JOINT HEALTH, CANCER, DEMENTIA & the BENEFITS of Cat’s claw (Uncaria spp.)
From Personal Exploration to the Current Science
INTRODUCTION
Cat’s claw, named after its curved thorn, is a traditional medicine of the Amazon Rainforest where it is known by the Spanish name Una de Gato. It is a vine that grows to the top of the canopy, and traditionally the bark is used to make a tea (decoction). There are two variants – Uncaria tomentosa which has a pointy claw, and Uncaria guianensis which has a curly claw. In the Amazon Rainforest both are used interchangeably as traditional medicines.
As a supplement one can purchase a range of low grade forms. I do not recommend them, in essence they are simply examples of processing the vine’s bark through a glorified woodchipper. Alternatively, I prefer the higher grade options of freeze-dried water or hydroalcoholic extracts, noting that the latter brings out a different biochemical profile than a water extraction. Alcohol extracts compounds that are more soluble in oil or lipids.
I had the opportunity to make numerous trips to Peruvian Amazonia in the ‘90’s and early parts of the 21st Century, with the goal of trying to find therapeutic gems. Movies were made about the opportunity, but I knew very few people that were active in this pursuit. So why not me? With the help of a Peruvian postdoctoral fellow in my team (Manuel Sandoval), I set about to take up the challenge. My approach was that despite my Professorial title, that I would engage as the student, asking endless questions as I learned from their experience e.g.,
· why do people use it
· how often is taken
· how do you prepare it
· what conditions are benefited
· how long does it take to see the effects
Repeating these questions over and over to hundreds of people I got consistent answers that led me to believe that Cat’s claw was effective anti-inflammatory agent. Having been an inflammation researcher since the early ‘80’s this was exciting. From the answers my initial thesis was that Cat’s claw was able to disrupt chronic inflammation as opposed to an action on acute inflammation. A botanical example of a therapy for acute inflammation is salicylic acid derived from the bark of the willow tree. In the late 1880’s this was modified by Dr. Hoffman with the intent to generate a superior therapy for his grandfather’s arthritis. The result of that biochemical transformation was acetylsalicylic acid, which was then trademarked as Aspirin.
However, cat’s claw did not fit that profile in terms of actions and timing. The benefits took days or weeks to mature. Hence the focus on chronic inflammation. At that time, researchers had recently discovered a vital gene switch called NF-kB. This particular switch drives the activation of thousands of genes that are involved in inflammation, whilst at the same time suppressing the genes for repair. Collectively these protein switches are called transcription factors because they drive the process of copying genes (DNA) into RNA (called transcription), and the RNA then leads to the formation of proteins (called translation).
This NF-kB switch is designed to marshal an army of forces that are needed to oppose invaders as the result of infection, cancer, and clean up damaged cells and tissue debris. In essence, NF-kB maintains the integrity of tissues from a host of internal and external forces. Once the job is done, the switch leaves its docking site on the DNA with NF-kB returning to the cytoplasm of cells where it is anchored by a protein (IkB) and kept dormant until it is needed again. The primary signal for releasing NF-kB from its inhibitory subunit, IkB, is oxidative stress, which is how free radicals and oxidants initiate chronic inflammation.
Because NF-kB oversees so many processes involved in inflammation it must be tightly controlled, in other words, used on a need be basis.
“The essential problem of chronic inflammation is when NF-kB is active and bound to the cells’ DNA but FAILS to come off and return to a dormant state. The SWITCH is left in the ON position. If one could reverse this and turn the SWITCH OFF, then one would have a major therapeutic approach for chronic inflammation.”
Appreciating this science led to a race to develop therapeutics centered on restoring order to the control of NF-kB. Essentially to harmonize cellular decision-making. Researchers in both the natural products world and the pharmaceutical industry were hunting for an effective inhibitor of NF-kB activation. Then an innovation in the pharmaceutical & biotechnology industry split the developmental paths.
My hypothesis was that cat’s claw could suppress of NF-kB activation as well as being able to return the switch to dormancy if had already been activated. Indeed, our groundbreaking research validated this concept, whilst at the same time affirming the traditional use for Cat’s claw in the Rainforest communities (Cat's claw & NF-kB). To this day it remains one of the most potent botanicals known for this action.
