Trade-Up with Gene Editing

Dr. Rand McClain on June 11, 2022

What if you could swap your not-so-great DNA with much better and healthier DNA, kind of like an exchange program where you trade up? Think about it. You’re genetically predisposed to have a certain disease until you swap it out. It’s not that farfetched. Several diseases are currently treatable through gene editing and those with promising results in clinical trials.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is the main technology for gene editing today. CRISPR technology is a process; CRISPR itself refers to specific DNA strands, and Cas9 (CRISPR-associated) is a protein/enzyme that can cut DNA strands. In layman’s terms, it’s a technology that allows us to edit genomes by changing cellular DNA.

We’ll probably see several new technologies, in addition to CRISPR, gain traction in the next few years, broadening the uses of gene therapy. In the meantime, let’s take a look at the main diseases/areas targeted by gene editing in clinical trials or available for medical use.

Targeted Diseases – First up… Cancer

Several diseases are being targeted by geneticists. High on their list of priorities is seeking cancer treatment. The process used here is called CAR T-Cell Therapy. CAR stands for Chimeric Antigen Receptor, a specific type of receptor; a gene for this receptor is inserted into a patient’s blood in the lab. The patient’s T Cells, which are part of the immune system, are changed by this gene insertion, causing the T Cells to bind to and attack cancer cells when put back into the patient. Blood cancers are currently the major target of this type of therapy.  

CAR T therapy has been used quite a bit in the U.S., and though it’s expensive, it’s been effective. As I’ve described, the process manipulates the patient’s cells in the lab, but ideally, we’ll find a way to use allogeneic stem cells—cells from other people. We’ll harvest stem cells from good candidates and alter them in the lab to fight cancer. The obstacle is preventing immune reactions to other people’s cells, but optimistically, we’ll find a way around this sooner rather than later.

In China, a different approach to cancer treatment using gene editing has been pioneered.  They’ve used CRISPR to strengthen the reaction of T-cells by removing the PD1 protein—a protein that tumors can use to stop T-cells from attacking. When CRISPR removed it, T-Cells were freed to attack and destroy the cancer.

Treating Additional Disorders

Gene editing has also been successful in treating various blood disorders such as sickle cell disease and hemophilia. In terms of the former disease, the process involves taking stem cells from patients’ blood marrow, harvesting, and editing them, so they produce fetal hemoglobin in red blood cells, countering the disease’s negative effect on these cells’ oxygen-carrying capacity.    

Many causes of blindness are hereditary, and for some diseases, the culprit is a single mutated gene. In certain instances, by changing one nucleotide in the cell, blindness can be cured. Trials are underway for the treatment of Leber Congenital amaurosis, a childhood blindness disease. Scientists are using CRISPR to attack mutations in a gene that causes the disease, and early results are promising.

CRISPR technology has been used to treat HIV in clinical trials. In fact, in China, they have done gene editing in embryos, inserting a gene mutation called CCR5 that makes cells resistant to HIV.  

At least two companies are working on a treatment for muscular dystrophy using gene editing. In the past, gene therapy struggled to address the causes of muscular dystrophy, because back then, you could only target one gene. Because muscular dystrophy is caused by multiple gene mutations, it was not an effective approach. Now with CRISPR, we can target several genes simultaneously, opening the door for possible treatments.

With cystic fibrosis, mutations in the CFTR gene can produce severe respiratory problems. Gene therapy introduces a healthy version of the CFTR gene into patients, resulting in improved patient outcomes. While various approaches are still being tested, gene editing seems well-suited for dealing with this type of genetic mutation.    

Huntingtin’s disease is a degenerative nerve disease—as nerves break down, everything from thought to movement is affected negatively. Typically, gene editing inserts a healthy gene into a cell to correct defects or supply what is missing. For this disease, however, gene therapy is designed to limit the production of the Huntingtin protein that is causing nerve and brain damage. An enzyme is also introduced to guard against damage to nerves, avoiding the “collateral damage” that can result from gene therapy for Huntingtin’s.

This list is incomplete in that many more diseases and disorders may benefit from gene editing in the future. Today, however, scientists are finding other applications for gene editing technologies beyond treating or preventing specific diseases. Genetically Modified Organisms (GMOs) are a subject of controversy, but there are clear benefits–some foods are modified to allow people with allergic reactions (peanuts, eggs, etc.) to eat them.  

Gene editing is also being used to help animals, fruits, and vegetables become more resistant to diseases.  Scientists are also using gene editing on pests (such as mosquitoes), so they can’t breed or carry infectious diseases, a huge problem in developing countries where malaria is a significant problem. There’s even a group of scientists using gene editing in an attempt to bring wooly mammoths back to life. Their theory is that if they can edit the embryos of existing species that are genetically similar to mammoths—elephants are one such species—and combine them with genes from recovered wooly mammoth DNA, they may be able to edit genetically until they get the right match. Bringing extinct species back to life or helping endangered species survive are applications of gene therapy that seem the stuff of science fiction.

