In this post, we'll discuss the scientific background and benefits of Restore for the gut and mitochondrial function.
Communication systems in your body
The human body has many different ways to communicate with itself. Proper communication is essential for cells, tissues, and organs to adapt what they are doing based on what is going on inside and outside of the body. A few examples:
- Hormones and cytokines (signaling molecules of the immune system) act both systemically (throughout the whole body) and locally because they are transported via the bloodstream.
- The nervous system sends signals back and forth from the brain to distant tissues using neurons spread all throughout the body.
- Adjacent cells exchange information through small channels or release signaling molecules in their immediate environment.
- Mitochondria (cellular organs that produce energy) communicate with each other using redox signaling molecules.
Redox Signaling Molecules
The term Redox is an abbreviation for chemical reactions where electrons are exchanged between molecules, so-called reduction and oxidation reactions. Reduction means the loss of an electron and oxidation means the addition of an electron. In redox reactions, both reduction and oxidation take place at the same time: it is an exchange of electrons from one molecule to the other. Zach Bush, Restore's designer and producer and MD, talks about redox in a recent podcast with Ben Greenfield. He says that that redox signaling molecules are used by mitochondria to communicate within a cell or between different cells. He compares the redox signaling molecules to cell phone towers that provide phone service.
Redox signaling molecules and the communication they facilitate are so potent that they are studied as a treatment for cancer in addition to standard chemotherapy. If mitochondria can communicate with their environment, they can adjust their actions based on external cues and signals. Mitochondria regulate cellular repair and programmed cell death (apoptosis), but also provide energy and produce antioxidants. Restore mitochondrial awareness of their surroundings in cancer cells, and the cancer cell mitochondria might induce apoptosis. In healthy cells, properly communicating mitochondria will promote cellular repair, making healthy cells more resistance to the effects of other cancer treatments.
Mitochondria, bacteria, and our microbiome
Mitochondria and bacteria are thought to share an evolutionary heritage. Some properties of mitochondria are common to bacteria as well, such as circular DNA, but also their communication systems. Dr. Zach Bush describes how bacteria in soil use similar redox signaling molecules as mitochondria do. However, the molecules used by soil bacteria are much more stable (have a longer shelf life) than those used by mitochondria. The robustness of the redox signaling molecules of soil bacteria allows for supplementation in our gut or airways. Redox signaling molecules of mitochondria would likely not survive this environment.
Bacteria and other microorganisms cover every outside surface of our bodies. If it is connected to the outside world, bacteria live there. They cover our digestive tract, airways, urinary tracts, and skin. This is not a bad thing. In fact, our bacterial buddies are essential to our survival and wellbeing. Populations of bacteria and other microorganisms are called microbiome or ‘flora’. They protect us from not-so-healthy microorganisms through competition and taking up all available living space and food supplies. In the gut, they digest our food for us, allowing us access to essential nutrients otherwise unavailable to us. Bacteria balance our immune system, keeping it focused on maintaining peace and balance, instead of (mistakenly) attacking relatively harmless substances (such as allergens) or the body itself (auto-immunity). In fact, the microorganisms that colonize our bodies outnumber our cells at least by 100 to 1. Also, about 1 kg (or 2 pounds) of our body weight come from the various microbes we share our bodies with.
The importance of happy and healthy bacterial populations in various sites of our respiratory and digestive systems are being examined more and more. This interest is spurred by the worrying trend of aging- and lifestyle-related diseases becoming more pronounced even with the accompanying improvement in health care. The microbiome is damaged and angered by the extensive use of antibiotics and toxic substances in our diet and environment. When our microbiome is threatened and unbalanced, their displeasure threatens our health and longevity.
