Where to buy quality Rapamycin Titanium dioxide free?

Hello everyone, Im 36 ans want to start Rapamycin asap… I read your post about quality control and different place to buy. However a problem seems to remain : the 2 brands recommanded here contains titanium dioxide wich is now banned in europe for instance.

EDIT: have a look here : Titanium dioxide: E171 no longer considered safe when used as a food additive | EFSA (the opposite you want, while using some large quantity for anti aging purpose…)

Where could we get a brand without it ? What do you think to order directly raw material instead such as here : Rapamycin, >99% | LC Laboratories ??

Thanks for your help

cheers

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Hi Tom, welcome to the site.

Are you sure that titanium dioxide is banned in europe? Can you share the scientific evidence that Titanium dioxide at the levels seen in the sirolimus tablets are a significant problem?

I haven’t done any research on it, but I do know that Rapamune (the brand name version of sirolimus / rapamycin developed by Pfizer) is sold in Europe and does have titanium dioxide in the formulation:

Also - There are issues with buying the raw material / rapamycin powder.

  1. First of all, rapamycin is not very bioavailable, so if you just take the powder it just gets destroyed in your stomach and little or none of it gets into your blood system. Some people here have tried to figure out a way to make their own enterically coated capsules with the rapamycin powder, but its a lot of work and you’ll need to do blood testing, etc. to validate that its actually working and the rapamycin/sirolimus is getting into your bloodstream at levels that are helpful. You can do a search on this site for “rapamycin powder” or “sirolimus powder” and you’ll see the discussions of people working to make their own capsules. Its not something that very many people do. The rapamycin tablets you buy typically have special formulations and coatings to increase its bioavailability, see this discussion: Rapamycin and NanoCrystal Formulations

  2. You don’t know the source (the manufacturer), the purity or the possible contaminants of the sirolimus powder unless you do a third party lab analysis of the product. Its typically difficult and expensive ($500 to $1,000 typically) to get a good lab to do a proper analysis of the product, and you have to know what you’re doing in terms of the analysis. A lot of pharmaceutical APIs (active pharmaceutical ingredients) are made in China in substandard manufacturing facilities… so you don’t know the quality (and you cannot just assume they are fine). The lab supply group you identified - LC Labs - you don’t know where they sourced the sirolimus powder from nor what possible contaminants are in it.

Also - from this attached document it seems clear that it has some titanium dioxide in the tablet:

Coated Tablets
The product is approved in tablet form consisting of 2 strengths, 1mg and 2mg. Rapamune 2 mg
coated tablets differs from Rapamune 1 mg coated tablets in that the tablets contain yellow and brown iron oxides (E172) therefore resulting in a different colour to the 1 mg tablets namely yellow to beige compared to white.

The inert tablet cores for both tablet strengths are composed of lactose monohydrate (diluent, PhEur), macrogol 8000 (binder, PhEur), magnesium stearate (lubricant, PhEur), and talc (glidant, PhEur).
The tablet coating for both strengths is composed of several layers of coatings consisting of the
Nanodispersion (sirolimus and stabiliser), macrogol 20000 (plasticizer, in-house specification),
glyceryl monooleate (plasticizer, in-house specification), pharmaceutical glaze (shellac, coating
agent), calcium sulphate anhydrous (coating agent), microcrystalline cellulose (reinforcing agent,
PhEur), sucrose (filler, PhEur), titanium dioxide (colorant, PhEur), povidone (binder, PhEur),
carnauba wax (polishing agent, PhEur) with a red printing ink. The composition of this proprietary
ink is presented. In addition, Rapamune tablets 2mg contain iron oxides as colouring materials to
distinguish them from the 1mg (white) tablets.

rapamune-epar-scientific-discussion_en.pdf (507.5 KB)
Source Document below:

Here is what the document states that you linked to:

Is EFSA banning titanium dioxide?

No. EFSA’s role was limited to evaluating the risks linked to titanium dioxide as a food additive. This included an assessment of relevant scientific information on TiO2, its potential toxicity, and estimates of human dietary exposure. Any legislative or regulatory decisions on the authorisations of food additives are the responsibility of the risk managers (i.e. European Commission and Member States).

It seems the focus is really as it relates to food, not medicines.

Prof Maged Younes, Chair of EFSA’s expert Panel on Food Additives and Flavourings (FAF), said: “Taking into account all available scientific studies and data, the Panel concluded that titanium dioxide can no longer be considered safe as a food additive. A critical element in reaching this conclusion is that we could not exclude genotoxicity concerns after consumption of titanium dioxide particles. After oral ingestion, the absorption of titanium dioxide particles is low, however they can accumulate in the body”.

2. What foods contain titanium dioxide?

The main food categories contributing to dietary exposure of E171 are fine bakery wares, soups, broths and sauces (for infants, toddlers and adolescents); and soups, broths, sauces, salads and savoury based sandwich spreads (for children, adults and the elderly). Processed nuts are also a main contributing food category for adults and the elderly.

