Safety Of Long-term Use Of DMSO As A Solvent

[haidut]

Some more information on dmso from Ray:
Ray Peat Email Advice Depository

Thanks. The study Ray mentions actually agrees with the study I posted in the original thread.
"...The reproductive toxicity of DMSO was evaluated in an in vitro culture of mammalian rodent embryos (Augustine-Rauch et al., 2004,cited in Annex 2, [ii]). At a concentration of 0.04% in culture media, DMSO
produced significant embryo toxicity, resulting in failure of neural tube closure. However, in vitro data is difficult to extrapolate to in vivo responses in humans. The first (and only) reported study evaluating maternal or developmental toxicity in rats, found no evidence for reproduction toxicity at doses up to 1000 mg/kg/day The authors reported the NOAEL for maternal and developmental toxicity as ≥1000 mg/kg/day, the highest dose tested (Magnuson et al., 2007; Annex 2,ii). DMSO3 exposure to developing mouse brains can produce brain degeneration (Hanslick et al., 2009). This neurotoxicity could be detected at doses as low as 0.3 ml/kg (DMSO > 99% pure), a level exceeded in children exposed to DMSO during certain medical treatments."

Assuming the dose 0.3ml/kg in a mouse model is the lowest dose at which in vivo effects start to be observed, this still corresponds to about 350mg/kg mouse dose, and that dose corresponds to several grams DMSO for a human. That dose is NOT achievable with a few drops of DMSO. But I fully agree that DMSO is something to not overdo.

 

[Wagner83]

Ok! I'm still against using the dmso on the testicles/scrotum directly, so far we have StAR inhibiting potential, acetylcholinestearase inhibition (for other members see the quote provided in the post above and this thread Acetylcholine Has Negative Effects On Gonadal Steroidogenesis ) , and dmso's half life is very long so it build ups in the body (as the information provided a few posts earlier suggest).

 

[haidut]

Ok! I'm still against using the dmso on the testicles/scrotum directly, so far we have StAR inhibiting potential, acetylcholinestearase inhibition (for other members see the quote provided in the post above and this thread Acetylcholine Has Negative Effects On Gonadal Steroidogenesis ) , and dmso's half life is very long so it build ups in the body (as the information provided a few posts earlier suggest).

Noted. Maybe if you correspond with Peat again you can ask if he think a few drops DMSO builds up when used over time. That would be very helpful to know.

 

[Wagner83]

Noted. Maybe if you correspond with Peat again you can ask if he think a few drops DMSO builds up when used over time. That would be very helpful to know.

Well I can always ask although I try to not overdo the mails and I still have a pending one on the issue of T3 concentration and why he suggested the 1/10 mcg per mL.
Isn't it what is suggested in the information I found and reported here?
Safety Of Long-term Use Of DMSO As A Solvent
The information was found here : The Cornell veterinarian. v.76 1986.
(jump to " page 65 and 70 in particular)

 

[haidut]

Well I can always ask although I try to not overdo the mails and I still have a pending one on the issue of T3 concentration and why he suggested the 1/10 mcg per mL.
Isn't it what is suggested in the information I found and reported here?
Safety Of Long-term Use Of DMSO As A Solvent
The information was found here : The Cornell veterinarian. v.76 1986.
(jump to " page 65 and 70 in particular)

Yes, but they did not specify how much DMSO was used. I think the half life depends on the dose as DMSO gets metabolized and some of it breaks down into MSM and other derivatives.
Btw, thanks for posting the link to the Cornell vet book. It has some very nice discussions on the benefits of DMSO as well - i.e. antiinflammatory, radiation protection, antibacterial, anti-ischemic, respiration/metabolism boosting, etc. Maybe we should have a separate thread called "Benefits of DMSO"?
Actually, I read through both the benefits and side effects and all the doses and concentration used are really not applicable to our case (re: supplementation). The book itself ends the section on "Enzyme Effects" (i.e. cholinesterase inhibition of 4% DMSO) with this statement.
"...The DMSO concentrations required may be too high to have clinical relevance." (page 67, last sentence of "Enzyme Effects").