Gene editing is still in the developmental phase. Just as CRISPR represented a quantum leap in the technology, other leaps in the future are likely to resolve some of the challenges and ethical quandaries gene editing is currently experiencing. But without a doubt, gene editing will help many of us live longer and better. 

Genetically Altering the Hand You Were Dealt

Dr. Rand McClain on May 11, 2022

Who doesn’t want to improve the hand they’ve been dealt? The genetics we inherit may increase the odds that we’ll suffer from a given disorder or disease; they may make us more likely to have heart problems at a young age, breast cancer, diabetes, and so on. Until recently, there hasn’t been much we could do about the hand we were dealt. With the advances made in gene therapy, however, we now possess a tool that can alter our genes, changing them in ways that can help us escape a predictable negative health outcome. 

Though we still have a way to go before we can change DNA to prevent any disease or fight a given disorder more effectively, we’ve made astonishing progress in this area. Hundreds of clinical trials are being conducted in the gene therapy area, and the FDA has approved a limited number of gene therapy products. For instance, in July 2020, they approved Tecartus, a cell-based gene therapy to treat a type of lymphoma. Additional products have also been approved by the FDA for a variety of conditions. 

So, what is gene editing and how does it work?

What is Gene Editing?

The most successful gene-editing process as of this writing involves CRISPR—it stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR technology is a process; CRISPR itself refers to specific DNA strands, and Cas9 (CRISPR-associated) is a protein/enzyme that can cut DNA strands. In layman’s terms, it’s a technology that allows us to edit genomes by changing cellular DNA. 

If, for instance, you have a genetically inherited disease or are genetically predisposed to get a disease, CRISPR allows us to alter nucleotides—deleting the gene that causes a disease or deleting the gene and replacing it with edited DNA that will have beneficial effects. Different diseases require different approaches—sometimes deleting is all that is required; other times a different editing/replacement technique is necessary because deleting may eliminate the disease but create problems with other cells.

The size of the gene-editing tool affects editing capabilities. This means that the “delivery vehicle” has to be large enough to accommodate all the necessary editing tasks.  Typically, this delivery vehicle is a virus, and it contains gene-editing material. If a gene requires three different deletions and insertions (for certain diseases), it may be impossible for a single virus to contain all this material. Therefore, it may be necessary to do a series of treatments rather than a single one. Or it may be advisable to find smaller editing tools to fit in the virus. Other options exist, but I want to convey that one size doesn’t fit all—gene editing can be a varied process, depending on the disease being treated. The potential of gene editing is staggering. Conceivably, it can be effective in helping people avoid everything from cancer to blood disorders to cystic fibrosis. 

Let me share a brief history of gene editing so you can see how much progress has been made in a relatively short period.

History of Gene Editing

Scientists began testing various editing techniques in the ‘70s, manipulating RNA and exploring the frontier of genome editing. Programmable nuclei were early editing tools until CRISPR was discovered as a superior technique—it was far easier to use than previous approaches and much more efficient. Whether done in vivo or in vitro (inside or outside of the body), the goal is to deliver the editing machinery to delete or correct targeted genes.  Gene editing studies really ramped up at the start of the 21st century. A great deal of the testing focused on animals and on bacteria; we’ve exercised an abundance of caution, wanting to make sure we do no harm before using gene editing on people.

Still, we’ve made a number of significant advances. Early on, scientists studied how a virus invades bacteria and how the bacteria destroy the virus but hold on to their genetic material, making a record of it in DNA’s CRISPRs—this allows the immune system to deal with the invading virus more effectively the next time it invades the bacteria.  

This process provides scientists with insights into how to use viruses and CRISPR technology to impact DNA within cells.  Over time, we’ve become much more sophisticated about these uses.  Initially, we could only target single-letter DNA mutations such as sickle cell anemia (DNA has four letters, each representing a nucleotide). With experimentation, however, we learned how to address multiple letter mutations such as Tay Sachs disease.  

The Great Thing About Genomes

I would be remiss if I didn’t mention a product related to genetic editing, a healthspan tool that’s affordable and worthwhile.

In recent years, we’ve seen several companies offering genetic testing directly to the public. Companies like 23andMe have successfully marketed themselves by promising to analyze DNA and tell people everything from the diseases to which they’re susceptible to their ancestry.  While some of these companies may be more reputable than others, mapping one’s genome is a good healthspan decision.

