The Resistant Starch Challenge: Is It The Key We've Been Looking For?

[Sasha]

Immunomodulating agents like liposomal Vitamin C and prebiotics are among the most potent of the known biological response modifiers. They amplify our NK, macrophage, T-cell responses, etc.

Interesting! I didn't know that.

Unfortunately for those of us with disproportionate pathogenic loads and limited bioenergetic/anti-inflammatory capabilities these effects are particularly damaging because of the ROS this creates. [...] I do think you need to ask yourself, what do you stand to gain from this approach? There has to be a cost benefit analysis, and I think everyone needs a plan before embarking on a trial of prebiotics/probiotics. I will also caution that there may not be an easy exit strategy once one begins the process of re-establishing immunocompetency.

I was hoping to gain improvement in my ME! I don't have a plan, that's for sure. I just started taking this stuff because other people seemed to be benefitting and the rationale made sense. What sort of plan did you have in mind?

I had an acute, post-viral onset to my ME nearly 30 years ago and was confined to bed for many years. After a while, I gradually went into enough of a remission to be able to live independently and work full-time before I relapsed several years ago. My process of remission from my first illness was smooth, however: I didn't get periodic worsening of symptoms, but just gradually got better on my own. It's odd that now, when I'm housebound rather than bedbound and able to live independently, I should get slammed when taking something as innocuous (?) as Vitamin C. During my first illness I was on 45g (yes, grammes) a day without any effect, good or bad.

I'm curious to know whether other PWME who are trying pre/probiotics have been having new symptoms appear, or a worsening of existing symptoms apart from GI symptoms (which might be expected to go haywire while a new ecosystem balance is being established in the gut).

We are also witnessing some very distressing symptoms paired with some impressive gains. This has been the pattern I have become familiar with, and it is my hope that eventually we can develop more ways to mitigate the adverse symptoms. I think until this happens, the most influential control point seems to be the quantity/type of prebiotic, so this should be used with great caution. I can tell you that on Sunday I felt better than I have felt in 5 years, but this has since been accompanied by a number of challenging days as I experiment with new prebiotics.

That's great that you've had such improvement - I'm sorry it's not a smooth ride.

I look forward to when we have genera and species level intestinal microbiomic data from a large ME/CFS sample. I truly believe we need this more detailed taxonomic data. [...] I welcome people to post intestinal microbiomic data.

Same here. I wish this kind of test was more accessible.

 

[Vegas]

You are precisely right. However, not all polysaccharides are created equal. As best as I can tell, it's the beta-glucans that seem to pack the most immune-modulating punch.

Other than producing SCFAs (a terrific set of metabolites in their own right) RS alone doesn't really stimulate the immune system in the same way that a tree bark or a mushroom or a high ORAC food will because RS doesn't really metabolize into these highly specific metabolites that unlock all of these anti-cancer and anti-inflammatory receptors like PSK or β-Glucans can.

My impression is that there are many different kinds of β-glucans and I see these unique polysaccharides and β-glucans as very unique "keys" to our immune system and different barks, mushrooms and plants seem to be good sources of these keys, each specializing in different aspects of the immune system.

We are clearly saying the same thing!

I am familiar with some of the various b-Glucans, and I am in fact using an insoluble fiber combination of chitin-glucan, which has been shown to stimulate the expansion of Roseburia Intestinalis. (Don't try this at home) The molecular differences in the polysaccharides clearly have import, but I have to think that this relates to selective microbial accessibility...although I may be, and am often, wrong.

I just took a look at the ORAC list and see that it is basically comprised of lipid dense foods and prebiotics. Great list of foods, but I cannot separate the effects these would have in stimulating microbes. Of course it really doesn't matter what induces the effects, you either benefit from it or you don't. I really like high ORAC foods too.

I think these fungal compounds are in fact "resistant" in that they obviously do stimulate the expansion of commensal organisms in the colon. The degree to which they can stimulate an immune response is likely dependent upon the microbiota and other environmental conditions. I agree that the compounds may have particular efficacy in doing so, but this is may be because of the microbial organisms they support. Unfortunately, as those with ME/CFS have discovered, the more immunostimulatory the substance the more inflammatory it is.

