK – the "energy sensor" of our cells

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

An important protagonist in this is AMPK – one of the four longevity pathways. The abbreviation stands for AMP-activated protein kinase. The suffix -ase already indicates that AMPK is an enzyme. You can think of its role in the body as a kind of "sensor". AMPK measures the energy content by assessing the ratio between AMP (adenosine monophosphate) and ATP (adenosine triphosphate). Through fasting or intense exercise sessions, AMPK is activated.

What follows is a series of changes in the energy balance of the cell. Glucose is increasingly taken up by the cells, which increases your insulin sensitivity. The diabetes medication Metformin is also hidden behind this mechanism of action. In addition, fatty acids are broken down, which helps you lose weight. AMPK not only activates countless energy pathways in your cells, higher levels of AMPK also seem to have anti-inflammatory effects on your body.

A final, important aspect of AMPK, in relation to fasting, is its ability to stimulate the autophagy of cells. During autophagy, your cells switch to "recycling mode." Everything that is no longer needed is removed.What sounds like a molecular form of "spring cleaning" is actually an important process for cells to remain healthy for as long as possible.

Meanwhile, the molecule Spermidine and autophagy are often mentioned in the same sentence. Researchers expect a direct activation of the recycling processes in the body from this substance. The Bruneck study from the Medical University of Innsbruck has already established a strong positive correlation between a spermidine-rich diet and longevity! Dr. David Sinclair and Bryan Johnson both rely on corresponding dietary supplements.

Did you know? The recycling of old cellular components is more significant than was assumed just a few years ago. Certain diseases, such as Alzheimer and cardiovascular diseases, as well as cancer, are associated with  altered autophagy . Particularly in old age, our ability for  autophagy  declines.

Fasting also seems to have positive effects on cognitive function. In particular, this could be exciting as a complementary therapy for Alzheimer.

mTOR – another important sensor

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

One task of mTOR is to assess the availability of nutrients. mTOR reacts particularly sensitively to two types of molecules: sugar, in the form of glucose, and proteins, in the form of amino acids. Simply put, our body, with the help of mTOR, knows 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 clarified. The excessive activation of mTOR is associated with various diseases, such as cancer.

During 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 "deactivation" of mTOR is given great potential for longevity in research. In many animal studies, it has already been shown that lower mTOR levels lead to a longer life. A medication that achieves this is Rapamycin. It comes from the family of immunosuppressants – thus suppressing our immune system – and is used in organ transplants. The consideration to use Rapamycin as a "longevity drug" already exists and is suggested by Peter Attia. However, we currently know too little about the effects on the various mTOR groups.At lower levels, as achieved by high doses of Rapamycin, we can be harmed more than helped by its immunosuppressive effect. Here, it seems at least, one can find a natural middle ground with fasting. Did you know? Some studies have provided evidence that secondary plant compounds like Resveratrol can downregulate mTOR. Furthermore, Resveratrol also interacts with sirtuins and seems to have great potential as a fasting mimetic. For powder fans and capsule lovers - Trans-Resveratrol from MoleQlar is for everyone.

Sirtuins: An elemental 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 types (SIRT1-SIRT7).

SIRT1 plays an important role during fasting. A calorie restriction activates SIRT1 and thus its potentially health-promoting properties. Sirtuins can promote cell health and increase their resistance to "stressors." Additionally, SIRT1 activates AMPK in the liver. As mentioned above, AMPK plays an important role in energy metabolism.

Currently, there is intensive research being conducted on sirtuins, as they show great potential in animal studies to extend lifespan and healthspan. SIRT1, in particular, seems to be a promising candidate.

The relationships are complicated by the complex biochemical mechanisms. One example is the function of sirtuins. A brief warning, it will be very detailed again, but then you have completed the excursion into the physiology behind fasting:

Sirtuins have a so-called enzymatic deacetylase activity. This means they can remove 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 cell nuclei of your cells.

And what does this bring us now? Imagine histones like the wrapping string around a gift. Sirtuins can loosen this wrapping string with the help of their enzymatic activity and thus expose the DNA underneath.Your "gift" can now be unpacked and used. So our body can "decide" which genes are currently being read and which are not. Sirtuins particularly act 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+ – both are needed. 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 work. Unfortunately, as we age, our NAD+ levels continue to decline.Our body has increasingly less energy available. One way to counteract this is to supplement with precursors of NAD+. This may enhance the effects of fasting. One of the leading researchers in this field, who also fasts and has integrated NAD boosters into his supplement plan, is the 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 compound found, among other things, in red wine, can also contribute to a longer life according to the research of Prof. Sinclair on the 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. These include glucosamine. This substance occurs naturally in our body – primarily in joint fluid and cartilage. For this reason, glucosamine has been studied in the treatment of knee pain – with mixed results. In animal studies, however, glucosamine has shown 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.Furthermore, glucosamine 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 better understand the (molecular) pathways through which fasting can contribute to a healthier and longer life. The question remains, which type of fasting is the best?

This question is hardly answerable 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, it probably requires 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 several days in a row without food. This is absolutely understandable, because a longer fasting episode does not always fit with our daily tasks. The side effects, such as fatigue and hunger attacks, 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 proposed 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 various foods, especially high-quality fats, such as Omega-3, hunger can be satisfied while still activating the molecular signaling pathways of fasting.

In addition to the right 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 on a molecular level

Utilize fasting benefits without actually fasting? That sounds almost too good to be true. Through the precise study of molecular signaling pathways, we can now "trick" our body in a way and make it believe that we are fasting. This approach is also referred to as simulated fasting and is being researched by Valter Longo .

With the help of glucosamine , for example, SIRT1 can be activated. Supporting this,  spermidine is important, as spermidine is not only a potent autophagy promoter, but studies show it has a positive effect on your heart health and has anti-inflammatory properties. This is particularly important, as SIRT1 can be activated less effectively in an inflammatory environment. Berberine  is a sensible addition due to its positive influence on carbohydrate metabolism and insulin sensitivity.

Disclaimer: Please note. Both spermidine and glucosamine can be taken during true fasting. Caution is advised with berberine.If you do not consume carbohydrates, the additional intake of Berbersome can lead to dangerous hypoglycemia. It is always advisable to fast under medical supervision.