This is one of the most important podcasts I have ever recorded. Travis Christofferson speaks on how metabolic conditions lay the foundation for many of our disease states. With better treatment methodologies, and better thinking around the system at large, we can drastically reframe the way we look at our health. Healthcare is a daunting beast, physically, emotionally, and financially–with cancer sitting at the helm. In his two books Tripping Over The Truth and Curable Travis reveals actionable strategies for you and your loved ones to not only optimize your likelihood of survival, but reframe the disease paradigm and take greater control of your livelihood. Please share this podcast and Travis’ books with anyone you know who has ever been touched by cancer or many of the diseases we discuss on the podcast. Who knows, it might just save someone’s life.
Travis Christofferson is a founder of Care Oncology US
Taking multiple different medications without proper medical supervision can cause more harm than good. You don’t have to do this alone.
- Taking more medications or supplements does not necessarily mean more benefit. Even the most common medicines and supplements can have potentially serious side-effects or can interact dangerously with other drugs, especially in the context of cancer.
- The risk of serious side-effects increases with every extra medication taken.
- At the Care Oncology clinic we regularly see patients who have become unwell through taking unregulated supplements or prescription medications without proper medical supervision. That’s why we believe that full and proper medical oversight by qualified clinicians is so vital.
- We also understand that as someone living with cancer, you want to help yourself as much as possible. We fully respect your right to do that.
- At Care Oncology, our specialist clinicians and nurses are here to help you safely navigate your repurposed medications. We do not judge, and we are here to help. If you have any questions about your medications, or any safety worries at all, please do come to us.
Around 1 million patients end up in US hospitals every year as a result of using prescribed medications. Taking multiple medications, sometimes called polypharmacy, can increase risk of side effects, poor outcomes and even death. With each additional medication and supplement, the risk of adverse outcomes due to medication interactions is also increased. . This is why our specialist clinicians take extreme care when prescribing the Care Oncology protocol medications, and each patient is regularly monitored for potential issues.
Every day our clinic hears from patients who have encountered problems caused by taking other medications alongside the Care Oncology protocol, without proper medical supervision. Some have ended up in the ER because they have added an unregulated supplement alongside their usual Care Oncology regimen. Others have suffered severe symptoms such as internal bleeding or liver problems as a result of using regular prescription medications without proper monitoring.
Cancer medicine requires constant balancing of potential risks and benefits against an ever-changing background of disease. But we also understand that as someone living with cancer, you want to help yourself as much as possible. That’s why we are here to help you safely navigate your own complex situation. You don’t have to do this alone.
More medicines can mean more risk
Taking more medications does not necessarily mean more benefit. Mismanaged or unregulated polypharmacy is a significant driver of prescription drug-related hospitalizations, and research shows that the risk of having a drug-related health issue increases by 10% for every extra medication taken (Gandhi et al., 2003). A patient taking ten medications has twice the risk of death compared to a patient taking just one (Leelakanok et al., 2017). In the US, polypharmacy mismanagement is estimated to result in healthcare costs of at least $1.3 billion every year, mostly due to inpatient care, visits to the ER and hospitalization as a result of complications and adverse side-effects. Put simply, if you take more medications, no matter how safe they are, you become much more likely to suffer a serious side-effect or drug-drug interaction as a result.
Even the most common medicines can have potentially serious side-effects, especially in the context of cancer. One reason for this is because both the disease and the standard-of-care treatments given can place body systems under extreme strain. The risk directly escalates with the number of medications used. Mild side-effects caused by just one medication can soon become problematic when several medications with the same or similar side-effects are used together.
Even painkillers carry risk
The widely used painkiller acetaminophen/Tylenol is invaluable in providing pain relief caused by cancer and cancer-related treatments. Yet this common medication can be toxic to the liver and fatal at high-doses – even in patients with no other health issues. In the context of cancer, extra care must be taken as acetaminophen is often used alongside chemotherapy drugs, which can also stress the liver and increase the risk of liver damage. Careful monitoring is required, even for this very common and very safe drug, to make sure the liver is not placed under undue strain.
Aspirin is another well-used analgesic, and some patients take this medication for its potential anticancer effects. However, aspirin can also cause severe internal bleeding if taken for too long, at the wrong dose, in combination with other medications, or with a background of certain health issues. At Care Oncology we regularly see patients who have become unwell from taking long-term or high-dose aspirin alongside their other cancer medications without medical supervision. Some of these patients have ended up in the ER.