One of the benefits is knowing how people might respond to certain medications. Genome testing can identify an individual’s SNP—single nucleotide polymorphism. An SNP is a DNA variation within a nucleotide, and scientists have been busy identifying them since certain ones can predict how people react to specific drugs as well as susceptibility to diseases. For instance, we know that one SNP diminishes the effectiveness of Losartan, the blood pressure medication.  

We also know that individuals with an ACE1 mutation are less susceptible to COVID than others (though it also makes them less responsive to ACE receptor blood pressure medication). We also have done sufficient testing to be aware of which diabetes medications are more or less effective, depending on one’s genome. When people possess a rare SNP, DEC2, they can sleep fewer hours than recommended without suffering any ill effects.  

In the future, we won’t have a one-size-fits-all approach to prescribing drugs. We’ll recognize that for a given condition, the preferred medication is only effective for 80% of the population with a specific DNA make-up; that 20% of the population should receive an alternative drug that works best given their genetic composition.  

The entire field of genetics is evolving rapidly, and though it’s impossible to predict exactly which diseases it will have the most effect on, we can predict that it will help many of us live longer and better. 

It’s Not Sci-Fi – Innovative Medical Devices

Dr. Rand McClain on April 11, 2022

If you recall the Star Trek television show, when someone would become ill or was injured, “Bones” (the ship’s doctor) would wave a diagnostic scanner over their bodies and immediately receive an accurate diagnosis. Then, Bones would often cure his patient with a single shot.

At the time the show was made, such diagnosis and treatment might have been called futuristic. Today, the future is starting to arrive. Artificial intelligence (AI) is changing how we diagnose and treat patients, and we’re making incredible advances in this area quickly. AI’s ability to hold and process huge amounts of information is especially useful today, helping doctors evaluate images. 

AI as a Game-Changer

AI is truly a game-changer in terms of medical intervention. For example, AI can input numerous images of a cell mutation present in early-stage liver cancer and then identify these types of cells from a new image (such as an MRI scan) better and faster than even the most experienced doctor or technician. 

While AI is currently used as a complementary or even a lead tool, it is not yet being used alone. Invariably, this situation will change, and AI will likely replace radiologists at some point in the future.  

Currently, we’re using “narrow AI,” focusing the use on a single task or goal. In the future, we’ll transition to “general AI” where it’s used much more broadly as a diagnostic and decision-making tool for a range of conditions and purposes.

Look at the benefits of AI another way. Imagine a highly experienced doctor, one who has been in practice for 40 years and has treated many patients successfully and learned enough to qualify as an expert. Now imagine being able to draw on the knowledge and skills of 5000 other doctors with the same amount of experience and expertise. And finally, imagine an AI tool that can store all this knowledge in a database, process and evaluate it in terms of a given disease or patient condition and extract the right information for treatment in seconds.

This isn’t a pipedream; it’s the future of AI, and it’s a future that’s approaching rapidly.  

The World of Wearables

The tech isn’t there yet, but we’re getting a glimpse of what that tech will be through “wearables.” Currently, the wearables aren’t particularly precise, and the acronym, GIGO (garbage in, garbage out), applies. We haven’t found ways to input all the necessary data/variables that we need to give us a highly useful output.  

The problems are many, including such simple issues as a wearable not being worn sufficiently tightly to provide accurate tracking. Another problem is that one size doesn’t fit all. People vary considerably in the data they produce depending on their weight, the way their bodies work, and other factors. 

Nonetheless, the wearables market is exploding, and that’s yielding at least some healthspan benefits. Even if the measurables aren’t always accurate, they raise users’ consciousness about important health factors, like heart rate, sleep quality and quantity, blood sugar (continuous blood sugar monitoring), and so on. Ideally, this increased consciousness will result in better diets, more effective and efficient exercise, and a stronger commitment to getting a good night’s sleep. In terms of valuable health data, some wearables can collect fairly precise measurements of temperature, respiration, blood oxygen saturation, heart rate, blood pressure, and electricity-measured ECG readings (sinus rhythm and atrial fibrillation). Paying attention to this data can alert patients and doctors to problems as well as motivate better health-related behaviors.  

Invariably, AI and related technologies will advance far beyond the current state of wearables.  

The Best Right Now
Let’s take a look at the digital devices that seem to be having the most positive effects on healthspan at the moment. 

The Oura ring tracks data conveniently, especially as it relates to EEG, the gold standard for sleep evaluation. It’s become smaller over time—it’s currently the size of a wedding band—and provides additional information about pulse rate, temperature, calories burned, and so on.

Meanwhile, the Apple Watch, which works well with other Apple products, tracks activity with an accelerometer (which helps determine the intensity of your workout) and measures heart rate. This is along the same lines as the Fitbit and Garmin. These devices do a good job of monitoring vital signs continuously during workouts, though for more serious athletes, the chest straps provided by Polar H10 and Wahoo are better.

