The APOE4 and the treatment of hypothyroidism connection, is a new one for me, so I'm just trying to wrap my head around it all. Can you advise on any resources/journal articles that I can share with my Dr. about this to help get her 'on board' so to speak? I've been taking Levothyroxine for just about 10 years but I still struggle with many issues.
Hi Megan, optimizing thyroid replacement is particularly critical for APOE4s who are already dealing with challenged brain energetics; Here are a few studies you can print and take with you.
The following paper tells us taking thyroid meds increases AD risk by 67%. I'd wager that this is due to insufficient/inadequate treatment with T4 meds only:
Thanks for posting this. I'm a 4/4, on levothyroxine AND a physician and I had no idea this was an issue. My 23andme data are showing variants. I'm wondering if you can tell me more about the testing. I assumed I would need a free T3 test (lcms), but you said rT3. Can you elaborate more on testing? I'll need to educate my PCP, as well.
Hi Barry, Yes, this is a major issue for many thyroid patients. Some never fully regain their health or stamina on T4-only treatment. At a minimum, labs should include free T3, free T4, and reverse T3. In people with DIO1/DIO2 variants, it’s very common to see elevated reverse T3. (learned from my participation in Facebook Thyroid groups over many years). For me, an rT3 level of around 14 was enough to cause noticeable brain fog. To correct this, I initially eliminated T4 by stopping my T4-containing medication (NP Thyroid) and replacing it with Cytomel (T3) for approximately three months. This has to be done gradually, since T4 has a long half-life and T3 is a potent, fast-acting hormone.
Without T4 as a substrate, the body cannot produce reverse T3, and existing rT3 is gradually cleared. Once my rT3 dropped into the 7–8 range, I slowly reintroduced NP Thyroid while tapering Cytomel, checking labs every six weeks. Over time, I dialed this in so that my free T4 stays at the low end of the reference range and my free T3 sits in the upper quartile of normal. (I never take thyroid medication the morning of a blood draw.)
It’s also important to understand that TSH will be very low on Cytomel, and that is expected. This is true for anyone taking Cytomel or natural desiccated thyroid since it also contains T3— a suppressed TSH in this context is not, by itself, a problem.
There is growing concern that recent FDA actions regarding "unapproved" thyroid medications could create significant challenges for patients who rely on natural desiccated thyroid (NDT) for symptom control. These medicines have been used over a century without problems!
Sorry to pester, but your units of measure must be different than mine. My rT3 and freeT3 are showing as "normal." But I never trust the reference range listed by labs as being optimal. I am at 320pg/dL free T3 and rt3 is 132 pg/ml. I've added cytomel 5mg bid since the testing. Haven't noticed anything different so far. Really helping it helps with the sleep symptoms you mentioned. Just wondering what the functional medicine guidelines are for optimal numbers. Thanks again. Barry
Hi Barry, you’re right. Relying on labs just because they’re “in range” can be very misleading. I spent years trial-and-error with thyroid meds before understanding what actually worked for my body. I feel best when my reverse T3 is in the single digits (in your lab’s units, ~100 pg/mL or lower). rT3 competes with T3 at the receptor, so when it’s elevated you can end up functionally hypothyroid even with “normal” labs. With DIO1 variants, there’s a higher tendency to shunt T4 into rT3, especially with stress, illness, calorie restriction, or inflammation. Because of that, my sweet spot is keeping free T4 at the very low end of normal, leaving little T4 available to convert into rT3, while keeping free T3 in the upper range. My free T3 lab range is 2.3–4.4 pg/mL and mine usually runs ~4.0–4.2. I don’t take Cytomel the morning of labs. My current regimen is 20 mcg Cytomel in the morning and 90 mg NP Thyroid at night.
Since doing this, I feel completely normal again — no lingering hypothyroid symptoms.
