194: Immunoglobulins + Histamine Problems: A Game Changer? w/ Kiran Krishnan

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Do you struggle with chronic itchy skin and hives caused by histamine overload? Immunoglobulin might be a game-changer!

Or, listen on your favorite app: iTunes (Apple Podcasts) | Spotify | Stitcher | TuneIn | Subscribe on Android

My guest today is Kiran Krishnan, a Research Microbiologist who has been involved in the dietary supplement and nutrition market for the past 18 years.

He comes from a University research background, having spent several years with hands-on R&D in the fields of molecular medicine and microbiology at the University of Iowa. Kiran established a Clinical Research Organization where he designed and conducted dozens of human clinical trials in human nutrition.

He is also a co-founder and partner in Nu Science Trading, LLC.: a nutritional technology development and research company.

In addition, Kiran is a co-founder and Chief Scientific Officer at Microbiome Labs that makes products like MegasporeBiotic + MegaIgG2000.

Kiran is currently involved in 16 novel human clinical trials on probiotics and the human microbiome.

Join us as we talk how immunoglobulins might be helpful for people with histamine problems.

Have you tried immunoglobulins for histamine issues? Tell me about it in the comments!

In this episode:

  • How can immunoglobulins help with histamine overload?
  • Why IgE responses can become more severe
  • How to start Mega IgG (and other immunoglobulin products)
  • Can you take immunoglobulins if you're immunocompromised?
  • Common FAQs asked by readers + listeners about using Mega IgG2000


“What is the root cause that is driving this histamine overload, this high eosinophils, this itchiness, intolerance everywhere throughout the body? It all starts in the gut, obviously.” [23:11]

“If you don't have a good, healthy, diverse microbiome, you've got constant leakiness in the gut, so lots of inflammation in the gut.” [26:19]


Click HERE to try MegaIg2000 + Megasporebiotic

Healthy Skin Show ep. 10 How Your Skin Health Is Tied To Your Whole-Body Health w/ Kiran Krishnan

Healthy Skin Show ep. 11 The Role Of Probiotics When It Comes To Skin Health w/ Kiran Krishnan

Healthy Skin Show ep. 181: Fascinating Research On Staph Infections + Probiotics (PART 1) w/ Kiran Krishnan

Healthy Skin Show ep. 182: Fascinating research on Staph Infections + Probiotics (PART 2) w/ Kiran Krishnan

Healthy Skin Show ep. 188: Histamine Intolerance + Skin Rashes

Healthy Skin Show ep. 166: Mold + Histamine Connection w/ Dr. Jill Crista

Follow Kiran Krishnan on Instagram

194: Immunoglobulins + Histamine Problems: A Game Changer? w/ Kiran Krishnan FULL TRANSCRIPT

Jen: Interesting. Okay, you have mentioned a bunch of time about toxins.

Kiran: Mm-hmm (affirmative)

Jen: Toxins in the gut and certain bugs produce toxins. We talked about C. diff on the last podcast in regards to MegaSpore because of how it could… What was it you said? It surrounds it like a circling wagons-

Kiran: Mm-hmm (affirmative)

Jen: … and helps get it out of the body. I have a lot of clients and a lot of listeners who are really struggling with a histamine overload picture.

Jen: So some of them have a high total IgE. They may show elevated eosinophils on their blood count panels. They may have loads of environmental allergies. They struggle at night sleeping because maybe they have hives, sometimes all the time. But a lot of times, people notice the symptoms get worse as they get into the day and into the evening, and maybe even the antihistamines aren't helping all that much. They can have eczema. I have a few clients that have psoriasis that have this picture. But then we've got the chronic urticaria people who they have no idea why they have these hives.

Jen: So how can immunoglobulins and this type of supplemental support, how is it possible that it might be useful in these types of cases or instances where their system's just inundated with so much histamine, and they just can't deal with it essentially?

Kiran: Yeah. I think to really understand that it's important to understand where some of these conditions are coming from. What is the root cause that is driving this histamine overload, this high eosinophils, this itchiness, intolerance everywhere throughout the body? It all starts in the gut, obviously. I think anyone listening to this could have guessed that, but let's talk specifically how it starts in the gut.

Kiran: Again, this is another factor that's driven by dysbiosis. So let's say you had a couple courses of antibiotics or you went through a period of just poor choices; eating, lifestyle, stress, so on. Now you got a dysbiotic which means that you've got lower levels of protective commensal organisms, higher levels of opportunistic organisms. What that can translate into is intestinal permeability issues which means that there's a constant influx of compounds into the inner lining of the gut, which continuously drives inflammatory immune responses to the lining of the gut.

