This article is part of the 2018 NMJ Oncology Special Issue. Download the full issue here.
In this podcast episode, we speak with Ross Pelton, RPh, CCN, about the variety of mechanisms of action that probiotics have when it comes to reducing cancer risk. Pelton also talks about colon cancer, H. pylori, and probiotic safety and dosage. Finally, he describes how to support a healthy microbiome with a healthy lifestyle.
(Approximate listening time is 32 minutes)
About the Expert
Ross Pelton, RPh, CCN, is Essential Formula's director of science, in addition to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin. A certified clinical nutritionist, Pelton was named as one of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners.
About the Sponsor
Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr. Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers.
Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, our topic is reducing cancer risk with probiotics. Before we begin, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. My guest is integrative pharmacist and nutritionist Ross Pelton who is an expert on the topic of probiotics and health. Ross, thank you so much for joining me.
Ross Pelton, RPh, CCN: Hi, Karolyn. It's really nice to be with you. I enjoy our conversations.
Gazella: Yes. Now, first of all, how does the scientific literature stack up when it comes to probiotics and cancer prevention? Are there published human clinical trials?
Pelton: Well there's really not a lot of human clinical trials, but there's really quite a bit of research that has been conducted looking at cancer with probiotics. Human clinical trials are lacking, but there's a lot of work that has been done, cell culture studies and animal studies. There's a lot of work being done in this area. We just don't have the longterm human clinical trials which are very expensive to do. I think there's a lot to talk about because we've got substantial studies that have been published on the relationship between probiotics and cancer.
Gazella: Right. So I'd like to begin by having you give us an overview of exactly how probiotics influence the microbiota to reduce cancer risk. Now, there are several mechanisms of action. So go ahead and fill us in.
Pelton: Sure. Well some of your probiotics produce compounds that have antioxidant activity. Some of them have anti-inflammatory activity. They help to regulate detoxification. A lot of these functions are due to the fact that your probiotic bacteria produce secondary compounds or secondary metabolites that are called postbiotic metabolites. This is really the new frontier in microbiome science, starting to learn more about the compounds that your probiotic bacteria produce when they digest and ferment the food that you give them. Remember, these compounds have anticancer activity or protectant mechanisms that help protect against cancer.
Gazella: So I'd like to focus on these mechanisms of action as they relate to reducing risk of cancer. So let's begin with a more well-known mechanism and that is, as you mentioned, probiotics influence immunity. Describe what the scientific literature tells us about probiotics and the immune system.
Pelton: Well we know that 70% to 80% of the cells in your immune system reside in the gut. So it's really critical to have a healthy microbiome, a healthy gastrointestinal tract because that is the bulk of your immune system cells. One thing a lot of people don't realize is in the first 6 months of life, the primary function of your probiotic bacteria is to train your immune system. So it's really critical that kids get a good start in life with a vaginal delivery and adequate breastfeeding and for kids that don't, that's a compromised immune system. The gut is the seat of the immune system, and your probiotic bacteria are what trains the immune system.
Gazella: So now, what about maybe a little less known activity which is, as you mentioned, the antioxidant potential of probiotics? This may not be on the radar of some practitioners. Describe this mechanism of action.
Pelton: Sure. We know that free radical damage causes DNA damage and can increase your cancer risk. In a highly inflammatory condition in the gastrointestinal tract, there's a lot of free radicals being produced and a number of your probiotic bacteria have antioxidant activity and they also produce compounds that have antioxidant activity. There's 2 things going on here. Some of the bacteria themselves are antioxidants, but more importantly, they produce compounds that have direct antioxidant activity. In that respect, they're reducing free radical damage and reducing cancer risk especially for colon cancer which is a site of a lot of the free radical activity in a highly inflamed colon.
Gazella: Yeah. We're going to definitely talk about colon cancer, but now, when it comes to this influence on immunity and antioxidant potential, are there research studies in vivo or in vitro studies indicating probiotics, which probiotics can help with immunity and antioxidant potential?
