Fasting and CBD: ancient tools for a healthier lifestyle and wellbeing in the new world

The modern Western lifestyle

The eating patterns of Western society usually mean at least three meals a day, often with excessive food intake. When combined with a sedentary lifestyle and stress, this can lead to metabolic disorders, as we are witnessing in many countries across the EU. Various different metabolic conditions can occur, such as hyperglycaemia, hyperinsulemia, obesity, diabetes and metabolic syndrome. Metabolic syndrome is a complex, widely emerging condition characterized by the disruption of metabolic homeostasis in several organs, including liver, heart, pancreas, and adipose tissue. Several lines of evidence now show that physiological autophagy plays a vital regulatory role in metabolic syndrome.

Since humans evolved in an environment where food was relatively scarce, adaptations of the body to food shortage developed and are now strongly challenged by our modern way of life. Using an array of molecular mechanisms, autophagy orchestrates several processes in metabolic syndrome and appears to be a very promising target to achieve metabolic homeostasis. Several plants and their components are known to induce autophagy, such as bergamot citrus, green tea, cinnamon, and resveratrol. Various studies have researched the role cannabinoids have in autophagy, and it has been shown that cannabinoids are mostly inducers of autophagy in both healthy and tumor cells. Cannabinoids also regulate appetite and blood sugar levels, making them powerful molecules to use as tools for maintaining a healthy lifestyle. By combining cannabinoids with fasting, we can stimulate the maintenance of cellular balance – homeostasis - positively impacting many aspects of health, lifestyle and wellbeing.

Fasting and its benefits for lifestyle and wellbeing

The term "fasting" refers to the complete or partial renunciation of solid food. There are many ways or methods of fasting: the best-known are therapeutic and intermittent fasting.

• Therapeutic fasting, according to the Buchinger method, includes a limited intake of vegetable and fruit juices and vegetable broths (200−400 kcal/day); tea and water ad libitum. It includes physical exercise and outdoor activities as well as relaxation techniques. An enema is recommended during the fasting period. The duration of the fast is adapted to the therapeutic goal of the individual. After the end of the fast, the gradual introduction of solid food follows. Special attention should be paid to the conclusion of a longer fast. After a long fast, it is necessary to strictly follow the instructions and slowly start eating smaller meals of easily digestible food, otherwise we may experience an unpleasant surprise in the form of severe pain.
• Intermittent fasting is a method of fasting whereby periods of fasting and feeding are alternated. Meals are timed such that the body will be in a post-absorptive state for a longer period. The term "intermittent fasting" is usually associated with the 16/8 method (fasting for 16h a day and eating normally for 8h). Another type of intermittent fasting is also alternate-day fasting (ADF), a method of fasting in which we fast every other day.

Fasting has been an important way of living and healing in many periods of human history. A new paradigm in science recognizes fasting as a highly effective tool to use for health and wellbeing. Fasting triggers positive stress in the human body, a process called hormesis (from Greek horman - to excite or stimulate). Hormesis refers to the adaptive response of biological systems to moderate environmental or self-imposed challenges through which the system improves its functionality and/or tolerance to more severe challenges. During lack of food, we induce hormesis and stimulate autophagy, a dynamic process of recycling or renewal. The process of autophagy (from Greek autos - self and phageîn - to eat, devour) is an evolutionarily developed self-renewal program of cells; cells actually eat themselves, recycling damaged and destroyed parts of themselves. Two Nobel Prizes were awarded for work on autophagy, in 1974 to De Duve and in 2016 to Ohsumi. Cells initiate the process of autophagy when they lack nutrients or are in a state of fasting; this process is especially triggered by protein deficiency.

The concept of activating the autophagy process by fasting is to put the body in a state of positive stress. It's important to distinguish between healthy positive stress (eustress) and unhealthy negative stress (distress). If the body is starving while it still has many reserves it can use, this is not a form of distress. When we expose the body to eustress through fasting, we activate autophagy, which is the body's natural way of adapting and responding to stress.

