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Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Fri Feb 21, 2020 6:35 pm
by Exodus
BHRT is the only prescribed medication I take in addition to many vitamins/supplements, but I'm noticing a woozy feeling similar to when a sleeping medication begins to take effect. It is micronized Progesterone by BionPharma. I very rarely even take anything known to carry an anti-cholinergic burden, so this is more than a little unnerving to say the least :o

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Fri Feb 21, 2020 7:03 pm
by Plumster
Do you take it in the evening before going to bed? If you don't like the sleepiness, you could switch to a progesterone cream instead?

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Fri Feb 21, 2020 7:14 pm
by Exodus
Plumster wrote:Do you take it in the evening before going to bed? If you don't like the sleepiness, you could switch to a progesterone cream instead?


Yes - take it along with other supplements at bedtime and I enjoy the calming and super relaxing effects and need to get to bed as soon as the wooziness begins, but I'm wondering if it might be majorly anti-cholinergic due to the similarity to sleep meds and narcotics. Can't find it on any of the Anti-Cholinergic Burden lists :?

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Fri Feb 21, 2020 9:12 pm
by circular
Exodus wrote:BHRT is the only prescribed medication I take in addition to many vitamins/supplements, but I'm noticing a woozy feeling similar to when a sleeping medication begins to take effect. It is micronized Progesterone by BionPharma. I very rarely even take anything known to carry an anti-cholinergic burden, so this is more than a little unnerving to say the least :o

I strongly suspect progesterone has a different mechanism to produce that effect. It would be on the Beer’s List of anticholinergic medicines. I’m very sensitive to anticholinergics. In my case they will always affect my urination too. Also some (many?) herbs touted for relaxation are anticholinergic. I think chamomile that many take for sleep may be one. Have you taken a blood lab to see if your dose of progesterone is too high?

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Sat Feb 22, 2020 9:25 am
by Exodus
Circular: "I strongly suspect progesterone has a different mechanism to produce that effect. It would be on the Beer’s List of anticholinergic medicines. I’m very sensitive to anticholinergics. In my case they will always affect my urination too. Also some (many?) herbs touted for relaxation are anticholinergic. I think chamomile that many take for sleep may be one. Have you taken a blood lab to see if your dose of progesterone is too high?"

Yes - labs are good - but wondering where you've read about the "herbs touted for relaxation are anti-cholinergic"??? I've seen many, many lists of anti-cholinergic medications including all published Beers revisions, but haven't seen progesterone or herbs listed on them - would you be able to give sources . . . this is concerning!?! Exodus

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Sat Feb 22, 2020 12:08 pm
by circular
Exodus wrote:... wondering where you've read about the "herbs touted for relaxation are anti-cholinergic"??? I've seen many, many lists of anti-cholinergic medications including all published Beers revisions, but haven't seen progesterone or herbs listed on them - would you be able to give sources . . . this is concerning!?! Exodus

I haven't seen it often and I didn't save what I did see. It wasn't in research papers but rather mentions on websites that I couldn't put my full faith in but which I found concerning. I should have said 'may be anticholinergic'. I don't have time to go beyond abstracts, but here are some things I found:

First is a paper studying three TCM herbal formulas for anticholinergic effects. I don't quite understand the abstract, but it appears to suggest that a given herb or herbal preparation may offset it's own AC effects.

The Screening of Anticholinergic Accumulation by Traditional Chinese Medicine
Abstract

Many Western drugs can give rise to serious side effects due to their ability to bind to acetylcholine receptors in the brain. This aggravates when they are combined, which is known as anticholinergic accumulation (AA). Some bioactives in Traditional Chinese Medicine (TCM) are known to block acetylcholine receptors and thus potentially cause AA. The AA of TCM was screened by quantifying the displacement of [³H] pirenzepine on acetylcholine receptors in a rat brain homogenate. We used a new unit to express AA, namely the Total Atropine Equivalents (TOAT). The TOAT of various herbs used in TCM was very diverse and even negative for some herbs. This is indicative for the broadness of the pallet of ingredients used in TCM. Three TCM formulas were screened for AA: Ma Huang Decotion (MHD), Antiasthma Simplified Herbal Medicine intervention (ASHMI), and Yu Ping Feng San (YPFS). The TOAT of ASHMI was indicative for an additive effect of herbs used in it. Nevertheless, it can be calculated that one dose of ASHMI is probably too low to cause AA. The TOAT of YPFS was practically zero. This points to a protective interaction of AA. Remarkably, MHD gave a negative TOAT, indicating that the binding to the acetylcholine receptors was increased, which also circumvents AA. In conclusion, our results indicate that TCM is not prone to give AA and support that there is an intricate interaction between the various bioactives in TCM to cure diseases with minimal side effects. [Emphasis added.]