As for the SCFA's, acetate and butyrate are of critical importance to immunity not just for their obvious role with colonocytes and preventing extraintestinal bacterial dissemination but I think there is evidence that their availability or lack therof inhibits the cholinergic anti-inflammatory pathways. Acetylcholine inhibits the innate immune response and prevents "excessive" inflammation. In ME/CFS there are various ways in which acetate, is in scarce supply, including via the oxidation by SRB and metabolic shift which is biased towards lactate and away from acetate synthesis.

 

[Ripley]

Yes, but how do these chemical changes take place?

Why do Procyanidins, catechin, epicatchin, epigallocatechin, or at least, in some cases, the plants from which these are derived, generally promote the growth of bifidobacteria? Why are high ORAC fruits so strongly bifidogenic?

I think much of the metabolic changes in these compounds can only be carried out by bacterial organisms. I don't think many of these polysaccharides are accessible without the contribution of certain commensal organism.

Aren't we saying the same thing? When the paper says "metabolites" it clearly says that it's due to the microbial metabolism of these compounds.

 

[Vegas]

Aren't we saying the same thing? When the paper says "metabolites" it clearly says that it's due to the microbial metabolism of these compounds.

I'm just trying to confuse you.

Seriously, I was simply trying to, but without any clarity, trying to suggests that these compounds are "special" only because of their selective accessibility by particular microbes that can chemically "unlock" these compounds for use by the host and without the microbes these compounds may be inaccessible.

 

[Ripley]

I'm just trying to confuse you.

I think these fungal compounds are in fact "resistant" in that they obviously do stimulate the expansion of commensal organisms in the colon. The degree to which they can stimulate an immune response is likely dependent upon the microbiota and other environmental conditions.

Yes, I'm sure we are saying the same thing. The microbiota chomp on the fungal compounds or high ORAC foods, and the byproducts help the body!

 

[Vegas]

Yes, I'm sure we are saying the same thing. The microbiota chomp on the fungal compounds or high ORAC foods, and the byproducts help the body!

And to your point about SBO's, which are abundant in those clays you mentioned. How about the symbiosis here. These clays are rich in organic matter. For those who don't have access to something like Prescript Assist, what about using humic/fulvic acid as a prebiotic. If you want more acetate, this may be another means of achieving this.

 

[adreno]

But is a stronger immune response always desirable? What about the idea that ME/CFS is of an autoimmune nature? Isn't there a risk of making things worse? Why is more = better? I thought a balanced and healthy immune response is what we want, not just a stronger one. Am I missing something here?

Here is a study showing autoimmunity prone mice develops illnesses after beta glucan exposure:

http://www.ncbi.nlm.nih.gov/pubmed/22328069

 

[Vegas]

But is a stronger immune response always desirable? What about the idea that ME/CFS is of an autoimmune nature? Isn't there a risk of making things worse? Why is more = better? I thought a balanced and healthy immune response is what we want, not just a stronger one. Am I missing something here?

Here is a study showing autoimmunity prone mice develops illnesses after beta glucan exposure:

http://www.ncbi.nlm.nih.gov/pubmed/22328069

No a stronger immune response is per se, not desirable, an appropriate immune response is desirable. Unfortunately, I think a balanced or appropriate immune response cannot necessarily be achieved until the underlying conditions that create this imbalance are corrected. If you are referring to the use of natural compounds to "overstimulate" the immune system. I think you can clearly increase inflammation beyond what is healthy, I would say that much of this is also outside your control. An immune response is also about reduced glutathione and nitric oxide and many things that both strengthen and minimize this response directed against our own tissues and those directed against pathogens.

Your question is a good one though. Can autoimmunity worsen? I really do not know, but I suspect it can, at least transiently.