Pelton: Sure. There's both some of the lactic acid-producing bacteria, Lactobacillus strains, and also some of the Bifidobacteria, bacteria that reside primarily in the large intestine and colon. One of the classes of antioxidants that they produce, they're called exopolysaccharides. That's a big word for people, but it just means that there are chains of sugars that the bacteria produce and then they excrete them and they have antioxidant activity. So this is just one of the mechanisms of action by which both Lactobacillus and Bifidobacteria are able to produce antioxidant compounds that reduce cancer risks.
Gazella: So the research tells us that probiotics can influence gene expression. Tell us how this impacts cancer risk reduction.
Pelton: Well various different strains of probiotic bacteria can influence gene expression. They can influence apoptosis, which is the rate of cell death. They can influence metastasis. They can influence cancer stem cells. They can up-regulate tumor suppressor genes. So a number of different ways that probiotic bacteria and the compounds that they produce, these postbiotic metabolites can influence gene expression which ultimately is going to influence cancer risks.
Gazella: So now, there's a significant amount of evidence and research showing that toxins can increase risk of cancer. What role do probiotics play in neutralizing some of these toxins or in supporting the detoxification of some of these toxins?
Pelton: Sure. This is actually a pretty broad category. There's a lot of different ways that probiotics can have detoxification capabilities. Some strains of bacteria can detoxify or decrease the absorption of a cancer risk factor called bisphenol A. There's a lot of studies on that substance now that show that it increases cancer risk. This is a compound that's in a lot of products that are on the market, especially baby products.
Some strains detoxify some of the agricultural pesticides. One of the Essential Formulas' products, Reg'Activ, contains a strain of bacteria called Lactobacillus fermentum ME3, and that strain of bacteria up-regulates a group of enzymes called paraoxonase enzymes. Those enzymes directly detoxify things like organophosphates, which are one of the commonly used pesticides in the agricultural industry.
Other strains can directly bind some of the heavy metal toxins like mercury and lead and cadmium. They also decrease the absorption of these heavy metal toxins when they bind them up so they don't get absorbed into your system. They get excreted. Some strains actually metabolize cancer-causing food preservatives like sodium nitrate, and Bifidobacteria are able to degrade and detoxify a very serious compound called perchlorate. We get exposed to perchlorate from fertilizers in the environment and a lot of that in the agricultural industry.
Heterocyclic amines are frequently caused by cooking meat at high temperatures. So our middle America, meat and potato people, they're out there with their barbecues and they're producing these heterocyclic amines. Some of the Lactobacillus organisms reduce the toxicity from heterocyclic amines. That's just a number of the different ways that your probiotic bacteria function as detoxifying agents in the gastrointestinal tract.
Gazella: Yeah. It's a long, impressive list. Now, I want to get back to the ME3 that you mentioned. Are there scientific studies on that particular-
Pelton: There are.
Gazella: ... strain, the ME3?
Pelton: It is a really, really fascinating topic because Lactobacillus fermentum ME3 synthesizes glutathione. Glutathione is the master regulator of your detoxification throughout your system and every cell produces glutathione, but it's hard to boost your levels of glutathione because, when you take it orally, it gets oxidized, it gets broken down and destroyed so you don't absorb it. But now we've got a strain of bacteria, this Lactobacillus fermentum ME3, where the bacteria actually synthesize glutathione.
Yes, we have human clinical trials showing that the antioxidant activity of glutathione produced by the ME3 probiotic bacteria will reduce levels of oxidized LDL cholesterol so you're reducing your cardiovascular risk, and it does a good job of increasing detoxification throughout your whole body. The human clinical trial, people taking ME3 had an astounding 49% increase in the ratio between oxidized glutathione to reduced glutathione with the reduced glutathione is the active form. A 49% increase in the ratio of the reduced to oxidized glutathione is a huge, huge meaningful marker.
This is really a revolution in healthcare and medicine to be able to boost your glutathione levels on a regular basis because, as I mentioned, glutathione regulates your detoxification. It's also called the master antioxidant and probably protects more of your body than all the other antioxidants combined. This is one area that is just really astounding both in terms of antioxidant protection and detoxification capabilities.