During fasting, the body removes toxic loads faster, and at the same time the cells produce more energy and live longer. During fasting, blood glucose levels are lowered, and the body switches the energy source to fat. In the process of burning its own fat stores or fatty acids from food, the body begins to produce ketone bodies. Of particular importance are beta-hydroxybutyrate (beta-HBA), which is a superior fuel for the brain and an important signal for our mitochondria to increase mitochondrial respiration and turn on genes for mitochondrial biogenesis and uncoupling. Ketones also modulate cellular redox ratios of NAD+/NADH and the activity of NAD-dependent deacetylases and promote a robust mitochondrial environment which lowers oxidative stress and inflammation and speeds up metabolism.

CBD and its benefits for lifestyle and wellbeing

Cannabidiol (CBD) is one of the most abundant cannabinoids of the Cannabis sativa L. plant, which has been used for centuries for both recreational and medicinal purposes. In 2018 a Critical Review Report was published by the World Health Organization which found, across a number of controlled and open label trials, that CBD is generally well tolerated, with a good safety profile, and does not have any potential for abuse. CBD is a small, lipophilic molecule with a huge spectrum of biological effects, with potential benefits in many conditions such as anxiety, inflammation, psychiatric disorders, cardiovascular diseases, neuropathic pain, cancer, autoimmune disorders, skin conditions, epilepsy, etc.

CBD effects our biology at all levels, beginning from the molecular, to the cellular and organ level, to our decision-making and lifestyle, and up to the level of stress management and to emotional and psychological levels. CBD is known to affect inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, and regulates many physiological and pathophysiological processes. CBD engages with different targets including cannabinoid receptor 1 and 2, TRP channels, Serotonin Receptor 1 A, GABAA receptors, adenosine receptors A1 and A2 and PPARγ receptors.

Figure 1: The cannabidiol (CBD) mechanism of action, source: Silva 2023.

Our lifestyle can be beneficial or detrimental for the endoacannabinoid system (ECS). Often, we are not even aware that the choices we are making daily affect the condition of our ECS. The foods, supplements and medications we consume affect the enzymes responsible for building and degrading our endocannabinoids. Fasting and food intake affect it, but the context in which meals are taken makes a difference, such as music, mood and alcohol consumption. Massage and aerobic exercise have been shown to increase the levels of endocannabinoids. We've all heard about the "runner's high", a powerful feeling of well-being when we exercise. It was long believed that endorphins are responsible for this state but, in fact, exercise increases the sensitivity of cannabinoid receptors and the production of anandamide in the part of the brain that is involved in pleasure and reward. In a way, it seems that the ECS is designed to reward exercise. Stress-reduction techniques, such as meditation, yoga, and deep breathing, have a balancing effect on the ECS. It seems that the ECS is a vital and integral part of our perception of reality and of our surroundings: in a sense, it is an interface between the world outside and our responses at the biochemical and behavioral levels.

Activation of the autophagic process is a part of the anti-tumor effects of cannabinoids. The mechanism by which cannabinoids trigger autophagy and apoptosis in cancer cells shows their potential in cancer therapy. The restorative effects of autophagy are shared by plant polyphenols (phenolic antioxidants), phytocannabinoids and fasting.

The tonus and function of the endocannabinoid system can be successfully supported with phytocannabinoids, especially CBD. Microdosing has gained much attention for the purpose of prevention, since the threshold for the medical benefits of cannabinoids is far lower than most people think. Microdosing just means taking very small amounts of cannabinoids throughout the day. How much counts as micro is very personal – there is no magic bullet when it comes to dosing – but a dose of about 2 mg per day is usually a good place to start. Many have reported that it helps them stay healthy, reduce stress, and stay sharp and focused at work.

When we look at metabolic health, CBD can maintain glucose homeostasis, sensitizes adipose tissue to insulin, and reduces glucose levels fasting. All these are essential elements in the metabolic disorders that are epidemic in Western society. CBD also shows some promising results in the treatment of lipid disorders, by decreasing LDL and increasing HDL. Research has shown that CBD has positive effects in hypertension, even though the hypotensive properties of cannabidiol are small and the timing of the dosing seems to play an important part. Stronger effects on lowering blood pressure were observed when CBD was taken before sleep versus taken in the morning. CBD can also be used to prevent blood pressure surges and stabilize them, and has a protective effect on blood vessels and heart muscle. The effects of CBD, due to its many molecular targets, extend far beyond CB2 receptor activation and while specific CB2 agonists may have their advantages, using CBD offers a more comprehensive and versatile approach to address the multiple processes involved in health and wellbeing.