So what are the options, do nothing and avoid crossing the threshold into what may be transient, but substantially heightened inflammation; pursue immunosuppressant therapies; use natural compounds known to stimulate the immune response with the hope that a pathogenic etiology can be eliminated, or a combination thereof.

It's only my opinion that bacterial pathogens set the conditions for the development of autoimmunity. I see 20% of US women on thyroid medications and 3 of the top selling Rx being immunosuppressants. Other meds in the top 10 include, psych meds, metabolic disease, and chronic GI conditions. We have a huge, rapidly expanding problem that includes autoimmune disease, and while I believe the evidence continues to point towards the GIT, those who pursue prebiotics as therapies must do so knowing that this is quite a leap of a faith.

Take RA for example, which has been correlated to high Prevotella, which has also been found to contribute to arthritic pathologies. You can take one of the traditional immunosuppresants, which inhibits TNF-a (Which of course is robustly induced by LPS), and you can feel better, and hopefully protect your joints from further damage, but the disease process will continue. I would actually be surprised if there wasn't a period of worsening, and this troubles me quite a bit when we are talking about people with pathology that cannot be reversed. On the other hand, inhibiting TNF-a is symptomatically beneficial, but it also impairs the subsequent immune response, which would participate in phagocytosis.

i do think people need to make up their minds about risks. I have tried to provide full disclosure including all the challenging days that I have experienced, but you are right, some will get worse. Do these effects stem from the autoimmunity, maybe. Does this modify the causative factors, I sure hope so. "Immunostimulation" has to be done to tolerance.

This study involved the INJECTION of b-glucan and mannan, which circumvents the processes that I am arguing are necessary to make the compounds fully bioavailable. If you inject the substance it doesn't pass through the GIT and those compounds are not microbially metabolized. A proteoglycan is a glycosylated protein, a protein bonded to Glycosaminoglycans. I would link what I just said the other day about GAGs, but I don't know how to do this. Idon't think this study has any significance not because of the species but the methodology.

 

[Ripley]

But is a stronger immune response always desirable? What about the idea that ME/CFS is of an autoimmune nature? Isn't there a risk of making things worse? Why is more = better? I thought a balanced and healthy immune response is what we want, not just a stronger one. Am I missing something here?

Here is a study showing autoimmunity prone mice develops illnesses after beta glucan exposure:

http://www.ncbi.nlm.nih.gov/pubmed/22328069

Fascinating.

I'm not sure what to say, But, the way β-glucans are usually described are like "keys" to our immune receptors. When humans ingest β-glucans, they unlock immune functions and activate them (NK cells, macrophages, lymphocytes, etc.). And while that would certainly open up the potential for autoimmunity, β-glucans can also normalize an overactive immune system (i.e. autoimmunity) by locking down receptors that are open for no reason, only re-opening them when needed. So, they appear to have adaptogenic properties.

That's how β-glucans are normally described. Could there also be the potential for triggering autoimmunity? I don't know. I suppose it could in certain situations like those mice.

The human experiences with medicinal mushrooms tend to be very good and are typically very safe. And you'll find a lot of papers explaining why β-glucans are good for managing autoimmune diseases. There's a loooong history of medicinal mushroom use. And as Turkey Tail mushrooms have supposedly been shown to help to some degree with ME/CFS, I think it's possible that certain β-glucans could probably help. But, you're right to be cautious.

EDIT: I'd also point out that there a lot of different kinds of β-glucans. For instance, there are β-glucans found in Candida cell walls, and those β-glucans appear to exacerbate autoimmune conditions. Whereas the β-glucans in medicinal mushrooms are pretty different and have a much better track record of treating autoimmune conditions.

 

[Vegas]

Fascinating.

The human experiences with medicinal mushrooms tend to be very good and are typically very safe. And you'll find a lot of papers explaining why β-glucans are good for managing autoimmune diseases. There's a loooong history of medicinal mushroom use. And as Turkey Tail mushrooms have supposedly been shown to help to some degree with ME/CFS, I think it's possible that certain β-glucans could probably help. But, you're right to be cautious.