I personally think their conclusion, inferring from three formulas to 'TCM' generally, isn't that scientific, but I do suspect that centuries of practice and observation probably ensure that traditional TCM formulas are safe in 'normal' patients. Maybe I would be more comfortable with TCM formula herbs for sleep as long as they have a long history of use. I know many turn to Ayerveda for this assurance as well. It's possible that some single herbs used outside of such traditional formulas are potentially more problematic (???).

One way such formulas may balance things out is if they have high flavonoid contents. This paper, although focused on bone health (and very interesting in that regard!) says:
Flavonoids, a group of natural compounds mainly derived from plants, are known to possess osteogenic effects in bone cells. Here, we aimed to test if flavonoid could induce a cholinergic enzyme, acetylcholinesterase (AChE), as well as bone differentiation. In cultured rat osteoblasts, twenty flavonoids, deriving from Chinese herbs and having known induction of alkaline phosphatase (ALP1) expression, were tested for its induction activity on AChE expression. Eleven flavonoids showed the induction, and five of them had robust activation of AChE expression, including baicalin, calycosin, genistin, hyperin and pratensein: the induction of AChE included the levels of mRNA, protein and enzymatic activity. Moreover, the flavonoid-induced AChE expression in cultured osteoblast was in proline-rich membrane anchor (PRiMA)-linked tetrameric globular form (G4) only. In parallel, the expression of PRiMA was also induced by the application of flavonoids. The flavonoid-induced AChE in the cultures was not affected by estrogen receptor blocker, ICI 182,780. Taken together, the induction of PRiMA-linked AChE in osteoblast should be independent to classical estrogen signaling pathway. [Emphasis added]

Wow!

This one looks at the flavonoid content of chamomile exerting cholinergic effects, in contrast to what I once read that it has anticholinergic effects:

Evidence Supports Tradition: The in Vitro Effects of Roman Chamomile on Smooth Muscles [Piggies]
The crude herbal extract induced an immediate, moderate, and transient contraction of guinea pig ileum via the activation of cholinergic neurons of the gut wall. Purinoceptor and serotonin receptor antagonists did not influence this effect. The more sustained relaxant effect of the extract, measured after pre-contraction of the preparations, was remarkable and was not affected by an adrenergic beta receptor antagonist. The smooth muscle-relaxant activity was found to be associated with the flavonoid content of the fractions

Here are some more papers investigating single herbs. It's just a smattering to show that there is some work being done in this area:

Butterbur ... 'anticholinergic effect possible'. [I'm not sure how reliable 'jpub' is.]

Lemonbalm ... 'no cholinesterase inhibitory properties were detected'. [n=20]

Kava Kava and Echinacea ... 'The three main herbal products that contribute to dry eye are niacin, echinacea, and kava. There was a strong association between anticholinergic alkaloids and dry eye'. [I can't see what other herbs were covered in this review.]

St. John's Wort ... 'The observations suggest that the infusions of these Hypericum species possess antidepressant activity in mice, without inducing muscle relaxation, anticholinergic and sedative properties'. [Mice]

Hops ... 'The results support the involvement of nAChRs in memory improvement in mice by MHBA. MHBA is thus thought to activate the vagal nerve and enhance hippocampus-dependent memory via nAChRs'.

From this handful of papers the message I take away is not to make assumptions about herbal remedies.

I don't mean this next part to be scary or a call to avoid all herbal approaches, but I found recurring mention of contamination of herbs with other plant matter that is anticholinergic causing ER visits. This appears to be rare but something to be aware of. It might be good to list herbal supplement providers that can guarantee purity.

Anticholinergic Poisoning Associated with an Herbal Tea -- New York City, 1994

Anticholinergic syndrome caused by contaminated herbal tea; acting swiftly to identify the source.

Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong

Worldwide Occurrence and Investigations of Contamination of Herbal Medicines by Tropane Alkaloids

I found that last one interesting because it equates nightshades (atropine) with anticholinergic effects. I knew nightshades could be a problem and I avoid them, but I hadn't realized any link to anticholinergic effects. This appears to be most notable with belladonna, 'the deadly nightshade'.
Abstract

Tropane alkaloids occur mainly in Solanaceae plants. In the present review, the main objective is to describe the worldwide occurrence and investigations of anticholinergic poisoning due to the contamination of herbal teas and herbs by tropane alkaloids. Tropane alkaloid poisoning can occur after consumption of any medicinal plant if Solanaceae plants or plant parts are present as contaminants. Globally, almost all reports in 1978-2014 involve herbal teas and one of the prescribed herbs in composite formulae. Contamination most likely occurs during harvest or processing. As for prescribed herbs, on-site inspection is necessary to exclude cross-contamination and accidental mix-up at the retail level. The diagnosis is confirmed by screening for the presence of Solanaceae species and tropane alkaloids. Herbal teas and herbs contaminated by tropane alkaloids can pose a serious health hazard because these relatively heat-stable alkaloids may exist in large quantities. The WHO repeatedly emphasises the importance of good agricultural and collection practices for medicinal plants. DNA barcoding is increasingly used to exclude the presence of contaminants (particularly toxic species) and product substitution. All suspected cases should be reported to health authorities so that investigations along the supply chain and early intervention measures to protect the public can be initiated. [Emphasis added]


This leaves one to wonder how often herbal supplements are contaminated with a steady drip of lower levels of these potentially AC compounds.

Well I haven't accomplished anything else I'd planned for this part of my morning, but thanks for sending me down this interesting rabbit hole!

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Sat Feb 22, 2020 6:31 pm
by Exodus
circular wrote:
Exodus wrote:... wondering where you've read about the "herbs touted for relaxation are anti-cholinergic"??? I've seen many, many lists of anti-cholinergic medications including all published Beers revisions, but haven't seen progesterone or herbs listed on them - would you be able to give sources . . . this is concerning!?! Exodus

I haven't seen it often and I didn't save what I did see. It wasn't in research papers but rather mentions on websites that I couldn't put my full faith in but which I found concerning. I should have said 'may be anticholinergic'. I don't have time to go beyond abstracts, but here are some things I found:

Well I haven't accomplished anything else I'd planned for this part of my morning, but thanks for sending me down this interesting rabbit hole!


WOW - so very grateful, circular - and relieved you said "thanks" for the "interesting rabbit hole"! I was a little nervous about asking for sources, but super concerned about these anti-cholinergic side effects.

Do you think this means herbal supplements have to be certified organic nowadays to be able to be 'somewhat' certain of what we're really getting???

I've been a paying member of Consumer Lab for the past decade, but they don't/can't analyze everything. They're doing a fair to middling job on branded and generic prescription fish oil, but not a lot else re: patented medicines.

Headed to medical dictionary website now to see if I can translate these gems to lay terminology - y'all amaze me with your ability to decipher this biological/medical information.

After I posted my question, I read one revision of Beers that used "Progestins" in an entry that listed "Estrogens with or without Progestins" - obviously 'fur piece' from the ReCODE protocol camp ;)

Again - much, much gratitude for this research . . . I'm excited to get into it further . . . meanwhile . . . should we be shopping for only organic, ayurvedic or TCM herbs/supplements for now???

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Sat Feb 22, 2020 10:20 pm
by circular
Exodus wrote:Again - much, much gratitude for this research . . . I'm excited to get into it further . . . meanwhile . . . should we be shopping for only organic, ayurvedic or TCM herbs/supplements for now???

You're welcome. I wish I had more time to be more comprehensive and nuanced to the point where I would be comfortable making firm recommendations. I probably shouldn't even have called it a rabbit hole ... it was more like scurrying around the ground's surface peering into various rabbit holes than going down them haha!

I'm not sure whether all certified organic herbs can be assumed not to be at risk of contamination by anticholinergic plant matter. In a sort of 'parallel world', organic spices are more likely to be contaminated with bugs (some would welcome the protein while others would recoil), if I recall reading that correctly some years back at ... wait for it ... ConsumerLab. (I really like ConsumerLab). I'm fairly sure there must be some reliable brands for purity, I just don't know what they are.

There's another caution to be aware of about herbs, not that it means there aren't some healthy, useful herbal remedies. In the early years of this forum I posted something about how often they have been shown to have adverse effects on the liver. Stavia, our primer author/doctor, spoke up and said she sees it a lot but she doesn't usually see the liver reactions to single nutrient supplements. It would be great if perchance she sees this post and can speak for herself, in case all these years later I don't recall that accurately or she has some new thoughts about it.

Ever since I became uncertain about possible anticholinergic and adverse liver effects of some herbs -- and despite that liver function can be cheaply tracked -- I just haven't spent a lot of time trying herbal remedies. I did try ashwagandha but reacted to it (probably more due to my own biochemistry, not an AC reaction). My functional medicine doctor wants me to take a thyroid formula with a number of herbs and I admit to feeling a bit leery, but at the same time I trust her, so I'm conflicted there.