The pharmaceutical industry was also chasing the same target, but a new technology diverted its attention, never to look back. The approach was redirected by the success of what is now known as “biologics”, which are engineered antibodies (a chimera of mouse and human segments) that are directed at specific biochemicals that drive chronic inflammation. The first successful prototype is known as Remicade or Infliximab, which acts to soak all the circulating TNFalpha. Results were impressive for hard to treat conditions like Crohn’s disease and rheumatoid arthritis. The price tag was also impressive much to the delight of the pharmaceutical industry, and as a result there are now a plethora of “…mabs” that target various cytokines involved in inflammatory diseases.
The pharmaceutical approach works, obviating a system that was excessive and out of control and cutting it off at the knees. Based on this early success there were an endless stream of copycats using this antibody-based approach, for the same or new targets. There are risks however, because they create a void in these defenses. One can get a feel for this consequence by the endless warnings and contraindications with these drugs. Simply put they can compromise the immune defenses. By contrast, the traditional medicine approach does not reduce the cytokines to zero, rather the take an excess amount and brings it back into balance.
Health demands a state of balance. Natural products rarely address a problem by total elimination of a wayward factor. Rather they seek to diminish excess levels or stimulate the inadequate, thereby re-establishing balance. Each approach has its audience. Once a fundamental, core problem has been identified it creates an opportunity for meaningful therapeutics. With that knowledge is obtained then one can make educated decisions as to how to manage the condition and restore health.
Timing is critical. Because our research on Cat’s claw came out around the time the pharmaceutical industry started a new, innovative antibody approach to chronic inflammation, the inherent value of the Amazonian traditional medicine was drowned out by the promotional activities and excitement with modern technology. Nevertheless, researchers plugged away and this article is directed at bringing attention to the potential of Cat’s claw in health maintenance and disease management.
SUPPLEMENTS and the FDA
As most should be aware, the passage DSHEA, the primary Act that regulates the supplement industry, restricted the terminology to be used in describing dietary supplements. Traditional medicines and botanicals fall into that category, unless they enter the drug pathway with its specific burdens of proof on safety and efficacy. DSHEA mandates that supplements cannot be advocated to diagnose, treat, cure, prevent or mitigate any disease. They are there for health maintenance, only.
Those are the rules, and we accept them as it brought structure to the natural products industry. However, it does disrupt the orderly application of natural products for health and disease. This article acknowledges those issues. The sole intent is to draw attention to knowledge, generated from research, and is not meant to promote any product. Simply put, this is an educational piece not designed for marketing or promotions.
Further, there are those that seek to exploit those with serious health issues – with arthritis, cancer and dementia are at the top of the “do not go there” list with the FDA in terms of product positioning. While this article will address the science related to these conditions, as directed by the research, we are merely describing the science and not promoting a product for these conditions.
JOINT HEALTH
It was very clear with my early questions posed to the locals in tropical Peru that Cat’s claw had a primary use in the managing of chronic joint health, arthritis and injuries. This led me to pursue its potential as an inhibitor of NF-kB activation. Remarkably that insight was accurate as upon bring samples back to the USA and my laboratory, we had the necessary proof-of-principle evidence within 6 weeks.
Follow up research goals were designed to flesh out this concept and explore it even further. We demonstrated that Cat’s claw was remarkably effective in lowering TNF alpha production in response to oxidants and bacterial endotoxin (LPS) as well as its potency as an antioxidant (Cat's claw and TNF Inhibition). This observation has stood the all important test of replication (TNF Inhibition via NF-kB).
In terms of chronic inflammation, we first focused on NSAID-enteropathy. NSAIDs are commonly used to manage the pain of arthritis, but they are not without untoward effects. They establish a serious inflammatory response in the small intestine that leads to over 16,000 deaths each year in the USA. Our goal, experimentally, was to ascertain if Cat’s claw could prevent this toxicity, thereby supporting its role as a valuable adjunct in the management of arthritis. As hypothesized, Cat’s claw was very effective in our preclinical studies in blocking the enteropathy created by indomethacin (NSAID Enteropathy & Cat's claw).
Research reported this year (Gastroprotection with Cat's claw) noted that an aqueous extract of Cat’s claw was an effective gastroprotective agent. Gastric ulcers induced by vinegar (acetic acid) were prevented and when Cat’s claw was applied to active ulcers, healing was promoted. The authors affirmed our established hypothesis of how Cat’s claw works as they concluded that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses.
