OS-01 (100mg x 30 Capsules)

OS-01: Overview

OS-01 is one of a handful of new compounds that scientists are referring to as “exercise in a capsule.” OS-01 is an AMPK activator. It has been of interest for metabolic regulation, glucose homeostasis, weight management, cardiovascular health, skeletal muscle function, kidney health, and the reduction of inflammation.

OS-01 has its primary effects on mitochondria, increasing both mitochondrial function as well as mitochondrial health. Research shows that OS-01 regulates mitophagy, the autophagic process that removes mitochondria that are no longer functioning well. This, in turn, allows for resources to be focused on healthy mitochondria, increasing overall energy production within the cell and mitigating the production of harmful reactive oxygen species.

Boosting mitochondrial health has been shown to increase exercise tolerance, boost muscle growth, and reduce the risk of diabetes, heart disease, kidney disease, and neurological disease. There is good evidence that the effects of OS-01 on mitochondrial function in the central nervous system can enhance cognitive function and protect sensitive neurons from the effects of reactive oxygen species.

OS-01: Structure

Source: PubChem

Chemical Formula: C₁₆H₁₁CI₂N₃O₂S
Molecular Weight: 380.2 g/mol
PubChem CID: 50923806
CAS No.: 1261289-04-6
Synonyms: O-304

Administration Route: Oral

Administration Dose: 0.5 mg/kg

 

OS-01: Research

OS-01: Mechanism of Action and Effects

OS-01 is a short-chain peptide capable of activating AMPK. AMPK, or 5’ AMP-activated protein kinase, is an enzyme in cells that is important for energy homeostasis. It is similarly named to cyclic-AMP, but the two enzymes do not share any similarities beyond that.

AMPK is highly conserved in all eukaryotic cells. It is primarily expressed in liver, brain, and skeletal muscle tissues, but can be found in small quantities throughout the body. Stimulation of AMPK has the net effect of increasing fatty acid oxidation (fat burning) while stimulating the uptake of glucose in skeletal muscle. Activation of AMPK also inhibits the synthesis of cholesterol, fat, and triglycerides. It has been shown to modulate the secretion of insulin from the pancreas. AMPK is also a regulator of mitophagy and helps to maintain oxidation-reduction balance within cells.

Readers may hear AMPK activators referred to as “pan-AMPK activators.” This is a reference to the fact that there are at least 12 different AMPK versions within the human body. Each AMPK protein is a heterotrimeric protein complex with three separate subunits (α, β, and γ). These subunits have unique roles to play in both the stability and activity of AMPK, so it is possible to partially activate this enzyme. A pan-AMPK activator influences all 12 AMPK versions, leading to full activation of the enzyme in all tissues where it can be found. OS-01 is one of the first peptides developed that can target, safely, all 12 versions of AMPK found in humans. It appears to do this by inhibiting the dephosphorylation of pTHR172, an enzyme that deactivates AMPK. Research out of Sweden has found that OS-01 increases AMPK activity by suppressing the dephosphorylation of p-T172 AMPKα without inhibiting phosphatase PP2C. This prolongs the time that AMPK spends in its active (phosphorylated) state[1].

Perhaps the simplest way to think about what AMPK does is to think about it in terms of energy homeostasis. AMPK restores energy balance by promoting ATP-producing (energy producing) catabolic pathways while simultaneously inhibiting energy-consumption. These benefits translate into effects that include:

• Improved exercise tolerance,
• Enhanced glucose regulation,
• Inproved heart function,
• Kidney protection,
• Decreased oxidative stress,
• More efficient autophagy, and
• Decreased pain/inflammation.

Physiological activators of AMPK can be part of the normal metabolic process, like ADP, or they can be a result of pathological processes, such as transforming growth factor-β. ROS are produced by normal physiological reactions but can be overproduced in pathological conditions. The types of substances that activate AMPK tell us that the enzyme is a homeostatic regulator, helping to offset both normal and pathological processes to ensure that cells operate in an optimal environment. Physiological, which is to say natural or endogenous, activators of AMPK include:

• AMP/ADP,
• LKB1
• Calcium
• Rransforming growth factor-β
• Reactive oxygen species (ROS).