For nutritional supplements I never use formulas. I hate that they throw in things along with the one ingredient I feel I need. I really try to tailor what I take to my self 'knowledge' and not just buy someone's off the shelf remedy that makes them money. (That's not at all to say that making a reputable supplement formula to make money is bad, or that choosing to try one isn't worthwhile, just that I don't want to take things I don't need and understand to my satisfaction.)

But back to herbs and formulas. After my 'research' this morning I think I would be more inclined to use traditional Chinese or Ayurvedic herbal formulas, since it may be more likely that any potentially adverse effects of one herb component will be offset by another. This really isn't rational though. It also might be that a formula has something beneficial to me but too much of something else with some adverse effect, whether or not I know that adverse effect is going on. I'd just want to find myself some assurance that they have a good history of safety. Some favorable PubMed paper on the exact formula would be best. And here again source is important, since for example there may be more heavy metals in products out of China.

All this is to say I'm an overthinker and you might want to find someone more helpful :lol:

My sleep has improved a lot from my insomniac pre-menopausal days. I've taken melatonin for years but I'm not really sure that it's doing anything. I take 100 mg progesterone and Magtein magnesium. I also recently started calcium citrate because I have osteopenia and don't get much calcium in my diet (other than what oxalates might carry away), and I think it may actually be having positive effects on my brain, including calming, which is good for sleep. (I'm surer than ever that I've been calcium deficient for years and it's been bad for my brain and bones, all while I feared supplementing due to possible vessel repercussions but when I have zero coronary plaque. This could have been a years long miscalculation in my n=1 protocol.) I use stretching and chi gong and no or little blue light before bed. If I wake up and can't sleep I often stretch again. I think people underestimate how much chronic muscle tension can effect sleep. I also meditate more and more as time goes on. In other words, I'm trying to focus as much as possible on non-supplement solutions to sleep, while ensuring adequate but not excessive magnesium and calcium -- both calming -- seems quite conservative. Mostly all this seems to really help.

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Sun Feb 23, 2020 8:43 am
by circular
Exodus wrote:BHRT is the only prescribed medication I take in addition to many vitamins/supplements, but I'm noticing a woozy feeling similar to when a sleeping medication begins to take effect. It is micronized Progesterone by BionPharma. I very rarely even take anything known to carry an anti-cholinergic burden, so this is more than a little unnerving to say the least :o

FYI there's an older thread on progesterone and the brain that discusses cycling the progesterone and then when to test levels. I haven't been cycling and think I may really need to do this.

Re: Anyone noticing Anti-Cholinergic-like symptoms with Progesterone?

Posted: Mon Feb 24, 2020 9:48 am
by Exodus
circular wrote:
Exodus wrote:BHRT is the only prescribed medication I take in addition to many vitamins/supplements, but I'm noticing a woozy feeling similar to when a sleeping medication begins to take effect. It is micronized Progesterone by BionPharma. I very rarely even take anything known to carry an anti-cholinergic burden, so this is more than a little unnerving to say the least :o

FYI there's an older thread on progesterone and the brain that discusses cycling the progesterone and then when to test levels. I haven't been cycling and think I may really need to do this.


Thanks, circular - this thread seems REALLY interesting. I have read about the cycling before, but not in-depth. My lack of knowledge of medical and biological terminology really slows me down reading this information, but I'm plodding through as someone wrote recently I feel like something's really missing in my life when I'm not learning something!

Like many of us, I have a history of treating chronic pain with traditional medicine's fixes - most were anti-cholinergic. My cognition suffered somewhat overtime as a result. Maintaining healthy BMI via ketogenic diet and daily exercise has majorly improved short term issues, and the pain is managed relatively well these days (in waking hours) with massive doses of prescription fish oil, ALA, Acetyl L Carnitine & CoQ10, Rhodiola, etc.

But . . . pain interrupted sleep continues to be an every night issue, so I am consistently investigating others' ideas here about sleep and pain issues while hoping to avoid ingesting substances that will cause cognition problems. I'm cutting back a bit on the Progesterone and will be eagerly waiting to see how this affects my labs. My insurance will not cover Functional Medicine Treatment and out of pocket is not possible, so my treatment is DIY for the most part, but since I have noticed improvement in many areas I will continue with the help of Dr. Bredesen's publications and the n=1 interraction on this forum.

Thanks again, circular, and have a great week!