Kiran: So now you've got an inflamed gut, you've got dysbiosis, you've got an imbalance of bacteria. What can all of that look like from the perspective of the things that you were talking about? Well, number one, which I mentioned earlier, when you have low levels of secretory IgA, you end up getting higher expressions of peripheral IgE being expressed. The big controlling factor to how much IgA you produce is what does your microbiome look like?

Kiran: Lots of your commensal organisms work very closely with your Peyer's patches which is an immune tissue in your small intestines, your mucus-associated lymphoid tissue, your gut-associate lymphoid tissue; they interact with those tissues to trigger your immune system to produce more IgA. If those organisms aren't present and you've got more opportunistic organisms, you don't get the stimulus to produce more IgA. So as a defense, your body naturally produces more IgE instead. So that could be one step, and often it's involved in this whole process of people that are histamine intolerant.

Kiran: The second part of that is that dysbiosis also brings down a system called a Treg system. There's a couple of different aspects of the Treg system. This thing called a FOXP3 Positive Treg System. But the whole point of that system is to regulate immune responses that are not favorable to the host. These allergic-type responses, the histamine, eosinophilic type of responses to things that aren't really harming you like food particles and environmental particles.

Kiran: The Treg system is supposed to created learning for the immune system. So the immune system recognizes that A, this is a food protein, we don't need to react to it, it's not causing the host harm. Then it creates a tolerance against that protein. But again, the function and elevation of the T-reg system is dependent on the interaction of your commensal bacteria with your gut-associated lymphoid tissue or your gut-associated immune tissue.

Kiran: So if you don't have a good, healthy, diverse microbiome, you've got constant leakiness in the gut, so lots of inflammation in the gut. You have more opportunistic microbes growing, less of your commensal microbes, and you've got a double whammy now. You've got no T-reg function, so your immune system cannot regulate itself, and then you've got an immune system that's in panic mode.

Kiran: It's just putting out as much IgE as it can to try to protect the host. So everything that you encounter gets an IgE eosinophilic, basal fill type of response. So now your default immune response to the world around you is through the IgE allergic hypersensitivity response because the other systems that are dependent on microbes are not functioning because your microbes are off. So that's the explanation for how all of this kind of goes haywire.

Kiran: Once it starts down that road, it just gets worse, and worse, and worse over time. You become more and more sensitive to more and more and more things. That's because your immune system is not learning, and you're not getting what we call oral tolerance. You're not building resistance to the things that you normally get exposed to that you don't need an immune reaction to.

Kiran: So how does something like the IgG help with that? Well, number one, if you've got an overexpression of opportunistic organisms, that IgG helps neutralize and reduce the toxigenic impact of those opportunistic organisms. Now that again gives your commensal organisms a better shot at starting to overcome the competition from the opportunistic. The IgG also has shown to be able to reduce the inflammatory type of responses in the gut lining.

Kiran: They've done studies on ulcerative colitis, for example, that is hallmark with huge inflammation in the gut lining. Using the IgG can bring down the inflammation. So it's starting to turn the environment a little bit within the gut lining so that now you have more ability for the commensals to start growing. You have microbes like [inaudible 00:28:29] bacteria; your keystone species that can produce butyrate and short-chain fatty acids so you can rebuild the lining of the gut.

Kiran: Then you can start then triggering the T-reg system so your immune system can run around and go, “Okay, we don't need to start reacting to that, to that, to that, and that,” and it can shut down all of those unfavorable immune responses. The good news about all of this is all of that can be done and achieved at any given point. It's not like, “Oh, I'm now sensitive to all these things. I'm going to be this way for the rest of my life.” If you change that ecosystem and the structure, it'll help you get to the other side, where you build tolerance. The IgG is a component of helping you get there.

Jen: I want to add to this. Many of you know I have talked about histamine overload on the podcast, and we'll link to some of those episodes because if you haven't heard them, it is helpful for you to understand that it's more than just, “I seem to be sensitive to everything.” Because one thing people don't realize is that some gut bugs cause mass cell destabilization, thus, they release their histamine. But some bugs actually produce histamine in the GI tract, like Morganella, for example.

