Physicians thoughts on microdosing

[Here2Learn]

Good breakdown at how he approaches microdosing with his patients. He has a few really good breakdown videos.


View: https://youtu.be/MA9KsoZOr3E?si=XQJrH_f4hgJWUNMx

 

[Rakusa]

Alright so he thinks it's fine to change up the injection interval from the recommended schedules in the studies. He thinks adherance played a big role in efficient therapy and many casuals will forget to inject more frequently. He finds that in the Initial phase, you should stick to the guidelines and later change up the injection frequency, like from 1mg every 7 days, to 1 mg every 5 days, increasing the peak concentrations from 1.4mg to 1.8mg.

Microdosing is interesting for people who hit their goal weight and achived satisfying glycemic control.

This is my summary and I don't claim accuracy.

The argument I've read before, that you should stick to the study protocol (bc they must know whats right) doesn't make so much sense to me for the reason mentioned (you need adherance to replicate your hypothesis), but I also like to microdose my TRT even taking it SC for more estrogen control. And there are no studys on, when I last checked and even the leaflets in my prescription tell me to inject 250mg every 2 weeks for TRT. Crazy peaks make no sense, when there is a huge drop afterwards. Balance & a stable level is key with Testosterone and maybe even GLP-1 agonists, who knows. Only time will tell.

 

[Here2Learn]

The main thing I got was microdosing isn’t really for those needing to lose but for those on maintenance. Keeps the doses lower but at a steady rate in the system.

 

[Rakusa]

The main thing I got was microdosing isn’t really for those needing to lose but for those on maintenance. Keeps the doses lower but at a steady rate in the system.

I'd be interested in the mechanism of this, because I would assume steady levels would be best for steady weightloss.

 

[Here2Learn]

I'd be interested in the mechanism of this, because I would assume steady levels would be best for steady weightloss.

In the video the Doctor stated he doesn’t recommend microdosing for those needing to lose because he hasn’t seen it be as effective for his patients. I don’t think he went further than that on the topic. He has several videos out on it so may address that specifically.

 

[Ghoul]

Alright so he thinks it's fine to change up the injection interval from the recommended schedules in the studies. He thinks adherance played a big role in efficient therapy and many casuals will forget to inject more frequently. He finds that in the Initial phase, you should stick to the guidelines and later change up the injection frequency, like from 1mg every 7 days, to 1 mg every 5 days, increasing the peak concentrations from 1.4mg to 1.8mg.

Microdosing is interesting for people who hit their goal weight and achived satisfying glycemic control.

This is my summary and I don't claim accuracy.

The argument I've read before, that you should stick to the study protocol (bc they must know whats right) doesn't make so much sense to me for the reason mentioned (you need adherance to replicate your hypothesis), but I also like to microdose my TRT even taking it SC for more estrogen control. And there are no studys on, when I last checked and even the leaflets in my prescription tell me to inject 250mg every 2 weeks for TRT. Crazy peaks make no sense, when there is a huge drop afterwards. Balance & a stable level is key with Testosterone and maybe even GLP-1 agonists, who knows. Only time will tell.

Testosterone isn't a protein therapeutic. Increasing the frequency of injection plays no role in immunogenicity, while injection frequently is a primary factor for causing stronger immune development against peptides and proteins.

 

[Ghoul]

Are we trying to increase immunogenicity? Do these doctors advising microdosing even know what immunogenicity is, and the threat it presents to patients? Just because someone's graduated medical school, and spent a few years in a small practice dispensing blood pressure medication and birth control pills, doesn't make them experts. or even vaguely familiar with concepts surrounding the relatively recent phenomenon of protein pharmaceuticals.

Most general practitioners couldn't even tell you what the mechanism of action of GLP class drugs is, with a lot of them under the impression it's an injectable diet pill.


It is commonly accepted that subcutaneous administration of therapeutic proteins, while more user-friendly, is more immunogenic than intravenous administration, likely because of migratory potential of cutaneous dendritic cells.92, 93 As discussed, prolonged, chronic therapies are often more immunogenic, and frequent administration has also been shown to increase immunogenicity.

