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

[Vegas]

@Vegas, this is the paper I've seen cited: Psyllium Shifts the Fermentation Site of High-Amylose Cornstarch toward the Distal Colon and Increases Fecal Butyrate Concentration in Rats

O.K. thanks. I'll take a look while trying to include some context into the differences in the rat vs. human GIT, insofar as I know how these compare and contrast. I guess I better figure out what is in psyllium too.

I don't understand enough about the physiology and kinetics of butyrate delivery to the cells, but there are clearly some positive and negative factors.

Positive.

• Enhanced MCT expression (as mentioned above)
• Greater colonic concentration of butyrate, duh
  
• Lower pH (a very prominent factor)
  
• Longer time in contact with cells

Negative

• The converse of above
• Accumulation of Carboxylic acids, for example a derivative of cinnamon would do this. I think a lot of plant compounds may do this to those with inflammatory disease processes. The intestinal epithelium (not the lumen to my knowledge) has a microbial specialists or rather a few that metabolize cinnamic acid, so I suspect many with ME/CFS may be sensitive to cinnamon. Cinnamic acid probably also has a role in modulating the immune response through its effect melanin which modifies the effects of UVB since cinnamic acid inhibits the synthesis of melanin in skin. (yet another built in way that our microbes participate in the immune response)
  
• The presence of monocarboxylates (pyruvate and L-lactate, propionate, acetate). So the accumulation of other SCFA's MAY have a deleterious effect in terms of inhibiting butyrate uptake. Perhaps this is why LAG may be too harsh for many given its ability to increase acetate concentrations paired with insufficiency of the butyrate synthesizers...or something like this.

 

[Sidereal]

O.K. thanks. I'll take a look while trying to include some context into the differences in the rat vs. human GIT, insofar as I know how these compare and contrast. I guess I better figure out what is in psyllium too.

Arabinoxylan, I believe.

 

[Vegas]

Arabinoxylan, I believe.

I'm hoping more xylan than arabinose given the former's propensity to increase acetate. It seems that too much acetate produces some negative symptoms.

Speaking of MCT, these transporters also have an ability to transport more than the SCFA's/carboxylic acids, they can also transport some aromatic amino acids, thyroid hormones-T3 & T4, and something I know you can relate to from a low carb perspective, ketone bodies.

MCT Enzyme inhibition is believed to produce side effects in skeletal muscle to include muscle fatigue and inability to tolerate moderate-to high-intensity exercise due to the build-up of intracellular lactate as well as hydrogen ions.

 

[Gondwanaland]

MCT Enzyme inhibition

Where can I read more about that?

 

[Sidereal]

I'm hoping more xylan than arabinose given the former's propensity to increase acetate.

Yep. Check out Table 1 of this paper. Ispaghula husk = psyllium husk.

 

[Vegas]

Yep. Check out Table 1 of this paper. Ispaghula husk = psyllium husk.

Getting a big cytokine response. Feeling a bit feverish, mild chills, intermittent mild headache, some lymphatic swelling in the legs. Lots of tenderness, discomfort in the axillary lymph nodes, which is similar to the effect of anaerobic fermented sauerkraut. Very pronounced laxative effect from 1 pill. Didn't take with any other prebiotic. I think this is a favorable response, but the dosage was far in excess of what would be comfortably tolerable.

I think it should be said that in studies of humans who took different prebiotics the metabolic effects are often quite variable and this has generally been correlated to the fact that we harbor different organisms.

As for the cytokine response, the lymphatic vessels affected, and the rapidity in which this response has developed, I suspect that this is a disproportionally "in situ" inflammatory reaction versus one resultant from translocation of endotoxin originating from the gut. I know, it's hard to get more speculative than this, but that is what my gut is telling me and I've been doing this a long time.

 

[Vegas]

Where can I read more about that?