Gazella: That's great. So I'd like to switch gears and I'd like to talk about specific cancers. When I think about probiotics and cancer, I often think about colon cancer. You mentioned that previously. What role can probiotics play in reducing the risk of colon cancer?
Pelton: Well there's a number of ways that this can happen. Pathological bacteria will convert bile acids into secondary metabolites that promote cancer. When you have the proper acid-base balance in the GI tract, there's a dramatic reduction in the conversion of these bile acids into the more cancer-causing secondary metabolites. So maintaining the proper acid-base balance, which is what the probiotic bacteria do when they produce things like short-chain fatty acids and organic acids and nucleic acids, they create the proper acid-base balance which reduces the conversion of bile acids into secondary cancer-causing metabolites.
Your probiotics can also inhibit the activity of carcinogenic enzymes. They suppress growth of bacteria that produce enzymes that deconjugate carcinogens. What I mean by that is that a lot of carcinogens get bound up and they're supposed to be excreted when you have bowel movements, but if you don't have good elimination and so things stay in the colon too long, those cancer-causing things that are bound up can get released and reabsorbed. So probiotics can actually suppress the growth of bacteria that produce these enzymes that are deconjugating these carcinogens. Good bacteria are actually keeping these carcinogenic byproducts bound up so they get eliminated from your body.
Gazella: Well speaking of bacteria, it's widely known that there's a connection between H. pylori and cancer. Can you describe that connection and tell us how probiotics can help prevent or even reverse H. pylori?
Pelton: Sure. That's another big topic because now that H. pylori has been discovered and understood, we realize it's the primary cause of stomach cancer and cancers in the upper small intestine. This is an interesting bacteria. It's got kind of a corkscrew tail on it, and it can just burrow its way into the lining in the stomach or the lining in the small intestine. When that happens, you've got a hole in your intestinal wall. Then you get the acids and the digestive enzymes leaking through, creating inflammation, and you end up with a higher incidence of cancer.
If you have a good, healthy microbiome and adequate numbers of your good bacteria, you suppress the growth or the overgrowth of H. pylori. There's a little bit of a controversy about whether people should try to totally eradicate H. pylori. Some people, some of ... Martin Blaser is one of the leading scientists that's exploring this and saying maybe we shouldn't totally eliminate H. pylori, but people that have H. pylori overgrowth certainly do have increased risk to gastric cancer and small intestinal cancers. It's having a good microbiome and adequate numbers of your good bacteria that will keep the H. pylori in check and not get overgrown so you reduce your cancer risk.
Gazella: What are some of the symptoms of H. pylori overgrowth? I mean how does a doctor recognize this in their patient population?
Pelton: Well as I described, the bacteria has this corkscrew tail that burrows through the unprotected mucus lining in your stomach or your small intestine. When you get that hole in the lining, you've got an ulcer. It's painful. Your digestive acids, your stomach acid, and your bile acids and small intestine. Then they go through the mucus membrane which is your protective barrier, and they come into direct contact with the cells that line your GI tract. When that mucus protective layer is breached, then those acids contact those cells that line the GI tract and it's painful. You've got an ulcer and you say "Oh, man. This is sore." So people actually oftentimes stop eating because every time they eat, they get more digestive juices in that ulcerative location. You need to heal that ulcer. Getting rid of H. pylori is one thing, but you also have to take time to heal the ulcer.
Gazella: Yeah, that makes a lot of sense. Now so far, we talked about colon cancer, stomach, upper GI. Are there any other cancers when it comes to using probiotics? I mean do you pretty much recommend probiotics as a risk reduction strategy across the board?
Pelton: I do because your immune system is so directly related to cancer risk factors. A lot of people don't realize that probiotics have an effect outside the intestinal tract. We now know that things like short-chain fatty acids get absorbed into your system and can actually reduce the risks of liver cancer. It's a whole body effect. These bacteria are not just a local effect in the gastrointestinal tract. I kind of use the analogy of Mission Control at NASA where those computers are controlling your space flights. Well your probiotics and the postbiotic metabolites in your small intestines and your colon are really Mission Control for all health-regulating effects in your whole body.