I can certainly understand the potential for concern with regard to food intakes, where you are taking the food on a daily basis. But I don’t have much concern with related to the small amounts used in medicines that you dose periodically ( rapamycin is typically taken only once per week).

Lastly, I think you want to look at the risk/reward of taking rapamycin tablets. The EU research suggests that there “may be” a risk (so there is no proven risk, just the chance that there may be a risk). And at the same time you have rapamycin as a proven (in dozens of dozens of studies) to increase lifespan (in mammals) by 15 to 30%. So small risk, big potential reward. Everyone makes their own risk/reward calculations, but for most of us here, we decide to take the tablets from major pharmaceuticals companies.

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Well, if you eat anything white, or use toothpaste, chances are you are regularly getting some titanium oxide into your system, it’s basically what makes many things white.
I have been eating all my life and am 82 and in excellent health. Titanium oxide is probably the least of your worries.
Toothpastes contain titanium dioxide, as it is an effective whitening agent.
Some of your favorite foods like:

  1. White sugar
  2. White chocolate
  3. Marshmallows
  4. Icing sugar
  5. White bread
  6. White flour
  7. Cupcakes
  8. Macarons
  9. Angel food cake
  10. Vanilla wafers
  11. Tic Tacs
    Etc.,etc.
    Contain titanium dioxide.
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Thanks all for your reply’s.

Well it also clearly states : After conducting a review of all the relevant available scientific evidence, EFSA concluded that a concern for genotoxicity of TiO2 particles cannot be ruled out. Based on this concern, EFSA’s experts no longer consider titanium dioxide safe when used as a food additive. This means that an Acceptable Daily Intake (ADI) cannot be established for E171.

So I understand the benefits risk and I fully agree with you guys. Its why I am here looking for rapamycin asap. And also understand TiO2 is in most products. However we should try to avoid

You have numerous paper about it really :

Also very neurotoxic : Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles - PubMed

I work in the dietary supplement field and believe me : for EFSA evaluation like that… you really really need it to be a poison.

So if we are 100% sure about the enteric coating value… very easy for anyone to get their hand on DRcaps capsules. And make their own dosage.

Or any chance we have another generic brand more clean ? :innocent:

I am not sure about the exact composition of all the generic versions of rapamycin. We have a list if them here. If you identify any that meet your requirements please post Rapamycin, Rapamune, Sirolimus and Other Naming Conventions

Thanks. I checked all your list and 100% contains titanium dioxide. So only 2 choices left :

  • order raw pure powder
    -order the classic generic

Just 2 questions to make my final choices please :

1/ I see you advice often to make third part lab test. But when ordering from India, normally all Rapacan tablets are same… isnt ? I dont see how it could be different.

2/ The “enteric coated” tablet is the only thing you state. But possible to make similar effect using such capsules : DRcaps from Lonza. However, is there others interest such as “crystal structure” or ?

Do you know a source for DRcaps from Lonza?

We don’t have much data really on quality of product coming out of India. We have 2 tests (two data points), on Biocon Rapacan, and Zydus Siromus versions of rapamycin / sirolimus. You can see the lab test results here: Rapamycin / Sirolimus from India, Lab Test Report on Quality / Purity

Quality / contaminants of pharmaceuticals is based on inputs, storage issues, and general quality control systems and motivations within the company (greater focus on production volume vs. quality, etc.) - so there are many reasons why quality of drugs may vary over time.

More broadly, here is why people are sometimes concerned about generic drugs more generally: Why and How to Test Your Rapamycin for Purity, Dosage and Contaminants

Regarding your second point - sure, I assume you could address the bioavailability issue via good capsules. Of course - you’d need to test via blood tests, to validate that its working. More details here: How to get a Rapamycin (sirolimus) Blood Level Test

Here is a discussion of some people doing what you are thinking doing: Rapamycin enteric coating vs powder bioavailability

I would note EU is going on a precautionary principle.

It’s important to understand that a potential hazard that cannot be ruled out based on lab conditions that do not resemble human consumption is not the same thing as an “actual risk”.

If you look at the actual studies, it’s not the same as what you’d get from the food matrix as titanium dioxide would bind to different compounds, further reducing the tiny bioavailability from ingestion in the first place. (Inhalation of nanoparticles is a different story)

“Cannot rule out genotoxicity” doesn’t mean as much as people think. DNA damage is reversible and toxicologists do not put much weight on these assays - it’s more of a screening tool at best. I literally looked at all the studies that the EFSA identified where titanium dioxide showed genotoxicity (at doses well beyond human exposure levels) - every single one of these studies was flawed.

You can also see here one of the studies used by the EFSA was even from a highly questionable journal: https://www.ingentaconnect.com/contentone/asp/jnn/2017/00000017/00000012/art00086

I personally am not particularly concerned about pharmaceuticals containing small amounts of titanium dioxide until there is better evidence showing otherwise.

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Thanks all for your replies ! very nice to have such discussion here.