So, maybe both the systemic benefits and side effects are really not relevant unless these high doses are used, which leave the skin irritation as the most relevant one. I would like to learn more about that long half life and how it relates to the dose so I will see if I can find something more on that.

 

[Wagner83]

Yes, but they did not specify how much DMSO was used. I think the half life depends on the dose as DMSO gets metabolized and some of it breaks down into MSM and other derivatives.
Btw, thanks for posting the link to the Cornell vet book. It has some very nice discussions on the benefits of DMSO as well - i.e. antiinflammatory, radiation protection, antibacterial, anti-ischemic, respiration/metabolism boosting, etc. Maybe we should have a separate thread called "Benefits of DMSO"? :)
Actually, I read through both the benefits and side effects and all the doses and concentration used are really not applicable to our case (re: supplementation). The book itself ends the section on "Enzyme Effects" (i.e. cholinesterase inhibition of 4% DMSO) with this statement.
"...The DMSO concentrations required may be too high to have clinical relevance." (page 67, last sentence of "Enzyme Effects").

So, maybe both the systemic benefits and side effects are really not relevant unless these high doses are used, which leave the skin irritation as the most relevant one. I would like to learn more about that long half life and how it relates to the dose so I will see if I can find something more on that.

Interesting. I think this one can do for both positive and negative effects but your call.
I'm also interested in the build up effects and of course if higher concentration is only achieved in the skin where it is applied or if it's possibly achieved in the gonads right beneath it when we apply dmso to scrotum . Similarly would applying dmso to forehead/arms/legs result in the same amount of dmso reaching the brain , liver etc... From what I understand after some time dmso is found everywhere, even teeth and bones. There's also the question on the effects on StAR (which dose does not affect it) and progesterone synthesis (same).
Perhaps the study on proteins aggregation (http://pubs.acs.org/doi/abs/10.1021/acs.jpca.6b00178) is also relevant to the area of the skin and elsewhere depending on how much it builds up , how quickly it dilutes and metabolizes in the body (see first question of the post). These last two questions may be all we need to know?

 

[haidut]

Interesting. I'm also interested in the build up effects and of course if higher concentration is only achieved in the skin where it is applied or if it's possibly achieved in the gonads right beneath it when we apply dmso to scrotum . Similarly would applying dmso to forehead/arms/legs result in the same amount of dmso reaching the brain , liver etc... From what I understand after some time dmso is found everywhere, even teeth and bones.

One of the references in that book (16) is what I have been looking for. The claim that DMSO potentiates effects of steroids inside the cell. I will post this as a separate thread. Also, another reference (105) shows that to increase topical absorption of a steroid, a very small mount of DMSO is needed - 2mg/cm^2 of skin. So, maybe the DMSO concentration in the supplements can be decreased even more. I always wondered why the animal studied with steroids, which almost always use DMSO as solvent, dissolve the steroid in pure DMSO and then dilute the solution until it becomes only 5% - 10% DMSO. I doubt it is a coincidence as all studies do it, so maybe much less DMSO can be used. I would love to be able to reduce the DMSO concentration even more, so I'll do some experiments and blood tests and maybe we solve this once and for all if the DMSO can be dropped to say 5% in the solution.
THE EFFECT OF DMSO ON PERCUTANEOUS PENETRATION OF HYDROCORTISONE AND TESTOSTERONE IN MAN
"...DMSO unequivocally increased the penetration of 14C hydrocortisone and testosterone. through normal skin. The quantity of DMSO required was small-2 mg per sq cm of skin. This amount is that used in topical therapy and is visually nonirritating. The minimum concentration of DMSO necessary to produce this enhancement is not known at present. We have verified this experimental observation clinically. We compared the effect of triamcinolone acetonide in a commercial cream base to a similar concentration in 90(% DMSO solution. In psoriasis patients, the triamcinolone in DMSO was generally more effective than the cream base."

