John Robinson, NMD - Thyroid Autoimmunity Causal Relationships (2017 Conference) (LDN, low dose naltrexone)
Let's begin with a cursory review of auto-immunity. Of course, many of us here understand all of this, but let's go through it as it specifically relates to thyroid. Thyroid autoimmunity begins with some form of environmental trigger. One good example is an antigen from food allergies, and we've been hearing a lot about that this weekend. An APC, or an antigen presenting cell, presents the antigen to a CD4 cell, and the cascade we see here is triggered. So classically, we believe Hasimoto's to be TH1 dominant. But this graphic, modified from an article published in 2002 in Nature Reviews Immunology, proposed that autoimmune hypothyroidism, or Hasimoto's thyroiditis, results from both B cell and T cell activation, which could be both TH1 or TH2 dominant. Both mechanisms are generally occurring. I think that's important. However, they do propose that for autoimmune hyperthyroidism, or Graves' disease, it’s largely B-cell and TH2 dominant.
We also have to appreciate the classic TH1 versus TH2 models being challenged. There are other discovered classes: we've got a less known TH3, there's another one called TH17 with its own chemotactic components which LDN has been proposed to influence and to modulate. The excellent thing about LDN is its ability to influence both TH1 and TH2 and TH2 dominance over other immune classes, due to overall immune modulation. This would be particularly important in Hashimoto's, as it seems to be both TH1 and TH2, and or some other immune class known or unknown. So again, immune modulation is the key to be achieved through all these multiple therapeutic vectors.
We've got four therapies here to consider, to create and reestablish immune modulation. There are others of course, as we all know, but these tend to be the most direct routes, at least for us at our clinic. So of course, LDN, as I just stated, one of the great things about LDN to wield as a therapeutic tool is this ability to sort of modulate the immune system. It's clinically forgiving, and the patient benefits. Also, the use of thyroid hormone product that contains both T4 and active T3. My particular practice focuses on comprehensive hormone replacement therapy that considers estradiol, progesterone, testosterone, cortisol, insulin, growth hormone. We know that estrogen, progesterone and cortisol tend to increase TH1, whereas testosterone, DHA, and androgens tend to influence an increase TH2. The balance of course is important. The consideration of all these hormones comprehensively will provide optimal immune modulation. And finally, the gut. We've been hearing a lot about that this weekend. We know that the gut is associated with immunity, and its dysfunctions related to opportunistic infections, food sensitivities, dysbiosis, and autoimmunity in general.
We've been tracking observational internal data on LDN and thyroid antibodies for the past about two years, the best we could in a very busy practice. Since Hashimoto's is far more common than Graves' disease, we placed our focus on Hashimoto's. We presented a total of 53 patients; they're replaced in two categories: LDN-only, and LDN with a gut repair treatment protocol. It's really important to note that the LDN-only group is also receiving comprehensive thyroid nutritional hormonal support - please don't think that it's just that. We deal with things very comprehensively in general, but what I'm trying to say is that there's a difference between the LDN-only group versus the people who were also on some kind of specific gut repair protocol that I'll explain in the next slide.
We simply calculated the average thyroid peroxidase antibodies and the average thyroglobulin antibodies, then we calculated the average values of each after a length of treatment. You can see the average there. We've got far more patients in our practice on LDN than this sample here, but we only included patients who had at least one follow-up lab to show a calculable difference in their antibodies, so we excluded some out. The LDN-only group of 39 patients with an average treatment time of about 13 months, showed a very significant antibody drop, particularly in anti-TPO, which is of course the most common autoantibody, but of course we always check both. Beginning average antibodies on gut repair patients was much higher and the change was also less significant. This is consistent with the general observation that significant gut compromise is related to autoimmunity; and as we'll see later, that compliance to gut modifications is significant.
The patients who chose to do the gut protocol in general had the most obvious outright symptoms of gastrointestinal distress, hence motivating them to want to do the testing and follow through with the diet and the supplement commitment. So again, compliance. We can see that the decrease in thyroid antibodies in the LDN plus gut repair group was not as significant as the LDN-only group. This could be due to compliance and adherence to the gut treatment protocol, and the very small sample size of only 14 patients versus the 39.