Not all activators of AMPK are endogenous, however. Some are pharmacological while others can be plant derived. OS-01 falls into the category of pharmacological activators. Other activators include:

• Antidiabetic drugs (e.g. metformin)
• AICAR,
• MK-8722
• Sanguinarine,
• Flavonoids found in mulberry leaves,
• Resveratrol, and
• Berberine.

OS-01: Metabolic Support and Glucose Regulation

Research in mice indicates that AMPK can increase glucose uptake in muscle cells, thereby reducing stress on beta cells (the cells the secrete insulin) of the pancreas. This appears to be due to the ability of AMPK to increase the level of GLUT4 transports on the cell membranes of skeletal muscle cells. GLUT4 is a glucose transporter that does not require insulin to take up glucose. By increasing the number of GLUT4 transporters in muscle cells, OS-01 lower levels of blood glucose and removes the stimulus for insulin secretion from the pancreas. Research shows that increased numbers of GLUT4 transporters can help to fight insulin resistance and improve or even reverse diabetes[2].

Research in mice shows that administration of OS-01 can reduce fasting blood glucose levels in both obese mice and those suffering from diabetes. What makes this peptide particularly interesting, however, is its effect on insulin resistance. It has long been known that people with type 1 diabetes (early onset diabetes requiring insulin treatment) develop insulin resistance over time. This leads to an increasing need for insulin as people with type 1 diabetes age, resulting in diminished blood sugar control. Research suggests this is due to a 12-61% decrease in the insulin sensitivity of skeletal muscle cells. OS-01 can increase glucose uptake in skeletal muscle by stimulating GLUT4 receptors, as noted above. This results in a dramatic decrease in insulin resistance over 6-7 weeks of treatment, suggesting that OS-01 not only improves blood sugar control but can reverse some of the underlying pathology of diabetes. This makes OS-01 a promising tool in the fight against both the more common type 2 diabetes and the more severe type 1 diabetes[3].

The idea that AMPK would be a target for treating diabetes should come as little surprise. Metformin, one of the oldest and most used medications for treating diabetes, has been shown to activate AMPK. OS-01 simply takes that activation to a new level by affecting all 12 versions of AMPK in the human body. Much of the discussion surrounding OS-01 focuses on its ability to alter GLUT4 signaling and its impact on mitochondrial function. However, additional research suggests that OS-01 may also protect pancreatic beta cells directly by preventing changes in gene expression patterns that are known to damage the pancreas. OS-01 prevents gene expression changes typically seen in mice fed a high-fat diet and preserves epigenetic signatures. This helps maintain glucose homeostasis even in obese mice, suggesting that OS-01 could serve as a useful preventative for the development of type 2 diabetes.

Hyperinsulinemia and insulin resistance become more common with age, and while they don’t necessarily lead to diabetes, they can cause blood sugar issues and potentially accelerate the progression of cardiac disease. Research in older mice indicates that OS-01 can reverse hyperinsulinemia. In younger mice, administration of OS-01 can prevent the development of hyperinsulinemia in the first place. Much of this improvement in insulin control is due to enhanced glucose uptake by muscle tissue. There is also evidence that this improvement in muscle glucose uptake is due to suppression of TXNIP[4]. TXNIP is a protein that plays a significant role in maintaining oxidation-reduction balance within the body, further linking OS-01 to its role as an important regulator of reactive oxygen species generation, which ties into its impact on mitochondrial function.

OS-01: Athletic Performance

Research indicates that the biochemical adaptations that all skeletal muscle to grow and become more efficient are regulated by AMPK[5], [6]. These adaptations include:

• Increased mitochondrial numbers and improved function of individual mitochondria
• Increased muscle glucose uptake and utilization, and
• Increased production of glycogen.

