Are endogenous depression and cfs close relatives?

[Sidereal]

@Sidereal

Have any thoughts on possible "hypo"functioning NMDA receptors? Could they possibly be hypo from a whacked out circadian rhythm issue? I've been taking some D-serine which does seem to help some.

Good question. The NMDA receptor problem in depression is quite complex. You'd expect D-serine to make things worse being an agonist at the glycine site, if I recall correctly. I'm not sure if the issue is a hypofunctioning NMDA receptor. It's possible that D-serine produces some beneficial downstream effects which then work through some feedback mechanism to beneficially modulate signalling at the NMDA receptor or something convoluted like that. This would reconcile why an agonist like D-serine works when antagonists like ketamine and magnesium are beneficial. I don't know. Have you looked to see what the literature says?

 

[Rand56]

This is a rather long article on D-serine. Reason I figured I'd try it, I feel worse when I take extra magnesium, and I know mag is an NMDA antagonist. No doubt I am atypical to most on here. I'd venture a good guess that mag helps a large majority of people on here. But the info in this article really caught my attention....

"The antidepressant potential of NMDAR antagonism has been unambiguously established during the last decade. Already in the early 1990s, preclinical studies indicated that several types of NMDAR antagonists exert antidepressant-like effects in animal models of depression [103–105]. Subsequently, a series of animal studies demonstrated that long-term antidepressant treatment produces adaptive changes in the binding profile of NMDARs [106]. The translational confirmation of these findings was achieved by the demonstration of a robust, rapid, and long-lasting antidepressant effect of ketamine in, usually treatment-resistant, unipolar or bipolar depression patients (rev. in [107, 108]). Furthermore, in addition to ketamine which acts as a noncompetitive antagonist at the intra-NMDAR channel PCP site, similar effects seem achievable with mechanistically diverse NMDAR antagonists. Recently, we reported that treatment with high-dose DCS, potentially having a net antagonistic effect at the GMS, also improves major depression symptomatology in treatment-resistant patients [109].

Nevertheless, an apparently contradictory body of data advocates in favor of NMDAR agonists efficacy as antidepressants. GLY and DSR adjuvant treatment results in alleviation of depressive symptoms in schizophrenia patients [91, 92], and SSR504734, a reversible GLY-transporter inhibitor, as well as DSR, has been shown to have antidepressant/anxiolytic effects in depression/anxiety models [110, 111]. Moreover, expression of NMDAR 1 and 2A subunit is decreased in postmortem brains of patients with major depression [112], and NMDAR binding is also reduced in suicide victims [113]. Taken together, these findings imply that NMDAR hypofunction may contribute to the pathophysiology of depression. Moreover, this hypothesis is supported by recent clinical data, although systematic investigation of antidepressant effects of NMDAR enhancement is still in an early phase. Acute administration of 2.1 g DSR to 35 healthy university students was reported to reduce, in a placebo-controlled challenge paradigm study, subjective feelings of depression and anxiety as measured by Visual Analog Scales [114]. The GLY-transporter-1 (GLYT1) inhibitor sarcosine [115] and the DAAO inhibitor sodium benzoate [116] were reported to be beneficial in depressed patients who were drug-naïve for at least 3 months and had no history of treatment-resistance"

http://www.hindawi.com/journals/apsy/2014/859735/

 

[Sidereal]

This is a rather long article on D-serine. Reason I figured I'd try it, I feel worse when I take extra magnesium, and I know mag is an NMDA antagonist. No doubt I am atypical to most on here. I'd venture a good guess that mag helps a large majority of people on here. But the info in this article really caught my attention....

LOL, I was just reading this great article when you posted it. Other relevant bits:

Present explanations for the discordant observations of antidepressant effect of both NMDAR agonists and antagonists include, theoretically, common -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated mechanisms [117] and similar net effects achieved by differential action at synapticversus extrasynaptic NMDARs [29, 32]. A stratified model of psychiatric phenomenology, as function of suboptimal/decreased versus overactive/increased NMDAR function, may also contribute to the conceptualization of available data by taking into account the vast heterogeneity underlying the overinclusive concept of depression. While schizophrenia is a typical NMDAR hypofunction disorder, responsive to treatment with NMDAR agonists, the opposite may be characteristic of treatment-resistant depression. Nevertheless, milder, nonrefractory forms of depression may represent predominately suboptimal NMDAR functioning and could be responsive to GMS agonism. Interestingly, depression feelings are improved in both schizophrenia [91, 92] and normal subjects [114] by DSR and in schizophrenia [92] and nonrefractory depression [115] by sarcosine. On the other hand, ketamine characteristically exacerbates schizophrenia manifestations [118], while it has antidepressant, mood stabilizing and procognitive effects in treatment-resistant depression [119].