1. This is a good overview: http://onlinelibrary.wiley.com/doi/10.1002/iub.572/abstract
2. This contributes to the explanation regarding elevated leptin/cytokines and ME/CFS (although still a poor disease marker, particularly in the sickest patients): http://www.jbc.org/content/277/31/28182.long

"In the present study, we bring important information to the field of MCT by providing the first evidence for its stimulation by a hormone. Indeed, luminal leptin significantly increased the maximal velocity (V max) for butyrate uptake, whereas the apparent Michaelis-Menten constant (K m) did not change. Moreover, the addition of an excess of butyrate or the use of the MCT inhibitor, CHC, suppressed the luminal leptin-induced increase in butyrate uptake. These results demonstrate that the increased of butyrate uptake induced by luminal leptin is mediated by the same transporter (MCT-1) involved in base-line conditions."

3. And...Regulation of Monocarboxylate Transporter 1 (MCT1) Promoter by Butyrate in Human Intestinal Epithelial Cells: Involvement of NF-κB Pathway. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673490/

The last paragraph might make this easier to understand:
"In summary, we have demonstrated that butyrate, the key SCFA, is a specific potent stimulator of MCT1 gene promoter. We have further shown that this stimulatory effect is specific to butyrate and is dose dependent. We also provide evidence that the stimulatory effect of butyrate on the MCT1 promoter activity is not secondary to its histone deacetylase inhibitory activity, as the mechanism of action of butyrate appeared to be distinct from that of TSA. We found several experimental evidences for the involvement of NF-κB pathway in mediating the effects of butyrate on MCT1 promoter. We speculate that the involvement of NF-κB pathway in the up-regulation of MCT1 transcription, resulting in increased absorption of SCFA by colonocytes, may be an adaptive response to epithelial inflammation."

 

[Sidereal]

Getting a big cytokine response. Feeling a bit feverish, mild chills, intermittent mild headache, some lymphatic swelling in the legs. Lots of tenderness, discomfort in the axillary lymph nodes, which is similar to the effect of anaerobic fermented sauerkraut. Very pronounced laxative effect from 1 pill. Didn't take with any other prebiotic. I think this is a favorable response, but the dosage was far in excess of what would be comfortably tolerable.

Very interesting. I agree this may be a good sign. When I react violently to a prebiotic, it usually (not always, LAG for instance was a disaster) pays off in the end but it does sound like you need a much lower dose. I generally only take between 1/4 and 1/2 teaspoon. I foolishly took a whole teaspoon last night and felt very energetic (relatively speaking) but today I am slammed with exhaustion.

Psyllium is a popular laxative over here. At the hospital I used to work it was used in combination with lactulose. I haven't seen any mood disorder cures from that approach so I'm not holding my breath. Actually, in hindsight I wonder how much indiscriminate supplementation with fixed high daily doses of these substrates was actually making the patients worse without anyone realising this stuff is not some inert waste material but actually has a profound impact on their immune system.

Vegas, which aloe vera acemannan product have you been using? They seem to come in different molecular weights.

 

[Vegas]

Very interesting. I agree this may be a good sign. When I react violently to a prebiotic, it usually (not always, LAG for instance was a disaster) pays off in the end but it does sound like you need a much lower dose. I generally only take between 1/4 and 1/2 teaspoon. I foolishly took a whole teaspoon last night and felt very energetic (relatively speaking) but today I am slammed with exhaustion.

Psyllium is a popular laxative over here. At the hospital I used to work it was used in combination with lactulose. I haven't seen any mood disorder cures from that approach so I'm not holding my breath. Actually, in hindsight I wonder how much indiscriminate supplementation with fixed high daily doses of these substrates was actually making the patients worse without anyone realising this stuff is not some inert waste material but actually has a profound impact on their immune system.

Vegas, which aloe vera acemannan product have you been using? They seem to come in different molecular weights.

http://www.swansonvitamins.com/glyconutrients

I think something like Mannan + Xylan polymer + Starch, maybe some humic/fulvic acid might be a good combination to the extent one can generalize. You can pretty well cover the core commensal anaerobes with these. Tiny, intermittent dosages (Q.I.D. perhaps) seems to work better, but then I have to account for the cumulative effect, so I play by symptoms and take a day, a week, or whatever off.

