Gluten, MTHFR, Mast Cells, and More | Office Hours (Ep 155)

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Dr. Linda Bluestein: [00:00:00] It does seem extremely common for people to be gluten sensitive, even when they don't have celiac in this population of people. Sometimes people will have eliminated gluten from their diet for a period of several weeks and say, well, gluten isn't the problem because nothing changed. And what I would say to that is imagine that you're sitting on two tax.

If you're sitting on two tacks, one on each butt cheek, and you remove one tack, you're still gonna feel the other tack.

Welcome back to the most popular EDS podcast, bendy Bodies. I'm your host and founder, Dr. Linda Bluestein, the Hypermobility MD. We have so much in store for you today. I can't wait for you to hear it. I also wanna share with you a new, fabulous resource, my Substack newsletter called The Bendy Bulletin. [00:01:00] My team has been putting a lot of work into these newsletters to make sure you get what you need, but we also want to hear from you.

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In this episode, I'm going cover EDS irregular rhythm patterns. EDS and Celiac disease, EDS and M-T-H-F-R, what clinicians should do if they can't get [00:02:00] patients in to see a geneticist yet they don't feel comfortable diagnosing hypermobile EDS and associated conditions. The million dollar question, should people with EDS stretch and so much more.

This is going to be really fun. So grab a salty snack, your favorite electrolyte drink. Get comfy in your favorite chair or in your car, and let's get ready to rock and roll.

So for this episode, we're gonna start with something a little bit different. For the A MA style portion. So I wanna tell you about an amazing podcast I was on recently. I was a guest on the Curb Siders podcast and this was episode number four 80 of their show. We'll put a link in the show notes, so be sure to check that out.

This is a top rated US medical podcast that it is designed for internists and other clinicians. I was so shocked and so happy to hear from the curbside staff clinicians. Over 40,000 [00:03:00] listened to this particular episode, so that means medical doctors dos, nurse practitioners, PAs, et cetera. This is a huge win for raising awareness about joint hypermobility and connective tissue disorders.

This episode actually ranks in the top 10 of their 2025 episodes. They also got a lot of great follow up questions from their listeners, so I'm gonna start this episode today by answering some of their listener questions. So the first question comes from Amanda, who is a nurse practitioner, and Amanda asks, I have a lot of people asking for help with EDS.

I don't have a geneticist anymore in my local area to rule in or rule out different types or subtypes of EDS or the Aler Danlos syndromes. In this case, is it okay to go ahead and make the diagnosis based on the criteria or should I be looking for a geneticist to test this definitively? So first of all, I want to say to Amanda, thank you so much for caring [00:04:00] enough to ask.

Um, the fact that you're even trying to help your patients with possible Ehlers-Danlos Syndrome or hypermobility spectrum disorders already puts you ahead of the curve. Many people struggle to find providers who are even willing to consider these diagnoses. So your openness is a huge gift. That said, I wanna gently so.

Trips up a lot of clinicians. The Beighton score alone is not enough to diagnose hypermobile EDS. It's just one small piece of the puzzle. And this is a specific tool to assess for generalized joint hypermobility. It's not an EDS scoring tool, and even for that, it has its limitations. Well, why does the BITTON score have limitations?

We know it's a really, really frequently used tool. Well, first of all, it's age and gender dependent. People tend to become less flexible with age, and women and children tend to score higher naturally. It also only assesses a limited number of joints. It says there's five joint [00:05:00] areas, so we know that it's, you know, can you touch your thumb to your forearm?

Can you bend back your fifth finger? Um, we look at elbow hyperextension, and if you're watching this on YouTube, you can see me doing some of these maneuvers. Of course, you're not gonna be as easily see my knee hyperextension right now. Um, but those are the first four maneuvers. And the last maneuver is, can you put your palms flat on the floor without bending your knees?

So we know that the Bitton score misses hypermobility in other places like the shoulders, the ankles, the hips, the jaw, and so many other really, really important places. Also, the bite and score is a moment in time test, and it doesn't reflect someone's history of hypermobility, which is especially important for adults who have stiffened over time due to pain, injury, arthritis, or surgery.

The Biden score is biased towards the upper extremities, but in many populations, for example, dancers, the lower extremities are injured more frequently. So that's where the 2003 five point questionnaire by Dr. Shakim and Graham [00:06:00] comes in. This is a very quick screening tool and it asks about historical signs of joint hypermobility.

This is very, very useful in adults, particularly when the bite score is no longer reliable. So let's talk really quickly about what that is. So first question, can you now, or could you ever place your palms flat on the floor without bending your knees? Second question, can you now, or could you ever bend your thumb to touch your forearm?

Next, as a child, did you amuse your friends by contorting your body into strange shapes? Or could you do the splits next as a child or teenager? Did your shoulder or kneecap dislocate on more than one occasion? And the last question, do you consider yourself double jointed? A yes to two or more of these questions is strongly suggestive of generalized joint hypermobility.

Now we know that there are four different types of joint hypermobility, so I wanna quickly explain what those are. So there's peripheral joint hypermobility where you're hypermobile in your hands and your feet, but not elsewhere. There's localized joint hypermobility where you're hypermobile [00:07:00] in just a couple of joints or maybe three joints.