Supplements are drugs too
Did you know that some types of supplements can cause toxic effects, or can interfere with your standard-of-care treatments and Care Oncology Protocol medications?
Any supplement which has an effect on the body will also have other side-effects, and can also potentially interact with other drugs too. And because many supplements are unregulated, these effects are not necessarily as well understood as for prescribed medications. We know of patients who have become unwell from taking supplements alongside their usual treatments and the Care Oncology Protocol. Common issues include:
- Severe gastrointestinal side-effects or serious blood pressure issues which have required ER treatment as a result of taking berberine alongside other medications,
- Liver problems caused by taking too much curcumin,
- Life-threatening illness due to taking high-dose combinations of multiple supplements alongside other treatments.
We can help by providing information and advice; please do tell us every medication and supplement you are taking, so we can make sure we’re giving you the best medical supervision that we can. While nobody fully knows the effects, the side-effects and the interactions of every supplement, we may have encountered the situation before, or we may have knowledge of that supplement.
Appropriate medical advice is essential
We commonly see patients who have developed issues when using combinations of medications and supplements suggested online, which have then been prescribed by multiple doctors, or by non-specialist doctors who cannot provide cohesive oversight in the context of a patient’s condition. For example, we have had patients who suffer daily nosebleeds due to taking warfarin alongside anti-inflammatory medications such as dexamethasone. And we have seen others with an increased risk of seizures caused by taking medications which lower their seizure threshold, such as the anti‑malarial drug chloroquine and tricyclic antidepressants. This is an especially important issue in cancer patients with disease of the brain.
At Care Oncology, we use oncologists and oncology nurses for support because they fully understand the full context of your cancer, the complex treatments that go with it, and how to safely integrate medications. We are a group of open-minded clinicians who can help you safely navigate your repurposed medications. We do not judge, and we are here to help. If you have any questions about your medications, or any safety worries at all, please do come to us.
Some other common issues from our clinic
We understand the goal of wanting to defeat cancer and doing all you can in terms of treatments. Every day we manage issues which have arisen due to the challenge of taking numerous medications and supplements without the oversight of a specialized Care Oncology clinician. Some common safety issues we have encountered include:
- Using out of date medications Out-of-date medicines can cause serious illness, we have even known of patients ending up in the ER, in part through taking expired medications.
- Using medicines provided by family and friends We always recommend proper medical supervision, as only trained clinicians can fully understand your specific situation, and how best to help you.
- Ordering counterfeit medications from countries where regulation is minimal. Medications ordered online may not be properly regulated, and without accountability, there is no way to be sure that what arrives is real and safe.
- Taking veterinary medicines, or other drugs with little or no data in humans. Medications designed for animals are not tested for human use. Nobody knows exactly how these drugs will affect the human body, or how they will react in the presence of other medications. There is usually no need to take these medications, as there are always much safer, and more effective alternatives. For example, mebendazole is the human equivalent of the veterinary treatment fenbendazole. Both drugs have very similar mechanism of action, but mebendazole has passed extensive safety and effectiveness checks and has been licensed for use in humans. There is also more anticancer data for mebendazole than there is for fenbendazole.
Why do we take patient safety so seriously?
At Care Oncology our overall aim is to repurpose certain already licensed and common medications to help treat cancer. But managing patient safety in this context comes with special responsibilities.
We know people with cancer must live with very specific, often very complex conditions, and are often already undergoing treatments that may be difficult to tolerate.. Maintaining overall patient safety and comfort is very important to us, and we take it very seriously.
When we developed the Care Oncology Protocol, we deliberately chose only those medications which are supported by huge amounts of safety data garnered from years of clinical use. And this is also one reason why we don’t prescribe other medications, which might not have the same level of safety data supporting their use. We also don’t recommend the unsupervised addition of other medications and supplements to the Care Oncology Protocol regimen without having a full understanding of all potential risks.
Our expert oncologists are on your side
Our oncologist and specialist nurses are here to care for you, here to help and guide you through every step of this particularly difficult and confusing time. We will stay with you, talk to you, and give you honest advice, without judgement. We will also not prescribe anything that we think is not in your best interests. We want to help you get the best outcome you can, while also staying safe.