Thus, balanced NMDAR activity is required for optimal cognitive performance and both over- or underfunction of NMDAR neurotransmission may contribute to cognitive dysfunction or neurotoxicity. This NMDAR function paradox may be related to different composition of NR subunits and receptor localization [164,165]. Accordingly, normalizing NMDAR dysfunction by selectively enhancing NR1/NR2B NMDARs, while avoiding excitotoxicity mediated at NR1/NR2B receptors, could be a better therapeutic approach than nonselective NMDAR antagonism which may actually impair cognitive functioning (rev. in [155]).

I thought I was the only one on PR who gets worse from magnesium. Magnesium makes me unable to think. I can't remember the start of the sentence by the time I get to the end of it. I've recently experimented with a couple of other NMDA antagonists and the results were catastrophic. Thanks for bringing D-serine to our attention. I'm going to try this and report back.

This review paper also explains Goldstein's confused writings on the role of glutamate / NMDAR in ME/CFS. He first thought there was too little, then too much. Seems the reality is 1000x more complex, as usual.

(@zzz, you might be interested in reading this paper)

 

[Rand56]

I also read a pubmed study stating hypofunctioning NMDA receptors is age related. Meaning, the older one gets, the higher probablility of hypofunctioning NMDA receptors. I thought I saved the article but apparently I didn't...grrrrrrrr. If I stumble across it, I'll post it on here.

WOW, you mean there is someone else like you who feels worse taking extra mag? HOLY COW!!!! LOL

 

[Sidereal]

I also read a pubmed study stating hypofunctioning NMDA receptors is age related. Meaning, the older one gets, the higher probablility of hypofunctioning NMDA receptors. I thought I saved the article but apparently I didn't...grrrrrrrr. If I stumble across it, I'll post it on here.

WOW, you mean there is someone else like you who feels worse taking extra mag? HOLY COW!!!! LOL

This paper is da bomb. I'm not going to be able to fully grasp its implications now at 1 am but I will return to it later when I'm not magnesium-ed.

 

[Rand56]

Not the study I was talking about, but interesting about Alzheimers....

Possible role of D-serine in the pathophysiology of Alzheimer's disease.
Hashimoto K1, Fukushima T, Shimizu E, Okada S, Komatsu N, Okamura N, Koike K, Koizumi H, Kumakiri C, Imai K, Iyo M.
Author information

• 1Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan. hashimoto@faculty.chiba-u.ac.jp

Abstract
Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site on the N-methyl-D-aspartate (NMDA) receptor that has been implicated in the pathophysiology of Alzheimer's disease (AD). The purpose of the study was to determine whether serum levels of D- and L-serine in patients with AD are altered as compared with normal controls. Serum levels of D- and L-serine in patients of AD and age- and gender-matched normal controls were determined using a high-performance liquid chromatography (HPLC). Serum levels of D-serine in the patients with AD were slightly (z=-1.77, p=0.078) lower than those of normal controls. In contrast, serum levels of L-serine in the patients were slightly (z=-1.73, p=0.083) higher than those of controls. In addition, the percentage (%) of D-serine in the total (L+D) serine in the patients was significantly (z=-2.36, p=0.018) lower than that of controls. The present study suggests that the reduced activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine may play a role in the pathophysiology of AD.

http://www.ncbi.nlm.nih.gov/pubmed/14751437

 

[Sidereal]

I also read a pubmed study stating hypofunctioning NMDA receptors is age related. Meaning, the older one gets, the higher probablility of hypofunctioning NMDA receptors. I thought I saved the article but apparently I didn't...grrrrrrrr. If I stumble across it, I'll post it on here.