There's generalized joint hypermobility, which this is an excellent tool for, and there's historical joint hypermobility. That means that you were hypermobile in the past, but you're not anymore. So if you do the five point questionnaire, this is a great tool for determining if someone has generalized joint hypermobility, either now or in the past.

Now, let's talk about specifically the hypermobile EDS diagnosis and how this is much more than just hypermobility. So the 2017 International Diagnostic criteria for Hypermobile EDS require number one generalized joint hypermobility as assessed by the BIT score and or the five point questionnaire. And if you look specifically at this worksheet, which is linked@bendybodiespodcast.com, under the resources page, you will see that you're only supposed to gain one more point if you test positive on the five point questionnaire.

Now, I personally, in my clinical practice, a person could have a [00:08:00] biting score of zero, but if they have two or more answers on the five point questionnaire, I will still consider that they probably have generalized joint hypermobility. I also will assess for a lot of other joints besides those that are represented in the biting score, so I don't just look at the wrist and the finger and the elbows and knees, et cetera.

But I'll look at other joints that they feel like are unstable or painful. So I'll look at the ankles and the shoulders and, um, other parts of the body. You also need for the 2017 criteria, at least two of the following systemic features of a connective tissue disorder, a positive family history, or musculoskeletal complaints like chronic pain or joint instability.

Number three, exclusion of other heritable and acquired connective tissue disorders. Now let's talk about that second part really quickly. When they talk about systemic features of a connective tissue disorder. You might have had somebody go through this list with you before. There's 12 different features and you need to have at least five of them.[00:09:00] 

But the really, really challenging thing is a lot of these features are very subjective, and the question is, where do we draw the line? So for example. Of the criteria is soft and velvety skin well to what? And of course that's gonna change with age. That's a very subjective thing, right? So that's really, really challenging.

It makes the criteria challenging. We can be more specific when it comes to hyper extensibility of skin because we measure that as greater than 1.5 centimeters at the forearm, and we can also like assess the neck and, and things like that. But some of these criteria. Another one would be a high air, uh, narrow arched upper palate.

You know, that's also subjective, um, because it's not like any of us are taking a tool and measuring exactly how wide that upper palate is, and a lot of people have had their palate expanded. So while hypermobile EDS is a clinical diagnosis made completely based on a combination of signs, symptoms, history, and exclusion.

There's [00:10:00] also a lot of nuance to this, and geneticists are often a great fit. If we have some of the red flags that we might be suspecting a more rare type of EDS, or maybe this makes us suspect something like Louis Dietz or Marfan Syndrome or something like that. So if a person has any of these red flags, then we want to make sure that we send those people to a geneticist for sure.

So those include dislocated hips at birth, um, club foot, uh, pneumothorax, which is where there's air in between the pleura or the lighting of the lung and the chest wall. People who don't just have a little bit of easy bleeding, but they actually bleed. Um, maybe they have ruptured their. Some of their internal organs, they've ruptured some blood vessels.

Um, these are some of the red flags that we wanna look for. For a complete list of red flags, please visit the bendy bodies podcast.com website and check out the resources. There's a red flags document there, but it's very important to know that these criteria are [00:11:00] being revised in a project called the Road to 2026.

So this is very exciting because we know that the 2017 criteria have some definite challenges to them. Number one, as I pointed out, a lot of these, uh, criteria are very subjective, and where do we draw the line? And they can change over time. So while a person might represent differently one day, then another day they actually could fall into the diagnosis.

So this has also happened to people. Where they meet the diagnostic criteria for hypermobile EDS at one assessment, but then they have another assessment and they don't meet the criteria anymore. So this also looks like we're flip flopping and is bad for the community as a whole. So hopefully this road to 2026 is going to provide much more clarity, reliability, and inclusivity in the diagnostic process for hypermobile EDS.

And this is especially important for people who don't meet the strict 2017 criteria, but clearly have a connective [00:12:00] tissue disorder. So I would say that we are on the cusp of a more refined framework, and it's very, very exciting. Um, back to Amanda. In the meantime, your willingness to evaluate patients thoroughly using tools like the five point questionnaire and listening closely to their lived experience puts you in a strong position to help.

Don't hesitate to consult with others or refer to clinics with expertise when possible, but know that your role is very, very important, especially in this huge diagnostic gap that so many patients fall into. Treating symptoms should take priority and fortunately there are ways to do that. Please check out my peer reviewed journal article, hope for Hypermobility, part two, an Integrative Approach to Treating Symptomatic Joint Hypermobility.

There will be a link in the show notes so you can access the full text of this publication. I also talked about this topic navigating treatment for Hypermobile EDS and HS D in newsletter, and we'll link that in the [00:13:00] show notes as well. Okay, so I have a corollary to this question. Patients often ask how they can find the right provider.

This is such an important, but also very tricky question. Finding the right provider for hypermobile EDS or hypermobility spectrum disorder evaluation can be challenging, but not impossible. First, it's important to know that a diagnosis does not have to come from a geneticist. In fact, for hypermobile EDS and HSD, which we don't have a known genetic marker for yet, the diagnosis is clinical, so it's based on medical history, physical exam, and specific criteria.

That means that a knowledgeable rheumatologist, physiatrist, sports medicine doctor, or primary care provider can make the diagnosis as long as they're experienced with connective tissue disorders and or are willing to learn. So what do I suggest patients look for? These are the things I think are most important.