Many here have read those so many similar papers and been perplexed when not only did benefits not develop, but we were met with only adverse symptoms. ME/CFS just sucks that way. I'm not real happy with what the β-glucans did for me, although to be fair, the intensity and particulars of the response suggests to me that it may have hit the target. I just feel like I'm the target. Dosage and frequency may be particularly important. I certainly can't challenge it's efficacy, but the "side effect" profile caught my attention.

 

[adreno]

Like I said earlier, beta glucans really overstimulated my immune response, and I did not feel any benefits, just increased inflammation. I tried a few different kinds for a few months:

Both the 20mg NSC and 500mg Transfer Point BG seem to cause some side effects in me, notably nausea, diarrhea, anorexia, slight headache, some depression and anxiety, and a general spaced out feeling.

I'm thinking it might be that concentrated and isolated beta glucans are simply too much of a good thing. Perhaps beta glucans needs to be balanced with the several other compounds present in medicinal mushrooms (MM). So I venture the guess that it is the safer route to take whole mushrooms, rather than isolates.

Also I can't help but think that if people here already feel overstimulated on PS or AG, should we really try even stronger compounds? It seems senseless to me. Perhaps it can be tried after lower potency fibers are tolerated without problems.

Here is a post from another thread discussing beta glucans:

BG and TF gave me a complete relapse. I was not fighting a known infection, was functioning at 80% (ME for 21yrs) and decided to try them and put up with the viral-like symptoms for a couple of months. That was 12yrs ago and I never went back to baseline. I am now worse off than before. The virologist told me I had an "immune response" and to should stay away from the stuff.

 

[adreno]

And from yet another thread:

I tried MGN3 for about three months and couldn't tell the difference.
I tried shiitake, reishi, maitake and cordyceps for almost a year and had no improvement, confirmed by no changes in immune markers including nk cells.

I must say that even though things look good on paper - and as you can see I was looking into MM years ago - I still haven't heard of a single person with ME/CFS who benefitted significantly.

 

[Sasha]

The cold sores are clearly a sign of enhanced immunocompetency. I think I first started experiencing these about three years ago, and they would episodically re-occur for about two years. I had never had a cold sore, until this time. In the past year, this has been replaced by apthous stomatitis, which is more of a T-cell phenomenon. I welcome these, because they seemingly represent steps in the restoration of an appropriate and effective immune response.

I've just been googling on liposomal Vitamin C causing cold sores and found this, on the 'Vitamin C Foundation' website in response to a query similar to mine:

Your experience does sound similar to what Linus Pauling wrote about in his book HOW TO LIVE LONGER AND FEEL BETTER (1986). People can and often do develop "cold sores" after beginning large amounts of vitamin C. The theory is that the vitamin is activating the immune system, which then pushes viruses and other toxins to the surface of the skin, creating the sore.​

The commentator goes on to say:

The protocol is to slow down, and detox more slowly, perhaps cut the dosage to a much smaller amount, and slowly increase.​

I've sent off for the book to see if there's more detail. I'm wondering if it's safer - not just with Vit C but with RS and PA and these other things - to cut the dose of anything that seems to be stimulating the immune system to a level just below that which provokes symptoms with a view to being able to build up slowly without provoking symptoms or whether that is, by definition, an ineffective dose.

 

[Ripley]

And from yet another thread:

Well... three things.

1) Your point about taking the whole mushroom, and not the isolate, is actually what I'm talking about. I definitely don't believe a β-glucan isolate would be a good thing. There's a reason why a very specific mushroom (Turkey Tail) is supposedly having an effect on ME/CFS, and it clearly has something to do with the mushroom as a whole and not any kind of isolate. If β-glucans were just an ingredient, like salt, then I wouldn't be talking about specific species of mushrooms (like Turkey Tail). Most isolates rarely work the way nature intended.

