Bimatoprost/Glaucoma - Prostaglandins

Spartan300

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Quote from Ray Peat article on Vitamin E:

The polyunsaturated fatty acids and their derivatives, the prostaglandins, act as effectors, or amplifiers, of estrogen's actions.

As the eye drops I'm having to use contain a prostaglandin (+ a beta-blocker) is it likely that they could be the cause of what seems to be estrogen like symptoms I'm feeling?
 

Blossom

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I previously asked Travis about bimatoprost. Here's his reply.
A person cannot indiscriminately hate on all prostaglandins, even under a Peat paradigm, because even in the complete absence of all dietary ω−6 fatty acids prostaglandins are still formed. In this event: our endogenous Δ⁹-desaturase and elongase enzymes will form Mead acid (20∶3ω−9) to replace some eicosanoids not produced—via arachidonate (20∶4ω−6) and dihomo-γ-linoleate (20∶3ω−6) under normal ω−6 intakes—and our desaturase & elongase enzymes will continue to elongate the essential ω−3 fatty acids. Since each prostaglandin series is named on account of the number of double bonds it contains, and also the fact that two are lost upon cyclicization, a person might think that Mead acid (20∶3ω−9) is the precursor for prostaglandin E₁. This is not the case, however, and it's the other 20∶3 fatty acid that produces the 1-series prostaglandins: dihomo-γ-linoleic acid (20∶3ω−6).

Mead acid forms leukotriene B₃, a chemotactic eicosanoid similar in function to the ω−6-created leukotriene B₄ yet having about threefold less potency. Leukotriene B₅, the EPA (20∶5ω−3) product, is roughly 5,000 less potent than leukotriene B₄.

Since both the 1 & 2-series prostaglandins are formed via elongase/desaturase products of ω−6 fatty acids, the prostaglandins found in our natural tropical environment would have predominately been of the 3-series. Members of this class are formed via eicosapentaenoic acid (20∶5ω−3), yet there is little data on their comparative potency vs the more-studied 2-series prostaglandins; this seems to be on account of: (1) their increased potency, (2) the near-universal consumption of ω−6 fatty acids in North America and Europe, and also (3) the incorrect assumption that they are actually 'essential.' Prostaglandin E₂ is the most studied prostaglandin by far, perhaps why prostaglandin E₃ is the only studied 3-series prostaglandin. The few studies which have analyzed them both have estimated that prostaglandin E₃ has about fourfold lower activity than prostaglandin E₂.

Since I'm having a very hard time finding data on comparative receptor affinities of prostaglandins D₃ vs D₂, the second-most studied prostaglandin, I would imagine that you could count the studies published on the more tangential prostaglandin F₃ using just one hand . . . or perhaps even less than just one hand (penguins can count up to two using their flippers).

Prostaglandins E & D exert effects on cell membranes expressing their receptors by either increasing or decreasing cyclic AMP. Changes is cAMP are always associated with Ca²⁺ influx/efflux, perhaps on account of the adenosine phosphates of different lengths also having differing affinities for Ca²⁺/Mg²⁺. Prostaglandin D has two membrane receptors, DP1 and DP2, and these work in opposite directions. This is by no means unusual, as melatonin receptors and two prostaglandin E receptors directly oppose eachother. This means that the exact ratio of DP1∶DP2 receptors, or the expression of either one alone, can determine how prostaglandin D effects the cell. Two prostaglandin E receptors oppose eachother in the same way, through cAMP & Ca²⁺, yet I have yet to read about the functions of the other two. Since prostaglandin F and its analogues have a peculiar affinity for lengthening eyelashes, I'd guess that follicles in that location express prostaglandin F receptors coupled to Gα protein.

Among G protein-coupled receptors, it is the specific G protein that determines the second messenger system while the receptor part determines what activates it. The Gα protein in particular is coupled to adenylate cyclase, the enzyme responsible for synthesizing cAMP. Increased cyclic AMP increases the metabolic rate of the cell, and this could increase the hair growth rate.

The initial function of prostaglandins could simply have been the detoxification excessive superoxide (Ȯ₂⁻). The most defining characteristic of prostaglandin H, which generates all the others, is its endoperoxide bridge. The creation of this cyclic dioxygen bridge is carried-out by cyclooxgygenase, and it needs both a lipid and superoxide (Ȯ₂⁻) for this to occur. Prostaglandin H has a half life of about five minutes, after which it spontaneously decomposes to either prostaglandin E or prostaglandin D.