Number one, ideally a clinician with experience in hypermobility chronic pain or autonomic dysfunction, [00:14:00] because we know that many people with Hypermobile EDS or HSD also have things like POTS or MCAS. Also visit local or online support groups to find recommended providers. Since lived experiences can be an incredibly useful guide, you wanna look for providers that are compassionate and curious.

'cause that is generally much more important than any given specialty, any specialty or a GP can be very helpful. A couple of tips for patients prepare a symptom timeline and any past records in advance because most providers aren't experts, so you definitely want to go in very prepared if you're having trouble finding a local expert.

Telemedicine can be a helpful. Providers are offering virtual. Consultations which can expand access, especially if you live in an area without specialists. Now that being said, there are important limitations to keep in mind. Medical licensing laws usually restrict doctors to seeing patients only in [00:15:00] the states where they're licensed, and some evaluations are much more effective when done in person.

Whenever possible. I strongly recommend that your first evaluation be face-to-face. An in-person visit allows for a more thorough assessment. It gives the clinician the opportunity to examine your skin texture and scarring, evaluate skin stretchiness, observe how you move and walk, and physically examine your joints, all of which are difficult or nearly impossible to do accurately via video.

To help bridge this gap, I created a unique service called EDU Coaching through my Bendy Bodies platform. This was in response to an overwhelming number of requests I received from individuals across the globe who were struggling to find guidance. In these one-on-one sessions, I provide personalized education, tailored resources, and clinical insight.

Now, this is not medical advice, but this will still help you advocate for yourself more effectively. Many clients have shared that after their EDU coaching session, they were able to move [00:16:00] forward with getting a diagnosis or accessing better care from their own medical team. Lastly, don't get discouraged if it takes time.

A diagnosis is valuable and you deserve to have a proper evaluation and treatment. A diagnosis is not just for clarity, but for access and care and accommodations. But also what really matters is getting the support that you need to feel better, whether or not you have a label right away. Hopefully that helps Amanda.

That was a very, very long answer to your question. Okay, so the next question that's kind of related is from Min. So this was a voicemail received by Curbside and Min called to ask about a 24-year-old patient she has with new onset SVT or Supra Ventricular Tachycardia. She's planning on sending this young patient to a cardiologist, but mom of this patient has EDS and wants the daughter sent to a specialist for a workup.

And she wants to know what I would recommend that they do. [00:17:00] So first of all, I would want to know is this s ventricular tachycardia, um, actually documented on a Holter study, which I imagine that it is. 'cause I don't think men would be asking this question this way otherwise. So first, what is s Ventricular Tachycardia?

It is a rapid heart rhythm that originates from the upper part of the heart. It causes a fast fluttering feeling in the chest. Palpitations and it can cause other symptoms like dizziness, fatigue, or shortness of breath. Now this may sound quite familiar for people that have dysautonomia or pots, they're thinking my heart raises all the time, um, and I feel dizzy and fatigued and short of breath.

But it's important to know that SBT is a very specific arrhythmia. And although heart rates can overlap with sinus tachycardia, they are two different things. So these two different things have different evaluations and treatment. Most patients that have dysautonomia or pots, if they do have a Holter study, they have sinus tachycardia, which means that the heart [00:18:00] is beating with the normal kind of rhythm, but it's just beating faster when they stand up or change positions.

Someone with SVT or sup, ventricular tachycardia could get even higher fast rates, and usually this has an abrupt start and an abrupt stop, and it is actually truly an arrhythmia or an abnormal heart rhythm. So assuming that this person, um, does have SVT, I would definitely want them to be seen by a cardiologist.

Because it is possible that they might be a candidate for a procedure like an ablation, um, where they actually go in and, and burn a part of the heart that is contributing to that arrhythmia. Um, and you wanna make sure that they get a proper and full evaluation. So I would send this person first to a cardiologist, and I would think most all cardiologists could do a really good evaluation for SVT.

Not all cardiologists, however, are very knowledgeable about Dysautonomia or one of the forms of dysautonomia called pots, which is [00:19:00] postural orthostatic Tachycardia syndrome. Pots is where when you change positions, you don't get enough blood flow to your head. So your heart races in an attempt to compensate and you may feel faint or you actually may faint.

You don't have to actually faint in order to have pots. Um, you, when you, when you go from like sitting to standing or laying down to sitting up, um, you can get like a black, uh, curtain feeling kind of closing in. Um, you feel, you feel dizzy. A variety of different symptoms can, can happen with pots. Not all cardiologists are very familiar with pots.

Unfortunately. I have seen cardiologists send people out for a quote, evaluation for pots. Um, just using a Holter study when really they should have either a tilt table test or they should be having, um, a NASA lean test or orthostatic mital sign test that lasts at least 10 minutes after standing in order to assess for the heart rate change.

Um, with that position change. [00:20:00] So while sending the person to a cardiologist is very important for the evaluation for SVT with mom having a history of EDS, that puts the daughter at an increased risk of having pots. 'cause we know there's a huge overlap between EDS and pots. So I would probably say that if you have a cardiologist who is number one, either more open-minded, um, or number two, more aware of.

