Building on several decades of innovative research
Pathways Bioscience scientists have developed a new Nrf2.0® Technology that led to the PB125® dietary supplement, a breakthrough next generation Nrf2 activator. PB125® uses safe, natural ingredients with a long history of human consumption. PB125® not only activates but modulates the Nrf2 pathway which regulates a network of hundreds of genes inside cells and supports health and wellness.
Nrf2.0® Technology
Nrf2.0® Technology is focused on enhancing the body’s natural defense system by understanding the control points in Nrf2 activation. By pinpointing specific control points in its activation process, we can essentially make it more effective in triggering protective genes. Imagine it like tuning a race car for optimal performance around curves – we’ve figured out how to keep Nrf2 activated longer, resulting in better protection against harmful factors. This advanced understanding has led us to develop a new generation of Nrf2 activators for use as dietary supplements, PB125®, aimed at boosting our bodies’ defenses and defying age-related challenges.
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Aging Bones
PB125® improved bone strength in aging guinea pigs
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Aging Muscles
PB125® improved mitochondrial respiration and decreased age-related declines in muscle protein synthesis in a guinea pig model
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Aging Cellular Energy
PB125® supports the expression of NAD pathway genes and improves NAD levels in cultured cells
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Aging Brain
The carnosol in PB125® crosses the blood-brain barrier allowing Nrf2 benefits in the brain
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Aging Immune System
PB125® prevents exaggerated immune response and helps control inflammation genes in cultured cells
Benefits of PB125®
Address age-related health and wellness challenges with PB125®, a research-backed supplement. Learn more about the key benefits below.
Pathways Bioscience
2022 US Patent
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Pathways Bioscience
Scientific Publications
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The need for Nrf2-activating supplements or therapeutics as we age
Why should we be concerned with supplements or therapeutics that can adjust the Nrf2 pathway?
Isn’t it, after all, part of a very large network of interactive and self-regulating pathways that automatically adjust to achieve proper balance based upon our metabolism? In a young healthy animal, this appears to be the case. In post-reproductive organisms, however, things begin to change, as Nrf2-activation capabilities decline with age. As harsh as it may sound, after animals have passed on their DNA and reared their offspring they have mostly served their purpose as far as Mother Nature is concerned. While it may not be nice to fool Mother Nature, perhaps people can agree that it’s now acceptable to tinker a little with Mother Nature.
Many studies have shown that the concentration of Nrf2 in cells declines as animals age.
Old age brings with it increased markers of oxidative stress and an assortment of “age-related diseases” such as atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer’s and Parkinson’s diseases. All of these diseases have been characterized by evidence of increased oxidative stress. By gently stimulating our aging cells’ ability to activate and modulate Nrf2, we aim to restore and enhance our body’s own ability to counteract the effects of oxidative stress.
Our experience with TBARS
In our experience with human subjects, the level of plasma TBARS (thiobarbituric acid)—which is a measure of oxidative stress—have all declined to the Target Range of 1.0-1.5 μM (μM malondialdehyde equivalents) within a span of about a month.
Polyunsaturated fatty acids (PUFAs) are among the most easily oxidized molecules in our bodies, and they are especially vulnerable to attack by free radicals. Their oxidation produces TBARS, which are widely used as a sensitive measure of oxidative stress. The oxidation of PUFAs is why dead fish begin to smell bad very quickly! It is also why omega-3 fatty acid supplements may start out as fish oil but can quickly oxidize and turn into TBARS supplements.
TBARS in your body gradually increase as you age, indicating a decrease in Nrf2-regulated pathways and a rise of oxidative stress.
What is Nrf2?
Controls the rate of production from hundreds of different genes that allow cells to survive under stressful conditions
Our DNA encodes about 20,000 genes, each representing a “blueprint” for the production of a protein or enzyme necessary for a healthy existence. Each of these “blueprints” requires a regulating control called a “promoter” that determines precisely how much of each product is produced, and under what circumstances. By binding to one specific type of these switch-like promoter regions called the “Antioxidant Response Element (ARE)” the Nrf2 factor controls the rate of production from hundreds of different genes that allow cells to survive under stressful conditions. These genes produce a large variety of antioxidant enzymes that create a network of protection by neutralizing primary and secondarily generated oxidants and by cleaning up the toxic byproducts they leave in their wake, as well as by helping to repair the damage they have caused.