Prostaglandins are only made pathological to the extent that our natural 3-series prostaglandins have been supplanted by the 1 & 2-series prostaglandins. The progressive ingestion of ω−6 fatty acids that had necessarily accompanied our escalating supra-tropical migration had created this problem, and this process had occurred faster than humans could evolutionarily adapt to.

I think it's easy to understand why the ω−6-generated leukotriene B₄ is more powerful than both leukotriene B₃ and leukotriene B₅, the respective natural products of ω−9 and ω−3: Humans have neither a ω−6-desaturase or a Δ¹²-desaturase so they cannot form ω−6 fatty acids, yet helminths and fungi freely make and excrete them. Since leukotriene B's classic function is to act as a chemotactic molecule for neutrophils and natural killer cells, you'd have to assume that this increased selectivity is intentional. However, I cannot begin to think why 2-series prostaglandins would be more powerful than those of the 3-series; there could be some reason for this, or perhaps it could simply be some incidental molecular property of the prostaglandin receptors (perhaps a valine, otherwise harmless in the absence of linoleic acid, had been used where an isoleucine would have been more fortuitous).
 
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Spartan300

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Thanks Blossom, might need someone a bit smarter than myself to interpret that!

I'm not sure which of the prostaglandins bimatoprost is & whether whichever it is is harmful or not from the information Travis provided.
 

Blossom

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Thanks Blossom, might need someone a bit smarter than myself to interpret that!

I'm not sure which of the prostaglandins bimatoprost is & whether whichever it is is harmful or not from the information Travis provided.
I've read his reply a couple times and the impression I'm under is that bimatoprost is an analogue for prostaglandin F.
 
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Spartan300

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Thanks Blossom, having re-read I agree.

@Travis it seems like you don't believe there's much study data available on prostaglandin F?

My perception since starting use of these drops is that my physical recovery ability from exercise is reduced & I'm seeing & feeling more estrogenic symptoms. Have you seen anything to corroborate this view? Ideally I'd like to not have to use the drops as the timing seems to correlate with a decline in my health/metabolism.
 
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you can use drops that are more Peaty -- carbonic anhydrase inhibitors and maybe beta blockers.

I don't think the prostaglandin drops are safe.
 

Travis

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Thanks Blossom, having re-read I agree.

@Travis it seems like you don't believe there's much study data available on prostaglandin F?

My perception since starting use of these drops is that my physical recovery ability from exercise is reduced & I'm seeing & feeling more estrogenic symptoms. Have you seen anything to corroborate this view? Ideally I'd like to not have to use the drops as the timing seems to correlate with a decline in my health/metabolism.

I am sure there's quite a bit of data on prostaglandin F₂ yet haven't seen anything on prostaglandin F₃, the main product formed under low omega−6 conditions. Since the differential potency between 2- and 3-series E-type prostaglandins is considerable, I would assume the same holds for the F-type.
 
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the Prostaglandin eye drops cause a common thickening or increase in eyelash size. And sometimes they change the eye pigment color.
 
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Spartan300

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Thanks All, I'm trying to understand the potential systemic effects but it doesn't seem like there's much out there.

A google search showed some information about some recent studies suggesting some patients experience insomnia which is a problem for me from which I think everything else stems. I'd love to be able to get off the drops for a while to see if they are causing me problems but it's too risky...

I certainly have the long eyelash thing going on - get's ladies quite jealous....
 

Charger

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Quote from Ray Peat article on Vitamin E:

The polyunsaturated fatty acids and their derivatives, the prostaglandins, act as effectors, or amplifiers, of estrogen's actions.

As the eye drops I'm having to use contain a prostaglandin (+ a beta-blocker) is it likely that they could be the cause of what seems to be estrogen like symptoms I'm feeling?
Did you ever narrow down whether bimatoprost was causing symptoms?

Been experimenting with PGE2 and latanoprost and wondering if they can cause estrogenic symptoms.
 
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Spartan300

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No I haven't but the development of the problems coincides with the last decade being the most stressful of my life.

My thinking is that it's more likely that the stress exacerbated a hypothyroid state and everything health wise descended from there. Broda Barnes claims to have seen glaucoma fixed with thyroid.

Fortunately I feel like I'm on my way back up now but I'm still using the eye drops. The fact that I'm feeling better suggests that it has more likely been my compromised health/metabolism causing the symptoms rather than the drops.
 

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