Jen: So unless your doctor knows exactly what to test for, which a lot of times they don't and sometimes people don't have any GI symptoms at all, but there is usually, when I've done stool testing in clients, there's usually a problem going on there. The other thing that I'll add to this conversation is that from a parasitic perspective, it is very common to see high total IgE levels and no explanation as to why it's elevated, and parasitic issues can be an underlying cause.

Jen: It's oftentimes overlooked because we assume that because we live in the United States or Canada or some, I guess, “first world country,” that we're not exposed to parasites. Kiran, right? We can be exposed to parasites anywhere.

Kiran: Mm-hmm (affirmative) Yeah, absolutely. Especially given our inability to maintain really healthy soil conditions and all that with good diverse microbial life in soil. We treat our soil chemically with so many things. That creates an unusual ecosystem that selects for resistant microbes and parasites and things like that. So absolutely, we can be exposed to those.

Kiran: I think one of the other things that people forget and maybe they just don't even know is that when you've got this imbalance of microbes in your system, when you've got an overgrowth of the opportunistic organisms, and they keep pumping out their toxins because they're trying to ward off the commensals from competing with them, one of the natural ways the commensals try to alert your immune system that there are pathogenic or problematic organisms is by triggering a histamine release.

Kiran: So histamine and taurine are two key chemical signatures that your microbiome, your commensals, use to alert your immune system that they're being a problem with the ecosystem in the gut lining. So now you've mass cell destabilization releasing a bunch of histamine, and then your commensals are trying to say to your immune system, “Hey, something is off here. You need to keep coming here and paying attention.” So they're triggering more histamine release because of that chronic overgrowth of opportunistic and pathogenic organisms.

Kiran: So it's a recipe for disaster, and it's a multi-prong problem. It's not just one thing, and it requires a multi-prong approach. It requires doing a number of things to try to bring back balance into the system. The IgG plays such an awesome role in assisting in bringing back that balance.

Jen: So let's talk about some practical things because the last time when we discussed the MegaSporeBiotic, you answered a lot of questions that listeners have about these types of products. Which for those of you who are listening, where can I get some Mega IgG2000? You can head to getmegaspore.com, and I gotcha. We got some available for you guys because I've just loved using this in my practice.

Jen: One of the things people ask is, can I take this out of a capsule? Will it destroy the immunoglobulins if, say, I have to add it to a protein shake because I can't swallow pills?

Kiran: Yeah. No, not at all. They can. In fact, the prescription version of this is done so in a drink powder which is you add to any soft foods, you add to a shake, you add to whatever you want. So absolutely, you can do it that way.

Jen: Okay. So how would someone get started if they wanted to test this out? Do you recommend really low and slow, and slowly increase, or do you just dive into two capsules twice a day? Is this done with food, or is it better done away from food?

Kiran: Yeah. Here's when I like to take it, and I take this every day. It's one of three or four things that I tend to be quite disciplined about. I take a dose at night before bed because there's a lot of cleanup going on in your gut and your microbiome when you sleep. A lot of the housekeeping genes and the housekeeping microbes become active in the nighttime, so there's a lot of cleaning up going on, and this plays a big role in cleaning up.

Kiran: Then I also like to take it in the morning when I wake up. So in both cases, I'm taking it on an empty stomach. There's no issue with taking it with food if it's easier for you to remember that way, but I like to provide my GI tract assistance as it's going through that cleaning up process. You don't necessarily have to go low and slow with this. It's not like the MegaSpore, where you can have die-off reactions and so on. Most people start off with two grams a day which is four caps.

Kiran: You can do that in the evening before you go to bed or when you wake up in the morning, either one is fine. It's probably better to do four caps at once than splitting it at two caps and two caps. You want to get a good volume in there, so you've got your binding, and you're neutralizing a lot of things at once. But you can take upwards of six/seven grams of this. The prescription version of this is five grams twice a day, so it's 10 grams of this stuff. That's the way that gastroenterologists are using it.

Kiran: So you could take upwards of 10, 15 capsules of this if it helps you. You'll find your own kind of dose that really is optimal for you. For me, when I was traveling a lot before the world ended, it was four caps twice a day was the best. I slept better. I felt less fatigue from all the moving around and eating all kinds of crazy food all over the place. So I would take four before bed, four when I woke up, but I know a lot of people that do great with just four.

Kiran: I've known people with real severe sensitivity issues that have had to go to like 16 capsules a day. You can keep going up and finding your threshold that really helps you, and there's no issue, danger going higher and higher. Remember, the approved prescription version they go upwards of 10 grams twice a day, so they're taking almost 20 grams per day. So no issue there.