So why did we do this? Why did we track this? What was the motivation? One, we want to make sure that we're incorporating a treatment strategy that was indeed effective at lowering antibodies. We wanted to see. Two, at least to my knowledge, there's little direct evidence and research about the use of LDN and its specific effects on thyroid antibodies, at least by what I could find If I am wrong about that, I encourage someone to let me know at the end of this presentation. Then three, because I'm a dork and I genuinely like to play this game and I like to crunch the numbers and see what we can find. We seek to add to the body of knowledge about LDN, however humble and modest this observation and methods are. It is our hope that other prescribers of LDN do the same as we have, or at least inspire the call to other researchers to provide in-depth analysis and results about LDN specific to thyroid autoimmunity.
Here's the gut repair protocol, a little bit of detail. We start off with a serum analysis of IgG reactivity to 154 different foods. It's a standard industry test. For those with high suspicion of wheat and/or gluten activity, we'll add a different test as well. And that'll include glutenin, gliadin, and what I think is very important, non-wheat, protein fractions as well. All patients in our sample had at least 11+ foods that they were reactive to. That could have been wheat, gluten, or the other foods. They were then instructed to follow a diet that of course removes these foods, and they have to do that for at least 90 days. Our gut repair protocol can, of course, go longer, but we start them off with a three-month process. During that 90-day restriction, they follow the supplement regimen designed to repair and restore gastrointestinal integrity and function. You can see the gut cocktail here. This is a simple, relatively taste neutral beverage, and includes glutamine, fructooligosaccharides, Acacia senegal, and n-acetyl-d-glucosamine, the classic herbs slippery elm in a powder form, and good old aloe vera juice. They can mix this in water, or a juice of their choice. It's consumed twice daily. We also use a professional strength, broad spectrum probiotic. We start off with a loading phase of 300 billion times 10 days, and then we go to 100 billion daily for about two months after that, and then about 30 billion as maintenance after that. Finally, we used a dual phase digestive enzyme formula that includes hydrochloric acid, pepsin, et cetera, as you can see here.
Let's do a quick couple of case reviews here. Here's a great example of a patient from our sample who was prescribed LDN and diagnosed with leaky gut, and placed on our gut protocol. He presented with a strong history of irritable bowel syndrome diagnosed when he was very young. He goes through the normal testing. He had several loose bowel movements when he first presented, including uncomplicated hemorrhoids with some occult blood. He was routinely screened by a gastrointestinal specialist. His thyroid antibodies are elevated. He also presented as hypogonadal, and he was only 28. Aside from the gut repair protocol, he was prescribed natural desiccated thyroid, and of course LDN 4.5 mg. He was really compliant for those first six months. Stools largely normalized, and his hemorrhoids improved. He got better and you can see his antibodies really got better as well, lowered drastically. Because he improved and it was part of the typical 90-day protocol, he was less compliant. A lot of times once patients get better, they start to slip a little bit, as we know, and you can see that his antibodies slipped, but he was still on the LDN, but his antibodies went back up a little bit. So this is an example of how important comprehensive care is when treating thyroid autoimmunity or any autoimmunity. The food sensitivities and gut permeability are not always fully corrected after 90 days. Sometimes we have to continue to go much longer.
Now to speak to his hypogonadism, I recently presented in London at the International Congress on Naturopathic Medicine, and my presentation was on the global decline of testosterone and sperm in men. I presented research regarding all of this and what I had found, and it was only maybe about three weeks after that presentation that another large landmark study came out of Jerusalem that did really, in fact, confirm that sperm is lowering in men. Okay. Part of that presentation was the causal relationships for lowering testosterone and sperm, and what the functional medicine practitioner can do to help. There are all kinds of reasons for this decline, but we think of diet and toxin exposure, gut compromise, and maybe even autoimmune thyroid disease. And maybe that's relevant to this example. So, in this patient, a change in diet and improvement, all of this, it actually helped with his testosterone. It's also important to mention that he and his wife were trying to get pregnant for about a year before he came to see us. And they got pregnant. So coincidence? I don't know, maybe, maybe not.
Here's another example from our sample. This was a 37-year-old female with high expression of autoimmunity, in an LDN-only group because she didn't do anything significant with her diet. She had other things going on: vitiligo, vaginal lichen sclerosis; and we discovered Hashimoto's. Interestingly, she had already known about that to some degree. They had seen serum elevated antibodies, but her conventional doctor said, well, there's nothing really you should do about that. I think we've seen some evidence here this weekend that it is important to preemptively work with someone who has that, despite what they may or may not be presenting with clinically. This patient also had low testosterone and suppressed estradiol production from oral contraceptive use. Oral contraceptives suppress ovarian function, it’s just what they do. It also can lead to gut dysbiosis, nutritional deficiencies, particularly magnesium. I gave her a low dose estradiol, optimal testosterone using subcutaneous pellets, something we focus on, and a plan to slowly wean off of her oral contraceptives. She was also placed on a nutritional regimen, of course desiccated thyroid, and of course LDN 4.5 mg. When she returned, you can see it was pretty straight forward. In a relative very short period of time, about five months, her antibodies lowered, her symptoms drastically improved. She had less headaches, which was another big concern when she first came in to see me. She's off the birth control pill, and we were able to just get her off the estrogen. She just didn't need the estradiol anymore; but she maintained the testosterone - she liked the libido from that, so we maintained that.