Wishing to further validate the traditional experience of using cat’s claw in arthritis, we performed a successful clinical trial at the incredibly low dose of 100mg/day (Uncaria Guianensis & Osteoarthritis). This study was done with the variant Uncaria guianensis, the version where the claw is curly. As an adjunct to this clinical trial, we compared the potential of the two variants of cat’s claw, Uncaria tomentosa and Uncaria guianensis, as antioxidants, inhibitors of NF-kB activation and anti-inflammatory agents. Both variants were effective but interestingly the curly claw variant, Uncaria guianensis was more potent (Comparing U. tomentosa & U. guianensis). Despite this knowledge, most of the attention within the Natural Products industry is ascribed to Uncaria tomentosa.
This was also an important observation because some researchers had suggested that alkaloids were the active biochemicals in Cats claw. This was largely speculative and based on presence rather than specific bioactivity. Uncaria guianensis is naturally devoid in these alkaloids, yet our research demonstrated that it was more potent. Clearly these alkaloids were not the primary active components although there are plenty of individuals who are still adopt that mindset.
Further validating the efficacy of Cat’s claw in arthritis, we performed a number of clinical trials that essentially validate the ethnomedical experience. Often these were in combination with other natural products (Osteoarthritis & Cat's claw, Maca, Leucine , Cat's claw vs glucosamine in OA )
More recently, quinic acid, a constituent of cat’s claw, has been shown to be an effective inhibitor of NF-kB (Quinic acid & NF-kB). The biochemical profile of Cat’s claw reveals a diverse array of constituents, one that is certainly rich in polyphenols (Polyphenol content of Cat's claw). Quinic acid has also been linked to longevity, as demonstrated in round worms, one of the prototypical models for longevity. Here quinic acid was able increase lifespan by up to 30% under stressful conditions (Quinic acid & Longevity). The mechanism of action was a proposed up-regulation of the heat shock protein hsp-16.2. Interestingly, quinic acid does not stimulate hsp-16.2 under baseline conditions but yet, is effective when cells are stressed. In other words, the benefits arise when it is needed, and only when needed.
While this article is designed around science, I must engage with my personal testimonial. After a decade of athletic endeavors including triathlons, marathons, martial arts, the status of my joints was marginal. Then I destroyed the ACL in my right knee in a skiing accident.
Affirmation that I fall into the third group of athletes – not professional, not amateur but the damaged & broken. A fellow Professor at my Medical School was going to replace my knee/ACL but at that time (1997) the surgery was barbaric, and I was concerned. At the same time my research on Cat’s claw was progressing well, and I opted to at least try my lab samples before the surgery. Within a week I was pain free and I cancelled my proposed reconstructive knee surgery. Some 27 years later I am still taking cat’s claw, and I have normal knee cartilage, I remain devoid of knee pain despite having no ACL.
With better results than outlined in the novel “Dr. Jekyl & Mr. Hyde” I trusted my research and placed my long-term joint health into the hands of the Amazonian traditional medicine, Cat’s claw.
Continuing our research, we explored this concept of cartilage health in detail, using human cartilage specimens obtained at surgery. What was clear was that Cat’s claw, alone or in combination with other natural products, could override catabolic signals that code for cartilage breakdown (the matrix metalloproteinases, MMPs) and stimulate the anabolic processes that code for the formation of new cartilage – specifically activating the genes for Type 2 collagen and glucosamine, critical elements in the cartilage matrix (Cat's claw promotes Type 2 collagen & glucosamine production). This includes actions to restore the production of the anabolic growth factor IGF-1, that is important for bone and joint health, but is suppressed with inflammation (Cat's claw, maca and IGF-1). Combining these laboratory findings with our experience with Cat’s claw in clinical trials for osteoarthritis, we affirm the traditional Amazonian medicine experience.
There is still a lot of noise as to various options that may stimulate the repair and regeneration of joint cartilage. Some may have value, but none are as easy, effective and affordable as my research on cat’s claw has defined. The long lasting disappointment is that so few are aware of it whilst they struggle to maintain a healthy, mobile lifestyle.
Osteoarthritis (OA) is quite common and has its focal point, loss of cartilage. The underlying cause is when cartilage cells are stressed by inflammation or torque, they become catabolic. What that means is that they become active players in destroying the cartilage matrix that they live in i.e., they trash their neighborhood. By contrast, rheumatoid arthritis (RA) is an autoimmune disorder. In this case, joint health is compromised by an immune system attacking its own tissue. With RA the entire joint structure is targeted, whereas on OA it is largely limited to cartilage noting that chondrocytes (cartilage cells) are the only cell type in cartilage.