Pots or other forms of dysautonomia, that would be a better place to send this person because while they're getting evaluated for the SVT, it would be a good idea to also evaluate them for pots. I would also want to find out who diagnosed mom. Uh, was it a physical medicine and rehabilitation doctor? Was it a rheumatologist?

Maybe it was mom's internist, um, or gp. But I would want to find out, you know, who does mom go to? Can the daughter go to that same doctor? Um, you know, unfortunately you are going to have to build a team. There is no one doctor who can handle all of the. [00:21:00] Symptoms and constellation of signs that a person with EDS and comorbidities have.

Um, it's very, very common for my patients who are working with me. I'm their, I'm their pain medicine doctor, and sometimes they call me also their quarterback, but they might also have a neurologist and sometimes they have multiple neurologists. They might have a neurologist that specializes in migraine, and then they might have another neurologist who specializes in pots.

Um, which I should point out that POTS is actually a neurologic condition. It's not a cardiac condition. So while some cardiologists are fairly knowledgeable about pots, neurologists are generally more knowledgeable. So this person might. If they do, um, meet the criteria for pots, they might benefit from having a neurologist that specializes in pots.

They probably should have a rheumatologic workup to rule out a rheumatologic condition if they do have joint pain, um, especially if they have any joint swelling or redness or anything that would suggest that they might have an autoimmune condition. [00:22:00] Um, and you also want to make sure that, uh, whatever symptoms that this daughter has that you're addressing, um, each of those.

So again, a. A neurologist is sometimes a, an important doctor to have. It's very, very common that gynecology is involved. Sometimes urology, sometimes a neurosurgery if they have, uh, problems with cervical spine instability or Chiari Malformation or tethered cord. So without knowing what the additional symptoms that the daughter has, um, it's hard to.

The daughter should definitely have a a point person for possible EDS and get evaluated for that because the sooner a person can get diagnosed, the sooner that they can get down the proper treatment path. Okay, next question, which is kind of related to these previous questions. One of my followers recently asked, how can I tell if my doctor is knowledgeable enough about dysautonomia to treat my daughter?

Obviously, this is kind of related to the previous question. [00:23:00] It's completely valid, and this is a very important question, but it can also be very tricky, especially when you wanna keep the tone collaborative and non-confrontational. So here's a thoughtful and respectful way to ask. I understand that as a primary care doctor or specialist, you're expected to manage a wide range of conditions, and I appreciate how complex that can be.

Right now I'm trying to build a care team for my daughter to help her feel and function better. We're exploring a possible diagnosis of dysautonomia or pots, and I'd love to ask a few questions to see if you might be the right fit to help us on this journey. How many patients with dysautonomia or POTS have you treated?

What's your general treatment philosophy? Do you tend to start with lifestyle changes or do you consider medications early on? Do you feel comfortable managing dysautonomia or would it make more sense to refer us to someone who specializes in it? So I hope that's helpful. I think that's a good approach because it respects the provider's expertise, but also [00:24:00] gently allows you to assess their experience and whether or not they're a good fit for your needs.

Definitely it's important to keep the conversation open and collaborative, um, especially because you wanna be building your care team. Okay, we're gonna come back to another curbside question. This curbside question is from Mark, who is a hospitalist in Madison, Wisconsin, right in my old, uh, backyard. I was in Wau, Wisconsin for 26 years.

So Mark from what Madison, Wisconsin wants to know the evidence behind the M-T-H-F-R gene abnormalities and how do I deal with the situation? Okay. Uh, mark. This comes up a lot, especially in patients with complex chronic symptoms who have spent years without answers. Many people turn to private testing or functional medicine sources and come in convinced that their M-T-H-F-R mutation is at the root of their health issues, sometimes including hypermobile EDS.

So first, let's talk about the evidence. As we [00:25:00] discussed a few minutes ago, hypermobile EDS is a clinical diagnosis based on connective tissue findings and no single gene mutation, including M-T-H-F-R has been linked to its cause. So, while classical and vascular and all the other subtypes of EDS are associated with known mutations, the gene or genes responsible for hypermobile EDS have not yet been conclusively identified despite extensive research.

So there is no scientific evidence that M-T-H-F-R mutations cause hypermobile EDS or any other subtype of EDS for that matter. But let's back up a little bit about the M-T-H-F-R gene. I'm gonna try to pronounce this. I'm not sure if I'm gonna get this right. Okay. The M-T-H-F-R gene methyl. TE tried hydro folate reductase does play a role in methylation, a biochemical process involved in folate metabolism and homocysteine Regulation.

Variants like C 6 7 [00:26:00] 70 T and A 1 29 8 C are common. Up to 30 to 50% of the population carries one or two copies of a variant. Most people with M-T-H-F-R variants are completely healthy and never experience any methylation related issues. Some individuals with two copies of C 6 7 70 T may have elevated homocysteine levels, which can be associated with cardiovascular risk, but even that link is modest and not causally connected to connective tissue disorders like hypermobile EDS.

But you might be asking, what about the studies out of Vanderbilt? And that's an excellent question. We are going to talk about that when we come back from this quick break. We'll be right back.

