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

[Beyond]

Yeah, good point. I had the same concern. Lower fecal ammonia means something and I gather from the tone of these studies something good?

 

[MeSci]

Yeah, good point. I had the same concern. Lower fecal ammonia means something and I gather from the tone of these studies something good?

I really don't know!

BTW I'm not sure whether I interpreted the d-lactic acidosis paper correctly, notably whether the differential excretion was a cause or a result of the anion gap size. My brain gets befuddled with pH! (in more ways than one?)

 

[Christopher]

Sure. I have no idea.

But as I said earlier, does faecal ammonia reflect serum ammonia, or could high faecal ammonia mean that more is getting into the blood or being retained in the blood? If it's higher in the blood, it might perhaps be reflected in high levels in urine rather than faeces. Just theorising here, but this paper on d-lactic acidosis says that different anions are excreted in the urine depending on the 'plasma anion gap'.

Without testing, it's very difficult to work out exactly what's happening, as the body has so many positive and negative feedback mechanisms.

Through what mechanism would RS reduce ammonia excretion? Guess we'll just have to go by symptoms. That's fine with me.

Also, I've been eating a s-ton of carbs lately, way more than usual. (rice, white potatoes, sweet potatoes, and some bad ones, like potato and corn flour chips). So I have to take that into consideration and cut back on the bad ones especially before I declare RS to be a failure.

 

[Ripley]

I'm not that familiar with ammonia, but I found this list of sources of ammonia in the body:

http://www.medschool.lsuhsc.edu/biochemistry/Courses/Biochemistry201/Desai/UREA CYCLE.pdf

Sources of ammonia
1) From amino acids:
2) From glutamine: Glutamine hydrolysis by glutaminase (from kidney and intestine) form ammonia. From kidney, ammionia is excreted into the urine.
3) From bacterial action in the intestine: Ammonia is formed from urea by the bacterial urease. This ammonia is absorbed from the intestine by the way of portal vein and then converted in to urea in liver.
4) From amines: amines from diet, and the monoamines that serves as hormones or neurotransmitters gives rise to ammonia by the action of amine oxidase.
5) From purines and pyrimidines: In the catabolism of purines and pyrimidines, amino groups attached to the rings are released as ammonia.

Transport of ammonia in the circulation
1) Urea: Formation of Urea in the liver is major route of disposal for ammonia
2) Glutamine: Is a nontoxic storage and transport form of ammonia.[

Hyperammonia
Increase levels of ammonia in the blood cause the symptoms of ammonia intoxication, which include tremors, slurring of speech, vomiting, cerebral edema, and blurring vision. At high concs. Ammonia can cause coma and death.

Acquired hyperammonia: Liver diseases—e.g. viral hepatitis, ischemia, or hepatotoxins Cirrhosis

Hereditary hyperammoina: Genetic disorders of five enzymes of the urea cycle

More details, with detailed graphics, are in the link.

 

[Ripley]

Truthfully, if RS were somehow related to hyperammonia, then there should be evidence that other forms of prebiotics are related to hyperammonia as well. RS isn't digested by the body, and it's only known mechanism on the body — after decades of research — is through modulation of microflora in the gut.

We know (as shown above) that bacterial action in the intestines can increase ammonia — absorbed into the portal vein and converted to urea in the liver. But, in a healthy person that doesn't seem to result in hyperammonia.

 

[MeSci]

I'm not that familiar with ammonia, but I found this list of sources of ammonia in the body:

http://www.medschool.lsuhsc.edu/biochemistry/Courses/Biochemistry201/Desai/UREA CYCLE.pdf

More details, with detailed graphics, are in the link.

Interesting, thanks. Rather a lot of spelling errors for an .edu site though!

I wonder whether I actually need more ammonia. I was unable from a quick search to get much info on hypoammonaemia.

