DMSO for Increased Flavenoid Solubility and Bioavailability?
The problem with the bio-delivery of senolytic flavenoids like Quercetin and Fisetin is that they are insoluble in water. Therefore, there is a good chance that if taken orally, they may pass right through the digestive system without entering the bloodstream. (A related problem is that if they DO enter the bloodstream, they may be removed before acting by clean-up proteins like P-glycoprotein. See the discussion on Bioperine.)
I notice from the Selleck Chemicals web site that both Quercetin and Fisetin, while insoluble in water, are highly soluble in DMSO (dimethyl sulfoxide). In particular, Quercetin has a DMSO solubility of 61 mg/mL (201.83 mM) and Fisetin has a DMSO solubility of 57 mg/mL (199.13 mM).
DMSO is a prescription medicine and a dietary supplement that can be taken by mouth, applied to the skin (used topically), or injected into the veins (used intravenously or by IV). DMSO is used medically for the management of amyloidosis (the amyloid buildup associated with old age) and related symptoms. From Amazon one can purchase without a prescription pharmaceutical-grade high-purity DMSO liquid for $13.70 for a 3.4 Oz (100 ml) bottle.
So the question is, should we be dissolving Fisetin and Quercetin in DMSO before taking it orally when doing senolytic doses of Fisetin or of D+Q? Note that a 10 ml shot glass of DMSO will dissolve about 610 mg of Quercetin and 570 mg of Fisetin, around the right amounts if one is doing a four-dose per day delivery to get to around 2,000 mg total of the senolytic.
I'm a PhD physicist, not an MD, and I don't know if there are hidden medical problems with doing something like that. DMSO is very penetrating stuff and is sometimes used to deliver drugs through the skin. Does anyone, particular an MD or bio-researcher, have an opinion about this proposed senolytic delivery procedure? Is there a danger of over-delivering the flavenoid or having it end up in unwanted places?
-
This dose not answer your question, but it is interesting.
https://academic.oup.com/biolreprod/article/97/6/883/4604773
-
Followup on my DMSO Question
Dr. John Sanderson sent me an email answering my question in some detail. He said that "using penetration enhancers such as DMSO may improve the picture slightly, but not significantly". He added that taking oral DMSO would bring its own effects, including changes in "gene expression, stem cell differentiation, and epigenetic alterations, even at low concentrations."
Looking at the literature in more detail, I found that Fisetin and Quercetin dissolved in DMSO are commonly used in cell culture tests, but are not administered orally.
It appears that for senolytic applications it would be better to stick to taking the capsules, even if only 1 to 3 % of the orally administered flavenoids end up in the bloodstream. I note that it would still be a good idea to take 10 mg of Bioperine an hour before the flavenoid dose to suppress the production of P-glycoprotein. See the discussion on Bioperine.
-
I had a similar idea and that’s actually how I found this site. However, my idea was to dissolve in DMSO and apply topically to the abdomen, under the chin, or any other place where one has adipose fat. DMSO was once used on the football field and applied topically to reduce swelling associated with injuries. It works exceedingly well to neutralize -OH radicals and it still used by thousands today “off label” as a topical pain reliever. What makes such practices risky is not the solvent’s toxicity (which is low), but rather it’s ability to take most anything across the skin with it including bacteria, viruses, and toxins. I have read that it can even take cellulose from a cotton swab across the skin. So, what I was thinking was to dissolve the flavonoid completely in the least amount of DMSO possible, dilute with distilled water or saline to reach the senolytic target concentration of 20uM and then add in a small quantity (1%?) of benzyl alcohol as a sterilization ingredient. I think I will give this a try once my order arrives and report back my findings.