There's a new study that I wanted to share with you, Karolyn, published just recently in a journal called Oncotarget. It's a cancer journal. It says cancer killers in the human gut microbiota. One of the things they're reporting here is that they identify intestinal bacteria that exhibit potent antimalignancy activities on a broad range of solid cancers and leukemia. So this is a relatively new paper just published in July of 2017, identifying that postbiotic metabolites and your probiotic bacteria are helping to reduce both solid cancer tumors and leukemia. It's just an exciting new report giving more emphasis on the anticancer capabilities of your probiotic bacteria.
Gazella: Yeah. I think this area of research is going to just really explode. Now, a lot of patients go into their doctor's office and they say "Oh, well I'm fine. I don't need a probiotic supplement because I eat yogurt everyday," or something like that. How easy or difficult is it to get the probiotics we need from diet alone?
Pelton: It depends on what you mean by diet. If people are eating fermented foods, that's a really good source of probiotic bacteria, but most people aren't eating sauerkraut and kimchi and tempe and things like that. Most foods don't have probiotic bacteria. People think about yogurt, but commercial yogurts have a lot of sugar which actually promotes the growth of your pathological bacteria and yeast like candida. So commercial yogurts are generally not a good idea either in terms of just not getting a good source of probiotic bacteria. You're really working against the health of your gastrointestinal tract and your microbiome.
If people produce their own yogurts, there are some good ones. Yes. But you're really not getting a diverse level of bacteria in yogurt, and a healthy microbiome is a diverse microbiomes which means you want to get a lot of different types of strains of bacteria. The best way to do that is to consume a diet that has many different types of fiber-rich foods, especially the multicolored vegetables. That's the number one food source for your bacteria.
Gazella: Right. We have to feed those good bacteria.
Pelton: That's right.
Gazella: So now, you represent a specific type of probiotic, the Dr. Ohhira's brand. Why do you recommend that specific brand of probiotic?
Pelton: Well I'm glad you asked that. I'm the scientific director of Essential Formulas, and Dr. Ohhira's Probiotics is our primary product line. Dr. Ohhira's Probiotics are made differently than every other probiotic in the world. In fact, it's kind of confusing, but Dr. Ohhira's Probiotics is really not primarily a probiotic. It is primarily a fermented food.
The Dr. Ohhira's Probiotics are produced in a fermentation production system. We have large fermentation vats in a warehouse, and we start with 12 strains of probiotic bacteria. Then at seasonally appropriate times throughout the year, we shred and harvest dozens of different types of organically-grown foods. There's fruits and vegetables and mushrooms and seaweeds. Then the bacteria get to digest and ferment these foods for 3 years before the product is finished.
During that fermentation process, the bacteria are breaking down the foods and producing this wide range of compounds that we now refer to as postbiotic metabolites. As I mentioned earlier, these are the master health-regulating compounds in our system. So Dr. Ohhira's Probiotics have been tested and we find out there are over 400 postbiotic metabolites in Dr. Ohhira's Probiotics. We are not primarily just delivering probiotic bacteria. We're delivering over 400 of these postbiotic metabolites that rapidly create change in the GI tract. You rapidly reduce inflammation, rebalance the acid-base level, promote the growth of healthy new cells that line the GI tract, cell signaling and gut-brain communication directly with postbiotic metabolites.
We get what we call rapid microbiome restoration or rapid microbiome repair. Other companies are just giving you bacteria in a capsule. That's kind of like a starter culture. Those bacteria haven't done any work yet. Our bacteria have been working for 3 years producing postbiotic metabolites by the time you ingest them. That's the big difference. Dr. Ohhira's Probiotics is different than every single other probiotic in the world. The new science in the microbiome, the new frontier in microbiome science is starting to realize that it's these postbiotic metabolites that have the master health regulatory effects in the gastrointestinal tract and health-regulating effects for the entire body. So by directly delivering this postbiotic metabolites, we get rapid improvement in the microbiome in the gastrointestinal tract for people who take Dr. Ohhira's Probiotics.