The BioStamp from MC10 will soon be on the market and is for people who want to dig deep into their health. This device has a sensor that conforms and adheres to at least 25 body locations and offers metrics to evaluate sleep, posture, activity, and vital signs. The measurements are of medical quality and can be used for clinical evaluation. Currently, MC10 has limited distribution for clinical trial use, but given its uniqueness and marketability, it should have a wider distribution in the near future. 

The Future is Bright

Of course, this is just the start of the AI’s revolutionary impact on medicine. Right now, the technology exists to increase the speed, accuracy, and efficiency of diagnosis. The real key, though, will be AI’s ability to process data and draw correlations that can be tested. This is already happening with the development of drugs. 

We can evaluate a particular virus or bacteria for multiple characteristics that can lead to a possible solution—a new drug or an existing one with the potential actions to combat the virus or bacteria. Without AI, the process of looking at and evaluating the multitude of pathogens and the various drugs and structures to make potential drugs can take decades to identify. With AI, it can be done much more quickly (some evaluations can take only minutes!).  

In the current pandemic, scientists have used AI to examine the potential for genetic variants that slowed or accelerated the course of COVID-19. Labs tested these models in vitro to validate AI predictions as to the drugs that would be helpful in slowing virus replication and the mechanism of action.

More significantly, AI has helped generate at least eight different types of COVID-19 vaccines. Without machine-learning systems and computational analyses provided with lightning speed by AI, we would not have produced the vaccine candidates so quickly – especially the non-conventional experimental candidates developed by AI. Without AI, it probably would have taken many months, if not years, to develop them.   

Don’t get me wrong; AI is not the complete solution to this and other healthcare challenges. AI isn’t a substitute for the necessary lab and clinical studies; it can’t shorten the time needed to test vaccines on animals and humans. But AI does accelerate theoretical aspects of development and does so at times with blinding speed.

AI can be a game-changer, applicable to preventative, anti-aging, and traditional medicine. It will help us connect the dots between theory, observable and quantifiable data points, especially ones in the area of biological aging and associated biomarkers. 

Ingenious Cancer Devices

Dr. Rand McClain on March 11, 2022

Many diseases are curable or at least manageable if caught early. This means that we can improve our health span if we monitor the signs and symptoms regularly and accurately. The good news is that technology has helped produce several tests and devices that can help us with these goals. The bad news is that awareness of them is low and access to them is limited. 

Though I can certainly help raise awareness, it will take time, education, consumer demand, and technological advances before the promise of early detection and highly effective health monitoring are achieved.

So, let’s first focus on the medical devices that can aid in detecting cancer.

PSA Cancer Screening

Doctors have used the Prostate Specific Antigen (PSA) blood test for prostate cancer screening for years. Even though it’s still in widespread use, its effectiveness is questionable at best. It’s telling that the inventor of the test, Richard Ablin, has admitted that it can show false positives and negatives and, therefore, is unreliable. 

Part of the problem is that a high PSA level may indicate prostate cancer, so it can save lives. But at what cost? 

Biopsies of the prostate can result in incontinence and impotence. It is worth it when approximately 15% of men with normal PSA tests have prostate cancer and when a significant percentage with abnormal PSA levels don’t. We know that PSA levels can be elevated by a variety of factors unrelated to prostate cancer, from chronic prostatitis to bike riding before the test.  

Yet the Urological Association still recommends PSA tests, and insurance companies still pay for it, incentivizing its use. For legal reasons, I’ve had to use it with patients.

The biggest problem I have with PSA tests is that a much better testing procedure exists: Multiparametric MRIs. Most people are familiar with Magnetic Resonance Imaging, which is a non-radiation-based, non-invasive test that uses a powerful magnet to align the body’s protons with the magnetic field. 

The Mighty MRI

As the name implies, multiparametric uses sequences from three different techniques to provide a more detailed view than a traditional MRI. The three techniques—T2-weighted imaging, diffusion-weighted and dynamic contrast-enhancing imaging—enable doctors to identify tissue types in the prostate, receive functional and anatomical data, and track blood flow using a contrasting agent (cancer shows up more readily using the contrasting material). All this communicates a tremendous amount of information that allows doctors to gain more insight into what’s happening with the prostate as well as make better decisions based on what they see.

While some people complain about the noise and feelings of claustrophobia in an MRI tube (the patient must remain relatively still for 20 minutes or so), it is a safe and accurate procedure—far more accurate than both a PSA test and a digital rectal exam. The latter has little value since it’s such an imprecise, subjective test, and many doctors who administer it—palpating the prostate through the anus with a gloved finger—lack the years of experience necessary to detect subtle, telltale signs of problems with the prostate. 