No drug is completely risk-free. Even the Care Oncology Protocol medications have some well-defined safety flags which our oncology team know how to monitor, and can address appropriately should they ever arise. The vast majority of patients (over 85%) who take the Care Oncology Protocol can take all four medications over the long-term without any issues. You can read more about our research safety data in our first scientific research paper, available online here. Our oncology nurses are also available to provide more information as well as to provide symptom management and problem solving for those taking the Care Oncology protocol.
The Care Oncology Protocol is so well tolerated in our patients for a number of reasons: because we understand these medications, because we fully monitor each patient and take care to understand each personal situation, because of the extensive data research we carried out when developing this specific combination, and last but not least, because of our own experience treating thousands of patients with these medications in our own clinic. We are building on this existing knowledge every day- crafting and refining how and when we treat our patients with different cancers, at different stages, and under different conditions.
If you have any questions around your care, or any other medications you are taking and how they might interact with the Care Oncology Protocol medications, please do get in touch with your Care Oncology Nurse and we will be very happy to help you.
Data from: Avoidable_Costs_in _US_Healthcare-IHII_AvoidableCosts_2013_Pg27
Agrawal, S., Vamadevan, P., Mazibuko, N., Bannister, R., Swery, R., Wilson, S., and Edwards, S. (2019). A New Method for Ethical and Efficient Evidence Generation for Off-Label Medication Use in Oncology (A Case Study in Glioblastoma). Front. Pharmacol. 10.
Gandhi, T.K., Weingart, S.N., Borus, J., Seger, A.C., Peterson, J., Burdick, E., Seger, D.L., Shu, K., Federico, F., Leape, L.L., et al. (2003). Adverse Drug Events in Ambulatory Care. New England Journal of Medicine 348, 1556–1564.
Leelakanok, N., Holcombe, A.L., Lund, B.C., Gu, X., and Schweizer, M.L. (2017). Association between polypharmacy and death: A systematic review and meta-analysis. J Am Pharm Assoc (2003) 57, 729-738.e10.
 Data from: Avoidable_Costs_in _US_Healthcare-IHII_AvoidableCosts_2013_Pg27
Towards the end of 2014 a 66-year-old British man named Alistair had a seizure. A scan revealed shocking news. He had an inoperable brain tumour—a glioblastoma—that was likely to kill him in a few years. Soon afterwards, he read a newspaper article suggesting that a cocktail of cheap, everyday drugs, chosen for their anti-cancer effects, had helped a patient with the same disease. His doctors were unimpressed but said: “We can’t stop you.”
Four years on Alistair is still taking this drug regimen alongside the “standard-of-care” treatment. The drug cocktail is prescribed by Care Oncology, a private clinic in London, which recommends a statin (a cholesterol-lowering drug), metformin (used to treat type-2 diabetes), doxycycline (an antibiotic) and mebendazole (an anti-worming agent). These may sound radical, but are actually safe, cheap, generic medicines with evidence of some anti-cancer effects. Nonetheless, their labels do not say they treat glioblastoma—nor any other cancer for that matter.
Care Oncology co-founder Dr Robin Bannister is a chemist and pharmaceutical scientist with 35 years’ experience working with licensed medicines. Close personal experience of cancer first turned his attention to the possibility of ‘repurposing’ licensed medicines to help treat the disease. Almost a decade later, Care Oncology is thriving in both the USA and the UK. Here is Robin’s story – the motivation, and the scientific drive, behind a very personal mission.
The beginnings of an idea
I am always fascinated by how little we actually know about new medicines when they are brought to market. It’s only with the passage of time and after long periods of use in humans that we really begin to understand exactly what it is that our medicines can do. Everyone of course knows the tale of aspirin derived from components of willow bark chewed by the ancient Egyptians for pain relief and even now, 2000 years later, we are starting to investigate its use in cancer.
Good science takes time – but I believe it doesn’t have to take that long.
Put simply, my passion is to understand old drugs better. My great friend and co-founder Greg Stoloff shares my belief and my frustration that potentially very useful medicines are not available to patients, and that it still takes far too long to develop a new drug.
Going back to the example of aspirin; as early as the 1950s people noticed that the way aspirin worked could potentially help in cancer. Yet here we are over 60 years later – and as far as cancer is concerned, this drug is still on the shelf. Only now are full clinical studies underway, and it will still be another few years before results of these studies are fully understood.