Some of the effects of toxic substances are quite clear and well-examined. For instance, antimicrobial agents (taken voluntarily or by accident) and gluten disrupt the lining of the gut. The gut lining separates the inside environment of our bodies from the intestinal content, such as partially digested foods, as well as bacteria and their (waste)products. To form a proper barrier between inside and outside environments, the gut lining (epithelium) arranges cells in close formation, using so-called tight junctions to close any gaps between the cells. The barrier is not complete, but only allows carefully selected particles through, such as nutrients, water, and minerals. Ingested gluten and antimicrobial agents disrupt tight junctions. Without tight junctions, the space between gut epithelial cells widens and allows access to a whole host of unwanted substances. As a result, the gut immune cells raise the alarm, inducing low-grade (or not so low-grade) systemic inflammation. Inflammatory cytokines, released by the triggered immune cells, put the rest of the body in a state of emergency and stress. Inflammatory signals disrupt normal activities and direct all available resources to fight off potential threats, thereby taking these resources away from other organs and tissues. Of course, inflammation is a good short-term (and temporary) response, but long-term (chronic) inflammation has been linked to aging- and lifestyle-related diseases, such as cancer and cardiovascular diseases.
Fig. 1: Chronic inflammation. Design by Dagmar Bouwer for LiveHelfi.com*
What Restore does
According to Dr. Zach Bush, this is where Restore can help out. Restore is made from stabilized lignite extract. Lignite extract is water that contains particles, minerals and amino acids found in fossilized soil (lignite). This soil was previously inhabited by an extensive range of microorganisms, including bacteria and fungi. The organisms themselves are long gone, but their communication systems (including redox signaling molecules) remain. Restore contains the molecules these ancient microorganisms used to form happy communities and have the same effect on bacteria living in, on and around us today. Dr. Zach emphasizes that Restore contains only minerals and amino acids, no actual living organisms or prebiotics. According to him, Restore has no effect on the body itself. It only improves the communication system (the telephone network) used by bacteria and mitochondria.
In a series of studies, Dr. Zach Bush and his team demonstrated the ability of Restore to protect gut and small intestinal cells in cell culture against the disruptive effects of gluten (gliadin) and glyphosate (herbicide commonly used on GMO crops). Both gluten and glyphosate disrupt tight junctions, making gut and small intestine epithelia more permeable. By adding Restore to these cell cultures, the effects of gluten and glyphosate were negated. Additionally, by adding just Restore without gluten or glyphosates, the barrier function of the epithelial layers was strengthened beyond their normal state.
Fig. 2: Leaky Gut. Design by Dagmar Bouwer for LiveHelfi.com*
The ability of Restore to reinforce our gut lining is indeed a great benefit. Dr. Zach Bush described additional benefits that he intends to study further. Dr. Bush mentioned that by reinstating a communication system, the microbiome rebalances itself, with effects being noticeable after just a few weeks. The gut microbiome contains many different species of bacteria, each with their own role. Some species of bacteria help with digestion, others are toxic and inflammatory. The relative number of bacteria matters too: too much or too little of any species is no good. Their composition is determined by our diets and (absence of) antimicrobial agents. When the microbiome is unbalanced, for instance containing more Firmicutes (fermenting) species and less Bacteroides (metabolism and reduced inflammation) species, problems can arise with weight control, energy, and low-grade inflammation. Restore seems to rebalance the composition of gut bacteria towards a more favorable population for human health. Remember, Restore does not add any bacteria or contain prebiotics. It only allows for better communication between bacteria.
To further optimize the microbiome and add in some new species, Dr. Zach Bush recommends exposing yourself to bacteria outside your house, breathing air and eating freshly harvested crops (not sprayed with pesticides). Of course, the standard recommendation of eating fermented foods was mentioned as well.
Other benefits of Restore
Dr. Bush also mentioned benefits of Restore going beyond just the gut (when ingested orally). Tight junctions are found in most barrier tissues, such as the skin, airways, nasal passages, the blood-brain barrier, and kidney tubules. Restore can reinforce tight junctions in tissues all throughout the body, but this remains to be studied in greater detail. Barriers are an important part of many of our bodily functions and having them not leak will save us and our organs a lot of energy and stress.
Additionally, supplementing redox signaling molecules can improve mitochondrial function (also not limited to just the gut). Restore may improve the ATP production of mitochondria, allowing them to generate more energy. Mitochondria burn carbohydrates or fat breakdown products with oxygen to produce ATP (cellular energy). To do this, mitochondria need non-leaky membranes. When mitochondria work optimally, they produce very little waste (damaging reactive oxygen species (ROS)) and create antioxidants to clean up their messes. They also produce a lot of ATP for each unit of fuel they burn. If mitochondria are stressed, they are inefficient. Their membranes are leaky and they produce more ROS, fewer antioxidants and less ATP per unit of fuel. A bad deal all around. The cell will have less energy at its disposal when their mitochondria are stressed. By restoring mitochondria to their former glory, our cells will have more energy for their given task. You think better, your heart works better and your muscles last longer. These tissues will receive the greatest benefit since they have the highest density of mitochondria.
