Is There Actually an Ideal “Thyroid Medication Ratio”?

Intro:

Welcome to Dr. Ruscio radio, providing practical and science-based solutions to feeling your best. To stay up to date on the latest topics as well as all of our prior episodes, make sure to subscribe in your podcast player. For weekly updates visit DrRuscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now let’s head to the show.

DrMichaelRuscio:

Hi everyone. Welcome back to another episode of Dr. Ruscio radio. This is Dr. Ruscio. Today let’s talk about a case study where probiotics were effective as a mono-therapeutic to clear H. pylori. Also, a clinical review of the evidence on combination thyroid hormone therapy, meaning T4 plus T3. Specifically, does a certain ratio matter in treatment. We will also discuss psilocybin-assisted psychotherapy for major depression, an article appearing in JAMA. All of these pieces are taken from our Future of Functional Medicine Review Clinical Newsletter. This is a monthly publication that consists of a case study from our center as well as a concise review of either an important topic, as in this case, the ratios of T4 to T3 in thyroid combination therapy or concise reviews of various research papers. In this case, the psilocybin-assisted psychotherapy paper. If you haven’t joined the newsletter yet, I hope that you will.

DrMR:

For the month of April, we are running this promotion so that you can access your first month for only $1. This provides you not only access to the current issue, but all of the back issues with a wealth of case studies and research study reviews. So I really hope you will head over to DrRuscio.com/Review. Have a look, sign up for $1, plugin and see if this is something that helps you. If the case studies help you better determine as a clinician, when to test, what to test, how to interpret, how to troubleshoot, what are some key red flags or key flags that may prompt you to use something like limbic therapy or HCL. Or, as this case study demonstrates, how, just because we see a potential pathogen in H. pylori, we don’t always need to go right to aggressive antimicrobial or antibiotic therapy. Like I’ve been harping on here for a while in the podcast, probiotics should really be the first consideration there because they do exert antibacterial antifungal and antiparasitic effects.

Probiotics as a Monotherapy for H. Pylori

DrMR:

So anyway, this is my attempt to try to share important case study findings and research study overviews with a broader audience of clinicians, or really enthusiastic laypeople as a showcase of what I think the future of the field should look like, hence the Future of Functional Medicine Review. So let’s start with a case study. This case study was published in our November, 2020 review. The title of the study was Probiotics as a Monotherapy for H. Pylori. Some key points, a 31 year old female presented with no prior medical history. Symptoms: constipation, fatigue, bloating, weight loss resistance, and a high allostatic or high stress load. These symptoms primarily appeared after antibiotics, kind of a longer-term use. Previous testing did show positivity for H. pylori, via a serum IGA. IGA alone, probably not fully diagnostic and antibody testing for H. pylori, out of the available testing, is probably the least reliable.

DrMR:

Although it is something that can be used. She was currently following a ketogenic diet and had done some probiotics and hydrochloric acid supplementation in the past with mild benefit. Key note here, and this is something that we’re starting to incorporate into our patient intake process at the center, she had not used probiotic triple therapy. This is an important delineation because if someone says I used probiotics prior, saw some effects, saw no effect, but they haven’t used the three different categorical types together, in synergy, as in probiotic triple therapy, then that’s an opportunity for clinical gain. We want to make sure we parse that out and make that distinction in our note-taking. The differential diagnosis for this patient: SIBO, dysbiosis, or a gut pathogen, an H. pylori infection, also potential given her prior lab work, potentially low HCL, but sometimes those symptoms are more red herring of dysbiosis.

DrMR:

Also when considering that there could be low HCL, we can look at antiparietal cell antibodies as an indication of autoimmune gastritis. Now remember, the APCA or the antiparietal cell antibodies seem to only elevate during damage to the tissues, but once significant damage has been done, the antibodies drop. You can almost think of this like, and this is my crude analogy for which I apologize, but like vultures on the carcass. As soon as the carcass has been picked clean, they fly away. So what may be happening here? Again, my crude analogy is that once enough damage to the tissues of the lining of the stomach, that release hydrochloric acid, the parietal cells has been done. Then the vultures of the auto-immunity go somewhere else and the antibodies drop.

DrMR:

We’ve also been looking, side note here, at gastrin per the recommendation of Richard McCallum as a potential marker when subclinically elevated above 70 or 75, that may indicate someone is not adequately releasing hydrochloric acid. We do intend to publish a retrospective chart review on that finding. Now that we’ve been running it in the clinic for about a year.