Figure 2: The role of the endocannabinoid system in the development of metabolic syndrome, source: Wiciński et al., 2023.

CBD shows many benefits in preventing and reversing many symptoms caused by modern ailments in the Western world, from obesity to metabolic syndrome and dysregulation of glucose and lipids, to chronic fatigue and stress disorders.

CBD can target multiple pathways associated with metabolic and inflammatory processes in cells and in the body. It produces effects on many organs crucial in metabolism, like liver, adipose tissue, pancreas and heart. Interestingly, it also causes changes in gut hormones, such as the concentration of glucose-dependent insulinotropic peptide and adipokines, and shifts in the microbiome. CBD supports the growth of beneficial bacteria and suppresses the overgrowth of pathogenic bacteria. A delicate balance of different microbial species is vital for our health and wellbeing. It is interesting that beneficial bacteria known to increase wellbeing and mood also have a positive effect on metabolism and weight loss. When depressed mice were fed Lactobacillus rhamnosus they performed better and had fewer stress hormones, and when similar tests were done on humans, similar results were observed. Similarly, Lactobacillus plantarum 299v was shown to improve cognitive functions in patients with major depression. It was also shown to support the gut-brain axis, and improve clinical outcomes across a range of conditions, including stress, cognition and mood states.

Stress is also a very important factor influencing our health and wellbeing in modern society. According to the World Health Organization, stress has now been classified as the health epidemic of the 21st century. Stress affects all aspects of our lives, from levels of energy and focus to metabolism, and from glucose levels to sleep and to the ability of the body to regenerate. The endocannabinoid system plays an important role in stress response and can be disrupted following a traumatic event or chronic stress. If that occurs in early life it can cause long-lasting disturbances in the endocannabinoid system. Changes in the endocannabinoid system can lead to disturbances in the hypothalamic-pituitary-adrenal axis and may be involved in lifelong increased fear and anxiety behaviors as well as increased risk of developing post-traumatic stress disorder (PTSD) and other stress disorders. In these aspects it is vital to consider the role of CBD in stress regulation.

In a very interesting study, mice were subjected to unpredictable stress, and it was found that after 5-6 weeks mice suffered very severe consequences. They did not want to eat or move any more, their adrenal gland was heavier and their thymus was lighter. More surprisingly, after 5-6 weeks of stress the mice had fewer neurons in their frontal cortex. This is the part of the brain behind our forehead, and it has vital functions such as motor function, problem solving, spontaneity, memory, language, initiative, judgement, impulse control, and social and sexual behavior. By exposing mice to chronic stress, researchers actually induced depression in mice. They could see this in their behavior and in the changes in their bodies. Interestingly, when they gave mice CBD after stress, the mice regenerated better and did not suffer adverse changes in their glands and brain. The result was even much better if they gave CBD to mice before they were subjected to stress. Researchers also found that even if the damage to the brain has already happened due to stress, where we have fewer neurons, CBD can stimulate the growth of new neurons, and these parts of the brain can regain their function.

Something very similar also happens in our body. This actually underlines the protective role of CBD. In a nutshell, CBD enables our body to function even in the presence of stress – and who does not suffer from stress today? CBD can help us perceive stress as less threatening and this helps our body to cope better with the same stress burden. In a way, it is like a shield, a protective molecule, that keeps our cells functioning properly even in extreme circumstances.

Conclusions

Fasting and CBD offer many interconnected benefits for our health and wellbeing, helping to make our bodies more resilient. Both are powerful tools for many of the issues we face in modern Western society, from metabolic disorders to microbiome dysbiosis, from emotional health to stress regulation. One of the key processes influenced by both is autophagy, and we hope that, by regulating autophagy at the right time, we will be able to impact the processes and progression of disease.

It is immensely important to recognize the beneficial effects of fasting and CBD and to have an open discussion with medical doctors about both tools for improving health in this new world full of challenges. We also need to recognize that neither CBD not fasting are miraculous panaceas, to be used in any given illness or condition. While both are safe and well tolerated by healthy individuals, some disadvantages and side effects can be observed, especially when co-administered with other therapies or medications. Both should be used as tools for balancing the effects of our modern lifestyle and as adjunctive treatment in serious conditions. As research on fasting and CBD continues to expand, their important roles in maintaining a healthy lifestyle and wellbeing are becoming increasingly evident.

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