I checked some of the data deeper for titanium dioxide. Im not convinced about it being that bad nor OK… actually some studies clearly state the mecanism of action by oral route. So if we could avoid, we should. Now the question is here because I want to test first the 20mg protocol. So 20x the tiny amount ot titanium dioxide in one shot :S but seems no choice.

I have free access to DRcaps, and I can also make perfect dose per capsules (0,1mg precision) in my laboratory, but issue is this :
https://www.researchgate.net/publication/327588761_Amorphous_Nanoparticulate_Formulation_of_Sirolimus_and_Its_Tablets

Seems like we also need to improve its solubility, probably to better perform at the gut level. And here we dont know what we do with raw material without proper studies.

So… yes, no choice : we need the tablets full of titanium dioxide.

Then I came back to the quoted study and also found out that someone on longecity only see clear result using Rapamune. Not the generic. So the dissolution process is clearly to consider, not only the dosage once we choose to supplement with it.

I will need to order a trusted Rapamune

1 Like

The best pricing I’ve seen on rapamune is out of Bulgaria… see here: How to buy Rapamycin (Sirolimus)? What is the cost? - #104 by pollux

looks like a scam : Bgpharmadrugs.com ghosted - Page 3 ??

FWIW

There are several members on this forum who have used BG.

The person who operates BG is a member of this forum.

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So why such high numbers of people complains in this forum ?.. and who are the several users of BG here ? Im really cautious of the owner self promoting using different identity in forums…

Search on this forum and you will locate/find.

I have nothing to do with BG.

No, that forum is clearly spam. See the different BG threads on that forum. They have all the same spam comments posted over and over. Look at the thread on thinksteroids instead, or on reddit. BG is so far a legit source.

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What are the ingredients in RAPAMUNE® (sirolimus)?

Active ingredients: sirolimus

Inactive ingredients: sirolimus tablets: sucrose, lactose, polyethylene glycol 8000, calcium sulfate, microcrystalline cellulose, pharmaceutical glaze, talc, titanium dioxide, magnesium stearate, povidone, poloxamer 188, polyethylene glycol 20,000, glyceryl monooleate, carnauba wax, dl-alpha tocopherol, and other ingredients. The 0.5 mg and 2 mg dosage strengths also contain yellow iron (ferric) oxide and brown iron (ferric) oxide.

This product’s label may have been updated. For current full prescribing information, please visit www.greenstonellc.com.

He hasn’t promoted himself here… Just other users here have recommended the site and have had success. Its the only place i know that sells rapamune without prescription.

https://www.bgpharmadrugs.com/

You can search here on our forums for bg pharma and see the comments.

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BTW, I didn’t completely rule out any sort of harm because that’s going to be very difficult to prove in the first place and it’s pretty unlikely whereas there are a million more issues that are potentially more likely harmful - like all the possible combinations of microplastics and nanoplastics one could take in through many different routes - pretty certain some forms are harmful - at the very least the inhaled route being most likely. I’m not saying we should be cavalier but at some point, one should consider having some probability cutoff about what you should worry about using a targeted selective approach or it’ll be physically impossible to figure out how to avoid potential toxins out there to a reasonably safe level. Partly why I quickly pointed out EFSA uses a precautionary principle. That’s ideal but not practical. Too many false positives will end up unnecessarily spending a lot more resources in time and money - there are better ways to spend resources which will likely yield net longer lifespan. It’s not as bad as CA Prop 65 - but it’s a similar analogy - one would end up not being able to buy anything if one follows meaningless warnings.

To be clear, I’m merely pointing out that there isn’t much reason to be particularly concerned, as there needs to be more evidence on the things that actually matter which unsurprisingly hasn’t been done probably because - it’s unlikely in the first place.

I’m not going to go in-depth and write a 5-page essay to explain why every single one of the methods in every single one of the cited studies is deeply flawed since it’s a lot more time than it’s worth. I’ll merely point out - one study literally didn’t follow the standard protocol for assays (which isn’t even that useful of an assay) and you should read the methods - if you’re familiar with some of the more advanced statistics used and why they’re likely false positives, you’ll quickly see what I mean by deep flaws.

Most of these can be quickly picked apart by a PhD in stats or even masters level stats equivalent knowledge, so it won’t be particularly difficult to find someone who will explain it in more detail orally if you’re already part of the supplement industry at large. If any single one of the studies actually proved stem cells had genotoxicity, I’d be far more concerned because that would be likely irreversible genotoxicity rather than known to be reversible - typical of mature cells. Not to mention, if you run the extrapolated numbers on human exposure - basically these are impossible levels.

EFSA does not look in depth context of the stats or study design that biases p-value (see American Statistical Association guidelines) BTW. See here they are literally not actually reviewing all of the science: https://efsa.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.2903%2Fj.efsa.2021.6585&file=efs26585-sup-0004-Appendix_D.pdf

Are you really going to put more trust in an authority who clearly indicates in their methods “we didn’t actually fully read and understand the full paper” from the get-go? It literally doesn’t make sense to me but if you can explain why I’m completely mistaken - I’m quite open to it

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