Nrf2.0® is the next level of understanding of the Nrf2 pathway. Informed by our own research in tandem with outside scientific studies on the nuances of the Nrf2 pathway, we have identified multiple control clusters that work together to optimize the effects of Nrf2 activation.
In 2007 when Dr. McCord tested his first Nrf2 activating supplement the activation process was thought to be a single-step process, because only one step had been discovered.By 2018 more control points had been identified in the activation pathway, as well as in a “deactivation” pathway.By 2024 we know of more than 40 distinct control points in the pathway.Why do all these ways of controlling Nrf2 exist?Imagine your house, which is connected to the power grid by one large switch on the outside where electricity enters.Inside there may be a hundred very different things that utilize this power—heating, AC, TVs, computers, ovens, lights, curling irons, toothbrushes, etc.
What if you only had that one switch to either turn everything on at once, or everything off?Instead, of course, every device has its own switch to regulate its activity as needed, and to the degree needed.Now imagine Nrf2, which has the job of regulating roughly 3,000 known genes, with only one on-or-off switch!The 40+ control points we now know about are only the beginning of a vast and complex system which we now refer to as the “Nrf2 Network”.We coined the term “Nrf2.0 Technology®” to describe our on-going efforts to understand the ever-expanding next levels of control required to optimally regulate Nrf2.We are a company of scientists, not a company of marketers.We are a company continually engaged in research to expand our understanding of Nrf2 activation, and to improve our products as new discoveries emerge.
We produce less Nrf2 as we age, and the balance slowly tips toward the oxidative side—a condition known as “oxidative stress.”
Oxidants such as the superoxide radical (O2-.) and hydrogen peroxide (H2O2) are produced by the process of “burning” the foods that sustain us, just as the internal combustion engines in our cars produce similar reactive chemicals. Cars have catalytic converters to neutralize and detoxify these reactive chemicals; our bodies have antioxidant enzymes to accomplish the same result. The Nrf2 pathway senses the need for these antioxidant enzymes and regulates their production to maintain metabolic balance. Several things can upset this delicate balance, and simply growing older is one of them. We produce less Nrf2 as we age, and the balance slowly tips toward the oxidative side—a condition known as “oxidative stress.” Disease processes can also result in overproduction of oxidants. Infections, allergies, and autoimmune diseases activate our immune cells, which produce reactive oxidants (O2-., H2O2, OH. and HOCl) in order to kill germs that the immune system assumes to be present, but our otherwise healthy cells get caught in the cross-fire and sustain collateral damage that we see and feel as inflammation. Other major diseases associated with aging, such as heart attacks, stroke, cancer, and neurodegenerative conditions such as Alzheimer’s disease also increase production of oxidants, creating oxidative stress, and inflammation.
Our bodies counter oxidative stress and injury via the activation of the Nrf2 pathway. The body’s ability to do so declines with age and various illnesses. This is when indirect Nf2 activation via PB125® can help restore the body’s own ability to counteract the stresses and heal.
The Nrf2 protein, known as a transcription factor because of its ability to control genes, is the key component of a pathway (a sequence of biochemical reactions in a cell) that senses and responds to changes in oxidative balance.
The sensing components of the pathway chemically modify and release Nrf2 (i.e., they activate it) so that it may diffuse into the nucleus of the cell where the DNA resides. It can then “switch on” or “turn off” the genes it controls (often termed survival genes) to produce the protected state within the cell. Fortunately, many of the chemical compounds that are Nrf2 activators are produced by certain plants, crude extracts of which were known to our ancestors centuries ago in traditional Chinese, Ayurveda, and Native American medicines. These phytochemicals appear to be just as potent, and to have fewer (if any) side-effects, as the Nrf2-activating pharmaceutical products that are beginning to appear.
Harman proposed a theory of aging based on free radicals
Noting parallels between the effects of ionizing radiation and aging, Denham Harman suggested in 1956 that free radicals produced during aerobic respiration over time might lead to cumulative oxidate damage in aging individuals.
Reference
1969
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1969
McCord and Fridovich discover the superoxide dismutase enzyme, launching the field of free radical biology and medicine
By discovering the enzyme superoxide dismutase, identifying that humans and other biological organisms have complex enzymatic defenses against oxidants, and demonstrating that oxygen radical compounds like superoxide anion are generated during normal biological processes, Drs. McCord and Fridovich initiated the field of Free Radical Biology and Medicine.