In the lay medical literature, there is a lot of misconceptions around the use of Cat’s claw and autoimmune disease. Who has not been led astray by Dr. Google? This is quite confusing, as NF-kB activation is a common feature that drives autoimmunity, therefore agents that suppress the activation of NF-kB should be beneficial.
Clinical trials evaluating Cat’s claw in rheumatoid arthritis validate that it is indeed effective as a therapeutic intervention (Rheumatoid Arthritis & Cat's claw). Subjects receiving Cat’s claw experienced a reduction in the number of painful joints by 53%, whereas placebo responded with 24%. When cat’s claw was introduced during the second phase of RA presentation over a 24 week period there were remarkable benefits with fewer painful (P<0.003) and swollen joints (p<0.007) vs placebo.
Suffice to say that Cat’s claw has remarkable actions in joint health, promoting lifestyle and limiting dysfunction across a spectrum of conditions and totally consistent with its potency as an antioxidant, anti-inflammatory and its ability to restore balance to gene expression. This re-balancing action on gene expression as it shows a suppression of catabolic, inflammatory genes, whilst enhancing restorative and repair genes. Often we focus on one side of the joint health coin, inflammation without simultaneously addressing repair. Cat’s claw is effective in harmonizing both states.
As an aside, be careful about conclusions and directions offered in various lay medical advice sites. My advice is to refer back to the original research for a more accurate guidance.
Related to this, many biochemicals are touted as being effective antioxidants, but the lay person struggles with placing this nomenclature in perspective, especially in ascribing benefits and dose. Overuse and misuse of the term has created confusion and falsely led to advice that is unfounded.
For example, the hormone melatonin is routinely described as being an antioxidant, and assays like DPPH, which is a free radical scavenging assay, affirm this (Melatonin as an antioxidant),… to an extent. The dose of melatonin that is needed to quench DPPH is in the order or 10 mg/ml (..), whereas Cat’s claw is effective at 100 pg/ml (Cat's claw as an Antioxidant). This is an enormous difference in potency, on the order of 100,000 times stronger for Cat’s claw. The bottom line is that dosage regimens of Cat’s claw that mimic the clinical trials, would be a million times more effective as an antioxidant than is melatonin. This concept, that the dose matters, struggles to be voiced in the lay literature and as a result poor decisions are made, and outcomes are frustrating.
CANCER
While I have been a cancer researcher, my specific research area was gastric cancer especially in the context of H. pylori infection and the generation of reactive nitrogen species as part of the immune response (Reactive Nitrogen species & H. pylori gastritis, Antioxidants & Antibiotics on Gastric mucosal response to H. pyloris). While there is an inflammatory, altered gene expression to this area of research, I did not specifically evaluate Cat’s claw in stomach cancer. For this reason, I will focus this section on the valuable research performed by others.
Most studies are of a preclinical nature, looking at cancer cell types and how Cat’s claw influences they growth and decision-making. When melanoma cells are given to B16-BL6 mice Zari et al (Melanoma & Cat's claw) noted that administration of Uncaria tomentosa induced apoptosis in the melanoma cells. Apoptosis is akin to cellular suicide, where damaged or deranged cells make the decision to remove themselves from tissues, breaking themselves up into little pieces that are ingested, recycled and cleared by other cells. Accompanying this observation, they noted that tumor size was greatly reduced (59% for ethanolic extracts, 40% by aqueous extracts). Tumor growth was reduced by 80% supported by a massive reduction in Ki-67, a marker for cellular proliferation. Suppressed angiogenic markers was also noted.
Reducing tumor size, suppression of proliferation and angiogenic factors and the stimulation of tumor cell apoptosis are impressive outcomes for this traditional medicine.
In thyroid cancer, Rinner et al (Thyroid cancer & Cat's claw) noted the within the biochemicals constituents of an aqueous extract of Cat’s claw there are distinct bioactivities. The alkaloids isopterpodine and pterodine display significant pro-apoptotic effects. On the other hand, an alkaloid poor fraction was vigorous in its ability to block cellular proliferation.
The induction of apoptosis (cell suicide) and suppression of proliferation was a common feature with Cat’s claw and acute lymphoblastic leukemia cells (Acute Lymphoblastic leukemia & Cat's claw) and a multitude of other cell lines (Cat's claw & apoptosis).
