This archived forum used to be called 'Peatarian' (in reference to Ray Peat).

Cascara works by raising NO

This study shows that cascara sagrada's laxative effect works through inducing production of nitric oxide in the colon. More specifically, cascara induced 12 percent of nitric oxide synthase. The laxative affects of cascara were eliminated with an anti-nitric oxide agent. Should we be concerned about this?

asked Mar 11, 2015 by QiGuy1997

*Waits for my long overdue encounter with anon

Sorry, I thought the question was for anyone, so I responded.

I was just joking, the question is for everyone!

Why don't the measure NO as opposed to a surrogate (NO Synthase)?

I believe the NO molecule itself is extremely short-lived.

2 Answers

The authors make a good case that cascara, as used in the studies, increases nitric oxide which is then involved in causing diarrhea. They also showed that in a prior study were they inhibited NO-synthase activity with L-NAME or stimulated NO production with L-arginine which reduced or increased cascara diarrhea respectively (

However, the dose used in both studies (800mg/kg cascara) was excessive, for a 70kg human it would equal 56g of cascara. The usual recommended dose are in the range of 250-2000mg, which would equal 3.5-28mg/kg body weight.

So I think from those studies we cant make any claims on the mechanism of action of cascara at the much lower doses as widely recommended. For this we would need an adequate trial with lower doses in humans.

In theory though, I find it likely that significantly increases gut motility or diarrhea must have some kind of irritating property through serotonin or other mediators. Its the physiologic function of the gut to retain as much water and nutrients as possible for proper nourishment of the body, and any emergency gut evacuation mechanism probably must involve some kind of stress response (i.e. get rid of dangerous bacteria and toxins).

answered Mar 12, 2015 by Bukowski
edited Mar 12, 2015 by Bukowski
I came across this quote in the Ray Peat email exchange  archive section with regards to cascara:
"I think cascara's most important effect is the reduction of the pro-inflammatory nitric oxide, which poisons mitochondrial energy production. Raw carrot or bamboo shoots can sometimes have a similar effect by reducing NO synthesis."  It's instances like this that make me wonder who's right and who's wrong.  Sometimes I think that Ray just over emphasizes the benifits of certain things he's tried and possibly conjures wishful attributes to them without certain fact to back them up.  This is another one of those instances. No one in opinion is sacrosanct for criticism and I am not an apologist for anyone.   Does casaca just work for Ray in that it corrects ,what I suspect, is a case of chronic constipation from eating cheese or being hypothyroid and he just as likely would get the same results from another laxative; hence, if tried and successful would become another esoteric element of legend?

I don't know but I do see that cascara was seen not to cause "induced" NO synthase activity. This is what Peat would expect, I think.

Meanwhile, the constitutive NO synthase activity that was observed can be the result of the experiment's insult to the epithelium. In other words, the epithelium may respond with NO synthase activity to any experimental insult, if the insult is severe enough.

So, if I'm understanding this, it would in no way suggest that therapeutic doses of cascara would cause any such insult, and if anything might reduce any "induced" NO synthase activity.

answered Mar 12, 2015 by visionofstrength

If that was the case, why don't we see the senna having similar nitric oxide producing effects? And why is cascara's anti-diarrhea effect removed with a nitric oxide antagonist?

Oh, wait. I had that backwards. Sorry! Cascara not senna had the "inducible" NO synthase activity. Thanks for pointing that out.

Now let me go look to see what "inducible" means. BRB.

Yes, I just checked. I see I was nearly duped into a semantic fiction. As Peat might say, the iNOS (inducible NO synthase) gene is a geneticist's fiction, fabricated in the hopes of exploiting some lucrative patent downstream.

In Peat's view, it is higher order morphogens or "wave-lengths" that interact with the molecular cascades of Lingian cell physiology, not specific lock-and-key tools for specific receptors.

In non-physiological conditions, we may think we see things like iNOS genes and receptors, but in the living body, cell physiology is not so reducible.