Reference
1991
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1991
Rushmore and Pickett discover the DNA antioxidant response element
In 1991, Rushmore and Pickett discovered the antioxidant response element (ARE), a specific DNA sequence in the gene promoter region of cell protective genes they were studying that we increased by chemical stressors on cells. This later led to discovery of how the body upregulates antioxidant and detoxification genes when confronted by various stressors.
Reference
1994
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1994
Moi and coworkers identify Nrf2 as a transcription factor
In 1994 Moi and colleagues discovered Nrf2, noted that it is widely found in different types of cells, and speculated on its probable role as a transcription factor to control the expression of certain genes.
Reference
1997
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1997
Itoh and coworkers reveal that Nrf2 controls detox gene expression through ARE binding
In their 1997 advancement, Itoh and colleagues discovered that Nrf2 is a transcription factor that binds to the antioxidant response element in DNA in the nucleus of cells and regulates the level of expression of cell protective detoxification genes.
Reference
2003
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2003
Itoh and coworkers identify Keap1 as controlling Nrf2 degradation
Furthering their work, in 2003 Itoh and colleagues determined that the Keap1 protein binds to Nrf2 inside of cells and directs it to be degraded unless the Keap/Nrf2 interaction is affected by various cellular stressors which then allow Nrf2 to avoid degradation and increase the amount of Nrf2 binding to ARE sequences in gene promoters.
Reference
2004
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2004
Hagen and coworkers discover that Nrf2 signaling decreases during aging
Examining the similarities in loss of glutathione synthesis in aging rodents and rodents lacking Nrf2, Suh and Hagen and colleagues found that the connection was that Nrf2 activity declines with aging.
Reference
2006
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2006
McCord and coworkers discover dietary approach for indirect antioxidant therapy
Instead of simply relying on consumption of antioxidant vitamins that get used up one to one in chemical reactions with oxidant molecules, Nelson and McCord and colleagues recognized in 2006 that a better approach is to induce small increases in endogenous antioxidant enzymes in the body that degrade vast amounts of oxidant molecules per molecule of enzyme.
Reference
2014
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2014
McCord and colleagues launch Pathways Bioscience to pursue R&D on Nrf2 activation
After his previous success with developing a dietary antioxidant supplement that he later determined to work in part by activating Nrf2, Dr. McCord decided to co-found Pathways Bioscience in 2014 with the goal of developing new, purpose-built combinations of plant extracts for better Nrf2 activating dietary supplements like PB125®.
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2017
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2017
Pathways Bioscience awarded US NIH small business research grant
The Pathways Bioscience team of scientists was proud to receive research funding from the National Institute on Aging at the US National Institutes of Health through a highly competitive Phase I Small Business Innovation Research (SBIR) grant. This allowed further research by Pathways Bioscience and their colleagues Professors Miller and Hamilton at Colorado State University to studying the Nrf2 activating dietary supplement PB125® in cultured cells and in a mouse model of aging-related changes in muscle health.
Reference
2018
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2018
Pathways Bioscience launches sales of PB125® product
After several years studying synergistic Nrf2 activation thousands of possible combinations of dozens of safe, widely recognized plant compounds, the science team at Pathways Bioscience discovered that the PB125® combination of specific extracts of rosemary, ashwagandha, and luteolin was an optimal formulation, so the PB125® was manufactured and launched for sale in 2018through the Pathways Bioscience (pathwaysbio.com) website.
Reference
Mitochondrial function is a crucial aspect of muscle health, and Nrf2 plays a key role in mitochondrial homeostasis. Nrf2 has been shown to regulate genes involved in making new and discarding old mitochondria, mitochondrial respiration, and energy metabolism.
Recent work has shown that Nrf2 activation helps protect cells in the central nervous system, support the health of mitochondria in the brain, and enhance cognitive function.
PB125® was developed with more than a century of combined research and development experience. Utilizing Nrf2.0® Technology, hundreds of natural, plant-based compounds were screened for specific, multi-control-point Nrf2 activation and modulation characteristics. We sought compounds with demonstrated efficacy, as shown by our own research and published scientific studies. We paid close attention to safety profiles of compounds — focusing on those with extensive and safe histories of human consumption. The optimal combination and composition of PB125® was determined and tested to maximize biological effects and minimize effective dose. Safety was evaluated and validated with internal research, results from other peer-viewed studies, as well as human consumption history. Modern genomic and proteomic technologies were used to generate gene and protein expression profiles for the ingredients and combinations, which were further analyzed to determine the range of biological effects. Health and wellness benefits of PB125® were assessed by our own research and published scientific studies.