SponsoredResources:

Hey everyone, this is Dr. Ruscio with a quick note about immunoglobulins. If you haven’t yet tried immunoglobulin therapy, I hope you will try our Intestinal Support Formula. To make it a little easier for you to do so, we are running a promotion of 10% OFF if you go to our website, DrRuscio.com/isf, you can use the code, TryISF. What’s novel and unique about immunoglobulins is they seem to attenuate immune system overzealousness in the gut by glomming onto and kind of deactivating, almost like taking a shard of glass and covering it with wax, against toxins and bacterial fragments like LPS. What ends up happening is instead of these fragments triggering an overzealous immune system, causing inflammation, exacerbating leaky gut, leading to a whole array of different things like dysbiosis, food reactive brain fog or bloating, that cascade is attenuated by the immunoglobulins. Perhaps the best study looking at this was the one by Weinstock that found a 75% response rate, albeit uncontrolled, in patients who did not respond to diet, who did not respond to Rifaximin, who did not respond to antispasmodics. Certainly an exciting and novel therapy. If it’s not one that you’ve tried, or if you want to try it again, go and check out our Intestinal Support Formula, use the code, TryISF for 10% OFF.

DrMR:

Okay. So the treatment recommendations. We ran a GI MAP stool test plus the antiparietal cell antibodies. We kept her on the keto diet with the intermittent fasting. We transitioned her from HCL to an HCL with enzymes. We reduced coffee intake. We recommended to get in the sun and also start on a vitamin D with vitamin K and on probiotic triple therapy. After a couple months on those recommendations, here is what was noted in terms of her responses. She had lost weight, her digestion had improved and over a seven month period, the GI MAP retesting showed resolution of H. pylori infection with only probiotics and these other supportive therapies, but no herbal antimicrobials and no antibiotics. I just want to restate that. There was a pre/post testing done on the GI MAP. So again, the history was, there was this potential signal of H. pylori from the serum IGA antibodies that were positive. That alone is not diagnostic. So you want to confirm that with more of a gold standard stool antigen recognition, or in this case, it’s stool PCR, but PCR testing has been validated.

DrMR:

So we retest with the GI MAP PCR, and we find initial positivity. After using probiotic triple therapy, not only did her symptoms improve, but the retesting showed symptom improvement, corresponding to a clearance of the H. pylori. This is a finding that I think really showcases how crucially important it is that providers realize there’s a lot of benefit from probiotics. And oftentimes we think that any significant pathogenic, or as in H. pylori, potentially pathogenic finding, has to be treated with antimicrobials or antibiotics. That’s an overtreatment paradigm that needs to be amended. This is a beautiful example of how, not only can we see symptom reduction, but also a corresponding improvement in an objective finding in this case, H pylori.

DrMR:

Now the patient did not complete the antiparietal cell testing. This is one of the challenges with doing multiple forms of testing. In this case, at home stool testing paired with going to Lab Corp or Quest or somewhere where they can do a phlebotomy in order to assess the antibodies. When people have limited time and limited resources, they don’t always follow through on all recommendations. Important note here. This patient was treated by Dr. Rob, and he makes an important note in his case write up that this is not a failure. It does not mean that you should berate the patient. I think that it’s really important that yes, as clinicians, we want to be able to be kind of firm at times. When I say firm, I mean, kind of firmly supportive and encouraging someone to take action.

DrMR:

But as this remark kind of encapsulates is the spirit of us being a team. We are on your side, and if you’re not able to do all the recommendations, that’s okay, we’ll make it work and we’ll keep the forward momentum going. That’s what I think is the really important takeaway here. I’m glad that Rob had made that note. So that’s the case study.

Combination Thyroid Therapy

DrMR:

Let’s now transition over to the thyroid review. This appeared in the December, 2020 review, and we entitled it “Clinical Review of Combination, T4 /T3 Therapy: Does the ratio matter?” I had discussed this on the podcast before. This re-analysis of the data, this quaternary deep dive, if you will, was inspired by discussions in the comment section of our clinicians newsletter. The comment essentially stated “I appreciate your reviewing all the data on T4 monotherapy as compared to T4 T3 combination therapy. However, you’re finding that there’s no significant benefits of T4 plus T3 over just T3 alone is incorrect. If you rerun the analysis and you compare T4 alone, as compared to only the studies using the combination, T4 and T3, but with a specific ratio, that’s the ratio that’s going to show you that the combination therapy is better.”

