Dihydroquercetin for MCAS

nerd

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I wouldn't say it's superior to quercetin (QCT) in general (10.1016/j.cbi.2009.06.007), but if it's really such a potent mast cell inhibitor, it might be a viable alternative to ketotifen, which is a mast cell stabilizer but also an H1 antihistamine.
H1 antihistamines can have undesired side effects on brain function and make the patient kind of sleepy or brain fogged.
This would be the potential advantage of DHQ, potentially not exhibiting such an H1 antihistaminic effect in the brain.

One study described its mast cell stabilizing effect as cromoglicic. Cromoglicic acid, a single-mechanistic mast cell stabilizer, has the disadvantage of very low oral bioavailability (ca. 1%), delimiting its oral efficacy to the GIT. Unfortunately, it's even worse for DHQ (i.e. ca. 0.5%) [10.3390/molecules21040494]. Not even liposomal delivery could improve it to any of the levels of QCT.

But it's also a dosing protocol question. Mast cell stabilizers, including Ketotifen, normally require you to take them in a tight schedule so that there are no time gaps without an active concentration at the mast cells. Only then, the mast cell inhibitory effect gradually builds up over one to two weeks. Cromoglicic acid has to be taken many times during the day, which is quite annoying. You have PEM and need to sleep 12 hours? And you missed it...

Just like QCT, DHQ also exhibits HDAC inhibitory activity (10.1177/1934578X19895370). This might be one mechanism for mast cell stabilization. But there are also others at somewhat lower doses (10.1016/j.intimp.2019.03.038).

DHQ might be fine to take two times per day (10.1155/2019/9348075). But I think the low bioavailability renders it relatively useless when compared to QCT or Ketotifen.
 
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I wouldn't say it's superior to quercetin (QCT) in general (10.1016/j.cbi.2009.06.007), but if it's really such a potent mast cell inhibitor, it might be a viable alternative to ketotifen, which is a mast cell stabilizer but also an H1 antihistamine.
H1 antihistamines can have undesired side effects on brain function and make the patient kind of sleepy or brain fogged.
This would be the potential advantage of DHQ, potentially not exhibiting such an H1 antihistaminic effect in the brain.

One study described its mast cell stabilizing effect as cromoglicic. Cromoglicic acid, a single-mechanistic mast cell stabilizer, has the disadvantage of very low oral bioavailability (ca. 1%), delimiting its oral efficacy to the GIT. Unfortunately, it's even worse for DHQ (i.e. ca. 0.5%) [10.3390/molecules21040494]. Not even liposomal delivery could improve it to any of the levels of QCT.

But it's also a dosing protocol question. Mast cell stabilizers, including Ketotifen, normally require you to take them in a tight schedule so that there are no time gaps without an active concentration at the mast cells. Only then, the mast cell inhibitory effect gradually builds up over one to two weeks. Cromoglicic acid has to be taken many times during the day, which is quite annoying. You have PEM and need to sleep 12 hours? And you missed it...

Just like QCT, DHQ also exhibits HDAC inhibitory activity (10.1177/1934578X19895370). This might be one mechanism for mast cell stabilization. But there are also others at somewhat lower doses (10.1016/j.intimp.2019.03.038).

DHQ might be fine to take two times per day (10.1155/2019/9348075). But I think the low bioavailability renders it relatively useless when compared to QCT or Ketotifen.

Thank you for the point in your opinion what would be a better solution ?