Unfortunately, the clinical utility of many therapeutic proteins has been undermined by the potential development of unwanted immune responses against the protein. The incidence of immunogenicity of several clinically approved products has been well documented6, 7, 8 (Tables 1 and 2), and some have failed before even reaching clinical trials. The development of antibodies can limit efficacy and negatively impact safety, hampering the clinical utility of the protein.

https://www.sciencedirect.com/science/article/abs/pii/S002235491830813X

 

[Rakusa]

The doctor works in a hospital, I doubt GLP-1 are a huge thing there, he seems more personally motivated, because of his success with it.

Regarding the immunity, I think this has been asked before, but can we say for sure, that developing immunity towards reta for example, reduces our sensitivity to the 3 different mechanisms of action (glp, gip and glucagon). Like some sort of downregulation or permanent tolerance?

 

[Ghoul]

The doctor works in a hospital, I doubt GLP-1 are a huge thing there, he seems more personally motivated, because of his success with it.

Regarding the immunity, I think this has been asked before, but can we say for sure, that developing immunity towards reta for example, reduces our sensitivity to the 3 different mechanisms of action (glp, gip and glucagon). Like some sort of downregulation or permanent tolerance?

Immunogenicity isn't binary, it's a sliding scale. At low levels, its effect can be inconsequential.

No protein based drug is unaffected by high levels of immunogenicity. None. It's only a question of how much must be induced before it's a problem.

The huge effort put into keeping immunogenicity to a low, clinically insignificant level is a top priority and worked out prior to the first human being injected in a trial. The FDA requires this.

The goal is to keep it low, and stable. If it continues to rise, dose after dose, sooner or later the efficacy of the drug WILL be reduced. There are potentially even worse consequences, but we'll keep it simple for this discussion.

If any factor known to increase immunogenicity is changed, from dose frequency, to manufacturing method, to the very container it's supplied in, immunogenicity must be reevaluated to the FDA's satisfaction. The material used as a stopper in a container is sufficient to cause enough aggregation particles to develop, a protein drug can become useless after several doses.

In UGL, and the haphazard ways the drugs are used, you quite literally couldn't. do much more if your goal was to deliver a peptide in a way that MAXIMIZES the immunogenic reaction.

The big tell really ought to be the number of people using UGL for whom these drugs fail to produce the same good results seen in the trials.

As for how long immunogenicity lasts? Like a vaccine, it can be short, long, somewhere in between, or permanent.

In the case of human growth hormone, where immunogenicity has been observed developing to the point GH stops working, sometimes a break of 3 months is enough, sometimes 2 years, and sometimes antibodies remain indefinitely and unfortunately in the case of children, never goes down and their window of growth opportunity is lost forever. See "stop treatment" below, and the amount of GH effectiveness lost ("inhibited") even in cases where treatment continued.

This is no joke, and the idea it's an obscure "bubble boy" topic borders on insanity.

 

[Rakusa]

It is commonly accepted that subcutaneous administration of therapeutic proteins, while more user-friendly, is more immunogenic than intravenous administration, likely because of migratory potential of cutaneous dendritic cells.92, 93 As discussed, prolonged, chronic therapies are often more immunogenic, and frequent administration has also been shown to increase immunogenicity.

So reta and other peptides would be best injected intramuscular and not s.c?

 

[Ghoul]

So reta and other peptides would be best injected intramuscular and not s.c?

From an immunogenic perspective, yes. From a pharmacodynamic perspective, that is, the rate of uptake of the drug, which influences side effects and the speed at which blood glucose levels drop, no.

The best thing to do is minimize immunogenicity with the factors under your control.

Adhering to the dose, frequency, dilution rate that were determined by the drug developers to keep immunogenicity down. Using pharma BAC, Which is guaranteed free of impurities that make immunogenicity worse, using smaller dose vials to keep the time in reconstituted form to a minimum, and filtering. Any or all of these things will reduce the amount of immunogenicity. Whether that's enough or not is impossible to say, but it makes a better outcome, especially over the long term, more likely.