Because of false positives, people often undergo invasive procedures like a biopsy that can cause unnecessary harm. A multiparametric MRI can detect lesions as small as 5 millimeters, which is quite tiny. As a result, multiparametric MRIs can help physicians assess whether watchful waiting is a viable option when a cancerous lesion is spotted but is small. 

Given all these benefits, why isn’t this technology widely available?

The Culprit in Slow Adoption of New Devices 

Ultimately, the culprits are a lack of awareness and cost. The former is a problem not only for patients but for physicians—the information about multiparametric MRIs and prostate cancer communicated here isn’t widely known even in the medical community. 

Because of this lack of awareness, insurance companies generally don’t cover the cost of this test, which can be considerable. Again, I hope that this situation will change as the medical community becomes more open to alternatives and aware of how these alternatives can save their patients’ lives or at least prevent painful and unnecessary procedures.

I know I’m harping on this point, but for a good reason: Early detection of cancer often turns it into a manageable, non-fatal disease. The problem has been that we catch cancer too late, and by then, it has spread, and it’s much more difficult to control.  

Detecting Cancer Earlier

But what if we had a test that could serve as an early warning system for cancer? Such a test exists—or at least it did. Let me explain.

Dr. James Morre was a professor of biochemistry and molecular genetics. He, along with his wife, Dr. Dorothy Morre, began studying how an herbicide created uncontrolled growth in a plant. He assumed that if he could understand the process by which the plant grew abnormally, he might gain insights into how cancer grows and spreads.

ENOX2 is a protein that is found only in cancerous tissues and fetal cells. Dr. Morre identified this protein, and he spent 35 years studying it, publishing a textbook on ENOX2 proteins. Based on this extensive knowledge, he was able to invent a test that identified 25 cancers using ENOX2, including bladder, colon, esophageal, breast, kidney, lung, lymphoma, melanoma, ovarian, pancreatic, thyroid, testicular, and others. It was called the Oncoblot.

By using antibodies to the ENOX2 protein, the Oncoblot creates a plot on a Western blot that identifies the weight and PH of the ENOX2 protein. This process allows the Oncoblot to figure out the cancer of origin, and it can do so even for cancers as small as 1 millimeter—that’s roughly the size of the tip of a needle. In other words, it can find cancers in their early stages—even earlier than the Multiparametric MRI, which, even with the most advanced software, can only spot at 3 millimeters.   

Given the almost miraculous capability of the Oncoblot test, then it’s tragic that it’s no longer available. Fortunately, another group has been working on replicating the Oncoblot process, and indications are that their process will be a new and improved version. This test can make a huge difference in how we treat cancer. 

It’s been estimated that if everyone had regular colonoscopies starting at the age of 50, we could cure or prevent the vast majority of colon cancers. While it’s premature to make the same statement about an Oncoblot-like test, it potentially can have an enormously positive effect on treating and preventing a wide range of cancers if widely adopted. We need a lot more studies once this test is available, but it’s tremendously positive news from a health span perspective.

Polyphenols, Cancer, and Alternative Thinking

Dr. Rand McClain on February 11, 2022

As I’ve mentioned previously, research has linked diets rich in plant foods to a lower risk of cancer, and many experts believe that polyphenols are partly responsible for this. So, let’s focus on one of the most studied polyphenols and what we’ve learned.

Got Green Tea?

As I noted, the polyphenol in green tea is epigallecatechin-3-gallate or EGCG for short. While many studies identify this polyphenol’s anti-cancer effect, let’s look at one particular study, titled, “Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of 110 subjects ages 40-84.” This study was conducted by Claudia Hanau, Dr. James Morre and Dr. Morre’s wife, Dorothy, and one reason the study is notable is that Dr. Morre spent almost 40 years studying ENOX2 proteins and their presence in cancer. I always respect when a study represents a scientist’s life’s work.  

These proteins are only found in two places, cancer and fetal development, which is significant from a testing perspective. Dr. Morre developed a test to detect the presence of ENOX2 and called it an ONCOblot Tissue of Origin Cancer Test. In fact, testing the ENOX2’s molecular weight and isoelectric point (pH), the tissue where the cancer originated can also be identified. The test is highly sensitive, able to spot as few as 800,000 cancer cells—that sounds like a big number, but from a physiological standpoint, it’s actually a small one.  No other method can identify cancer based on this small number of cells.  

Cancer forms when mutating cells begin to grow rapidly and out of control. Cell mutations occur in our bodies all the time, but they don’t become cancers because we have a natural process that destroys these mutations. But when this process fails, cancer starts.  In these instances, we still possess the capacity to control and even reverse cancer. But we need to intervene early, and chemotherapy light can be a highly effective intervention, as the Dr. Morre study demonstrates.