DrMR:

That’s actually a fair question. Now, I’m assuming that if there was a signal there, we would have picked it up during our initial analysis. Really at this point, it was probably the third time we’ve gone through this analysis. As you know, my thoughts on thyroid are ever evolving kind of a way from standard functional medicine paradigms, because both my clinical experience when being open to things, working, and also open to things, not working has shown me that the deeper, meticulous array of testing and/or specialization of medications doesn’t seem to offer any additional benefit.

DrMR:

Then, when you juxtapose that with what the research is finding, you see a reinforcement of that same thing, but it is possible that a certain ratio would yield a high response rate and would therefore modify my conclusion. So it is a question worth examination. So we go back into all the data tables and re-analyze the evidence. The key points here: There is no evidence from a review of 16 randomized controlled trials, assessing various ratios of T4 toT3 for a clear benefit of a specific ratio of T4 to T3. I believe the person who made this comment wanted to see a four to one ratio. Yes, I just cross referenced that. So the theory here is that four to one ratio is the special ratio and this is the ratio that will show more consistent benefit or favoring of T4 plus T3 over and being better than T4 alone. Okay. Probably the best data point we can point to here from the review of 16 RCTs did not corroborate that. Now there’s a little bit of nuance. Continuing: while there is some evidence for patients preferring a combination of T4 to T3 as we’ve discussed in the past. It’s 10% or less, so it’s something, but certainly not every patient or the majority.

DrMR:

This preference for T4 T3 combination therapy is not correlated to any particular ratio of T4 to T3. When we go into the data and we apply the filter system that we should all be using as clinicians to make sure we don’t get caught up reading a bunch of mechanistic conjecture, but rather look at the evidence as it comes higher into the evidence-based model of the pyramid, we find our conclusion.

DrMR:

Now it is also possible that there is some bias in the research community, which is why I always like to do this in juxtaposition to laying the data out in a data table and seeing if the conclusion from the review seemingly corresponds to what the hard data actually says. Normally the research papers are correct, but there can be bias. So I try to factor this in. We’ll come back to that in just a second, the data table and what that shows. We really just take all of the evidence points and lay them out. But there’s another study from 2019 entitled: A Systematic Review and Meta-Analysis of Patient Preference for Combination Thyroid Hormone Treatment for Hypothyroidism. It examined 348 hypothyroid individuals from seven blinded, randomized control trials, assessing patient preference for combination therapy. To quote “in a sensitivity analysis combination, treatment preference was explained in part by treatment effect on TSH” , that makes sense TSH is important, “mood and symptoms, but it did not correlate with quality of life, or body weight”. So what they’re saying there is that people who preferred combination therapy had better TSH, better mood and better symptoms, but no difference in quality of life or body weight. This is the more important part of that statement. So again, that tells us that there can be a preference for combination therapy, right? Important that we can not paint this as an all or none dichotomy. Again, to frame this, about 90% of patients see complete or adequate resolution of their symptoms from T4 alone. There’s a subset, who perhaps are genetically poor converters, who prefer combination therapy. What we see when we look at that cohort of 10% is TSH concentrations, mood and symptoms are what dictate that patient reported preference.

DrMR:

Now, again, coming back to quoting this paper, this is the key finding in a secondary dose response, meta-regression analysis. So when you do a meta-analysis and then you do a regression analysis of one of the confounders that would be a meta-regression. A statistically significant association of treatment preference was identified for total T3 dose, but not the T4 to T3 ratio. So said more simply, it seemed that giving people a higher dose of T3 was more likely to cause them to report preference for the T4 plus T3, but it did not track to any specific ratio. To this person trying to defend that combination therapy should be a mainstay of medicine, when we fact check, we see that there is a small subset of people who prefer combination therapy, but no, as this person was claiming, it does not seem to be due to a specific ratio.

DrMR:

That’s actually good because that tells us that we don’t need to be subjecting the patient to all of these follow-up visits, trying to dial in the ratios. How this translates into clinical practice is very important because this could save a patient thousands of dollars. If we’re going to be retesting and having a follow-up visit and then modifying, and then retesting and having another follow-up visit and potentially trying different forms of medication, some of which are, or are not covered by their insurance, this translates to quality of life lost, worry, and financial loss. So some key conclusions. Combination therapy at any dose or ratio does not appear to be a clinical game-changer. Addressing other areas of root imbalances, such as gut, nutrition, environmental will likely yield better impacts than manipulating the T4 to T3 ratios. There does appear to be a small signal for patient preference of combination therapy, T4 plus T3.