Gazella: Now, I know this particular product does not have to be refrigerated. Why is that?
Pelton: Well these bacteria learn to thrive and survive at room temperature during the 3 years of fermentation. They don't need to be refrigerated, which makes them very user-friendly. Also they are in a patented capsule that stays hard in the harsh acid environment in the stomach. Then it preferentially releases the contents in the small intestine. So it doesn't make any difference if you take it with food or on an empty stomach. Any way you take it, just the main thing is 2 capsules once a day. Get Dr. Ohhira's in on a regular basis and you'll be maintaining a healthy microbiome.
Gazella: Yeah. I'd like to talk a little bit about dosage because honestly it seems like you can ask 3 different experts about dosage and they'll give you 3 different answers. When it comes to dosage specific to cancer prevention, is that the 2 caps per day? What does that deliver in terms of CFUs or different strains for that two caps per day?
Pelton: Well 2 capsules a day is the recommended dosage. One thing we emphasize, we're not concerned about how many million or how many billion bacteria we have. There's a numbers game that is really a misconception by people when we're talking about probiotics that they call the bacteria that are available CFU which stands for colony forming units. It really means just the number of viable bacteria, but people have a misconception that more is better. They say "Mine has 30 billion. Mine has 50 billion. Oh, mine's got 100 billion." They think more is better.
One of the most critical factors in a healthy microbiome is balance. If you take massive doses even as a healthy strain of bacteria, you're not working in favor of balance. You're actually working against creating balance in the microbiome. So it's not important to have high strains of, high dosages and high numbers. It's better to have a multistrain probiotic, a lot of different strains but at lower dosage levels.
I really talk in my lectures and seminars against the high-dose probiotics. I'm not saying they're never appropriate. A product like VSL3, which is a prescription probiotic, I think it has 112 billion bacteria per dose. Those people have some good research and have documented benefits from their high-dose probiotic, but I don't think high-dose probiotics are appropriate on a longterm maintenance basis. You want to strive for balance and diversity.
Gazella: Yes, I would agree with that. How many strains are in the Dr. Ohhira's product?
Pelton: Dr. Ohhira's has 12 strains. We start out with 12 strains in the manufacturing process. We are a multistrain probiotic. I'm not sure, but Dr. Ohhira may have been the first scientist in the world to understand the concept and the importance of a multistrain probiotic because he created Dr. Ohhira's Probiotics 30 years ago.
Gazella: Yeah. So let's talk a little bit about safety. When it comes to cancer prevention, are probiotics safe for the majority of patients or is there any patient or group of patients who should not take probiotics to help reduce cancer risk?
Pelton: No, everybody should take probiotics. One of the most important things for health is a healthy microbiome. We now understand that a healthy microbiome is the foundation of health. I think it's important for everybody to realize that supporting and maintaining a healthy microbiome is a critical factor for health regulation. There's no contraindications.
I do want to mention briefly, Karolyn, there are 2 studies that were recently published in the journal Cell that have gained a great deal of publicity because they cast doubt on the effectiveness of probiotics. The scientists who conducted these studies stated that their results suggested probiotics are almost useless. There's been a lot of pushback after the publication of these studies. It turns out there was some methodological shortcomings in the way they set up their studies, and there were a very low number of people. I think there was only 8 to 12 people in these studies.
What's more disturbing is that it has been learned that the scientists that conducted these studies, they have a personalized approach to probiotics that they promote in their studies. Turns out that they have a vested interest. They have financial interest in this company that's promoting this personalized approach. So it's a very serious flaw and their conclusions should not be generalized of the whole field of probiotics. Allowing studies to be published in which the authors state that probiotics are almost useless is really grossly misleading and a disservice to the general public.