http://www.jneurosci.org/content/30/5/1914.full

The contribution of the NMDA receptors (NMDARs) to synaptic plasticity declines during aging, and the decline is thought to contribute to memory deficits. Here, we demonstrate that an age-related shift in intracellular redox state contributes to the decline in NMDAR responses through Ca2+/calmodulin-dependent protein kinase II (CaMKII). The oxidizing agent xanthine/xanthine oxidase (X/XO) decreased the NMDAR-mediated synaptic responses at hippocampal CA3–CA1 synapses in slices from young (3–8 months) but not aged (20–25 months) rats. Conversely, the reducing agent dithiothreitol (DTT) selectively enhanced NMDAR response to a greater extent in aged hippocampal slices. The enhancement of NMDAR responses facilitated induction of long-term potentiation in aged but not young animals. The DTT-mediated growth in the NMDAR response was not observed for the AMPA receptor-mediated synaptic responses. A similar increase was observed by intracellular application of the membrane-impermeable reducing agent, L-glutathione (L-GSH), through the intracellular recording pipette, indicating that the increased NMDAR response was dependent on intracellular redox state. DTT enhancement of the NMDAR response was dependent on CaMKII activity and was blocked by the CaMKII inhibitor—myristoylated autocamtide-2-related inhibitory peptide (myr-AIP)—but not by inhibition of the activity of protein phosphatases—PP1 and calcineurin (CaN/PP2B) or protein kinase C. CaMKII activity assays established that DTT increased CaMKII activity in CA1 cytosolic extracts in aged but not in young animals. These findings indicate a link between oxidation of CaMKII during aging, a decline in NMDAR responses, and altered synaptic plasticity.

So once again we're back to the redox problem and why tinkering with neurotransmitters is of such limited value in the ME/CFS symptom complex.

 

[Valentijn]

We can disagree on whether I have PEM, commas etc.

Well, I do have a problem with defining PEM so broadly that it's indistinguishable from generic exercise intolerance, rather than being distinct from other forms of it. If PEM starts during or immediately after exertion, and doesn't feature immune or neurological symptoms, then there's no need for PEM to exist at all and we can just call it generic exercise intolerance. Yet patients, clinicians, and researchers have seen a need to define it separately, which should indicate that it is indeed rather different.

I still believe in the big tent and that ICC supports this.

Most patients would disagree, since ICC requires PEM and has a neurological and immune focus. It's intended to be specific, not broad.

To be trite, the most important thing is for everybody to find out what they have, and more importantly how to cure it.

Certainly. But I'm not sure how a broad definition would support that goal. Indeed, the broad definition leads to problems with misdiagnosis and mistreatment for all parties, as well as prematurely ending investigations into alternative diagnoses.

 

[Richie]

Valentijn
We read the criteria differently. We can go round in circles forever on this.
ICC defines PENE and I am happy with that definition, which is imo not as narrow as yours. You are also in no position to tell me my PENE does not sound like PEM. My view is in accordance with ICC as are my symptoms, allowing for fluctuation.If many patients want a narrower definition, they will work on that.

Of course, if a better diagnosis of an underlying disorder should surface for my case, I would accept it. And I presume many with the ME diagnosis would too.

We can disagree on this, no worries, I don't think there is much point in continuing this dispute, but if you want the last word (no sarcasm implied), go ahead.

As said I hope we all find what will help us.

 

[Rand56]

The GLY-transporter-1 (GLYT1) inhibitor sarcosine [115] and the DAAO inhibitor sodium benzoate [116] were reported to be beneficial in depressed patients who were drug-naïve for at least 3 months and had no history of treatment-resistance"

http://www.hindawi.com/journals/apsy/2014/859735/

Sodium benzoate is a metabolite of cinnamon. I'm going to get some Ceylon cinnamon <the more pure form> to see if I get any beneficial effect over and above the D-serine I'm taking. Sodium benzoate also helps to clear excess ammonia.

I realize there is some precautionary info about benzene, in particular when it reacts with Vit C, about it possibly being carcinogenic. I'll go easy on the cinnamon.

I've read some good anecdotal reports on sarcosine, but seems many have to multi dose it numerous times during the day to maintain effects.

Next on my plate is to try some DAA < D-aspartic acid >. Maybe it could help raise my T. I do understand it's best to cycle it.

 

[Sidereal]

Cinnamon crashes my mood personally.

 

[Rand56]

Cinnamon crashes my mood personally.

