Thread by @JeffLubell_C19

It's still early, but I wanted to share some initial indications of a significant breakthrough in the treatment of my daughter's #hEDS & #MECFS. I attribute progress to Calcium D-Glucarate, a supplement known for improving phase 2 detox of estrogen & other steroid hormones. 1/

The usual caveats: I am a patient caregiver, and not an MD or a medical researcher. It is early. This is just one patient. This is a very complicated area. I am sharing not so much to encourage people to try the supplement but rather to encourage more research in this area. 2/

My daughter is part of the cohort of (mostly) women whose #hEDS took a severe turn for the worse around puberty, prompting #MECFS, #craniocervicalinstability, #POTS, #Chiari, #tetheredcord and other manifestations. This is important context. 3/

Given timing of progression to severe disease, the clear relationship of symptom severity to monthly menstrual cycle, and role of elevated estrogen in histamine production & fluid retention, I have long suspected impaired estrogen metabolism may play a role. 4/

We ran a genetic profile through 23&Me and ordered a Genetic Lifehacks Cheat sheet and annual membership to analyze data, and sure enough, found multiple impairments in both phase 1 & phase 2 processes, including NQO1*2, Slow COMT, CYP2C19*2, & CYP19A1 (RS700518) among others. 5/

We initially tried DIM, which promotes Phase 1 detox and found it made her worse. We then tried Calcium D-Glucarate, which improves Phase 2 detox by inhibiting beta-glucuronidase, which promotes the reabsorption of estrogen metabolites after glucuronidation. 6/

As I noted earlier in this thread, it is still early (only 2 1/2 weeks), but so far, the experiment with Calcium D-Glucarate has been a success! She reports a reduction in fatigue (she feels less weary) and feels lighter overall. She has more energy and can do more. 7/

To be clear, she is still in bed most of the day and significantly disabled. This is not a cure! But it is consistent with my hypothesis that impaired metabolism of estrogen & other steroid hormones may be contributing to her illness. 8/

A few thoughts: First, dosage seems to matter. She feels better at 500 mg daily but worse at 1,000 mg daily. Second, timing may matter. We take with dinner to minimize likelihood of interfering with LDN, which she takes in morning as it is also eliminated through liver. 9/

I would love to find a detailed resource that walks through the different genotypes that impair estrogen metabolism and provides clear guidance on how to address each one as the Calcium D-Glucarate addresses only one issue. Does anyone know of such a resource? 10/

There's a lot out there about slow COMT as impairment of the methylation pathway has been proposed as being involved in ME/CFS. (The MEPEDIA article on this provides a good point of entry.) But it's hard to find similar precision for other pathways. 11/ me-pedia.org/wiki/Methylati…

Is anyone aware of research looking at the extent to which estrogen metabolism is impaired in the cohort of people with hEDS and ME/CFS whose symptoms worsened dramatically at puberty? Seems like low-hanging fruit. 12/

This article found a cluster of shared genetic pathways in people with ME/CFS that involved "hormone related pathways such as steroid hormone, estrogen, and androgen biosynthesis, glucuronidation, and the pregnane x receptor pathway." 13/ ncbi.nlm.nih.gov/pmc/articles/P…

If not already completed, I would encourage research focusing on the entire spectrum of estrogen metabolism pathways and related genetic variants rather than trying to find one common single SNP that people w/ MECFS have in common. 14/

One approach would be to construct a model that assigns a weight to each of the variants believed to impair metabolism corresponding to the extent of the impairment and then come up with an estrogen metabolism score that could be compared between treatment and controls. 15/

I do not know whether and if so how these observations apply to people with ME/CFS (or LongCOVID) whose chronic illness was triggered by a virus/bacteria rather than puberty. It's possible there is no connection at all, but my gut tells me it could still be relevant. 16/

I also don't fully understand relationship to #hEDS. One possibility: #hEDS is triggered by other genes or illness & impaired hormone metabolism makes things worse. Another possibility: impaired metabolism actually causes or aggravates #hEDS. 17/

The formal medical literature on this topic is complex. It may be helpful to start with informal articles. Here's one from Debbie Moon at @GeneticLifehack: 18/ geneticlifehacks.com/estrogen-how-i…

And here's another one from Kith and Kin Wellness, which interestingly notes the importance of starting with phase 2 rather than phase 1 detox, which we discovered the hard way. 19/ kithandkinwellness.com/blog-posts/pha…

There's a lot more that could be written on this topic, but I'm going to stop here and see what you all have to say. I'll look forward to hearing the experiences of @pwME and #longCOVID and your caregivers and clinicians. Also hope to hear from researchers in this field. 20/

@CortDoesScience -- Have you or others at Norris Lab looked at this pathway?

P.S. This study is worth reviewing if you are interested in this topic. It reports on extent of aggravation of symptoms related to menstrual cycle in 386 women with #hEDS and response to oral contraceptives. ncbi.nlm.nih.gov/pmc/articles/P…