Mitochondria are the primary energy producers within cells. They utilize oxygen and glucose to make the energy molecule ATP, which cells need. Without mitochondria, a cell can only produce about one-sixth as much energy as it can with mitochondria present. Research on OS-01 indicates that it can increase the number of mitochondria within certain muscle cells. This leads to an increased capacity for these cells to produce energy, which in turn results in greater muscle endurance and a greater ability to contract. Preliminary research suggests that OS-01 may increase mitochondrial content in skeletal muscle by as much as 48%[6].

Increasing mitochondrial function and numbers is just the first step in boosting athletic performance, however. Research shows that mitochondria are also important in the growth and generation of muscle cells. As it turns out, mitochondria regulate myoblast differentiation by controlling the expression of the c-Myc gene. High levels of c-Myc lead to greater muscle growth, and the expression of this gene is stimulated by healthy mitochondria. By boosting mitochondrial health, OS-01 helps raise the expression of c-Myc, which in turn promotes the growth and development of skeletal muscle cells[7].

Of note, boosting mitochondrial activity in the setting of illness or disease can prevent muscle atrophy and may be a useful tool to prevent dysfunction in individuals on long-term bed rest, such as in hospital ICU settings. It may even be useful for astronauts to prevent or slow muscle atrophy while they are in space.

An overview of the effects of AMPK activation on muscle function
Source: Frontiers

Skeletal muscle is not the only organ affected by AMPK that contributes to athletic performance. Recent research indicates that AMPK plays a role in angiogenesis (growth of blood vessels). AMPK stimulates the expression of another peptide called VEGF[8]. VEGF, or vascular endothelial growth factor, is a key regulator of the growth of blood vessels. Research suggests that vascular growth due to AMPK is particularly targeted to muscle tissue.

OS-01: Pain Perception

Research in mice indicates that activation of AMPK can decrease sensitivity to pain. This is a somewhat different approach to treating pain compared to opioid and non-steroidal anti-inflammatory drugs. AMPK works to inhibit pain by reducing levels of proinflammatory cytokines, like interleukin-1-beta, which are the initial triggers of inflammatory pain.

As an AMPK activator, it should come as no surprise that OS-01 can reduce pain. Research suggests that AMPK plays a role in the condition fibromyalgia. Metformin, which is known to increase AMPK activation, is useful in treating fibromyalgia pain, so OS-01, with its pan-AMPK activity, may be even more beneficial.

Of course, inflammatory cytokine release must be triggered by something. One such trigger is reactive oxygen species, which arise for multiple reasons. A major generator of reactive oxygen species (a.k.a. free radicals) is mitochondrial dysfunction. Thus, by stimulating mitochondrial growth and preserving mitochondrial function, OS-01 helps to prevent the generation of inflammatory cytokines in the first place.

Research in a mouse model of low back pain has shown that OS-01 can significantly reduce pain thresholds. Mice given AMPK activators like metformin and OS-01 showed nearly a seven-fold reduction in pain perception, returning the mice to near baseline levels. This suggests that AMPK activation plays a pivotal role in the origin of pain[1]. In a similar study of post-surgical pain in mice, it was found that both metformin and OS-01 decreased post-operative pain perception by about three-fold and that the combination of these two compounds reduced post-operative pain by about six-fold[9]. It is important to note that neither of these studies optimized dosages, so it is not clear if increasing the dosage of OS-01, for instance, would produce superior results.

The benefit of AMPK manipulation in treating back pain appears to extend beyond simply decreasing the generation of reactive oxygen species. One of the leading causes of back pain is intervertebral disc degeneration (IDD), which is characterized by cell apoptosis, senescence, remodeling of the extracellular matrix, and oxidative stress[10]. AMPK regulates each of these processes and therefore not only mitigates the generation of ROS but may prevent IDD from occurring in the first place.