Potential Suramin Alternatives - Sytrinol and Kudzu (Anti Purinergic Therapy)

[Jesse2233]

I've come across two over the counter supplements that inhibit the same purinergic receptors P2Y2 and P2X7 that Dr Naviaux mentions as Suramin's targets.

1. Sytrinol is is a proprietary formula consisting of polymethoxylated flavones (PMF's) from citrus (including tangeretin), palm tocotrienols and other proprietary constituents. Flavones are antagonists of the purinergic P2Y2 receptor (1).
   
   
2. Kudzu contains a number of isoflavones, including puerarin, about 60% of the total isoflavones, daidzein (an anti-inflammatory and antimicrobial agent), and daidzin (structurally related to genistein). Kudzu has been shown to be an antagonist of the P2X7 receptor (2).

Whether or not these supplements effectively emulate Suramin's effects, or whether Suramin itself actually does anything beneficial is unknown. Suramin is of course an IV drug with better bioavailability than over the counter oral pills. FWIW I've not found much mention of Sytrinol on PR and have seen Kudzu only mentioned in passing.

Further afield I've found some parents reporting benefits from these supplements for their autistic children:

Sytrinol

I was desperate, and I gave her one capsule, 150mg, of Sytrinol. Within minutes, behavior returned to normal. One hour later, she became happy and began engaging and playing with me. Two hours later, wanted to do class with me and did her toughest one, reading. Did it excellently as well.

Link

Kudzu

Regarding our own experiment with natural antipurinergic therapy, we've been trialing Kudzu for the past three weeks and the outcome has been pretty impressive. It is still early to say but maybe this will enter the top three interventions. The first thing we noticed was the improvement in his articulation. It happened with the first a few days and soon I realized he started to sleep very well without Melatonin. I haven't seen night awake or silly giggling in the middle of the night since he started Kudzu. Most importantly the mysterious seizure-like episode has disappeared

Link

 

[Deltrus]

Funny how uridine is a p2y2 agonist and so many people take it as a nootropic.

Kudzu has been shown to be an agonist of the P2X7 receptor (2).

Shouldn't this say antagonist?

And uridine is a nootropic p2y2 agonist that is neuroprotective and stimulating, makes me think p2y2 antagonists wouldn't be that great. Maybe the other purinergic receptors would be better targets. Or maybe suramin works in different ways.

 

[Sushi]

Kudzu contains a number of isoflavones, including puerarin, about 60% of the total isoflavones, daidzein (an anti-inflammatory and antimicrobial agent), and daidzin (structurally related to genistein). Kudzu has been shown to be an agonist of the P2X7 receptor (2).

Move to Alabama and start grazing:

 

[Jesse2233]

Shouldn't this say antagonist?

Yes brainfog, I will edit, thanks!

Or maybe suramin works in different ways

Funny you should say this. I say a study today showing Suramin's inhibiting effects on IL-6, will try to find it again

 

[dreampop]

1) In this paper, the experimental drug Suramin is shown to inhibit in a dose-dependent fashion the cell response to these cytokines, with the exception of TNF-alpha. The action of the IL-6-type cytokines is more sensitive to suramin inhibition that that of IL-1 beta.

2) Blocks Il-6 activity and binding to Il-6 receptor in cancer cells

I'm not too concerned about Il-6 being a problem in CFS but I've thought about that receptor a bit.

 

[msf]

I think you should take this post down, if someone were to try this remedy and then get worse they kudzu.

 

[slysaint]

Kudzu etc discussed here:
https://www.autismweb.com/forum/viewtopic.php?t=30356&start=20

 

[adreno]

Kudzu contains a number of isoflavones, including puerarin, about 60% of the total isoflavones, daidzein (an anti-inflammatory and antimicrobial agent), and daidzin (structurally related to genistein). Kudzu has been shown to be an antagonist of the P2X7 receptor (2).

So soy isoflavones could work as well?

 

[msf]

Hmm, if it does, my father might have been on to something. When he had an ME attack (as he called them), he would boil a load of soya beans, which he claimed made him feel much better.

This study is kind of complicated (and in rats), but rats given soy did show changes in P2rx7 (I assume this is just an different way of writing it).

http://joe.endocrinology-journals.org/content/202/1/141.full.PDF

I´ve been putting off trying the soya beans so far, partly because I´ve tried a small amount of soy without much effect, and also because boiling soybeans produces one of the most horrible food smells I´ve ever experienced, but I think it may be time to hold my nose and try it.

 

[Jesse2233]

I'm not too concerned about Il-6 being a problem in CFS but I've thought about that receptor a bit.