Mushrooms/Algal sources seem to contain a few too many adverse prebiotic compounds for me.

 

[Sidereal]

This is a complex topic, and one I only have a limited handle on, but I will note that abnormal MCT transport has been discovered in muscle tissue in ME/CFS.

Do you have a reference for this?

 

[Vegas]

Not that I can immediately find. I think this may have come from a journal article on post-infectious fatigue not specifically ME/CFS. I have about 30,000 pages of articles, so if it doesn't show up in the title it is not easy to find.

Psyllium has proven to be pretty interesting. That one pill caught up with me after about three days. It eventually resulted in what I would characterize as a more extraintestinal response, some kidney pain, and then lots of upper back lymphatic engagement. The lymphatic symptoms seem to be moving away from the mesenteric lymph nodes, where they closely communicate with the bowel to more upper back, axillary area where they are so heavily concentrated.

I'm trying to figure out the process behind this and what this means about progress and course. We now know that bacteria is much more "invasive" than was previously believed; it is found in diverse tissues throughout the body remotely located from the GIT with growing evidence that localized or regional dysbiotic populations now correlated to disease. (like breast cancer and E. Coli).

We demonstrate an immunotolerance to pathogenic microbes, which is in large part a result of having sufficient commensal microbes and their roles in the creation of t-regs,and other anti-inflammatory molecules. The right commensals will inhibit quorum sensing, mobilize an appropriate phagocytic response, and regulate the passage of both commensal and pathogenic microbes through the intestinal epithelium and into the mononuclear phagocyte system, where the pathogenic microbes create so much havoc. So it is important to note that having the right balance in the gut affects not only the integrity of the intestinal lining, but it also dictates what bacteria is ushered across the barrier by immune cells and into the tissues where the immune response can be so taxing.

The mesenteric lymph nodes serve as reservoirs for both health and disease. These communicating immune structures harbor good and bad guys. Studies have investigated the effects of taking antibiotics for an infection. The infectious organism may be readily eradicated from the gut and initially, not cultured in the mesenteric lymph nodes, but eventually, the organism is re-detected in the MLN.

 

[Sam7777]

Oh wow. . .. 104 pages, but this is one post I came to read on phoenix.

So honestly, I am still digging through all of Dr. Grace Liu's blog articles, and Nikoley, et al.

What I am hung up on is the beginning of Cutler's chelation protocol and coffee enemas. For me, even trying to do 4 mg of ALA or RLA is proving challenging, and I believe it boils down to diet and much of this ancestral health issue. What I want to figure out is what Grace was eating in terms of paleo during her initial chelation process, because she says that the RS and SBO and adrenal function and SIBO and other probiotics and her 7 steps did not begin to take effect until AFTER most of the metal was out. Mercury really is that rooted.

SIBO will be there mercilessly during the initial hard months of chelation. I'm not sure about GAPS or a potato or diet, or anything like interval fasting. But Grace made some strong arguments against VLC beyond 6 weeks because it starves the bugs.

Its all quite a lot to digest. (pardon the pun)

 

[xjhuez]

aaron_c,

Cooking the Bob's potato starch to make RS3 is something I'd considered but never tried. Definitely going to do it tonight.

Honestly, I just set out to heat up some potato starch like a cooked potato. I didn't want to cook it in water because I saw discussion about how cooking releases water from the RS matrix and I didn't know if cooking it in water would fail to produce RS3. So I cooked it in oil. Which is all to say that you may not need to follow these directions at all.

Where did you read about this?