Finally, Dr. Zach spoke of the mechanism by which Restore helps with hydration (and detoxification). For the gut to be able to absorb fluids properly, it needs to generate an electrical charge across the epithelial cells. This charge cannot be sustained properly when tight junctions are weakened. By reinforcing the gut tight junctions, the body is better able to take up water from the gut to hydrate our tissues. Hydration is key to elimination of waste through urine by the kidneys and sweat through the skin. In this manner, Restore can aid in detox and general hydration effort.
An important concern with products of this type is safety. Dr. Bush had this product tested and can confirm that it does not cause any kidney toxicity even at high doses (which is the most common concern). In fact, Restore may even improve kidney health.
On the topic of dosages and frequency of supplementation, Dr. Zach recommends frequent (multiple times a day) and small doses over just daily larger doses. The reasoning behind this has to do with the physiology of the gut. The entire gut lining is renewed every three days. Throughout the day, cells that were previously exposed to Restore are lost and replaced by new cells that have not been exposed to Restore. By taking frequent, small doses, you will have continuous benefit from the detox signaling molecules throughout the day. The product itself has a long shelf-life and does not need to be refrigerated.
Conclusion about Restore
We have only recently started to appreciate the importance of our microbiome and the impact it has on our health. Restore has several scientific studies to back up its ascribed effects and more studies are still to come, as promised by Dr. Zach Bush. Though the effects of Restore remain to be studied in-depth, these early observations indicate that Restore could be a very potent supplement for anyone who wishes to optimize their health and performance.
Figure 1 – Effects of low-grade chronic inflammation
This figure provides a summary of some of the potential side effects of long-term (chronic), low-grade inflammation somewhere in the body. This state can be caused by a leaky gut or other problems in the digestive system.
The signal for inflammation is delivered by cytokines (signaling molecules of the immune system) and is transported by blood. Transportation via the bloodstream means that every cell in the body will know and prepare to fight. A persistent signal of inflammation means a lot of being ready for anything without relaxation and recovery. Functions for long-term survival are put on hold in favor of immediate action. Without recovery, many tissues become tired and don’t work as well. Energy is diverted to fight or to be stored for later. Waste is left lying around, and damage accumulates.
The symptoms of inflammation include fatigue, low mental clarity or brain fog, and problems with digestion and elimination. On the very long-term (years/decades) one might get metabolic problems, disrupted hormones, cardiovascular diseases, cancer and (literal) aging.
Figure 2 – Leaky Gut
This figure gives an overview of 3 different situations in the gut and how they affect tight junctions between epithelial cells.
- In a healthy gut, epithelial cells form a barrier between the content of the gut and the inside of the body. Tight junctions between epithelial cells block passage of large molecules and particles, including bacteria. However, nutrients and water can be absorbed easily. In a healthy gut, bacteria are happy and digest food we would be unable to. We feed them and they feed us.
- In a leaky gut, tight junctions between epithelial cells are disrupted by toxins or upset bacteria. Angry bacteria will make even more toxins. These toxins weaken epithelial cells, which causes unregulated passages of all kinds of unwanted particles. Harmful particles will activate the immune system to protect the body from bacterial infections or toxic substances. The effects of inflammation in the gut affect other parts of the body as well. The inflammation persists until the leak is plugged.
- Tight junctions can be reinforced by Restore, which contains redox signaling molecules. Redox signaling molecules allow gut bacteria to communicate, which calms them down. Restore also strengthen tight junctions, even in the presence of toxins that would otherwise disrupt them. In this manner, Restore creates the same situation as we observed in a healthy gut: the uptake of nutrients is regulated and bacteria are happy.
More information about Restore?
Restore was discussed in-depth by its creator, Zach Bush (MD), in a recent podcast with Ben Greenfield.