This is very interesting. As far as I can recall, I've always been "normal range" for T4 but will be going to my primary care for up to date bloodwork. I went to check my genetics. I have 23andMe data. In that data, found that I am homozygous for risk allele in DIO1 gene. AND that 23andMe doesn't include DIO2 in their survey. As far as I can tell, neither do Ancestry.com or another vendor that I've used for diet direction. Suggestions for vendors that give us a more complete survey including DIO2 are appreciated. Thanks in advance.
have you logged into 23andme and browsed your raw data under the "resources" tab (under your name), plugging in the rs#? I found several snps there that were not included in the raw data file I downloaded! Good luck!
I am always trying to balance my thyroid (previous nodule, negative biopsy that resolved itself). Currently have high thyroid antibodies and low T4 but high reverse T3, I’m on Armour Thyroid and compounded T3. I never thought of taking more T3 at night! I’ll try it, thanks Karin!
sorry you are dealing with that. I tried compounded T3 and it didn't work for me at all. I think I wasn't absorbing it. Have you ever taken Cytomel? It's odd that your reverse T3 is high with LOW T4. Did you adjust dose recently? Maybe it's taking a while to clear? If you aren't already on LDN, I would look into that to help get that immune activity under control.
Yes I’m on LDN, long history of autoimmunity in my family, but I actually have non-Hodgkins lymphoma on top of 4/4, but have been able to control it naturopathically for 6.5 years now w my ND oncologist. My lymphocyte map is cleanest he’s seen, only slightly veered toward Th2. I’m on mistletoe as well. I haven’t tried Cytomel. Doc thinks high reverse T3 and antibodies are related to my recent mold exposure and high stress.
sounds like you are taking every last bit of T4 and putting it all into rT3. Cytomel works well for me, and is possibly lower cost than compounded T3. Glad you have good doctors and that your NHL is under control. Keeping my fingers crossed you get the mold and stress taken care of now. Happy Thanksgiving!
The APOE4 and the treatment of hypothyroidism connection, is a new one for me, so I'm just trying to wrap my head around it all. Can you advise on any resources/journal articles that I can share with my Dr. about this to help get her 'on board' so to speak? I've been taking Levothyroxine for just about 10 years but I still struggle with many issues.
Hi Megan, optimizing thyroid replacement is particularly critical for APOE4s who are already dealing with challenged brain energetics; Here are a few studies you can print and take with you.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5561599/
https://pmc.ncbi.nlm.nih.gov/articles/PMC9039072/
https://pubmed.ncbi.nlm.nih.gov/17105838/
The following paper tells us taking thyroid meds increases AD risk by 67%. I'd wager that this is due to insufficient/inadequate treatment with T4 meds only:
https://pubmed.ncbi.nlm.nih.gov/19666883/
You can also print out my substack article and share it. Good Luck!
Thanks for posting this. I'm a 4/4, on levothyroxine AND a physician and I had no idea this was an issue. My 23andme data are showing variants. I'm wondering if you can tell me more about the testing. I assumed I would need a free T3 test (lcms), but you said rT3. Can you elaborate more on testing? I'll need to educate my PCP, as well.
Hi Barry, Yes, this is a major issue for many thyroid patients. Some never fully regain their health or stamina on T4-only treatment. At a minimum, labs should include free T3, free T4, and reverse T3. In people with DIO1/DIO2 variants, it’s very common to see elevated reverse T3. (learned from my participation in Facebook Thyroid groups over many years). For me, an rT3 level of around 14 was enough to cause noticeable brain fog. To correct this, I initially eliminated T4 by stopping my T4-containing medication (NP Thyroid) and replacing it with Cytomel (T3) for approximately three months. This has to be done gradually, since T4 has a long half-life and T3 is a potent, fast-acting hormone.
Without T4 as a substrate, the body cannot produce reverse T3, and existing rT3 is gradually cleared. Once my rT3 dropped into the 7–8 range, I slowly reintroduced NP Thyroid while tapering Cytomel, checking labs every six weeks. Over time, I dialed this in so that my free T4 stays at the low end of the reference range and my free T3 sits in the upper quartile of normal. (I never take thyroid medication the morning of a blood draw.)
It’s also important to understand that TSH will be very low on Cytomel, and that is expected. This is true for anyone taking Cytomel or natural desiccated thyroid since it also contains T3— a suppressed TSH in this context is not, by itself, a problem.