The reason I wonder is related to a link I posted earlier about d-lactic acidosis, plasma anion gap, etc. I appear to be prone to losing a lot of sodium in urine. According to the paper on d-lactic acidosis, losing sodium or potassium happens in some situations whereas in others it is ammonia/ammonium that is lost. Maybe if my ammonia levels were higher I would lose more ammonium and less sodium.

 

[MeSci]

Truthfully, if RS were somehow related to hyperammonia, then there should be evidence that other forms of prebiotics are related to hyperammonia as well. RS isn't digested by the body, and it's only known mechanism on the body — after decades of research — is through modulation of microflora in the gut.

We know (as shown above) that bacterial action in the intestines can increase ammonia — absorbed into the portal vein and converted to urea in the liver. But, in a healthy person that doesn't seem to result in hyperammonia.

But we're not healthy!

 

[Ripley]

But we're not healthy!

I know that. I'm just trying to explain why other people aren't having those problems.

 

[Ripley]

I wonder whether I actually need more ammonia.

Am I mistaken that protein consumption is directly related to ammonia production? Or is that too simplistic? I know increasing bacteria would increase bacterial action, but you'd think that it could be modulated by protein a bit.

 

[Gestalt]

I am reposting @Vegas posts on ammonia since they clearly articulate how ammonia is decreased by increased bifido populations which can be done with RS. He uses a cultured milk method instead.

One can reduce ammonia by first cutting back on protein and other high-nitrogen foods and then gradually introducing bacteria that will both assist with the metabolism of these nitrogenous compounds, including NH3, but also lower the concentration of those species that are contributing to this problem. In my opinion the problem is not created by a collection of SNP's, but an imbalance among nitrogen-fixing/urea-splitting bacteria. Many pathogenic strains of bacteria actually provide benefits in reducing this ammonia to less toxic metabolites, and the irony is that attempts to manipulate the intestinal microbiome (probiotics/antibiotics) often makes matters worse because the pathogenic organisms that are eradicated may have been simultaneously providing beneficial effects.

Consider trying Bifidobacterium strains, infantis and bifidum; these should be singularly cultured in milk for 24 hours. These will lower pH in the large intestine and dramatically reduce ammonia levels, inhibit the growth of pathogenic organisms, increase SCFA production, increase LAB numbers in the proximal bowel, inhibit/kill H. Pylori in the stomach, increase HCL production, dramatically reduce LPS concentrations in the intestinal lumen, dramatically reduce histamine, increase GSH locally and systemically, lower formaldehyde concentrations, produce b vitamins, folate & others, etc.

It's not just the 1/2 kilo of bad bacteria in your GI tract that is keeping you ill, but rather the absence of necessary anaerobic species that counterbalance and correct this. Bifidobacteria have high GC-content and they stimulate MAF. What they also possess, however, is an ability to attenuate NF-kB and TNF-a. Lowering the inflammatory and histamine response is critical. One's reactivity to "methylation" supplements is a consequence of dysbiosis.

Good luck.

As you probably know, people with ME/CFS are known to have hyporuricemia. In this regard, I don't consider the low uric acid the problem, rather this is a consequence of the impaired metabolism of nitrogen, which I think is a consequence of dysbiosis. (Obviously limited cofactors like zinc, Mo, and low ATP don't help this).

It has taken me years to understand some of the food "sensitivities" and understand how to correct them. In fact this really came about by accident when I started "rebalancing" my intestinal microbiome and as a result became extremely sensitive to many foods. In other words large amounts of probiotic rich foods resulted in a very uncomfortable reaction to nitrogen-rich foods. The purine alkaloids were probably at the top of the list. I'm guessing this is what you are describing. It became clear that the displacement of normally pathogenic organisms left me without the full-complement of species required to handle nitrogen byproducts. That is, pathogenic organisms were filling a void and species like psuedomonas were reducing the toxic nitrogen metabolites to less harmful byproducts.

At first I was looking for a microbial solution to rebalance the nitrogen "problem," but the solution ended up being much more comprehensive. The solution I came up with was that those organisms that were most beneficial were truly anearobic species, and it was my conclusion that the lack of commensal anaerobes was what was keeping me (and probably others) from healing the gut, lessening the immune response, translocating bacteria, etc.