More Than a Single Cup

This study also reveals that it takes more than a cup of green tea daily to control or reverse cancer. The amount of green tea concentrate used in the study was the equivalent of 16 cups of green tea. The green tea was combined with concentrated capsaicin to facilitate the polyphenol’s availability to cells, dramatically increasing its cancer-killing power. When they treated patients who were re-tested for the ENOX2 proteins, they were absent, indicating how effective the treatment was.

I’ve used the ONCOblot test in my practice, and it has identified a number of patients with ENOX2 in their blood. We followed up with additional testing, such as a multiparametric MRI for prostate cancer and mammography and biopsy for breast cancer. I also gave myself the ONCOblot test, and to my surprise, I discovered I had ENOX2 proteins in the prostate, and subsequent tests confirmed early-stage cancer. I and the other patients who tested positive underwent 90 to 180 days of treatment with CAPSOL-T use (green tea extract); some of us also combined CAPSOL-T with doses of metformin, depending on the type of cancer and patient circumstances. Some patients also had surgery.

Every patient (including myself) tested negative for ENOX2 proteins after these treatments, and additional, traditional testing confirmed that the cancer was gone.

Proceed with Caution 

As positive as I am about polyphenols, I also know that even seemingly “harmless” products such as over-the-counter medicines come with a warning. With polyphenols, the warning has to do with toxicity. Too much of anything can be a bad thing, and liver toxicity is a concern with polyphenols if you take too much or are fasting.

Perhaps more significantly, they also can have overall systemic and cellular toxicity when used as chemotherapy light. Like traditional chemotherapy, polyphenol treatments disrupt DNA beneficially in cancer cells but also in healthy cells. Chemo’s goal is to target cancer cells while sparing (through wounding) healthy cells. Thus, the polyphenol dose needs to be calibrated judiciously. Too high a dose of polyphenols, like too high a dose of traditional chemo, can devastate healthy cells while it’s destroying cancer cells.

Also, not all polyphenols are created equal. Put another way; one polyphenol may be better for a particular type of cancer than another. In addition, one polyphenol may work particularly well with another polyphenol—or you may want to avoid a particular combination because of potential toxicity or one canceling out the effects of another.  

In addition, absorption can be a problem with polyphenols. Fortunately, we can improve their bioavailability by combining them with an extract of pepper—an alkaloid extract of the black pepper family (Piper nigrum). We can also combine polyphenols with phospholipids to facilitate absorption.  

The good news is that polyphenols aren’t expensive and don’t require prescriptions. They do require consultation with a doctor who has experience using them to treat particular types of cancer to figure out the right ones to use and the doses. From a preventative medicine standpoint, however, everyone can take advantage of their cancer-fighting properties. Empirically, there’s a lot of evidence to suggest that because the French drink so much red wine and the Japanese so much green tea, they have better health and longevity than many other populations.

The Business of Medicine 

None of my enthusiasm for polyphenols blinds me to the continued need for surgery, chemo and radiation, especially for advanced forms of cancer. At the same, I’m also aware that the business of medicine causes doctors to be less aware of and enthusiastic about polyphenols as they might be.

There isn’t as much financial incentive for scientists to research anti-cancer treatments using polyphenols as there are for other, more lucrative approaches. At the same time, we’re also seeing greater medical community recognition of alternative methods and the value of naturally occurring chemicals like polyphenols. As someone who began my career studying nutrition, moved on to naturopathic and orthomolecular medicine, studied traditional Chinese medicine and then went to medical school, I’ve witnessed a shift in attitude and practice regarding alternative and complementary methods.  

Admittedly, it’s difficult to create credibility for forms of medicine such as acupuncture, where you can’t do the double-blinded, placebo-controlled studies that provide scientific validity.  Polyphenols, however, are chemicals that can be studied and should be studied more using rigorous scientific methods. 

Interestingly, traditional Chinese medicine and Indian Ayurvedic medicine use herbs and herbal formulations containing polyphenols to fight cancer.  

It’s time we become even more open-minded about how we treat the illnesses and disorders that confront us, whether they are viruses, aging-related issues or cancer.

Healing and Hope

Dr. Rand McClain on January 12, 2022

It’s an exciting time as we see the emergence of a wide range of preventative and healing therapies that offer great hope, now and especially in the future. These alternative treatments represent a huge field, and it’s encouraging, particularly in terms of cancer.

Chemotherapy and radiation are effective, traditional medical tools, and I’m in no way suggesting that people should ignore them in favor of alternatives. But I want to discuss the ones I’m most excited about and explain how and why they work.  

