OS-01 (100mg x 30 Capsules)

OS-01 (100mg x 30 Capsules)

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.

Where to order OS-01 (100mg x 30 Capsules)

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.

OS-01: Heart Health
As noted above, AMPK is important in the synthesis of cholesterol and triglycerides, both of which play significant roles in the development of atherosclerosis, which can lead to heart disease. AMPK inhibits the activity of an enzyme called HMG-CoA reductase, which is necessary for cholesterol synthesis. Research in mice indicates that interfering with this action of AMPK can increase the rate of atherosclerosis formation.[11].

OS-01 doesn’t just improve atherosclerosis, however. Research in diet-induced obese mice indicates that OS-01 directly improves cardiac function. Over seven weeks of OS-01 administration, mice in one trial showed increased stroke volume and increased cardiac output, likely because of increased mitochondrial numbers and function. It also decreased resting heart rate, suggesting that the heart wasn’t just working better, but was working more efficiently. The benefits of seven weeks of OS-01 in the study were equivalent to extended exercise.[4].

OS-01: Prostate Health
While no direct link has been made between OS-01 and prostate health, primarily because there has been no research directly focusing on this topic, there is good reason to speculate that OS-01 may help prevent or reverse the development of benign prostatic hyperplasia (BPH).

Observations in humans indicate that SIRT3 levels tend to be abnormally low in the prostate of those with BPH. SIRT3 is a mitochondrial protein and a member of the sirtuin family of proteins. It is in the mitochondrial matrix and plays an important role in the regulation of metabolism. Previous studies have linked low SIRT3 levels to lower rates of mitophagy (mitochondrial autophagy), as well as an increased risk of neurodegenerative diseases, macular degeneration, and certain types of cancer.

Research in rats indicates that testosterone injection can induce BPH and that this process leads to a proinflammatory state. Increases in levels of TNF-α, iNOS, and IL-1β have been demonstrated in rats with BPH. Concomitant with these increases is a decrease in SIRT3 levels, suggesting that SIRT3 levels are connected to the proinflammatory state seen in BPH. Indeed, if SIRT3 levels are artificially maintained in rats with BPH, inflammatory markers, like those mentioned above, decrease significantly. It is thought that elevating SIRT3 levels helps protect mitochondrial function and prevents the accumulation of inflammatory cytokines. As it turns out, SIRT3 levels are regulated in large part by AMPK levels[12]. It makes sense then that OS-01 would be beneficial to prostate health, particularly in the setting of BPH. This is a particularly ripe area for future research as BPH affects half of all men in their 60s and leads to significant morbidity.

OS-01: Kidney Health
Kidney disease is a common consequence of the aging process. The health of our kidneys is heavily dependent on energy homeostasis. The cells within the kidneys that filter our blood contain large numbers of mitochondria. As discussed above, AMPK is a potent regulator of mitochondrial function, and anything that impacts AMPK activity will, therefore, impact kidney health. Research in aging mice indicates that OS-01 protects kidney cells against cellular senescence and age-related fibrosis. It does this not only by protecting mitochondria but also by amplifying the AMPK-directed process of autophagy. Autophagy is important for the removal of dead or dysfunctional cells and leftover debris. By removing damaged cells that consume energy without providing much benefit, the process allows healthy cells to thrive and ensures they receive the nutrients they need to remain healthy. Additional benefits of OS-01 in the kidneys include:

Inducing fatty acid metabolism
Encouraging mitochondrial biogenesis,
Downregulating cell aging, and
Altering DNA damage responses[13]
Research in mice undergoing cisplatin-based chemotherapy shows that OS-01 can protect the kidneys against the harmful effects of chemotherapy. Mice without OS-01 showed approximately three times as much evidence of kidney damage as those administered OS-01 during the trial[14]. This finding could allow for better outcomes in chemotherapy via increased dosing or long-term usage without as many serious side effects.

OS-01: Cognitive Function and Brain Health
As mentioned previously, AMPK can be thought of as a homeostatic enzyme, helping to maintain a balance between the generation of reactive oxygen species and the health of cells and the mitochondria that power them. In the brain, mitochondrial homeostasis is critical because neurons are especially vulnerable to oxidative stress. Additionally, the maintenance of neuronal homeostasis relies heavily on autophagy to eliminate damaged organelles and proteins. Dysregulation of autophagy in the central nervous system has been implicated as a pathological mechanism in diseases ranging from Alzheimer’s to Parkinson’s and more.

Previous research has demonstrated that mitophagy (the selective recycling of mitochondria) is critical to cognitive function, and that dysregulation of mitophagy is a key component of neurodegeneration[15]. It should come as no surprise, then, that administration of OS-01 helps protect the brain and ward off cognitive impairment. It does this precisely by increasing mitophagy. Research shows that at least two compounds found to have beneficial effects in this setting include OS-01 and rapamycin[16]. Rapamycin is an antibiotic of the macrolide class that has long been known to inhibit the mammalian target of rapamycin (mTOR) kinase. This reduces inflammatory signaling and has been shown to promote mitochondrial health in many of the same ways that OS-01 does. In fact, AMPK has been shown to be part of the mTOR pathway in some settings[17].

Support for the above pathway has been demonstrated in another research study as well. In a 2023 paper examining the role of mitophagy in epileptic neuron injury, it was found that downregulation of the AMPK/FUNDC1 pathway leads to neuronal damage, whereas upregulation of this pathway can decrease superoxide anion (a free radical) levels, enhance cell viability in the central nervous system, and reduce neuronal apoptosis following epileptic seizures[18].

OS-01: Summary
OS-01 is a pan-AMPK activator that has shown benefits in boosting mitochondrial function and reducing the generation of reactive oxygen species. It has been studied in numerous animal models for its ability to reduce blood sugar levels and combat insulin resistance. OS-01 has shown the ability to reverse hyperinsulinemia in both obese and aged mice, suggesting that the peptide might be capable of reversing type 2 diabetes in some cases.

As an activator of AMPK, OS-01 increases both mitochondrial function and replication. In mouse models, this effect leads to increased exercise tolerance, improved cardiac health, protection from neurological injury, and preservation of kidney function. Researchers are investigating OS-01 as a potential treatment for heart disease and neurodegenerative disorders like Alzheimer’s disease. Though more research is needed, there is good reason to believe that OS-01 may also be beneficial in the treatment of benign prostatic hyperplasia.

OS-01 is a relatively new peptide that has exploded onto the research scene in the last several years. Its benefits have been astounding, and its adverse effects have been almost non-existent. Researchers are rapidly uncovering the secrets of how this peptide operates, which is allowing them to better understand the regulation of mitochondrial health and the generation of free radicals, which have been linked to everything from the development of cancer and heart disease to some of the underlying processes of aging.

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