Greg and I talked about this conundrum for a long time. But the spark that lit the fire finally came in 2011, when my wife’s breast cancer became metastatic. And like so many who have faced that numbing reality, and felt that raw frustration, I asked myself what could I do to help? Greg was the first to listen and we realized that with our combined skills, we could do something practical – and so the Care Oncology Clinic was born.
Our guiding principles
From the very beginning we had three guiding principles:
One: We knew we wanted to work with already licensed drugs, as anything which looked promising could then be brought into the clinic very quickly. My wife did not have a lot of time.
Two: Modern medicine has such a lot to offer, and we wanted our treatment to build on that – I wanted my wife to have the best of the old and the new. Only in this way could we build upon some of the hard-won knowledge and the gains that have been made in treatment over the years.
Three: We wanted to make a change that would not just help my wife but had the potential to help anyone with cancer. We knew that the only way to do this was to generate evidence showing that what we are doing works. We also knew that this evidence had to be of sufficient quality that it could be accepted by the entire medical community.
I wanted to realize my wife’s vision, and her wish to make a difference. She wanted to know that if cancer claimed her life, she had done something that could help make sure better treatments are available. She wanted to help people who must navigate a similar path. It’s a wish that I’m sure everyone is familiar with. We are all human.
The metabolic theory
So now we had our mission. I had the list of 6,000 or so compounds available in the Pharmacopeia of drugs and compounds as a starting point, and with this, we started to research aspects of cancer.
I was fascinated to learn about Otto Warburg’s original ground-breaking work in cell metabolism, for which he received the Nobel prize for medicine in 1931. Metabolism is the conversion of food to energy to run cellular processes and construct cellular building blocks. Warburg’s work really laid the foundations for the theory that the metabolism of cancer cells is fundamentally different to that of healthy non-cancerous cells. Since then, the science and understanding of cancer cell metabolism has of course hugely advanced, in a discipline now known as ‘metabolic oncology’.
Greg and I were convinced that manipulating the metabolic processes used by the vast majority of cancer cells represented a potentially effective way to target any cancer, regardless of type or stage. The theory goes that by using metabolically-targeted drugs to weaken the cancer cell’s ability to grow and thrive, the cell would then become much more susceptible to standard cancer therapies, such as chemotherapy, radiotherapy, and hormone or immunotherapy. With this insight, we decided to search for already licensed drugs that could target these metabolic processes.
We set about researching and ranking available evidence for existing licensed drugs which have a metabolic mechanism of action. This work was painstakingly centered around a number of scientific criteria we had predetermined as being very important.
Above all, we understood that whatever treatment we developed, it must not add significantly to the burden of a patient with cancer, who obviously can be very sick. Many patients must take cancer treatments which themselves can cause a range of difficult side-effects. It was therefore important that our treatment, which was to be taken alongside these standard treatments, was to be as gentle as possible from a side-effect perspective. Safety was very important to us, and we restricted our search only to drugs that had a strong record of use in the general population, (including in cancer patients). This way, we would have some evidence of their compatibility in patients who were also taking cancer treatments.
Next, we knew we wanted to find a combination of drugs that targeted related mechanisms involved in cancer cell metabolism. In this way the activity of each drug combined could potentially produce an additive or ‘synergistic’ effect and would definitely not interfere or impede each other. We termed this approach ‘mechanistic coherence’.
Finally, we also wanted to make sure that the drugs already had as much published evidence as possible supporting their activity and use in cancer. We took evidence from all available sources and weighed this evidence very carefully.
The COC Protocol
During the development stage we studied and discarded a huge number of drugs from the protocol. For example, drugs that did not have a good safety profile in cancer patients, or which had questionable or mixed evidence of effectiveness, or no real mechanistic reason for inclusion.
There are a huge number of drugs out there with evidence of activity against cancer, but which did not meet our strict criteria for inclusion in the protocol. We eventually arrived at an optimal regimen of four medications: metformin, atorvastatin, mebendazole, and doxycycline. We chose this combination not only because they met all our criteria very well, but also for one other very important reason. We believe this specific combination, with this particular number of drugs, gives us the best chance not only of providing patient benefit, but also for gathering sufficient evidence to start achieving our original vision, of really making a difference to all patients with cancer.