This episode of the Bendy Bodies podcast is brought to you by EDS guardians, paying it forward. In the Aler Danlos syndromes community patient to patient for the common good. I'm proud to serve on the inaugural board of directors for [00:27:00] EDS Guardians, a small charity with a big mission and a big heart. Now seeking donors, volunteers, and partners, patient advocacy and support programs available now.

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This helps us reach so many more people and spread the information to everyone. Thank you so much again, and enjoy the rest of the episode.

Okay, we're back and we are answering some fabulous questions from the curbside podcast listeners. So I want you to be sure to check out episode four 80 of the curbside. We're gonna link that in the show notes. I was so honored to be a guest on their show, and I also wanted to point out that one of their co-host, Dr.

[00:28:00] Matt Wado, was a guest on Bendy Bodies. So we will also link that in the show notes. And in that episode we talked about the role that an internist plays in patients that have Hypermobile EDS and HSD. So that was a really important conversation. I hope that you'll check that out Also. Okay, so now back to our M-T-H-F-R conversation.

So there was a recent study published in a CR Open Rheumatology that examined the presence of M-T-H-F-R polymorphisms among patients with hypermobile EDS and HSD in a US hypermobility clinic. The researchers found that 85% of the.

A C 6 7 70 T or a eight mt. HFR Polymorphism in heterozygous or homozygous states. So heterozygous meaning they only had one abnormal copy or homozygous, meaning that they had two abnormal copies. Specifically, 53% [00:29:00] had the 6 7 7 CT slash TT genotype, and about 50% had the 1 2 9 8 ac slash cc genotype.

Notably, about 40% of the patients exhibited two copies of MT HFR variant alleles. This study does suggest a high prevalence of M-T-H-F-R polymorphisms among individuals with hypermobility, which might support the hypothesis that hypermobility could be influenced by folate metabolism. However, it's important to interpret these findings with caution.

While this study indicates a notable presence of M-T-H-F-R variants in this patient population, it does not establish a causal relationship between M-T-H-F-R, polymorphisms and H EDS or HSD. Further research is needed to determine whether these genetic variations contribute to the development or severity of hypermobility disorders.

In clinical practice, when patients present with concerns about M-T-H-F-R mutations [00:30:00] in relation to hypermobile EDS or HSD, it's important to acknowledge their concerns and provide evidenced-based information. While M-T-H-F-R polymorphisms are common in the general population and may influence folate metabolism, their role in hypermobile EDS remains unclear.

Clinicians should focus on comprehensive evaluations and evidence based. Strategies for Hypermobile EDS while staying informed about emerging research in this area. So the bottom line is most people with M-T-H-F-R variants are healthy. Patient concerns can still be addressed respectively without indulging pseudoscience.

M-T-H-F-R mutations are not a proven cause of hypermobile EDS. It's a balance between meeting patients where they are and steering them towards evidence-based care. And in patients with EDS and similar conditions, trust and rapport are half the battle. So how do I actually approach this? This is what I usually do.

Number one, I validate their [00:31:00] efforts. I really appreciate how much time and effort you've put into trying to understand your health. You're clearly invested in getting answers, and that's important. And I will tell you that I learn from my patients every single day when they come to me having done research on various different things.

Sometimes they've seen the research before I have, and I learn so much from them. So this is really, really important that we encourage them to do their research, but also in an evidenced based way. We also want to gently remind them that the M-T-H-F-R gene does affect how the body processes folate. And yes, there are variants that slightly affect this process.

We don't have really solid evidence yet. Linking it to Aler Danlos syndromes or joint hypermobility. Having an M-T-H-F-R mutation is very common, like eye color or blood type. And for most people it does illness.

Say if you're experiencing fatigue, pain, mood issues, or GI symptoms, these [00:32:00] are very real and deserve a thorough evaluation. I'd like to focus on understanding these symptoms fully, whether or not M-T-H-F-R is involved. We can support methylation if needed. If they're concerned about methylation or homocysteine levels, I may offer to check homocysteine or B12 and folate levels, and if warranted, recommend methylated B vitamins, for example, methylfolate and methylcobalamin.

These are generally safe, inexpensive, and give patients something actionable. Okay, so hopefully that helps with the M-T-H-F-R question. This does come up all the time in my practice, and I'm so curious to see further research in this area. I'm excited about the research that has been done at Vanderbilt, and I really think we need so much more study, but at this point, that's really one study and it's not that large of a population, especially when you consider how common these variants are in the general population.

We need a lot more data. Okay, the next curbside or question comes from Martina. Martina asks, [00:33:00] I have a couple of patients with EDS and celiac disease. Is there a relationship? I get this question a lot. Um, the short answer is that while there's no officially recognized direct link, there are many people with EDS who do report having celiac or other form of gluten sensitivity, and there may be some overlapping mechanisms that are worth paying attention to.

Both conditions are often underdiagnosed, especially in women, and both can involve gut symptoms like bloating, abdominal pain, and nutrient malabsorption in celiac disease. That's due to an autoimmune reaction to gluten that damages the small intestine. In EDS, especially the hypermobile type gut symptoms may stem from dysmotility.

Connective tissue laxity in the GI tract or co-occurring conditions like mast cell activation disorders or pots, postural orthostatic tachycardia syndrome. Some researchers are starting to look into whether people with EDS may be more prone to immune system dysregulation, which could explain why autoimmune conditions like celiac show up [00:34:00] more often in this group.