Why did her antibodies lower? In this case it could be several variables. It could be just getting off of the oral contraceptives, it could be the use of the natural desiccated thyroid, the normalizing of her sex hormones, all of which have immune modulating effects in and of themselves. Or, at least these could be obstacles to cure, something we say in naturopathic medicine. But of course, it could just be the LDN.
We’re here at an LDN conference. We've gathered under the basic premise that we believe LDN is worth prescribing. I certainly do, but I'm seeing changes with its use in my patients. I'm not a fan of the statement that science is settled. I think it makes us intellectually sluggish. So I think we should continue to look deeper for the sake of our patients.
A final case review, another example from our sample, technically in the LDN-only group, but who did make specific diet changes I'll explain here. This is a 56-year-old menopausal female. A large percentage of our patients would fall into this demographic. She's on desiccated thyroid, estradiol, testosterone subcutaneous pellets with oral opposing progesterone. Her initial anti-TPO was 2315. It rose up a little bit after that. At that point, she got a little more motivated to get on the LDN. We gave her that, and you can see that it started to lower.
Hashimoto's presents with these flares. You can have up and down of the antibody response anyway. But about six months later, on July 8th, 2016, we discovered mild insulin resistance and suboptimal glucose; hemoglobin A1C, insulin, homocysteine levels, all being suboptimal. At that point, I'd given her 500 mg tid of Metformin, and a proprietary palladium alpha lipoic acid mineral complex that some of you may be familiar with. Those were an injection form. I reduced her net carbs at 125. That seems to be a very reasonable and effective number, and all this of course led to getting rid of a lot of her grain-based carbohydrates as well. You can see, in a mere four months after that her anti-TPO antibodies dropped to only 74, essentially normal. This was the lowest reading she had ever had.
Was it the LDN by itself? Perhaps. I've observed that LDN very often takes several months for the full impact on thyroid antibodies to be realized, yet the idea that she avoided, or at least limited excessive carbohydrates, particularly grain-based carbohydrates, that could be part of it. Her treatment for the insulin resistance included the use of Metformin and the low carb diet. Maybe that's the reason. There is evidence that overproduction of insulin leads to B cell stimulation, possibly potentiating the TH1 pathway.
Ultimately, comprehensive strategies help the patient to realize optimal results. That should be the perspective of any functional medicine practitioner who decides to use LDN. I believe it's important to approach thyroid management in this comprehensive fashion. Tolle causam, or treat the cause. This is another tenant in naturopathic medicine that is known within the functional medicine world. I believe that the use of LDN helps us to treat that core cause, that often is autoimmunity. Another saying in naturopathic medicine is to heal the gut and the rest will follow. And this is a generalized idiom that so often is true. It's almost always an excellent place to start.
The endocrine system is one, if not the most vital system within the body. We have hormonal influences and production within the womb before we ever develop a nervous system. So dare to balance the endocrine system and you help many things with your patients, including thyroid autoimmunity. A healthy immune system is also key to managing thyroid disease. LDN proves to be one of the most effective tools in doing this, particularly when it comes to lowering an antibody response, I believe.
And finally, one of the most overlooked possibilities in thyroid hormone diagnosis and management is the clinical measurement of metabolic rates. It's something that we look at very, I believe, somewhat uniquely. And certainly of course, we look at mitochondrial function, as thyroid hormone influences mitochondrial function, second to none. If we can look at things from that perspective and correct that. even above and beyond the conventional perspective of serum analysis, then the patient realizes optimal outcomes, the patient actually gets well.
I look forward to your feedback and input on this presentation. I hope that it helps to lessen the pain of at least even one person. Thanks for your attention. Thank you.
Keywords: low dose naltrexone, LDN, thyroid, Hashimoto’s, autoimmune, antigen, TH1, TH2, Graves', immune modulation, hormone, gut, dysbiosis, thyroid peroxidase antibodies, thyroglobulin antibodies
Presentation at the LDN 2017 Conference