Yes likewise. Interestingly @StrayCat has reported an ME patient in Japan who went into remission using the IL-6R monoclonal antibody Actemra/Tocilizumab

I think you should take this post down, if someone were to try this remedy and then get worse they kudzu.

lol I see what you did there

So soy isoflavones could work as well?

Worth a shot I guess

 

[alicec]

I have been taking Sytrinol, 150 mg x 2 daily, for well over 6 months. I tried it for the lipid modulating properties and have seen some improvement in various serum lipid ratios (though of course I don't know that this is specifically attributable to the Sytrinol).

I haven't noticed any improvement in my overall condition.

 

[Alvin2]

So soy isoflavones could work as well?

likely safer

 

[dreampop]

Yeah

Yes likewise. Interestingly @StrayCat has reported an ME patient in Japan who went into remission using the IL-6R monoclonal antibody Actemra/Tocilizumab

I'm just a layman, but the recent results showing fatigue correlated with normal range CRP fluctuations in a subgroup of CFS patients is interesting (something I really doubt is lowgrade chronic infections trying to come out - maybe that might explain mild fatigue). Il-6 isn't high, but different expressions of Il-6R can be correlated with CRP fluctuations independent of IL-6 levels. It just seems such a prime candidate for a fatiguing condition - esp. fatigue in RA & even in depression. It's even released with muscle contractions...

In conclusion, exercise increases IL-6 receptor production in human skeletal muscle. This effect is most prominent 6 h after the end of the exercise bout, suggesting a postexercise-sensitizing mechanism to IL-6 when plasma IL-6 is concomitantly low. Exercise-induced increases in IL-6 receptor mRNA most likely occurs via an IL-6 independent mechanism as shown in IL-6 KO mice and the human rhIL-6 infusion study, whereas IL-6 receptor protein levels are responsive to elevated plasma IL-6 levels.

and sickness behavior.

Taken together, the results show that sgp130 may exert an anti-inflammatory effect on microglia and neurons by inhibiting IL-6 binding. These data indicate that sgp130 inhibits the LPS-induced IL-6 trans-signal and show IL-6 and its receptor are involved in maintaining sickness behavior.

Ironically, Hornig found IL-6 levels low in CFS, and Il-6 does have some beneficial effects on memory. But I'm more concerned with the receptor, which can have effects independent of IL-6. There so much more but it's all above my pay grade. I'm willing to try anything at this point, my life is pretty shit, the only real way to know would be to try Actemra. Its less risky than what a lot of people on these forums are trying, but it's a new drug so I can't get it overseas, I would have to find a doctor to rx it.

 

[Jesse2233]

@dreampop yea pretty much my thoughts as well. IL-6 may also fluctuate with symptoms as Dr Younger found with other markers

FWIW people with RA tend to tolerate Actemra well. An understanding rheumatologist would possibly try it

 

[dreampop]

Looks like part of my theories is debunkable - one of the authors did think to check IL-6 and IL-6R before and after exercise in CFS patients (good on him) and found no differences between them and the controls, although he did find "F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise." The differences are about 20% higher.

Now that's a biological abnormality I have not heard about before. Wikipedia says they may be related to oxidative stress and "these nonclassical eicosanoids possess potent biological activity as inflammatory mediators that augment the perception of pain.[5]"

Won't post about this stuff again cause I don't want to derail this thread about Suramin alternatives but I did want to follow up my post.

 

[Rrrr]

are there any meds that might be good alternatives to suramin? what about plavix? i'm not sure why i'm saying that med, but for some reason it came up in my research around suramin alternatives. anyone with more of a brain than me have any ideas?

 

[Rrrr]

i wish i could grasp what this means, as it states both suramin and plavix in one study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143661/

 

[Rrrr]

and this webpage
https://news.ycombinator.com/item?id=14458230

 

[Rrrr]

i just emailed a well known ME/CFS doctor i know (who wishes to remain anonymous) with the names of the two herbs/supplements mentioned at the top of this thread, and he said: "I have talked with every prominent herbalist I know to see if there is a similar substance out there, and so far, nothing."

 

[Jesse2233]

i just emailed a well known ME/CFS doctor i know (who wishes to remain anonymous) with the names of the two herbs/supplements mentioned at the top of this thread, and he said: "I have talked with every prominent herbalist I know to see if there is a similar substance out there, and so far, nothing."

Interesting, thanks for checking Rrrr. I imagine the two sups I mentioned up top might have some benefits mirroring Suramin (assuming it is beneficial) but would not be as pronounced

Suramin seems to be quite unique as a compound. I really curious to know if it's been used by any doctors in West Africa for post Ebola syndrome