 

[Vegas]

I think looking at a combination of genomic, metabolic, and enzymatic characteristics of the microbes that have demonstrable roles in augmenting the host immune response and opposing pro-inflammatory molecules is particularly useful when trying to establish what polysaccharides may be not only most efficacious, but most tolerable. It's really not that complicated of an approach, just a simple exercise of reverse-engineering. The expanding knowledge about microbes, their phenotypes, their symbionts is making this process much easier.

While there are a number of genera involved in this greater process, bacterioides for example, Clostridial cluster IV, XIV-A, and XVIII appear to be the core microbes involved in butyrate synthesis, which as a metabolite can exert some pretty important functions independently.

This chart represents a very good overview of the chemical abilities of many of the commensal clostridial organisms known to positively affect t-regulatory cells. I thought this might be helpful in better understanding the interdependent processes that I hope will lead to restoration of immunity.

Some things to notice.

• Some indole synthesizers, which I talked about having a role in colonic epithelial function, tryptophan metabolism, t-cell regulation,depression, etc.
  
• A number of strong esterase enzymes, which I think has implications in acetylcholine regulation/Co-A metabolism. From a practical standpoint this may imply that there needs to be an appropriate balance of prebiotics that do not ovestimulate the organisms that synthesize these enzymes.
  
• Cluster XIVA dominated by enzymes aimed at alpha-glycosidic bonds versus Cluster IV and XVIII favoring beta carbohydrates...not necessarily for growth but for cross-feeding or other functions. (A question of soft woods vs. hard woods?)
  
• The key indole synthesizer on this chart is a sulfate reducing, lactate metabolizing, butyrate-synthesizing machine. The "anti-CFS organism," although one organism will always require its partners.***
• An apparent role in the BCAA metabolism, which of course is not surprising.
  
• beta-glucosamine glycosides were made for Cluster IV and XVIII organisms, that means many things, including that these organisms almost certainly disrupt biofilms formed by pathogens.

I think one of the key points is that while humans have some innate (host) mechanisms for converting and synthesizing some of these key compounds, a break in the microbial partners seems likely to have vast metabolic consequences.

EDIT

***that would include Both D & L isomers, and some other very useful properties.

Also, I think the commercial classsification of "soil-based probiotics" is a bit misleading. These microbes described herein are all "soil based" and flourish in humans. If you want to fix the nitrogen metabolism, you need these guys.

HTG to my US compatriots

 

[Sidereal]

@Sam7777, dealing with the metals is tricky. 5mg of ALA on a FDC schedule lights up all my areas of chronic infection/dysbiosis like a Christmas tree - kidneys, lower back, reproductive organs. Simply intolerable pain. 2.5mg doesn't seem to do much except make my mood labile. I don't really know how to proceed but I suspect we need to deal with the gut first. Dr Cutler would of course disagree with that view in his inimitable style.

 

[Sam7777]

One thing Grace did mention, is that she did have to do a great deal of anti-fungals early on along with what I suppose was her 10,000 steps advice. I am not sure what I have - but I know its some combination of the baddies.

What I believe I may have to do is weed/cut/fast/kill ->chelate ->backoff ->bulk/rest/refeed/reseed x rinse/repeat

It is certainly beginning to look like a battle of attricious chicken-egg argument with gut bugs and mercury as one without the other addressed and you get no where. Circular reasoning from hell.

 

[NilaJones]

I've had an exciting result! I started ortho-biotic a couple weeks ago, every other day, in addition to the intermittent tapioca starch, cold/reheated potatoes, mushrooms, etc. that I have been doing for a while.

Ever since I was a teenager (decades before getting sick), I can't eat much at midday . Two bites of a sandwich make me hardly able to keep my eyes open for the following 4 hours. So I eat breakfast and dinner, and just fruit, juice, etc. in small frequent bits during the day.

But this seems to have changed. I get HUNGRY at lunchtime and I have not pushed it, but have been eating gradually more and so far no problems!

Honestly, to me this is astonishing. No doctors, including natural ones, have ever suggested a cause, or that this was something I could change.