"...Radio-labeled 4C hydrocortisone and testosterone were applied to human skin in acetone alone and in DMSO. Penetration quantitated by assaying the 14C appearing in urine for five days. Without DMSO, 12 times as much testosterone penetrated as hydrocortisone. DMSO increased the penetration of both steroids three-and-one-half times. The significance of these findings is discussed."

 

[Wagner83]

You had posted something about how the concentration of dmso potentiated steroids differently and how 5% would work way less than 70%, but if blood tests show it's not true that would be very nice indeed .. Btw I was slow but edited my post in the meantime.

 

[Fractality]

Long live DMSO!

 

[Elias]

Thanks haidut!
Here's another resource for DMSO literature.
Pharmacology of DMSO

 

[haidut]

Thanks haidut!
Here's another resource for DMSO literature.
Pharmacology of DMSO

Thanks.

 

[Jsaute21]

Why are people so opposed to DMSO? Is it just the organic crowd being hyper hesitant to use additives, even when there is some benefit?

 

[Wagner83]

Did you read all the back and forth discussion in this thread? It seems to be a very potent substance and has various effects in the body, to me being cautious makes sense.

 

[Jsaute21]

I read a lot of the back and forth. Didn't seem to be a whole lot of conclusive evidence regarding the danger of it. Maybe being cautious with it makes sense, but avoiding it completely may be a bit over the top.

 

[Texon]

I'd be very interested to see the results from regular milk you can easily get as well. As well as the other "Peaty" things mentioned, OJ, coke, water, red bull.

I wondered about the Starbucks they sell in cans in the supermarket, the doubleshot espresso. They taste so good but the combination of coffee plus aluminium never felt right for me.

Depends how many things @haidut is interested in sending, if it was just an after thought of 2-3 products it'd be best to test the "big ones" milk, oj, coke.

Beware of the larger plastic containers (pints/quarts) of Starbucks in the refrigerated section. They have carageenan in them whereas the glass bottles in 6-packs on the shelf done not...go figure???

 

[Wagner83]

Noted. Maybe if you correspond with Peat again you can ask if he think a few drops DMSO builds up when used over time. That would be very helpful to know.

See here for a reply to a related question : Ray Peat Email Advice Depository

 

[schultz]

See here for a reply to a related question : Ray Peat Email Advice Depository

Haha classic Peat response. I like his subtle sense of humour.

 

[Such_Saturation]

Haha classic Peat response. I like his subtle sense of humour.

I think this forum pretty much single handedly scared what few sympathies he had for DMSO away lol

 

[goodandevil]

See here for a reply to a related question : Ray Peat Email Advice Depository

I had trouble breathing on it, as well as other symptoms. I believe it's responsible for many of the side effects from haidut's supplements. Ray told me that small amounts, for example to dissolve lisuride, taken orally, presumably with food, are likely safe. It seems he's against the transdermal route, and of course haidut cant recommend oral use of his lab chemicals, but people should be very cautious with transdermal dmso. I applaud haidut for increasing the concentratjon of his dmso supplements and making tocopherol/mct solutions available when possible.

 

[Wagner83]

Haha classic Peat response. I like his subtle sense of humour.

Are you referring to the way he phrases his answer?

I had trouble breathing on it, as well as other symptoms. I believe it's responsible for many of the side effects from haidut's supplements. Ray told me that small amounts, for example to dissolve lisuride, taken orally, presumably with food, are likely safe. It seems he's against the transdermal route, and of course haidut cant recommend oral use of his lab chemicals, but people should be very cautious with transdermal dmso. I applaud haidut for increasing the concentratjon of his dmso supplements and making tocopherol/mct solutions available when possible.

Why would using it topically be worse than orally? In this case we were talking about scrotum/testicles not other areas.