It's not conclusive yet, but a conversation that's growing in the medical community. If you're dealing with one or both of these conditions, or if you're wondering if gluten is playing a role in your symptoms, you're definitely not alone. It's always worth talking with a healthcare provider about testing for celiac disease, which includes blood work and possibly an endoscopy, and exploring whether a gluten-free diet might help you personally, even if you don't meet the full criteria for celiac disease.

Everyone's body is different, and while I encourage you to tune into what works for you, be kind to yourself throughout the process. A couple other things that I wanna point out. It does seem extremely common for people to be gluten sensitive, even when they don't have celiac in this population of people.

Sometimes people will have eliminated gluten from their diet for a period of several weeks and say, well, gluten isn't the problem because nothing changed. And what I would say to that is imagine that you're sitting on two. If you're sitting on two tacks, one on each butt cheek, and you remove one [00:35:00] tack, you're still gonna feel the other tack.

So sometimes doing an elimination diet where you remove all the most common triggers of mast cell activation and then slowly add them back in one by one, sometimes that's a more effective approach. Now, this is very, very challenging and it requires a lot of preparation. I did this in January a few years ago, and so.

When I was getting ready for the holidays, I was planning out what am I going to eat? Because you are eliminating a lot of things, but it's temporary. You're only eliminating those things for three weeks. So for three weeks, you're eliminating the most common triggers of mast cell activation, which include things like meat, dairy, gluten.

Eggs, citrus. Um, it's a whole list of things. Okay. And it's something that I work with my patients on individually and definitely good to work with a dietician if possible, especially if you know that you're someone that's more prone to disordered eating or have a history of an eating disorder. What you do is [00:36:00] you eliminate all those foods for three weeks.

And generally what I ate during that time was, um, I ate a lot of, uh, I, I did eat a lot of fish during that time to try to get the protein in and then I would eat vegetables. Those are kind of the main things that I ate. And then at the end of the three weeks, I slowly started adding things back in. And at that time I did determine that I was sensitive to gluten and dairy, both, um, because I definitely felt like I had an increase in inflammation and symptoms when I added those things back in.

So if you think you might be gluten sensitive but have done a gluten-free trial before and it didn't necessarily change your symptoms, you may want to consider doing a more full elimination diet and work with a dietician in order to get a better sense as to whether or not, um, this is something that would be appropriate for you.

Because going gluten free is not a small thing. Going wheat free is not a small thing. Um, you lose out on a lot of nutrients like your B vitamins, so you don't wanna do that without being very, um, thoughtful about it and [00:37:00] very, uh, conscientious and making sure that you're going about it in the right way.

Well, you might ask, what about food allergy testing? And this is something that we've talked about in a. Multiple previous solo episodes, and I'll link those in the show notes. I also talked about food allergy testing with Dr. Theo Theo, her, and we will link that episode in the show notes as well. And in that episode, he talked about food allergy testing and how problematic it is because people will test positive for foods that they've recently been exposed to, even though it's not an IgE mediated, uh, food allergy.

So it's. Complicated and tricky. So what he suggests is that people eat just. Plain organic chicken and quinoa for several days before they have food allergy testing in order to get a better sense of what food allergies they actually have. And then we also know that food allergies are different from food sensitivities that are related to mast cell activation in the gut.

So, [00:38:00] uh, please check out that episode with Dr. Theo, her for a much more, uh, detailed conversation on that. Okay. Back to the curbside questions. Um, the next question is from Melissa. Melissa asks, where does Lipedema fall on the hypermobility and EDS spectrum, and how can primary care providers help? So Lipedema spelled L-I-P-E-D-E-M-A is a chronic condition that causes painful, symmetrical fat accumulation most commonly in the hips, thighs, and legs, and is often misdiagnosed as simple obesity or lymphedema spelled L-Y-M-P-H-E-D-E-M-A.

While Lipedema is not classified as a subtype of EDS, many patients with lipedema also meet criteria for joint hypermobility or even hypermobile EDS. This overlap is being explored in the medical literature, but growing clinical experience suggests that connective tissue fragility may play a role in both conditions.[00:39:00] 

So what is the connection with lipedema and joint hypermobility or hypermobile EDS? So let's talk a little bit more about these shared features. People with lipedema often report symptoms that overlap with hypermobility disorders, including joint instability, fatigue, chronic pain, easy bruising, and skin tenderness.

There is emerging research and an an increased recognition that a subset of patients may fall into both categories. The lipedema remains its own diagnosis, distinct from hypermobile EDS and HSD. Inflammatory and connective tissue elements are important. Lipedema involves not just abnormal fat deposition, but also microvascular inflammation and pain, which may be worsened in patients with underlying connective tissue fragility.

1. So how can PCPs help Primary care providers or PCPs are in a key position to recognize lipedema early and initiate appropriate referrals and supportive care. And here's how. Number one, [00:40:00] you can recognize red flags. Be alert for classic signs, disproportionate fat distribution that doesn't respond to diet and exercise.

Tenderness to the touch. Bruising, leg heaviness and a negative stemer sign. This means no thickened skin over the toes, which differentiates from lymphedema. You can also screen for comorbidities, ask about symptoms for joint hypermobility, such as frequent sprains, strains or dislocations, chronic pain or stretchy skin, as well as conditions like pots, fibromyalgia or mast cell activation, which co-occur very frequently in both lipedema and hypermobile EDS or HSD.