Gazella: Yes, I would agree. Now, I often like to ask experts to grab their crystal ball and look into the future. In your case, I'd like to have you tell us what you'd like to see happen when it comes to probiotic or postbiotic metabolite research in the future. What do you want to see happen as we go into this next phase? Because I'll tell you, there's a lot of exciting stuff happening. There's a lot of different directions we could go into.
Pelton: You're absolutely right. It is a very exciting field and rapidly evolving. As I've talked about these postbiotic metabolites, the compounds that your probiotic bacteria produce, in the future, we will learn a great deal more about the health-regulating effects of these compounds that your bacteria produce and we'll learn more about which strains of bacteria are more effective at producing some of these health-regulating postbiotic metabolites.
I think in the future, we'll probably make a great deal of inroads and progress in designing personalized probiotic programs for people. We'll be able to assess your own innate microbiome and be able to know more accurately how to promote and enhance the growth of your own innate what we call your probiotic fingerprint, the bacterial population that you've developed early in life. I think we'll get into more of a personalized microbiome and personalized approach to probiotics to help promote health in individuals.
Gazella: When you think about cancer specifically and reducing cancer risk, I mean now obviously, it's estimated that 1 in 2 men and 1 in 3 women will develop cancer in their lifetime. I mean this is now reaching near epidemic proportions. How critical is it that we look at things like probiotics when it comes to reducing cancer risk?
Pelton: Well again, I go back to the immune system. It's absolutely essential that people have a healthy microbiome so that they have a healthy immune system. This is really where it starts. Your gastrointestinal tract and your microbiome are literally the foundation of your health for everything that happens. It is the number 1 thing that people need to be aware of and it's not just the microbiome.
As we mentioned earlier, you have to learn how to feed your probiotic bacteria well. This is another key message of mine. This is why diet is so important because you're not eating just for yourself. You're eating to feed 100 trillion guests. It's a pretty big party that's going on down there. Every time you eat, you have to realize that you're feeding your microbiome, and your microbiome is the center and the foundation of your health and your immune system and your anticancer activity. So people need to realize how important it is on a regular basis to eat a wide range of different types of fiber-rich foods, especially the multicolored vegetables, because a more diverse fiber-rich diet will promote the growth of a more diverse microbiome which means your bacteria will produce a wider range of these health-regulating postbiotic metabolites and you will be a healthier person with a stronger immune system.
There's a recent study that was just published that shows that, reports that people that consume more probiotics take less antibiotics. That's just another insight into probiotics being able to support your immune system. So these people using probiotics more have a stronger immune system. They have less need over time for antibiotics.
Gazella: Yeah. That antibiotic issue, that's something that we ... That could be whole other topic for us.
Pelton: It's a big one.
Gazella: But as an integrative pharmacist, you share a philosophy with our listeners who are, most of them are integrative practitioners. It's not just about giving a pill and calling it a day. It's a very comprehensive approach, and I like the fact that you focus so heavily on diet and using a healthy diet to feed the probiotics and the bacteria and that you use probiotics hand-in-hand with that comprehensive lifestyle approach which I'm assuming, beyond diet, you counsel people to exercise and get enough sleep and those other lifestyle factors as well.
Pelton: Absolutely. Those are critical factors. There are studies now that show that your probiotic bacteria respond to exercise. Exercise needs to be emphasized. So it's diet and exercise, lifestyle. All these healthy things go into creating and maintaining a healthy individual and having a healthy aging process. It's not just probiotics and it's not just diet as you mentioned. It's exercise and sleep and learning how to avoid environmental toxins. There's lots of things that go into it.
Gazella: Right. Treat your microbiome well and it will serve you for a long time to come.
Pelton: It will work for you. Absolutely.
Gazella: Well great. Well Ross, this has been very informational as per usual. I want to thank you for joining me. Once again, I'd like to thank Essential Formulas Incorporated for sponsoring this topic. Thanks so much, Ross. Have a great day.
Pelton: Nice to be with you, Karolyn. Always enjoy speaking with you.