There is growing concern that recent FDA actions regarding "unapproved" thyroid medications could create significant challenges for patients who rely on natural desiccated thyroid (NDT) for symptom control. These medicines have been used over a century without problems!
https://www.fda.gov/drugs/enforcement-activities-fda/fdas-actions-address-unapproved-thyroid-medications. The above information is based on my personal experience and research and is not medical advice; thyroid therapy is highly individualized and should be managed by a qualified clinician, ideally a Functional Medicine Expert.
Sorry to pester, but your units of measure must be different than mine. My rT3 and freeT3 are showing as "normal." But I never trust the reference range listed by labs as being optimal. I am at 320pg/dL free T3 and rt3 is 132 pg/ml. I've added cytomel 5mg bid since the testing. Haven't noticed anything different so far. Really helping it helps with the sleep symptoms you mentioned. Just wondering what the functional medicine guidelines are for optimal numbers. Thanks again. Barry
Hi Barry, you’re right. Relying on labs just because they’re “in range” can be very misleading. I spent years trial-and-error with thyroid meds before understanding what actually worked for my body. I feel best when my reverse T3 is in the single digits (in your lab’s units, ~100 pg/mL or lower). rT3 competes with T3 at the receptor, so when it’s elevated you can end up functionally hypothyroid even with “normal” labs. With DIO1 variants, there’s a higher tendency to shunt T4 into rT3, especially with stress, illness, calorie restriction, or inflammation. Because of that, my sweet spot is keeping free T4 at the very low end of normal, leaving little T4 available to convert into rT3, while keeping free T3 in the upper range. My free T3 lab range is 2.3–4.4 pg/mL and mine usually runs ~4.0–4.2. I don’t take Cytomel the morning of labs. My current regimen is 20 mcg Cytomel in the morning and 90 mg NP Thyroid at night.
Since doing this, I feel completely normal again — no lingering hypothyroid symptoms.
This is very interesting. As far as I can recall, I've always been "normal range" for T4 but will be going to my primary care for up to date bloodwork. I went to check my genetics. I have 23andMe data. In that data, found that I am homozygous for risk allele in DIO1 gene. AND that 23andMe doesn't include DIO2 in their survey. As far as I can tell, neither do Ancestry.com or another vendor that I've used for diet direction. Suggestions for vendors that give us a more complete survey including DIO2 are appreciated. Thanks in advance.
have you logged into 23andme and browsed your raw data under the "resources" tab (under your name), plugging in the rs#? I found several snps there that were not included in the raw data file I downloaded! Good luck!
Thanks for your suggestion. When I browse my 23andMe data, rs225014 comes back, "not genotyped". I'll have to look further afield. Ah well
I am always trying to balance my thyroid (previous nodule, negative biopsy that resolved itself). Currently have high thyroid antibodies and low T4 but high reverse T3, I’m on Armour Thyroid and compounded T3. I never thought of taking more T3 at night! I’ll try it, thanks Karin!
sorry you are dealing with that. I tried compounded T3 and it didn't work for me at all. I think I wasn't absorbing it. Have you ever taken Cytomel? It's odd that your reverse T3 is high with LOW T4. Did you adjust dose recently? Maybe it's taking a while to clear? If you aren't already on LDN, I would look into that to help get that immune activity under control.
Yes I’m on LDN, long history of autoimmunity in my family, but I actually have non-Hodgkins lymphoma on top of 4/4, but have been able to control it naturopathically for 6.5 years now w my ND oncologist. My lymphocyte map is cleanest he’s seen, only slightly veered toward Th2. I’m on mistletoe as well. I haven’t tried Cytomel. Doc thinks high reverse T3 and antibodies are related to my recent mold exposure and high stress.
sounds like you are taking every last bit of T4 and putting it all into rT3. Cytomel works well for me, and is possibly lower cost than compounded T3. Glad you have good doctors and that your NHL is under control. Keeping my fingers crossed you get the mold and stress taken care of now. Happy Thanksgiving!