While the current state does not allow for a direct evaluation of Cat’s claw as a single approach in chemotherapy, for ethical reasons, research has been conducted to determine its value as a combinatorial approach (Cat's claw as an adjunctive chemotherapeutic agent ). Here co-administration of Cat’s claw was able to reduce the adverse events associated with chemotherapy in the management of breast cancer. In particular, Uncaria tomentosa was able to suppress the neutropenia (loss of white blood cells) associated with chemotherapy, as well as being able to protect DNA from damage.
Figure : Cat’s claw abrogates the neutropenia associated with chemotherapy.
https://onlinelibrary.wiley.com/doi/10.1155/2012/676984
All in all, there is encouraging research, cell-based, animal models and clinically to suggest that Cat’s claw should not be avoided in the management of cancer, and indeed future research should include assessing its potential role as an adjunctive therapeutic agent.
DEMENTIA
Dementia, in its various forms from Chronic Traumatic Encephalopathy to Alzheimer’s Disease represents a major societal concern. Losing cognitive functions is devastating to the individual, their family, their friends and colleagues. Long have we sought to alleviate this burden by understanding the core drivers and promoters. Much focus has been on the anatomical manifestations that are clearly evident on autopsy i.e., Beta- amyloid plaques and tau protein tangles.
However, with new research we learn that these are relatively late-stage events and the primary drivers lie upstream and center on neuroinflammation both of vascular and glial origins. For this summary, is there a role for Cat’s claw in maintaining a healthy cognitive function, or even as a therapy to limit cognitive decline?
Starting with beta-amyloid proteins and neurofibrillary tangles, Snow and colleagues have published some remarkable studies. Using a specific extract of Cat’s claw, called PTI-00703, they observed that there were able to effectively target brain plaques, tau tangles and inflammation (Cat's claw ameliorates brain plaques & neuronal tangles). Other Cat’s claw extracts that are commercially available, have comparable activities but their PIT-00703 version was the most potent. Associated with these activities, is a substantial improvement in memory (Cat's claw & Memory Loss).
The question is what with the array of chemical compositions in Cat’s claw could be responsible for these remarkable actions? Snow et al. (Cat's claw proanthocyanidins & dementia) consider that specific proanthocyandins (short chains of epicatechin molecules) possess the desired functionality. In particular, proanthocyanidin B2, which is a dimer of epicatechin-4beta-8-epicatechin, is quite potent and demonstrated remarkable ability to reduce plaques and improve memory in a mouse model of Alzheimer’s disease.
Additionally, as noted above that there is now significant attention to the role of inflammation as an early driver of dementia, this proanthocyanidin B2 biochemical is a potent inhibitor of brain inflammation.
One conundrum when devising strategies for brain function is – Can the ingested biochemicals cross the Blood Brain Barrier (BBB)? These researchers noted that the major components in the Cat’s claw extract cross the BBB and enter the brain within 2 minutes of being in the blood. Clearly, they can reach the desired sites of action. That is not to diminish any potential benefits on vascular inflammation.
Altogether, this research opens up the strong potential that this traditional Amazonian Medicine would represent a solid treatment for brain health, both as a preventative and as a potential therapeutic agent.
SUMMARY
The current legal constructs for discussing botanicals as dietary supplements has fostered commerce and development. Society is now open to a wide range of traditional medicines that have massive experience and trust in other cultures, for example Ayuvedic medicine or Traditional Chinese Medicine (TCM). From my experience, less well-known cultures also deserve our attention. In Amazonia we have 16% of the planets plant species and a plethora of experience for their use in health and disease management. The reason why Amazonia has not featured as highly as other cultural experiences is that their knowledge base was never committed to paper. All history and knowledge was passed on orally. However, that does not mean it is less important.
Nevertheless, revered botanicals like Cat’s claw do not get the respect that they deserve. When one considers the mechanisms of action and the current degree of scientific support, I would advocate that they represent a major untapped resource for health, wellness and as therapeutic agents in some of our most challenging disease states.
Whilst it is not easy to discuss all their actions and benefits within the constructs of the current healthcare system and legal framework, my hope is that this educational piece will capture the imagination of researchers to continue their work, and to arm consumers with solid scientific knowledge so they can explore their health options.
“Enhanced knowledge leads to better decisions, and from there Superior Outcomes”