The next steps
One problem which is repeatedly encountered, and is well understood in the field of ‘drug repurposing’, is that although for many of these drugs there is a growing base of evidence supporting their use in cancer (which includes ‘test tube’ based studies, animal studies, patient tumor studies, small clinical trials, and epidemiological studies), there are no Phase III randomized placebo controlled trials. These trials are historically considered the ‘gold standard’ for evidence of effectiveness in patients. But they are also enormously expensive to run. As the drugs we work with are already licensed, and usually off-patent, there is little financial incentive for commercial pharmaceutical companies to pursue their further development.
So, we recognize that to help as many people as possible, we need to produce our own ‘gold-standard equivalent’ patient evidence. Therefore, we are very focused on our own research, to produce and publish high-quality real world data from patients attending our clinic. This is the reason why we spent an enormous amount of time and effort in designing a clinical study which the regulators would approve and endorse. In 2017, we secured approval from the MHRA (the regulator in the United Kingdom, the equivalent of the FDA) and their Research Ethics Committee (the equivalent of an IRB in the USA) to conduct an “Interventional Service Evaluation” which we have named METRICS. This was a big achievement for us as it allows us to publish our outcomes and to share our findings with the world.
We believe that our initiative is one of the only ways through which it is possible to generate the evidence we need. And we really are incredibly grateful to every patient who attends the Care Oncology Clinic, and who is helping to turn our vision of bringing benefit to all patients with cancer into reality.
Historically, patients have often presented to Care Oncology physicians with advanced disease– either they have been diagnosed with a type of cancer associated with a particularly poor prognosis or they have suffered a recurrence/disease progression and feel their conventional treatment options are becoming more limited.
However, there are good reasons to also consider the adjunctive COC Protocol if you are a patient with either an early stage cancer diagnosis or someone who is currently well with more advanced stage 3 or 4 disease. Indeed, the likelihood of a positive outcome is greater than with late-stage presentation.
First, a significant body of research literature suggests that using anti-metabolic drugs such as metformin and statins as adjunctive therapy to standard of care can enhance overall treatment response.
Second, in a scenario where the patient is well in him/herself and/or has a lighter burden of disease, there may be an even greater likelihood of effective disease control.
Our own cohort analysis of 95 patients with Glioblastoma IV (the most common and aggressive type of primary brain tumour in adults) supports this conclusion. These patients were all prescribed the COC protocol alongside their standard of care treatment. Median overall survival of the cohort as whole is considerably better than median overall survival with standard of care alone (https://www.abta.org/tumor_types/glioblastoma-gbm/). But, those patients who commenced the COC protocol during or soon after first line chemo-radiotherapy have a longer median overall survival than those coming to it after having suffered progression/recurrence.
Importantly, in‘’well patients” with a good performance status, we would also expect to see better compliance with the COC protocol medicines and fewer side-effects and/or a requirement to interrupt or stop treatment as a result of abnormal blood counts or organ function.
In addition to the work we are undertaking, a number of other studies are currently underway to explore reduced relapse in patients taking anti-metabolic medications, for example, the very large Cancer Research UK funded ADD-Aspirin trial enrolling 11,000 patients across 5 different types of cancer.
When a patient hears that they are well and perhaps ‘in remission’, they often assume that this means they are cured and are done with treatment. While the words‘remission’ and ‘no evidence of disease’ (NED) are clearly good news and can mark a major positive turning point in someone’s care and overall health,unfortunately, the true situation is often more complicated.
There is no way for doctors to know that all of the cancer cells in your body are gone, which is why many doctors don’t use the word “cured.” If cancer cells do come back, it usually happens within the 5 years following the first diagnosis and treatment. 5 year survival rates or survival statistics are available for all the different types of cancer seen in the community. These statistics are based on research from information gathered on hundreds or thousands of people with a specific cancer.
An overall survival rate includes people of all ages and health conditions who have been diagnosed with a specific cancer, including those diagnosed very early and those diagnosed very late.
Doctors are then often able to provide more detailed statistics based on the stage of cancer at diagnosis. For instance, 56% or a little more than half, of people diagnosed with early-stage lung cancer live for at least five years after diagnosis. The five-year survival rate for people diagnosed with late stage lung cancer that has spread (metastasised) to other areas of the body is 5%.