Use tools like the five point questionnaire as discussed earlier for hypermobility history, and consider the BITTON score as a starting point. Though remember, it's not sufficient on its own to diagnose hypermobile EDS. You also want to refer strategically. A lipedema evaluation is important. You can refer to a vascular medicine specialist, plastic surgeon, or [00:41:00] physiatrist with experience in lipedema diagnosis and care.

You want to consider a hypermobility evaluation? Consider referral to a rheumatologist, a geneticist, or a physiatrist with experience in diagnosing hypermobile EDS or HSD, or consider supporting your patient yourself through a self-advocacy pathway using the 2017 diagnostic criteria. We talked about the problems with that earlier and how it is changing and the 2026 criteria will probably be coming out in late 2025.

You can also support self-management. You can encourage conservative management such as compression therapy, lymphatic massage, anti-inflammatory diet, and gentle exercise, such as water aerobics. You can validate their experience and avoid framing symptoms as quote, just obesity or in their head. This common support goes a long way in building trust.

You can also document symptoms. Clearly use language that supports future insurance coverage for interventions like [00:42:00] manual lymphatic drainage or liposuction if appropriate, which are often denied. If Lipedema is not clearly diagnosed and documented. For a deeper dive into the relationship between connective tissue disorders and lipedema, I highly recommend the Bendy Bodies podcast episode with Dr.

Karen Herst. Dr. Herst is an MD PhD and leading expert in fat. Disorders. In this episode, she explains how Lipedema fits into the broader connective tissue landscape, how it differs from lymphedema or obesity, and what treatment options are available. Some of these treatment options came as a very big surprise to me, so definitely check out this episode.

It's a must listen for patients, caregivers, and healthcare professionals alike who wanna better understand this underrecognized condition. Okay, next question from curbside comes from. Kelyn says, I just listened to the hypermobility episode first. Wow. Thank you so much. Second, the three meds she mentioned are [00:43:00] Naltrexone, Keine, and Chromin.

Does she recommend all three for our hypermobile patients or does she choose from them to treat certain symptoms? So thank you so much for asking Kelyn. I love this question because it gets to the heart of personalized care for conditions like Hypermobile, EDS and HSD. Well, low-dose Naltrexone, keto and chromin are among my most used medications for people with connective tissue disorders.

I typically do not use all three at once, especially not right away. I tailor these medications based on the person's symptom profile, medical history, tolerance, and treatment goals. This is how I generally approach it, low-dose naltrexone. I've talked about this in great detail in previous episodes of the podcast, and we will make sure to link that here.

Low-dose naltrexone is often my first choice for centralized or widespread pain, fatigue, brain fog, and neuro immune dysfunction. It's particularly helpful in people with overlapping fibromyalgia or me CFS features. It also stabilizes the immune system and can help with mood. [00:44:00] Kein is great for mast cell activation symptoms and inflammation, especially if there's a strong component of GI symptoms like bloating, abdominal pain, food intolerances, et cetera, along with skin itching, flushing, or sleep issues.

It's an oral mast, cell stabilizer, anti-inflammatory, and H one antihistamine, and often well tolerated when started at low dose and increased slowly. Clin sodium, another mast cell stabilizer. Often more targeted for people with food reactivity, histamine intolerance, or GI track specific symptoms. It's a very old medication.

I was prescribed inhaled clin as a teenager for my asthma. Oral clin is usually given before meals and can be incredibly helpful for reducing post-meal flares or GI upset. That said, it can be hard to find in commercial pharmacies due to supply chain problems and can take longer to show benefits. Many patients with mast cell activation disorders and related conditions, face challenges accessing commercially available oral [00:45:00] chroma and sodium known as gastro chrome.

It can be so hard to find at retail pharmacies, and some insurers might not cover it easily due to the cost or its designation as a niche medication. As a result, some people turn to compounding pharmacies to obtain clin in a more accessible or affordable form. Additionally, the commercial version of gastric comes in plastic ampules, which can be problematic for certain highly sensitive patients who react to plasticizers or leachates from the packaging.

In these cases, compounded chromal and prepared in glass containers or alternative packaging may be better tolerated. As always, sourcing should be done through a reputable compounding pharmacy, and care teams should ensure consistency and quality in the formulation.

Commonly used to help manage mast cell related symptoms affecting the gut. It's also available in other formulations that can target different systems. Chrom and nasal spray can be helpful for upper respiratory symptoms like [00:46:00] congestion or allergic rhinitis. I also find that it can be helpful with brain fog, and if you think about it, it does make sense in that it will absorb through the cribriform plate, which is at the top part of the notes.

And that's where it gets into the brain. Chroma and eyedrops, such as optic chrome can help relieve ocular itching or irritation due to mast cell activation. Inhaled forms like intel were historically used in asthma, though they're less commonly available now. These targeted roots can be especially useful when symptoms are localized and may allow for better tolerability than systemic formulations.