I'll be on the lookout for that. Thanks for mentioning. I've only used it before for seasoning on food with no negative reactions. Of course I could react negatively if I injested more of it. I'll find out!

I know it can lower blood sugar. I typically don't deal with hypoglycemia. I suppose eating enough carbs like I do has something to do with it.

 

[Sidereal]

I'll be on the lookout for that. Thanks for mentioning. I've only used it before for seasoning on food with no negative reactions. Of course I could react negatively if I injested more of it. I'll find out!

I know it can lower blood sugar. I typically don't deal with hypoglycemia. I suppose eating enough carbs like I do has something to do with it.

There was some discussion of cinnamic acid on the resistant starch thread somewhere, why it might be beneficial for ME/CFS and why it might be a problem.

 

[amaru7]

Written or reviewed by a board-certified physician. See About.com'sMedical Review Board.
Could drugs meant for hyperactive children be an effective treatment for chronically fatigued adults? Is illogical as it sounds, they might be.

Some doctors prescribe ADD/ADHD drugs for their patients with chronic fatigue syndrome (ME/CFS) and say they've seen positive results. We have some studies to back this up -- at least in a subgroup of ME/CFS -- but a lot more research is needed.

These drugs

are classified as neurostimulants, which means that they stimulate brain activity. The most popular neurostimulants are:

• Ritalin and Concerta, which contain methylphenidate
• Dexedrine, which contains dextroamphetamine
• Adderall, which contains amphetamine and dextroamphetamine

Why Use Neurostimulants?
The exact mechanism of these drugs isn't known (which is actually quite common in drugs that affect the brain), but they're believed to change the availability in the brain of norepinephrine and dopamine, two neurotransmitters that are possibly dysregulated in both ADD/ADHD and ME/CFS.

Low norephinephrine is linked to loss of alertness and memory problems, while dopamine deficiency is linked to cognitive impairment and inability to focus attention. These symptoms are shared by ADD/ADHD and ME/CFS.

One small study demonstrates that, in adults, the two conditions share a lot of other symptoms as well, including unexplained fatigue, widespread muscle pain, and diagnoses of ME/CFS or the similar condition

fibromyalgia. Some doctors even hypothesize that children with ADD/ADHD may be at risk for developing ME/CFS as adults.

Some drugs used for fibromyalgia also impact the availability of norepinephrine. These drugs include Cymbalta (duloxetine) and Savella (milnacipran), two of the three FDA-approved fibromyalgia treatments. These drugs are classified as serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs haven't been well researched for ME/CFS, but they are widely prescribed, in part because many doctors believe fibromyalgia and ME/CFS are the same or closely related conditions.

A 2006 study of methylphenidate for ME/CFS demonstrated a significant improvement in about 20% of participants. That's hardly an overwhelming endorsement. However, many researchers believe ME/CFS consists of several subgroups that each require different treatment. Do the people who responded to methylphenidate represent a particular subgroup? We don't yet know enough to say either way.

A 2003 preliminary study of dextroamphetamine showed that 9 out of 10 participants with ME/CFS had significantly less fatigue while taking the drug compared to a placebo. However, further research has not been published.

A 2008 review of neurostimulants for ME/CFS called these drugs "potentially promising." Still, more research is needed.

These medications are already on the market and are relatively inexpensive, which makes them easy for people to obtain. A drawback is that they carry a risk of addiction and therefore may require frequent doctor's appointments.

http://chronicfatigue.about.com/od/treatingfmscfs/a/Add-Adhd-Drugs-For-Chronic-Fatigue-Syndrome.htm


This one is about ADD, another mental disorder and an alternative way to try treatments off label for CFS. I tried Methylphenidate, it gave me short improvements in mood and energy, but later on it seemed to worsen me for whatever reason. I've yet to try out Dexamphetamine,

is there anyone who tried stimulants like Dexedrine/Adderall/Dexamphetamine with success?