The Power of Polyphenols

The best place to begin is with a discussion of what polyphenols are and why they’re beneficial.

The science behind polyphenols is important in that it explains why some polyphenols are so useful in treating cancer and why some can be harmful. 

Polyphenols are a group of chemicals consisting of connected phenols that are usually sufficiently large in number to form a single chemical structure. Based on the number and nature of phenols in this structure, unique properties develop. For example, they can act as antioxidants, meaning they can neutralize harmful free radicals that would otherwise damage your cells and increase your risk of several conditions such as heart disease. Polyphenols are also thought to reduce inflammation, which is considered the root cause of many chronic illnesses.

Polyphenols are naturally occurring, and they’re in fruits, vegetables, herbs, spices, teas, coffee, wine, and some grains.  As a general rule, the more colorful the food is, the more polyphenols it contains. Specific, well-known polyphenols are resveratrol found in red wine, epigallcatechin-3-gallate in green tea, and curcumin in turmeric.  

Flavonoids are sub-classes of one type of polyphenol, and as you can see, they too have their own sub-classes—flavonols, isoflavones, and others. The polyphenol in green tea and curcumin in turmeric, for instance, are flavonoids. Red wine’s resveratrol, on the other hand, is a non-flavonoid polyphenol.  

Regularly consuming polyphenols is thought to boost digestion and brain health. The polyphenol-rich plant extract Ginkgo biloba is thought to boost memory, learning, and concentration. It has also been linked to improved brain activity and short-term memory in those with dementia. Polyphenols also protect against heart disease, type 2 diabetes, and even cancer. 

To demonstrate the validity of polyphenols, try this experiment: Type “Polyphenols, cancer” into the Google search box. You’ll receive almost eight million results.  If you narrow down your search to “green tea extract, cancer,” you’ll receive over 33 million hits.  About 174,000 of those are peer-reviewed or scholarly articles testifying to its effectiveness. The first result is from the Memorial Sloan Kettering Cancer Center website, and it recognizes that green tea extract has proven to be a promising anti-cancer treatment.

Waging War on Cancer

Now let’s dig down into how polyphenols work to fight cancer. My friend, colleague, and former college professor, Gagik Melikyan, deserves credit for first explaining to me the process by which polyphenols function. What he pointed out then and what has stuck with me since is that polyphenols convert to orthoquinones, and as such, they can do both harm and good through their effect on cellular DNA. This is especially true of polyphenols that contain ortho-hydroxy groups, such as catechins found in green tea—they oxidate easily, facilitating their ability to destroy cancer cells. It’s a similar process to traditional chemotherapy.  

For instance, Daunorubicin is a chemotherapy drug produced naturally by bacteria and is used to treat leukemia.  Like drugs such as doxorubicin, idarubicin, and epirubicin, they are highly effective anti-cancer drugs that depend on orthoquinones like those in green tea. In addition, anti-cancer research is focusing a significant amount of effort studying quinones and certain derivatives, attempting to create effective synthetic preparations.

Other naturally-occurring quinones such as juglone (from henna) and emodin (from rhubarb) also have anti-cancer activity. Still, as I alluded to earlier, the downside is that they exhibit toxicity and attack healthy cells. This has been an issue with traditional chemotherapy as well.

Where Toxicity and Effectiveness Meet

The key, therefore, is to find the sweet spot between toxicity and effectiveness. Polyphenols such as EGCG are less powerful than other ortho-quinone methide derivative drugs for cancer, such as anthracyclines, so they’re less toxic and safer.  

As such, they are useful as preventative measures for early-stage cancers. Because of this less powerful chemotherapeutic trait, many polyphenols are essentially “chemotherapy light.” Admittedly, the studies that demonstrate the viability of polyphenols for this purpose are epidemiological rather than more thorough, more rigorous studies.  Still, epidemiological studies backed by laboratory investigation suggest the effectiveness of polyphenols in the prevention and treatment of early-stage cancers.  

Ideally, medical researchers will undertake more studies of this type, but because polyphenols are not proprietary, pharmaceutical companies’ financial incentive isn’t to research these chemicals.  We really need research about how to improve the absorption of polyphenols—they’re generally poorly absorbed. 

It may be that some enterprising scientists will be motivated to develop improved absorption methods.

At this point, though, studies have correlated specific polyphenols with reducing the risk of specific cancers or preventing them. In next week’s blog post, we’ll focus on one of the most studied polyphenols and what we’ve learned.

The Muse in the Middle

Dr. Rand McClain on June 3, 2021

Stem cell replacement therapy— A gift from the gods or the end of our ethics?

