Hi all,
I got contacted by a guy from Reddit (id: randomtard1), other than Vincent as I mentioned my reddit username (id:
FranzTurtle) on this thread. This person, who was sadly unable to sign up at HairLossTalk.com, shared an interesting thesis:
https://discovery.ucl.ac.uk/id/eprint/10024622/1/11 oct 2017 PhD THESIS NORHAYATI.pdf
I will quote his conclusions:
"I'm still reading through the paper so haven't got any solid conclusions, but it does seem like a large part of the study focuses on the gel realising slowly to targeted areas. The vehicle does seem to differ slightly from what the italian pharmacy is using, but it seems that theres is still a viable solution.
Any conclusions I could come to would be infierior to those who wrote the paper though, here's one of the conclusions they came to for chapter 4, on page 188:
"For all formulations, no dutasteride was detectable by HPLC in the receptor chamber after 48 h of the permeation studies, suggesting no systemic exposure from these formulations in clinical studies. The highest permeation in the skin was found from ethanol-based solutions, then from DST-NLCs uncoated and coated with CSO-SA or CSO-LA."
page 196 has general conclusions which seems positive also.
"The main aim of this study has been achieved. DST-NLCs coated with CSO- SA or CSO-LA were successfully formulated and characterised; NLCs were stable and showed enhanced local drug delivery, reduced systemic exposure, slower drug release and reduced cytotoxicity.""
Chapter 3 and 4 are the most relevant.
To whomever cannot join this thread and wishes to
contribute, I suggest you contact me on reddit - I will repost your content on the thread. Please do not spam me for questions and stuff but rather create a dedicated reddit post on the topic if needed.
I ran into that thesis a couple of weeks ago, it's interesting for sure and lends more credibility to the idea that topical dutasteride might actually be promising.
After reviewing all the literature I could find for last couple of weeks, this is basically what I'm thinking:
1. Lack of data and experience: Topical dutasteride has never really been properly researched or experimented with. There are some studies from India I believe, but they're not very reputable as far as I'm concerned. Essentially, finasteride has taken the spotlight, and even proper studies into
topical finasteride - and it's effect on scalp and serum dht - are rare. There are the Polichem studies by Caserini et al, but it's not much. Exactly
because the consensus in the literature is that finasteride and dutasteride taken orally are relatively safe and only rarely lead to side effects (which I personally no longer believe at this point), ways of reducing systemic exposure have never been the primary focus for researchers. Although there has been somewhat of a shift recently.
2. Dutaseride's half-life: Many people dismiss topical dutasteride as a possibility out of hand because they believe the half-life of 5-6 weeks is too long. However, as I've mentioned before, I believe the half-life is dose-dependent. Less dutasteride in serum leads to a quicker clearance rate.
3. Anecdotal reports of side-effects: Many people who have personally experimented with topical dutasteride note side effects. However, this is not surprising because they almost always apply it daily or every other day. Probably using regular vehicles. If it penetrates, it's likely that dutasteride starts accumulating, which actually increases the halflife in a way which wouldn't happen with finasteride. The body not only has to clear more dutasteride from the system, but the rate at which it is able to do so decreases as the amount in the blood increases. This leads to a snowball effect. The inevitable outcome is significant inhibition of 5-alpha-reductase type 1 & 2, and thus dht.
4.
The 500 Dalton rule: The 500 Dalton rule is not a hard limit, but it does probably mean that dutasteride has more trouble permeating the skin. This may lead to reduced systemic absorption. Dutasteride may also have other characteristics we're not aware of that lead to reduced systemic absorption compared to finasteride.
5. Liposomal vehicles: It is possible that special vehicles, like liposomes, would reduce systemic absorption as well.
Taking all of the above into account, I'm hoping that dutasteride, taken topically, preferably with a special vehicle to reduce systemic absorption as much as possible, has a much greater effect in the scalp and follicles in relation to the rest of the body. The Polichem studies by Caserini et al show that this is the case for finasteride: localized application leads to a greater degree of dht-inhibition in the scalp compared to serum. I would expect this to be the same for dutasteride.
Unfortunately, I do not understand exactly how the body replenishes 5-alpha-reductase; and especially how the body and scalp compare to one another. I also do not know whether dutasteride behaves differently in serum compared to the skin. As far as I know, drugs have a different half-life in the skin. The body cannot act upon it as it would in the bloodstream. What I do know however is that 5-alpha-reductase turnover is a slow process. I'm hoping that Vincent's (and Mustang's) success is due to the fact that applying it every 7-10 days gives the body enough time to clear (most or all) dutasteride from the system, while 5-alpha-reductase in the scalp remains mostly inhibited due to the slow turnover rate of these enzymes. The key, then, is ensuring that only a miniscule amount hits the bloodstream. This is why I would recommend using a liposomal vehicle. As a safety precaution, it might also be wise to take a break every couple of months to guarantee that the body has time to clear everything from the system, so that the snowball effect doesn't occur.
Take all of the above with a grain of salt. I'm not an expert in this field and this is just the best I could come up with based on the literature as I was able to understand it. I hope that more people trying it out (and hopefully getting bloodwork) will shed more light on it.