2) Not all β-glucans are the same. So, for instance, I don't know why anyone would think that someone taking a yeast-extracted or candida-extracted β-glucan would have the same effect as the β-glucan that comes with Polysaccharide-K (PSK) or the β-glucan that comes with Polysaccharide peptide (PSP). For instance, both PSK and PSP are found in Turkey Tail, but they have completely different effects. Every different kind of β-glucan supposedly fits into a different kind of receptor. Totally different compounds. No point lumping them all together like they are generic or something. And polysaccharides like Polysaccharide-K does what it does because it's Polysaccharide-K, not because it only contains a β-glucan.

3) I agree that I probably wouldn't take a medicinal mushroom with other prebiotics. Seems unnecessary to double up when trying something new anyhow.

Maybe we're saying the same thing.

I must say that even though things look good on paper - and as you can see I was looking into MM years ago - I still haven't heard of a single person with ME/CFS who benefitted significantly.

Has anyone on this board actually tried Turkey Tail?? It sounds like people just gravitate towards the isolate or other non-related species, or a blend of species, and assume they are all the same. They're definitely not. There's a reason why the research is focussed on that one species.

 

[Violeta]

I had taken reishi for 6 months and it improved a lot of symptoms for me. At one point I added cordyceps, and had a negative reaction. I found this site http://www.shen-nong.com/eng/exam/specialties_menopause_herbs.html
that shows that just like herbs, mushrooms have specific actions, so if one doesn't work, another might.


If you see some herbs that helped you in a section of one of the charts in the link you can use that to determine which mushroom might help you.

Both resistant starches that I tried in small amounts caused me a lot of negative symptoms while reishi caused none.

A friend of mine with skin cancer was very impressed with the list of symptoms at eartherbs.com that chaga is good for and bought some. She started to feel better in 3 days. I tried chaga but found reishi more helpful. Different people, different cure.

 

[Vegas]

l. I'm wondering if it's safer - not just with Vit C but with RS and PA and these other things - to cut the dose of anything that seems to be stimulating the immune system to a level just below that which provokes symptoms with a view to being able to build up slowly without provoking symptoms or whether that is, by definition, an ineffective dose.

This, I believe, represents a prudent strategy, although I think that you will find that symptom abatement is not so readily carried out insofar as there are many variables that control the induction of symptoms. One of the big ones, I think, is reduced glutathione. If, for example, you push yourself to where there is noticeable P.E.M., this correlates to having heavily depleted your antioxidant capacity. So, what happens when you concurrently mobilize endotoxins superimposed on high oxidative stress is that you have a greatly reduced capacity to neutralize the oxidative consequence of these, particularly in the Kupffer cells in the liver. Reactive oxygen species, like H2O2, which is produced by the inflammatory response LPS elicits will burn through your GSH reserves in the liver very quickly. This leaves little to export to the other tissues.

Fortunately, there are controls which put the brakes on the immune response, which kills the pathogenic bacteria and mobilizes the endotoxin. Actually, there are many mechanisms to keep the immune response in check, but the depletion of intracellular glutathione itself is, with bacterial toxins, one crticial way that the immune response, especially T-lymphocyte function, is suppressed. As a consequence the immune response stops punishing you, except that you already will have mobilized endotoxin that still needs to be neutralized. The research done at NIH has demonstrated that these endotoxins can remain in the lymphatic tissues for weeks. In immunocompromised individuals, the capacity to neutralize these endotoxins in the extraintestinal tissues is significantly impaired, so at first the symptoms may not seem so harsh, but as the endotoxin burden builds, and the antioxidant capacity and hydrolysis falters, symptoms can start to emerge. This ineffective extraintestinal endotoxin hydrolysis, I believe, in part accounts for the lymphatic congestion, many experience. These are in some ways, holding vessels sequestering the endotoxin from general circulation.

I guess the takeaway is to stay below the tolerable symptom threshold as you suggest, but also, at least at first, spread out any "doses" by at least 3-4 days to see what is happening. I would speculate that the cumulative effect is more consequential in those who are immunocompromised because the transit time is greatly lengthened. In fact, I have reason to believe that this process is already more efficient after my own efforts. Sorry, I hope this makes sense.

 

[Sasha]

Thanks, @Vegas - extremely interesting, as always.