When it comes to stem cell news, there seems to be no middle ground. It’s reported that either stem cell replacement therapy is a gift from the gods or it’s the end of our ethics as we know them. Very few news articles have taken the time to step away from the hype and answer some very basic questions. So, if you will, please allow me.

What’s in a Name?

Regenerative medicine focuses on regaining lost or impaired body function. Adult stem cells can replace cells that have died or just stopped working effectively. Athletes have found that they help to heal or prevent injuries. Research has also shown stem cells can help fight certain diseases and serve as an anti-aging treatment. And, of course, stem cell transplants have been used since 1957 to restore the immune system after chemotherapy for cancer and these treatments continue to be improved and used today. It’s all good stuff.

Part of the controversy surrounding stem cell replacement, pounced on by the media, is the idea that stem cells must be retrieved from human embryos or specifically the umbilical cord, which has raised ethical concerns. But the reality is that all approved therapies in the United States do NOT include cells harvested from fetal tissue and are either performed using adult stem cells or those collected from donated (and otherwise typically discarded) umbilical cords of successful healthy births. And yes, more investigation into adult stem cell use needs to be done, but the idea that medical researchers are looking to “frankenstein” the human body or scavenge for stem cells is hyperbole, to say the least. One impetus for stem cell treatments is the success observed using what one person already has an abundance of to give someone else a new lease on life, much like a transplant but much less invasive and more accessible. It’s a procedure that dates back to 1948 and was expanded in 1968 when the first adult bone marrow cells were used in clinical therapies for blood disease.

There are different kinds of adult stem cells, categorized differently depending upon their capability or potency, their use and their derivation (as well as by the branch of science or medicine that is doing the categorizing): three main types found in the blood and bone marrow called hematopoietic stem cells, mesenchymal stem cells, endothelial stem cells, but there are other types found throughout the body, and each of these has a predilection to replace a particular type of cell. One of the most versatile types of cells is called a Muse cell – a type of cell that resembles a stem cell that increase in number under conditions of considerable stress, and exist in the blood, bone marrow, and connective tissue of various organs. So, when an organ isn’t working properly, stem cells and Muse cells collected from a donor can be administered to a patient through an IV infusion, intramuscular or intraarticular injection to regenerate tissue and restore functionality. Some might call them a doctor’s muse for healing. Too much? 

Why is the FDA Being Cautious?

The FDA is in the middle of the debate over these new therapies. They are tasked with regulating regenerative medicine products to ensure that they are safe for patients. Just like any other type of drug or medical procedure, the FDA must be cautious because they have to protect the best interest of the patient. They demand strict testing and evidence to show that these treatments aren’t harmful. But sometimes oversight can be a slow process, and, while use of stem cells and even Muse cells have been proven safe and often efficacious in many other countries, the process of proving the efficacy and safety here in the United States has not been completed. Meanwhile, patients should be wary of unqualified doctors trying to take advantage by marketing therapies that have not yet been approved or for which they have not undergone proper training.

It’s important to be your own medical advocate and do your homework. Know what regenerative therapies have been approved and what products or services are undergoing legal clinical trials. Work in consultation with your physician, and don’t take any unnecessary risks. Seek advice as if you were undergoing any other medical procedure.

Options Available Now

So, what’s available now for those interested in stem cell therapies? First, you can ask your doctor if there is a trial in your area or a reputable clinic in another country. Look for studies that mention “IRB Approval” or are part of an “IND Study” since these are those that have FDA oversight and approval to be undertaken. Take advantage of websites that provide an overview of trials and clinics throughout the world.  One of the best sites is run by The International Society for Stem Cell Research. It provides links to a wide range of other resources too. Depending on your ailment, you could also try to work on the reverse by matching your issue with a potential stem cell treatment. 

Educate yourself about whether a given clinic or treatment has been the subject of lawsuits, controversy, or negative (and well researched) publicity. Some stem cell purveyors exaggerate claims, take shortcuts with their techniques, and engage in other practices that are morally dubious. Look for clinics run by individuals with strong science and medical credentials.  Ask your doctor about the validity of their methods and specific stem cell extraction and infusion approaches.  Beware of any clinic that is selling stem cells like a late-night TV pitchman hawking slicers-and-dicers.  

Then, set a budget and determine how much, if any, insurance is willing to cover. Currently, most insurance plans will only cover stem cells collected through bone marrow transplants. Be mindful that different methods have different associated costs. In many cases, liposuction is the most cost-effective option, and those stem cells can be expanded, offering more bang for the buck.

Finally, keep track of emerging treatment developments.  Stem cells represent a rapidly evolving field, not just scientifically but from a regulatory perspective.  Invariably, new and more effective treatments will emerge for a wide range of conditions. At the same time, stem cells will gain greater acceptance overall—while the media continues to play catch up.