DrMR:

Although the research has not readily identified a clinically causative factor, perhaps that could be genetic conversion. Supporting weight loss and improving quality of life may be two domains leading to proceed patient preference. The other part here. There’s also a really nice writeup of thyroid physiology. What you see when you look at the total T4 production as compared to peripheral and central T3, you see a ratio of around four to five to one, and then central production of thyroid comes out at about 15 to 17 to one. If that’s difficult and you’re not following me, give the table a look. Cause if you look at what the body is doing naturally in juxtaposition to some of the medications, it helps fill in some of these gaps. Essentially the normal central thyroid production appears to be 15 to one.

DrMR:

So if we’re going to give a hormone, we would likely want to give the hormone in that ratio instead of this four to one ratio. We want to let the body metabolize the pill the same way as it would the hormone that the thyroid gland is going to squirt out naturally. We’re replicating through an exogenous hormone what the thyroid gland is producing itself, rather than trying to give the metabolized version, so to speak. Zooming out and getting out of the weeds, that data table, and this is the other thing I try to do because Ireally do not care about anything other than truth. I don’t have a certain philosophy that I’m trying to champion here regarding thyroid. All I care about is what helps improve patient wellbeing and how should we be navigating a patient through these various facets, in this case, thyroid hormone replacement therapy, so as to improve their wellbeing.

DrMR:

To that end, I like laying the data out in a table. Once you subscribe, I think the $1 fee for the month is worth just being able to look at this table, so that you can hopefully feel confident in taking a position on this controversy once and for all. In this review table, we take the eight studies that have really looked at the specific ratios. We label them according to do they find a specific ratio as best, or do they not? And what this breaks down to is two of the eight studies suggest that a specific ratio is best. One of the eight studies suggests that specific ratio, that four to one, is actually worse. Then five of eight studies, the majority, suggest the ratio does not matter.

DrMR:

So if we take the five of the eight studies that show the special ratio doesn’t matter. We add to that the one of the eight studies that found the special ratio makes people worse. That’s six of eight studies that refute the claim that a ratio is important and only two of the eight studies that find the ratio is helpful. Why that’s so important, to share some of my frustration, after we posted this analysis, we had someone comment, “well, I don’t think your analysis is right, because look at this one study”, pointing to one of the two studies that found the ratio did matter. All the while this person misses the fact that that study is already in our analysis. This really showcases to me that, and we’re all trying to help people here, but when we don’t take the time to read someone’s argument and we just reflectively throw at them the evidentiary point we have in our heads defending our position.

DrMR:

What we do is we don’t learn and we don’t get any better. When the first person asked the question, I thought it was a question worth examination. So I took the time to double, triple, and quadruple check and read all the references. We lay that out there and then unfortunately this person who I’m picking on here, admittedly, doesn’t even take the time to read all the hard work we’ve gone through to layout the clear answer to this question. She just parrots back the one study that has likely been cherry picked by whoever is teaching her on thyroid. Pardon me for editorializing this a little bit, but it speaks to part of the problem that we’re in, which is you can’t learn if you’re not going to look at someone’s argument, because if your evidence is included in our argument, and we’ve also incorporated that into a summary and displayed that your evidence is only one eighth of the data. When you add it all up 2/8 of data show you’re correct, 6/8 of the data show that you’re incorrect. It’s a pretty clear conclusion. We came at this analysis from a few different angles and it always nets out to the same finding, which is high level T4 alone will be fine for the majority of individuals, especially if you also address their gut. For a small subset, they will need and prefer T4 plus T3. The specific ratio of T4 T3 does not seem to matter.