 

[16542]

Re Candida and PHD (Perfect Health Diet).
I have read the posts of Ripley, read the PHD book and found statements that
1. Candida feeds on ketons
2. Friendly bacteria feeds just on carbs
3. Fungal immunity needs carbs
4. Furthermore, I read a study that in the presence of ketons Candida develop resistance both to immunity and antifungals.
However, with all my respect I am sure that both Ripley and the authours of PHD had just a minor case of Candida. I was thinking a lot of time if to take this step and to strart my diet, because my candida is extremely severe. I have not found anyone on the forums to have such sensitiveness. I am getting flare ups even when I literally touch with my hands some carbs.
But I started the diet, with the 450g boiled and overnight cooled potatoes and 450g fruits. Today is my day 3. The first day I got severe bloating, itches all over my body, I woke up at 3:45 AM and I couldn't sleep all night. I got severe psychical symptoms, such as shyness, social paranohia, irritability, anxiety, all that which I perfectly know I get when I eat carbs and my candida goes crazy. On the second day I felt at some point strangely very good, from long time in the past. Then I got an oral trash, something which I have missed in the past. The severe bloathing continued. On the third day, e.g., in the current moment, in the morning my penile candida flared up like crazy. And I am writing this post just after my lunch with potatoes and I feel weak, fatigued and with severe brain fog.

With all my respect to Ripley and PHD, I still do believe their diet is the solution for milder cases and that these people have never had severe candida. What makes me more confident regarding this is that I emailed Paul, the author of the PHD and asked him about my concerns about carbs even before I had started the diet. His answer was "If you have infection so severe that you can not follow a healthy diet you should be under a doctor control and antibiotic treatment". To me, this means obviously, that:
1. Paul has never had even 1/100 of my candida, as it is much more severe than anything I found on the internet, and everything I found on the internet was people who was still getting symptoms when eating carbs, which seems not to be the case with Paul.
2. With all my respect to him and the wonderful book (which I really loved!) it is obvious to me that anyone who believes that chronic systematic Candida can be cleared "by doctors with prescribed antifungals" is at least to say not well informed about all the candida stuff, first, because of course candida can not be cleared with Fluconazole and other antifungals, prescribed by doctors, and second, because doctors have not clue of how to deal with candida and anyone with 1/10 of my experience should know that after his or her visit to the let's say 5th doctor, who either looks at him/her like at alien and don't understand their symptoms, either says "it's all in your head, go ahead and eat everything", either prescribes things which just not work.
P.S. I am taking as well biofilm disturptor, Interfase Plus, as well as SF722 and Colloidal silver and almost 1liter per day of kefir and yougurt.

The purpose of this post is not to insult neither Paul, neither Ripley. I am actually grateful to these guys and I appreciate their work. I just wanted to share my own experience and opinion. Their theory seems to be right as I saw with my own eyes why on keto diet I was getting worse for years.
However, maybe it is just too late for me to get the right path back, as if the only solution is the carbs diet and I can not tolerate it, what else is left... Anyway, I will be on this diet for some more time, hopefully a month, to see if all this hell will turn out, and after that, I will think again. I taught that I am so bad that I have nothing to loose if I give it a try and it can't get worse, but I am not right and I was not also during all that years when I was indeed getting worse and worse, year after year.

 

[Sidereal]

http://www.swansonvitamins.com/glyconutrients

I think something like Mannan + Xylan polymer + Starch, maybe some humic/fulvic acid might be a good combination to the extent one can generalize. You can pretty well cover the core commensal anaerobes with these. Tiny, intermittent dosages (Q.I.D. perhaps) seems to work better, but then I have to account for the cumulative effect, so I play by symptoms and take a day, a week, or whatever off.

Mushrooms/Algal sources seem to contain a few too many adverse prebiotic compounds for me.

I've been taking the aloe vera mannan for a few days now with no noticeable effect. The capsules are only 100mg which seems very little. How much do you take?

 

[adreno]

Would d-mannose powder do?