Kiran: What was the other part of the question? I think we can remove it out of the capsule.

Jen: Yes.

Kiran: You can use it that way. Oh, you don't have to go low and slow. I would recommend everyone start with at least four caps on this. If you need to take it with a meal, totally fine, but I like taking it on an empty stomach before bed or when I wake up.

Jen: This is obviously a podcast for adults. Everybody knows that I work with adults though I do have some practitioners on who work with kids. But if there is a parent listening and they're like, “Oh my goodness, my seven-year-old or my three-year-old or my teenager has problems,” and I know again, everybody, you've got to check with your practitioner and your doctor because this is not any type of advice. This is for informational purposes. But is this an option for little ones?

Kiran: Mm-hmm (affirmative) Yeah, it's absolutely fine for little ones. Again, check with your healthcare practitioner. The studies that were done, like the ulcerative colitis study I mentioned, that study was actually in a pediatric ulcerative colitis patient. So it's kids with UC, and they tolerated it beautifully. It really supported their better GI function, really helped support healthier responses in these kids. So there's no issue there at all.

Kiran: My kids, I have a 10-year-old and a seven-year-old, and during certain times during the year, especially when we get into the cold and flu season time, on average, I think they take about two or three caps a day. I open it up, mix it into their yogurt, whatever soft food they like to eat. Mix it in with the spores at the same time, and there's no issue at all.

Kiran: I have given them higher doses when we travel and we're eating questionable things in Cambodia, then they get four caps just in case. So yeah, absolutely. Perfectly fine with kids.

Jen: I was going to ask you that. You brought up at the spores, which I know you mean MegaSporeBiotic.

Kiran: Mm-hmm (affirmative)

Jen: Is this okay to take along with MegaSporeBiotic?

Kiran: Yeah. They go hand-in-hand beautifully. We wanted to launch this product, and I'll give you a quick bit of history as to how I even came across this product. The NIH, the National Institutes of Health, published a study a long time ago, maybe now eight years ago, saying that the biggest driver of mortality in HIV is HIV enteropathy or leaking gut.

Kiran: So one of the biggest drivers of going from having HIV positive to AIDS, which now it's not terminal anymore, but it used to be terminal, is leakiness in the gut. How leaky is your gut? That's a profound thing for the NIH to do a study and show that. So in the world of HIV researchers, it became very clear that we needed to find solutions for dealing with severe leaky gut, inflammation, and intestinal permeability issues in the gut.

Kiran: So we got involved in that because one of those HIV researchers reached out to us based on our studies on leaky gut in using MegaSpore. So we were at a meeting, I think in Portland or somewhere like that, where it was a research meeting with the top HIV researchers in the U.S. and a few of us companies that have products that may work in that condition. The company that makes this product was also there because they not only had studies on helping with gut lining issues, but they actually had studies already on HIV.

Kiran: They published a couple of studies on HIV patients with really severe inflammation and leakiness in the gut and showed really impressive data on that. So seeing that and understanding how the immunoglobulins work and how that is compatible and complementary to how the spores work, it became very clear that the combination could be really quite powerful.

Kiran: Our approach from that point on was, “Okay, If you guys are going to study this in HIV, study the combination of it.” So that's how we started working together, and then we started to realize quickly that we really need to offer this to our healthcare practitioner audience because even though that kind of enteropathy is driven by HIV, it's no different than the leakiness and all that that occurs for other reasons that leads to other problems.

Jen: So that leads me to a quick, interesting question. HIV means you're immunocompromised, essentially. So for someone who does legitimately have an immunocompromised system, and obviously again, check with your health care provider, but would that mean that these could possibly be an option for you if you are immunocompromised?

Kiran: Yeah, and there's no reason to think that it's not compatible for someone immunocompromised. If someone is immunocompromised, it either means one of a couple of things. One is their immune system is acting in an erroneous way, meaning it's not protecting against the things you should be protected against. Instead, it's attacking a bunch of stuff that you don't need it to attack. Or B, it's simply non-functional at the level that it should be, so it's not reacting to things the way it should.

Kiran: At the end of the day, what immunoglobulins do when you take them as supplements is it's lending a helping hand to your immune system because it's taking off some of that toxic burden and response requirement from the immune system because you already are taking in antibodies which is the end product of an immune response in your body. You're already taking the end product that's neutralizing and reducing the toxic load of a number of things in your gut.