Chronic Fatigue Syndrome (ME/CFS) Physicians Report
Dr. Teitelbaum states Dexedrine can helpful by increasing blood pressure (and standing), decreasing the weight gain often seen (leading to better sleep and less pain) and increasing energy. He has found it to be ‘very safe and effective’ with the proviso that the rest of the body is supported by a comprehensive treatment program. He believes Dexedrine is underused in ME/CFS. A recent paper in the Medical Hypotheses journal by Dr. Check proposes Dexedrine is an effective tool for fighting chronic fatigue syndrome (ME/CFS) and other disorders.

http://phoenixrising.me/treating-cf...s-central-nervous-system-stimulants-dexedrine

Here's a promising experience of a member I found on PR:

Kade January 9, 2015 at 4:58 pm
I have had ME for too many years now – with a few brief times of feeling well
But since moving location 4 yrs ago my ME & the desperation of the fatigue I feel daily seems to be getting worse. I too am a mother & the guilt I feel for being ill is overwhelming too. I can identify with all your comments & have tried for years to get my Dr to prescribe a stimulant – just for a short time to get out of this rut of sleeping, feeling useless & just functioning – but with no success. I’ve tried gluten free diet which did help but it was yeast, sugar, alcohol & dairy free & I just didn’t have the strength to stick to it.
I know that awful feeling when I see my husbands face when I can’t do something. It really is hell for everyone around me. I live in uk & managed to find 10 dexamphetamine & the difference I felt was incredible. Within 20 mins I could get up & felt alive!
[...]

on the other hand..

CINDY1212 March 24, 2015 at 10:17 pm
HI All,

I too, suffer from the fatigue that literally steals your life and leaves you feeling guilty for not being able to keep up or even get through the day. It is a horrible fate, and like many of you, I have looked at every possible cause with no success.

After a result of “idiopathic hypersomnia” from a sleep lab, my doctor prescribed me stimulants. I have been on Provigal, Vyvanse, Concerta and Adderall. Yes, these stimulants worked, but it was short lived as I gained tolerance. Not long after starting, my doses would need to be increased and then I was left with a racing mind and an exhausted body.

I just want to encourage everyone to keep searching, as I am, for natural remedies. The stimulants will not last, and will give you hope that will come crashing down at some point. I wish I had the answers, and maybe everyone does not become immune, but I was taking 25 mg Adderall, drinking several cups of coffee and then taking another 10 mg in the afternoon. And, if the opportunity to nap presented itself, I would almost never be able to fall asleep despite feeling incredibly fatigued. The stimulants created for me a no-win situation, and then I had to wean myself off of them.

http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/energy-ii/pharmaceuticals

 

[out2lunch]

I've done both bupropion and reboxetine. I fared better with bupropion, but I got wicked insomnia from it. Helped my depression, but there again, was it the AD effect from the drug, or just the lack of sleep that made me feel better LOL.

Diagnosed with ADHD at a young age, which finally impacted my school work in college. (Honor student in high school, D student at university.) Volunteer psychiatrist at Student Health first prescribed Ritalin, then Desoxyn when rebounding became a problem. I never would have made it through undergrad and grad school without it.

After becoming ill with ME/CFS/FMS and Lyme, standard stims were too much for my cardiovascular system. I'd be tachy and anxious for hours after even a low dose. What seemed to work better was low dose Strattera (atomoxetine). I'd take a 10mg capsule and divide it into four doses, one dose in the AM and another mid-afternoon if I had to use my brain that night LOL. I also tried modafinil which helped my afternoon sleepies until my orthodontist put me in the sleep lab because of my narrow airway and short jaws. Now that I use my CPAP faithfully each night for moderate hypopnea, afternoon sleepies are no more.

But in terms of being able to think more clearly at any time of the day, I wish I could still take drugs like these. The only thing my heart can tolerate now is low dose caffeine. Anything else feels like the inside of my chest is being used as a dog's chew toy.

In any event, I'm now trialing a histamine H3 antagonist. What the hell, give something else a whirl LOL

OOOH!!! Tell us more, please, if you can.

Are you taking Ciproxifan?

 

[Valentijn]

I'd be tachy and anxious for hours after even a low dose. What seemed to work better was low dose Strattera (atomoxetine). I'd take a 10mg capsule and divide it into four doses, one dose in the AM and another mid-afternoon if I had to use my brain that night LOL.

Several of us here have found low doses of Strattera to be very helpful with ME/SEID Orthostatic Intolerance (OI) issues. It helped raise my pulse pressure to something closer to normal, and that can help a lot in avoiding the reactionary tachycardia.

I've never had anything resembling ADHD.