23Improved Molecular Detoxification
Nrf2 activation has been shown to upregulate a variety of genes that create enzymes and other proteins involved in detoxification and cytoprotection. This enhancement of protection and age and stress-induced damage may help extend the human healthspan.
NAD+/NADH serves as the energy currency for our cells, and these molecules can be recycled in our bodies from any of several “building blocks”– Nicotinamide (NAM), nicotinamide riboside (NR), or nicotinamide nucleotide (NMN). Several highly marketed supplements claim to solve the problem by providing more of these recyclable building blocks, but to make a biochemical pathway go faster, piling on more of the building blocks is usually not the answer— the rates of pathways are controlled by enzymes, and one enzyme in any pathway is always rate-limiting (i.e., the slowest person in a cafeteria line). Furthermore, the concentrations of these “building blocks” are kept low in your body for a reason—NMN becomes toxic at high concentrations.
Because Nrf2 regulates both enzymes required for recycling, PB125® increases the levels of both NAMPT (the rate-limiting enzyme for recycling NAM) and NMNAT1, the enzyme required to convert NMN to NAD+. The result is a better, safer way to restore youthful levels of NAD+/NADH.
We are constantly exposed to oxidants that come from both inside and outside of our bodies, and the human body has its own antioxidant defense system to protect itself.This system is controlled by Nrf2 which regulates the gene expression and protein production of antioxidant defense enzymes.
Nrf2 activation has been shown to promote the expression of protective genes that promote a healthy balance in bone remodeling, improve bone fracture recovery, and reduce inflammation in cartilage cells.
The major active ingredients are Carnosol/Carnosic acid, Withaferin A, and Luteolin derived from rosemary, ashwagandha and natural luteolin sources.
PB125® Product Info
23Can I take PB125® while pregnant?
Customers who are pregnant or nursing, and customers with specific health issues should consult with their qualified health care provider prior to taking PB125®. These statements have not been evaluated by the Food and Drug Administration (FDA). PB125® is not intended to diagnose, treat, cure, or prevent any disease.
23Do you sell and ship internationally?
We do not ship outside of the United States at this time. Please contact us if you have questions.
23How was PB125® developed?
PB125® was developed with more than a century of combined research and development experience. Utilizing Nrf2.0® Technology, hundreds of natural, plant-based compounds were screened for specific, multi-control-point Nrf2 activation and modulation characteristics. We sought compounds with demonstrated efficacy, as shown by our own research and published scientific studies. We paid close attention to safety profiles of compounds — focusing on those with extensive and safe histories of human consumption. The optimal combination and composition of PB125® was determined and tested to maximize biological effects and minimize effective dose. Safety was evaluated and validated with internal research, results from other peer-viewed studies, as well as human consumption history. Modern genomic and proteomic technologies were used to generate gene and protein expression profiles for the ingredients and combinations, which were further analyzed to determine the range of biological effects. Health and wellness benefits of PB125® were assessed by our own research and published scientific studies.
23Is PB125® a dietary supplement?
PB125® is a dietary supplement that activates the Nrf2 pathway to increase the expression of cell protection mechanisms.
23What are the active ingredients in PB125®?
The major active ingredients are Carnosol/Carnosic acid, Withaferin A, and Luteolin derived from rosemary, ashwagandha and natural luteolin sources.
23What if I have other questions?
If you have additional questions, please complete our contact form.
23What is PB125®?
PB125® is a next-generation Nrf2 activator, developed using our Nrf2.0® Technology. It is a potent antioxidant that works by activating and modulating the Nrf2 pathway. PB125® has been shown to combat issues associated with aging and oxidative stress. This patent-pending formulation is a synergistic blend of naturally-occurring plant-based ingredients, rosemary, ashwagandha and luteolin.
23Where can PB125® be purchased?
PB125® is created by and sold only by Pathways Bioscience. A 60-count bottle (60-day supply) of PB125® can be purchased here.
PB125® is a safe, potent Nrf2 activator containing active ingredients carnosol, withaferin A and luteolin. Derived from natural plants, these ingredients were extensively studied for their synergistic properties. Every ingredient and the final product undergo triple testing in Pathways Bioscience’s laboratory to ensure optimal quality and biological activity.
Nrf2 factor controls the rate of production from hundreds of different genes that allow cells to survive under stressful conditions.
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Based on the extensive amount of new, published scientific literature and our own research, we have identified at least five control points in Nrf2 activation...