Kiran: So it's really a helping hand to your immune system because remember, in your own immune response, the end product of your immune response is an IgG antibody to whatever it is that your immune system is responding to. Now what you're doing is taking in a bunch of IgG that helps neutralize things that are driving inflammation and all that in your gut lining already. So it's a huge help to your immune system.

Jen: Very cool. So I have one last question. Any side effects? I know you had mentioned with MegaSporeBiotic, we can have die-off.

Kiran: Mm-hmm (affirmative)

Jen: Any side effects or anything that people should be aware of if they're taking it and maybe they need to slow down, or is pretty… Most people tend to see improvements as a result of working with this type of supplementation.

Kiran: Yeah. There's only one to keep in mind of, and it maybe impacts 15% or so of people, and that is that they could get a little bit constipated when they first take it. Now, the easy way to overcome that is to increase your water intake and in part because when your gut is loose, when your bowels are loose and you have loose bowels all the time, what's happening is your intestines are not absorbing liquid very well. So more of the liquid goes out of your system rather than getting absorbed in, so it comes out as loose stool.

Kiran: Now, when you counteract that, what can happen is you may absorb now more liquid than you did before, thereby creating less liquid to move the stool down the system. So what we tell the people is some people who take it may experience that better absorption of liquid, which is a good thing, but it can slow down the bowels then. So what you need to overcome that is just taking in more water.

Kiran: So we say, “Hey, just have an additional 12 or 16 ounces of water throughout the day, and you're perfectly fine.” There's nothing wrong with having more water anyway.

Jen: This is not a binder like activated-

Kiran: Clay and things.

Jen: … charcoal, right?

Kiran: Yeah.

Jen: So for people who are nervous that it's going to bind up their nutrients or other supplements. When we say bind, it's not the same type of binder, correct, as those-

Kiran: 100%. That's a really important thing to bring up, which I'm glad you did because a lot of people ask me about this compared to things like clay and charcoal and diatomaceous earth and so on. Those things are like mudslides going through your gut. It's just grabbing everything and sweeping it out, good stuff and bad stuff. That can be problematic in some ways, especially if you do it a lot.

Kiran: This is highly specific because remember these are antibodies, and these antibodies, each one is highly targeted towards a single target whether it's a mold, toxin, it's a bacteria, it's a virus, it's an environmental toxin. Whatever it may be, each antibody has a specific target. If there happens to be an antibody in there and it doesn't have a target, meaning you don't contain one of the targets that it has, it just moves out through defecation. So it's not binding up good stuff that you really don't want to bind up.

Jen: Perfect. Oh my goodness, you answered every question that I have gotten from listeners of the show, folks who've seen that Mega IgG2000 in my shop. This has been so helpful. I think for everybody listening, you have to understand that there is this incredibly intricate connection between what's happening in the GI tract and on the skin, and so this may be really helpful for you.

Jen: I use it in my practice, and I've really loved the results that I've gotten with it. So if you have any questions, certainly let us know, and if you're interested in checking out more information on the product, you can go to getmegaspore.com and check everything out there.

Jen: Thank you, Kiran, so much for joining us. You have just unleashed this mountain of incredible information, and I deeply appreciate you and your willingness to share this type of information because it can be so life-changing because quality of life when you're really sick, you lose out on time, you lose out on experiences, and for someone who can get their life back and start to have more normalcy is just so crucial. I know everyone listening really appreciates all the time and energy, and wisdom that you've imparted and shared here on the show, so thank you so much for joining us.

Kiran: Yeah, it's my absolute pleasure. I would say to people, if this made sense to them, if they now understand a little bit better what's happening in their system, how it goes awry, and all that, hopefully, people are encouraged to share that information with others because this is the kind of knowledge that needs to get out there. People need to be empowered with a better understanding of what's going on in their system because ultimately, we have to advocate for ourselves.

Kiran: We can't lean on others for our own health and wellness. We have to advocate for ourselves and our loved ones. So share this information, share this recording, share the concepts if you understood it well from this. For me, that's my mission. I'm always out here trying to educate people and make these complicated concepts more “digestible.” No pun intended. But thank you so much for having me, and I appreciate the opportunity.

“What is the root cause that is driving this histamine overload, this high eosinophils, this itchiness, intolerance everywhere throughout the body? It all starts in the gut, obviously.”