Because survival rates can’t tell you everything there is to know about your individual situation, the statistics may seem impersonal and unhelpful. But, many people feel that that knowing as much as possible about their cancer, actually helps them to reduce their anxiety, as they can then analyze the different options available to them.
While, of course, it’s up to each individual patient to decide just how much they want to know about survival rates and overall prognosis, Care Oncology physicians believe the risk/benefit of metabolic adjunctive treatment to be in the patient’s favour if there is judged to be a significant risk of cancer progression or recurrence.
The COC protocol is:
- Evidence-based; the weight of the available data demonstrates a significant opportunity for patient benefit. Some mechanisms which underpin the utility of the protocol drugs may be particularly helpful in a preventative setting e.g. inhibition of Cancer Stem Cells.
- Low toxicity, generally well-tolerated and ‘easy to do’ (i.e. tablets, capsules to be taken at home).
- An adjunctive therapy with a low drug interaction burden which can be incorporated alongside other lines of treatment
- Almost always safe to combine with standard of care treatments (chemo-, radio-, hormone-, immuno-therapy)
- Able to potentiate standard treatments by making cancer cells more sensitive to chemotherapy or radiotherapy than would otherwise be the case.
What’s the ultimate cause of cancer? Travis Christofferson is interviewed on the FutureTechPodcast.
It’s not an easy question to answer, and according to Travis Christofferson, author of Tripping Over the Truth: The Return of the Metabolic Theory of Cancer, there’s no single cause, but a series of complex interactions and events that depend at least somewhat on our environment. Christofferson explains this in terms of epigenetic responses, which result in the turning off or on of certain genes–allowing some to be expressed and blocking others from being expressed. Diet, toxins, medications, and even loneliness are just a few of the factors that could trigger epigenetic responses and ultimately contribute to the determination of whether or not someone will develop cancer.
Our Care Oncology physicians often get asked their opinion on various supplement including common and uncommon antioxidants: vitamin C, vitamin E, beta-carotene, N-acetylcysteine (NAC), and glutathione to name a few. Understandably, newly-diagnosed cancer patients and their friends and family often embark on a deep search for anything that can be done to support health and immune system function. And why not antioxidants? A steady stream of media and supplement manufactures have told us for decades that antioxidants offer a panacea of health benefits. And rightfully so, a light internet search can easily lead to articles touting the virtues of antioxidants. The calculus: They may help fight my cancer, and, in the very least, they can’t hurt. Right?
Where did the idea antioxidants are good come from?
In 1972 Denham Harman, a luminary in the field of free radical biology, proposed the mitochondrial theory of ageing. It goes like this: Inside every cell mitochondria are the center of oxidative metabolism and hence the primary source of free radical generation within the body. Free radicals generated from mitochondria then precipitate a cascade of damage to surrounding mitochondria, lipids, carbohydrates and even nuclear DNA. The cell can repair most of this damage, but over time the cell slowly loses the ability to keep up with the free radical induced damage and the net damage that ensues is the proximal cause of ageing.
A simple and intuitively seductive assumption sprang forth from Harman’s theory: free-radical quenching antioxidants should slow ageing and prevent disease. This seemingly innocent prediction has confounded a generation of molecular biologists. In the over forty years that followed Harmon’s prediction researchers have shoved antioxidants into cell cultures, mice, rats, monkeys and humans trying to prove they slow ageing and prevent disease.
Despite their best efforts to prove otherwise, an overwhelming consensus has emerged from the decades of research on antioxidants and ageing: they just don’t work. They might correct dietary deficiencies and/or perhaps confer a slight protective effect against certain diseases, but they do nothing to prolong lifespan—worse, there is evidence to suggest they may even promote certain diseases. Yet, almost a half century of inertia and a billion-dollar supplement industry that grew out of Harmon’s prediction have managed to continue propping up the notion that antioxidants are a well-spring of health. (Don’t confuse foods containing antioxidants and antioxidant supplements. Most quality food contain high amounts of natural antioxidants and a good diet has been shown to be very beneficial.)