There's such a thing as liposomal glutathione. I wonder if that's a good addition or a bad one. I think some people take it with liposomal Vit C and maybe that's to shift the endotoxins produced by the action of the Vit C (if I've understood you correctly).

 

[Ripley]

Just want to give you guys a heads up.

Dr. Grace and Tim Steele have been digging more and more into the RS2 and RS3 research over the past few months, and they are taking a bit of a course correction. I expect them to clarify this in a post sometime next week and apparently their upcoming book downplays potato starch as well.

http://freetheanimal.com/2014/05/magazine-interview-presentation.html#comment-614784

...VLC + powdered RS2 is un-natural and not ideal imho. RS2 (raw starch granules) feeds slightly different gut populations than RS3 (cooked and crystallized) that our microbes may be more co-evolved and adapted to.

RS2 alone ferments fast early and proximally. That’s a problem. VLC probably only delivers ~5-15 g fiber from salads, fruit and nuts which may not be sufficient to carry fermentation all the way to the end. RS2 alone doesn’t do many of the things that cooked/cooled starches, legumes and whole GF grains do for instance:
–bulk stools
–increase wet fecal matter (only dry)
–dilute ammonia or bile acids
–bind bile acids
–lower (carcinogenic) secondary bile acids compared to RS3 head-to-head
–carry fermentation distally to where butyrate and fermentation are typically low

The synergism of RS2 with other fibers (cellulose, hemi-cellulose, pectin, oligos, inulin, etc) mimics whole food (tiger nuts, tubers, yams, seeds, etc) and is likely more ideal. Bile acids become lower and butyrate will flood the entire colon, not just burning ‘hot’ in the caecum, with lower pH, ideal gut populations selected and improved immunity through out the entire length of the colon.

For the most bang for the bugs, consider a synergistic combo of fiber (25 g/day), RS2 0-15 g/day and RS3 10-40 g/day

I second this whole-heartedly!

Some critical missteps we made early on with regard to gut health were:

1. Not considering gutbugs
2. Not considering other fibers (prebiotics and non-fermentables)
3. Considering RS2 and RS3 exactly the same
4. Underestimating RS3 contents in foods

When we went back and looked at studies where they fed isolated RS2, the results were always less impressive than when the RS2 was fed alongside other fiber types.

Consider just getting RS from real foods for the bulk of your needs. One cup (~200g) of cooked and cooled potatoes, then reheated, for instance supplies approx. 15g of RS3. A banana, still green at the tips, will have approx 15g of RS2. I think this combo is much healthier for gut than a VLC day with 4TBS of potato starch.

More than one person has remarked that potato starch at much more than 1-2TBS is more ‘medicinal’ than ‘real-food.’ We are after growth of health gut bugs and the resultant butyrate/pH changes…this can be done with real foods.

Tim also gave this simple cheat sheet in another comment:

A 40g RS day would include these things:

- 1 med size green banana – 10-30g (depending on green-ness)

- 1 cup of Uncle Ben’s converted rice…cooked, cooled 24 hours, reheated or eaten cold – 20-30g

- 1 cup of cooked/cooled beans – 20-30g

- 1 cup of cooked/cooled potatoes – 10-20g

- 1/2 cup of almonds or cashews – 5-10g

- Raw carrots, med – 1-3g

 

[adreno]

So, no more PS is recommended? Only foods?

 

[Ripley]

So, no more PS is recommended? Only foods?

I believe PS will not be recommended for long term use, as some kind of replacement for a healthy prebiotic-based diet. I believe PS will be one of those things that is used for therapeutic situations or occasionally when one can't obtain food-based prebiotics (maybe once or twice a week, if you're too busy to cook, or while on vacation). I used PS for about a year and I had great results, but I'm going to see how I do with getting my prebiotics from cooked/cooled foods and plants.

The goal is to feed the microbiota naturally, but being smart about it with cooked/cooled dishes.

Of course, I'm sure it will still be fine to have a horchata (prebiotic starch-based drink) every once in awhile