 

[amaru7]

I have resembling ADD without hyperactivity but hypoactive ADD.

Here's another interesting documentary with Saporovsky about stress and what it causes in biochemical level. My theory is that the lower physical health is not a result of a lower level in the hierarchy only, but it goes the other way around and IMO a bad health (heart, neuro-endocrine, etc) leads to a low level in hierarchy.

 

[Rand56]

Diagnosed with ADHD at a young age, which finally impacted my school work in college. (Honor student in high school, D student at university.) Volunteer psychiatrist at Student Health first prescribed Ritalin, then Desoxyn when rebounding became a problem. I never would have made it through undergrad and grad school without it.

After becoming ill with ME/CFS/FMS and Lyme, standard stims were too much for my cardiovascular system. I'd be tachy and anxious for hours after even a low dose. What seemed to work better was low dose Strattera (atomoxetine). I'd take a 10mg capsule and divide it into four doses, one dose in the AM and another mid-afternoon if I had to use my brain that night LOL. I also tried modafinil which helped my afternoon sleepies until my orthodontist put me in the sleep lab because of my narrow airway and short jaws. Now that I use my CPAP faithfully each night for moderate hypopnea, afternoon sleepies are no more.

But in terms of being able to think more clearly at any time of the day, I wish I could still take drugs like these. The only thing my heart can tolerate now is low dose caffeine. Anything else feels like the inside of my chest is being used as a dog's chew toy.



OOOH!!! Tell us more, please, if you can.

Are you taking Ciproxifan?

@out2lunch

No I'm not taking Ciproxifan. I'm taking a product called Kutaj. It has conessine in it which is the histamine H3 antagonist. Another similar product is called Yamoa. It's suppose to be more potent, but more expensive than Kutaj.

It is helping my depression, although I'm also taking some D-serine, so there might be some good synergy, although I did notice a better boost when I added in the Kutaj. At first I started with 2 caps a day and stayed on that dosage for about 1.5 weeks, and didn't notice much, but I think I found more of my sweet spot by upping it to 3 caps a day. I"ll just have to see if the positive effects last, since I've been there done that before.

I got it on amazon. Only bought one bottle at first, but they do have multiple bottle packs to order, which saves on the cost per bottle.

 

[Rand56]

@out2lunch

No I'm not taking Ciproxifan. I'm taking a product called Kutaj. It has conessine in it which is the histamine H3 antagonist. Another similar product is called Yamoa. It's suppose to be more potent, but more expensive than Kutaj.

It is helping my depression, although I'm also taking some D-serine, so there might be some good synergy, although I did notice a better boost when I added in the Kutaj. At first I started with 2 caps a day and stayed on that dosage for about 1.5 weeks, and didn't notice much, but I think I found more of my sweet spot by upping it to 3 caps a day. I"ll just have to see if the positive effects last, since I've been there done that before.

I got it on amazon. Only bought one bottle at first, but they do have multiple bottle packs to order, which saves on the cost per bottle.

Just an update. I'm still maintaining the AD effect. Crossing fingers, knocking on wood, and I guess I should stick a rabbit's foot in my pocket too..haha. @Sidereal pointed out to me that my AD effect may not entirely stem from the conessine in Kutaj, and since Kutaj is anti-dysentary, it could be related to better gut related functioning. Sorry, I'm not technically knowledgeable enough to explain this in more detail. Maybe Sidereal or someone else who knows more about this herb can explain it, and how I can get an AD effect from it.

 

[Sidereal]

Just an update. I'm still maintaining the AD effect. Crossing fingers, knocking on wood, and I guess I should stick a rabbit's foot in my pocket too..haha. @Sidereal pointed out to me that my AD effect may not entirely stem from the conessine in Kutaj, and since Kutaj is anti-dysentary, it could be related to better gut related functioning. Sorry, I'm not technically knowledgeable enough to explain this in more detail. Maybe Sidereal or someone else who knows more about this herb can explain it, and how I can get an AD effect from it.

I just heard of this herb yesterday when you told me about it but I see it's used in Ayurvedic medicine to treat gastrointestinal disorders. Many people on the RS thread have been using prebiotic herbs of this sort and have found that effects reach beyond the intestinal tract. We don't know how it all works but the assumption is microbiome modification.