Studies began to challenge many assumptions about antioxidants
The blanket assumption that antioxidants slow ageing and prevent disease was first seriously challenged from a large study in 1994 that followed smokers taking massive doses of the antioxidant beta-carotene. The stunning result: The smokers taking beta-carotene had an 18% increased risk of developing lung cancer. As researchers were still scratched their heads about the confusing result a trial two years later was stopped early after it was discovered that high-dose beta carotene and retinol was shown to increase the risk of developing lung cancer by 28 percent in smokers and workers exposed to asbestos. And these early studies are not proving to be flukes: a 2011 trial involving more than 35,500 men over 50 found that large doses of vitamin E increased the risk of prostate cancer by 17 percent.
Antioxidants and cancer therapy
The above studies highlight a trend of studies suggesting that antioxidants may contribute to the incidence of certain cancers under specific conditions and may make cancer more aggressive when it occurs. However, the series of studies sparked a more immediate concern to practicing oncologists: because traditional standard of care therapies like radiation and chemotherapy kill cancer cells by the generation of free radicals perhaps patients taking antioxidants were negating or diminishing the effects of their cancer treatment. Yet, despite a flurry of studies in the early 2000’s―both observation and randomized controlled trials―no clear consensus of the effect of antioxidant on standard therapies emerged. The studies reached a wide variety of conclusions, some showing improved survival and status and others, a reduction in survival. Most likely, the common antioxidants, given at normal doses, are simply to weak to overcome the powerful effects of radiation and chemotherapy.
The smoldering debate about antioxidants and cancer was rekindled again in 2012 when Nobel Prize winner and former head of the NCI, James Watson, sounded off on the danger of antioxidants in cancer, penning a review titled Oxidants, antioxidants and the current incurability of metastatic cancers, claiming the work was “His most important work since the double helix.” His epiphany, in part, was the claim that antioxidants may be thwarting most cancer therapies if not outright causing cancer by preventing the mitochondrial driven apoptotic cascade triggered by free radicals. “For as long as I have been focused on the understanding and curing of cancer (I taught a course on Cancer at Harvard in the autumn of 1959), well-intentioned individuals have been consuming antioxidative nutritional supplements as cancer preventatives if not actual therapies. In light of the recent data strongly hinting that much of late-stage cancer’s untreatability may arise from its possession of too many antioxidants, the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.” Watson goes on, “Free-radical-destroying antioxidative nutritional supplements may have caused more cancers than they have prevented.”
A series of studies in the years following Watson’s revelation seemed to support his claim. A 2015 study published in Science Translational Medicine, looked at melanoma because rates have been increasing and because the cancer is known to be sensitive to the effects of free radicals. They fed the antioxidant N-acetylcysteine (NAC) to mice that had been bred to be susceptible to melanoma at a dose consistent with what people typically consume in supplements. Although the treated mice did not develop more skin tumors than the control mice, they developed twice as many tumors in their lymph nodes, a hallmark of the spread of cancer. When the researchers added NAC or a form of vitamin E to cultured human melanoma cells, they again showed that the antioxidants improved the cells’ ability to migrate and invade a nearby membrane.
Additional evidence surfaced pointing to the danger of antioxidants new classes of free radical generating therapies. A study that came out immediately before Watson’s paper convincingly showed the importance of free radical induced apoptosis by the finding that the ‘first-in-class’ anti-cancer mitochondrial drug elesclomol kills cancer cells through promoting ROS generation. When these resulting free radicals were neutralized through the simultaneous administration of the antioxidant N-acetylcysteine, preferential killing of cancer cells stops. The failure of elesclomol to generate apoptosis in non-cancerous cells probably arises from the inherently lower ROS level generated by normal mitochondrial electron transport machinery.
Critically, many new therapies are being developed that lower the glutathione level in cancer cells rendering them more vulnerable—it is not clear how antioxidants will affect this new class of drugs and therapies.
The picture remains murky
Although there is no overwhelming consensus that antioxidants taken during cancer treatment will lead to worse outcomes the existing evidence throws up enough red flags to warrant caution. Not much is known about the effects of antioxidants in relation to many of the new metabolic-acting and immunotherapies. It must be considered that adjunctive therapies like the ketogenic diet, hyperbaric oxygen and the Care Oncology Protocol are also proposed to work by triggering oxidative stress in cancer cells while simultaneously reducing the cancer cells ability to manufacture internal antioxidants. It is not unreasonable to question the use of antioxidants concurrent with these therapies―especially considering they tend to generate much milder oxidative stress than tradition cancer therapies and therefore antioxidants might have the capacity to influence outcomes to a greater degree. In fact, evidence exists highlighting this tenuous relationship. It has been shown that some of the medications in the Care Oncology Protocol act by inducing oxidative stress within cancer cells. Both doxycycline and metformin are proposed to work by inducing an intolerable surge of free radicals within already oxidative-stressed cancer stem cells while simultaneously inhibiting a transcription factor called STAT3 that the cancer cell upregulates in order to manufacture internal, adaptive antioxidants—a sort of one-two punch. A 2017 study showed that the addition of the potent antioxidant N-acetylcysteine was able to cancel-out the therapeutic effect of doxycycline in a glioblastoma mouse model.