RuscioResources:

Hi everyone. This is Dr. Ruscio. In case you need help, I wanted to quickly make you aware of what resources are available to you. If you go to drruscio.com/Resources, you will see a few links you can click through for more. Firstly, there is the clinic, which I’m immensely proud of. The fact that we deliver, cost-effective, simple, but highly efficacious, functional medicine. There’s also my book, Healthy Gut, Healthy You, which has been proven to allow those who’ve been unable to improve their health, even after seeing numerous doctors, to be able to help them finally feel better. There’s also our store where there’s a number of products like our Elemental Heal line, our probiotic line, and other gut supportive and health-supportive supplements. We now offer health coaching. So if you’ve read the book or listened to a podcast like this one, or are reading about a product and you need some help with how or when to use, or how to integrate with diet, we now offer health coaching to help you along your way. And then finally, if you are a clinician, there is our clinicians’ newsletter, the Future of Functional Medicine Review. I’m very proud to say, we’ve now had doctors who’ve read that newsletter, find challenging cases in their practices, apply what we teach in the newsletter and be able to help these patients who were otherwise considered challenging cases. Everything for these resources can be accessed through drruscio.com/Resources. Alrighty, back to the show.

Psilocybin Assisted Therapy

DrMR:

Okay. So coming to the final point here, which is a study that we found noteworthy because aspsychadelics are coming more into the spotlight, I think clinicians are wondering how can they be used. At least for me, for patients who’ve had prior physical or sexual abuse, or perhaps have really been harmed by the fact that you can go to a functional medicine provider, spend $2,000 on lab work and leave their thinking you have 15 things wrong with you because of all the lab findings. Now you take someone who has a predilection toward anxiety, and you just pour a ton of gas on that fire. When you see these people who are in psychological and emotional disarray, you can’t help but wonder, well, might there be a really attractive therapeutic recommendation of therapy plus psychedelics and in this case psilocybin. Here’s the study: Effects of Psilocybin Assisted Therapy on Major Depressive Disorder, A Randomized Control Trial. A few notes here, the growing study of psychedelics to treatment resistant psychological conditions at Johns Hopkins is growing. A few key points from this study. The study involved 27 total participants with 24 completing. 15 participants participated in immediate treatment with two sessions of psilocybin assisted psychotherapy, 12 participants served and were this kind of delayed treatment, waitlist control group. Over 50% of the total participants had rapid clinical improvements in depressive symptoms after just one treatment.

DrMR:

And over 50% of total participants were in clinical remission four weeks after the intervention. So pretty powerful results. The author has concluded: Findings suggest that psilocybin with therapy is effective in the treatment of major depressive disorder. Thus extending the results of previous studies of this intervention in patients with cancer and depression and of a non randomized study in participants with treatment resistant depression. So really exciting. Soon, around this podcast, either slightly before or slightly after, an interview with a clinical director from a center that uses ketamine. What’s attractive about ketamine is that it is different but similar to psilocybin. What’s so alluring about this is that ketamine is a prescription compound, whereas psilocybin, is very limited in terms of where you can use it. I don’t know of any state other than maybe perhaps just one region within California where psilocybin, AKA mushrooms are legal. So if a clinician thinks that a patient isn’t going to want to go the road of months of therapy or limbic retraining or EMDR, then psychedelic assisted psychotherapy has a lot of attractiveness. However, where are you going to send some of these people? To the underground world of psilocybin therapy? This is fine. I don’t mean to imply that there’s any sketchy business there, but for some people they’re going to be uncomfortable doing that. This is where a ketamine clinic may be a proximal stand in for psilocybin until regulations there expand.

Episode Wrap-Up

DrMR:

This is a showcasing of what we cover in the Future of Functional Medicine Review clinical newsletter case studies documenting important findings. In this case, probiotic triple therapy alone was able to eradicate H. pylori. Also the mini review on thyroid T4 monotherapy as compared to thyroid T4, plus T3 combination therapy, and really digging into the nuances and giving the argument from the camp of being meticulous with thyroid dosages, an earnest and honest examination, and concluding that there’s not ample data there showing us that that is something that should be brought into the clinical model. Also keeping abreast of some of what’s going on with psychedelic assisted psychotherapy.

DrMR:

Remember, if you go over to DrRuscio.com/review, you can plug in during the month of April for your full month of access for only a dollar. So even if you go in there on April 23rd, you’ll have a month from there, the clock doesn’t start until you go into your month trial. You’ll have access to all of this or the data tables, all the references, all the resources, our thyroid algorithm and all of our case studies. So I hope you will go over there and join up with us as we try to put forward the information that showcases a more efficacious and cost effective way of applying functional medicine. So as to help people get well quickly with minimal psychological and financial burden. All right guys, we will talk to you next time.

Outro:

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