Topical Chromin can be helpful for skin symptoms. I instruct patients to mix their oral chromin solution with a topical cream that they know they tolerate and apply that to the skin. There's no magic formula for this. You just have to kind of experiment and see how it goes. In some patients with mast cell activation affecting the genitor urinary tract, a chroma and sodium vaginal douche may help reduce vulva, vaginal, uterine, or [00:47:00] bladder related symptoms such as burning irritation, heavy bleeding, or pain that might be triggered by local mast cell activity.

Although this is not an FDA approved use, some clinicians and patients have used compounded chromin or oral chromin from a commercial pharmacy in a saline solution as a vaginal rinse to calm, localized inflammation. This approach is particularly considered when standard treatments have failed and when symptoms clearly seem to flare in response to hormonal shifts.

Physical triggers or certain exposures. As always, they should be done under guidance from a knowledgeable healthcare provider, ideally with support from a compounding pharmacy experienced in this type of formulation. I will link an article in the show notes that specifically discusses chroma and douche.

It's also essential to understand that people with Hypermobile EDS HSD, mast Cell Activation Disorders, pots, et cetera, also have increased sensitivity to medications. This can mean that they experience side effects more intensely, react unpredictably to standard doses, or find that their therapeutic sweet spot is lower [00:48:00] than what is typically prescribed.

Because of this, I almost always start at a lower than normal dose, sometimes even a fraction of the usual starting dose and titrate slowly and carefully. The goal is not to load up on medications, but rather to find the lowest effective dose that brings meaningful relief with the fewest side effects.

Less is more with these complex sensitive systems. Another core principle that I follow, one change at a time with space in between interventions. This helps clarify what's working and what's not, and avoids layering multiple variables that make it hard to interpret a patient's responses. I typically advise waiting a week or so before adding or adjusting medications, and longer if there's a really strong concern about side effects.

Finally, I encourage patients to keep a symptom and treatment journal tracking, not just medications and doses, but also things like sleep, pain levels, activity, diet, and any new symptoms. I always suggest approaching this with a curious, not anxious mindset. Think of it like a data collection, [00:49:00] not judgment.

Over time, patterns often emerge that helps guide the next step in care. So in short, I choose based on the dominant symptoms and often start with one, sometimes LDN to see how the person responds. If there's partial improvement or a different set of symptoms emerges, we may consider adding another carefully or gradually for more information.

On my three favorite medications to prescribe, check out my substack newsletter. I did a three-part series on this and definitely want you to visit hypermobility md.substack.com to learn more. Thank you so much to curbside for having me on your show. I'm so thrilled that we got such a great response to this show and we got so many wonderful follow-up questions.

And I wanna give a special thanks to those who submitted questions after listening to episode four 80 of the Curb Siders, where we talked about hypermobility and connective tissue disorders like EDS. We're gonna finish this episode like we always do with a [00:50:00] hypermobility hack. Today's hypermobility hack is to ask why.

When you're working with clinicians, sometimes it can be really hard to get answers to your questions without feeling like you're being difficult or at risk of getting labeled as difficult, like an annoying child, though, you can keep asking your clinicians why when your doctor says that your labs are normal and therefore you are fine, you can ask them why they think that.

Why do they expect that normal labs mean that you're fine? You could ask them, aren't there some conditions that are not caught on the lab testing that we did? Is it even remotely possible that something else is going on? What did these labs test for and what did these labs miss? What else is in your differential diagnosis?

The diagnosis or the working diagnosis is the thing that they most likely think is going on, but the differential diagnosis is other things that could be going on as well. So if we [00:51:00] wanna think about mast cell activation disorders, and under that umbrella we have mastocytosis, we have mast cell activation syndrome, we have mast cell activation, unspecified, et cetera.

If someone presents with symptoms that fit under that umbrella, we also wanna be thinking about lookalike conditions. Like one of them might be carcinoid, for example. So it's very important to be asking your doctor, well, what's something that routine labs wouldn't catch that would fit with my symptoms?

We. And it wouldn't hurt to do your own search ahead of time so you can help make some suggestions. Hopefully, your clinicians are open-minded and are willing to accept that they don't know everything because of course they don't. None of us can know everything, so try gently asking why. To try to get at the bottom of what's going on with you and your symptoms and try to get your quality of life improved.

Well, I hope you found today's episode of the Bendy Bodies podcast helpful. I really love hearing from you. So please visit the Bendy Bodies podcast [00:52:00] website@bendybodiespodcast.com to submit your questions, leave a review, share feedback, et cetera. We really love hearing from you. You can help us spread the word about joint hypermobility and related disorders by leaving a review and sharing the podcast.

This really helps raise awareness about these complex conditions and makes it more likely that other people will also find the show. If you'd like to dig deeper, you can meet with me one-on-one. Check out the available options on the services page of my website@hypermobilitymd.com. You can also find me, Dr.

Linda Bluestein on social media at Instagram, Facebook. Twitter or LinkedIn at Hypermobility md. You can find human content by producing team at Human Content Pods on TikTok and Instagram. You can find full video episodes of every week on YouTube at Bendi Bodies Podcast. To learn about the Bendi Bodies program, disclaimer and ethics policy submission verification, and licensing terms and HIPAA release terms, or to reach out with any questions, please visit vende bodies podcast.com.[00:53:00] 

Bendy Bodies podcast is a human content production. Thank you for being a part of our community, and we'll catch you next time on the Vende Bodies Podcast. Podcast.

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