“What we’re starting to learn is that there can be bad cells from cancer that appear to benefit more from antioxidants than normal cells,” said researcher Sean Morrison from the University of Texas Southwestern Medical Center, who’s lab studies the effects of antioxidants on cancer cells. “Personally, from the results we’ve seen, I would avoid supplementing my diet with large amounts of antioxidants if I had cancer.”
Martin Bergö, Ph.D., of the University of Gothenburg in Sweden, said he was extremely concerned with the aggressive marketing of antioxidants to cancer patients. The data strongly suggest that using antioxidants “could be really dangerous in lung cancer and melanoma, and possibly other cancers,” he said. “And because there’s no strong evidence that antioxidants are beneficial, cancer patients should be encouraged to avoid supplements after they have a diagnosis.”
Care Oncology Science Advisor, Thomas Seyfried of Boston College shares Morrison’s and Bergö’s sediment. “Why would you give antioxidants to cancer patients? It runs completely counter to metabolic therapeutic interventions.”
Indeed, the general idea that oxidative stress might be one of cancer’s greatest vulnerabilities, and that antioxidants, both exogenous (taken orally or by IV) and endogenous (manufactured intracellularly), may represent a thin veil of protection that can be therapeutically targeted is also proving to hold true with the emerging class of immunotherapies. New research has shown that by reducing intracellular glutathione, the cell’s “master antioxidant”, the cell-killing effect of immunotherapies can be enhanced. The authors of the recent study state: “The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells.”
Well what now?
In the over forty years since Harman’s proposed free-radical driven mitochondrial theory of ageing we’ve learned that free radical biology is certainly more complex than originally appreciated. While there is no question free radicals are destructive to the cell, emerging evidence suggests mitochondrial derived free radicals may also be an important signaling system, instructing the DNA within the mitochondria to manufacture mitochondrial proteins. Free radical biology and its ultimate role in ageing is still unsettled science that has yet to be conclusively decided.
However, the relationship of antioxidants and cancer, although still murky, seems to be tilting toward a note of caution when it comes to including antioxidants as part of cancer therapy. While little if any benefit has ever been proven, the evidence pointing against their use does demand attention. A cautious approach would be to avoid high doses of antioxidants during cancer treatment. A very cautious approach would be to avoid antioxidant supplements altogether. Indeed, most dieticians agree that enough micronutrients can be obtained―and in the right ratios―from a good diet.
Some common antioxidants:
Vitamin E, selenium, zinc, N-acetylcysteine, glutathione, Vitamin C (low dose only—high doses administered by IV are oxidative), and beta-carotene
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How will the COC Protocol help treat breast cancer?
The COC protocol is a patented pharmaceutical composition of four repositioned medications. The medications have long histories treating type-2 diabetes, reducing cholesterol, parasite infection, bacterial infection and inflammation. After four years of clinical research, we know that these drugs – in combination – offer significant therapeutic value for cancer patients. Each of these drugs plays a role in weakening cancer cells and making them more susceptible to standard-of-care therapy (e.g., chemotherapy, immunotherapy).
One of the biggest problems breast cancer patients face is when their cancer becomes resistant to standard-of-care therapies. Multi-drug resistance (MDR) occurs when a patient develops resistance to one or more treatment drugs.
The study — which was led by Rutgers Cancer Institute of New Jersey in New Brunswick — is to feature at the 2018 annual meeting of the American Association for Cancer Research, which will be held in Chicago, IL.
This study is not the first to suggest metformin as a potential treatment for pancreatic cancer, but it is the first to show that the underlying mechanism involves the drug’s effect on the REarranged during Transfection (RET) cell signaling pathway.