Bifidobacteria and their unique hexose metabolism and certain species of LAB that rely upon obligative heterofermentation appear to be the winners. The similarities in what would happen if one developed a scarcity of these organisms is really striking when compared to the observations in ME/CFS. In fact I have come to find many more similarities in other seemingly unrelated diseases. Disruptions in the purine/pyrimidine metabolism have just in the last year been identified in a number of GI diseases, and riboflavin perturbations are also common as are SCFA imbalances. These are signatures of bifidobacteria. I've also learned that the importance and numbers of Bifidobacteria have been greatly underestimated, and traditional tests not combined with pcr analysis are not likely useful.

Through careful testing, I learned that single strain bifidobacteria yields much more potent results, especially when compared to LAB mixed with bifido strains. A commercial starter culture will be dominated by LAB, and many of these homofermentative strains are not desirable. They are energetically inefficient.

I would suggest starting out with one of the bifido strains from Natren and culturing in milk for 24 hours. Both B. Infantis and B. Bifidum have histamine-degrading ability. They also don't create unwanted metabolites, like biogenic amines. LAB strains are similarly important and these predominantly colonize the small intestine, but I think altering the pH in the large intestine and the inherent ability to metabolize nitrogen, and bolstering SCFA production is the priority in healing the intestinal tract. This has so many implications including glutamine availability, creating a bacteriocidic effect, lowering pro-inflammatory response, etc. It is a bottom-up approach, and as I have found if you displace too many pathogenic organisms in the proximal colon, you can create collateral problems.

Use raw milk if you have it, but otherwise just sterilize it at 170 degrees before you culture it. I anaerobically ferment this with C02 off-gassing, but I am not convinced that this is necessary. The key is getting the right strains and not combining them. Different strains have different effects, and different culturing methods greatly influence the properties of each strain. For example many strains of bacteria will provide tremendous ability to degrade formaldehyde if they are anaerobically cultured, but culturing in oxygen will completely inhibit the capacity of this trait. It has become clear to me that the formaldehyde concentrations that people with ME/CFS demonstrate are a product of their own intestinal microbiomes. The by-products of the histamine degradation are aldehyde, ammonia and hydrogen.Tetrahydrofolate is critical to the metabolism of aldehydes. It acts as a donor of a group with one carbon atom.

As I see it, the lack of the right bifidus strains has adverse consequences on the conversion to reduced forms of folates, it potentially reduces the availability of biotin and riboflavin, hinders the recycling of ADP, reduces NADP availability, results in the accumulation of gram-negative bacteria, increases the pH of the large intestine, diminishes the metabolism of histamine, aldehydes, and ammonia, reduce the availability of energy available (about 15%) due to SCFA's.

Making cultured bifidus strains is easy, just take it slow because its effects as an immune stimulant will build over time. If you have intestinal permeability, the lower lymphatic vessels will become noticeably engaged (sore, painful, cytokines). (LAB strains that populate the upper GI tract will more prominently effect the messenteric lymph nodes-e paraspinal and brach off to the axillary. These strains are highly adherent, in fact you will struggle to clean this fermented milk from a glass jar. Milk is the preferred substrate, and the substrate does influence the adhesion efficiency. This is not an overnight fix, but it works. It seems to be particularly effective at re-balancing fluid levels, which I think is simply a consequence of lowered ammonia. In other words, you don't need as much fluid to dilute the caustic substances, so once one starts getting bifidus strains on board, they may notice having to urinate a lot for a little while.

 

[Gestalt]

I recommend B. Infantis and Bifidus for their full complement of enzymes able to convert and interconvert all forms of folate, but for the specific purpose of lowering ammonia, B. Bifidus is going to be the most effective. This process happens via a number of different mechanisms.

First, the Bifidus through production of bacteriocins and organic acids results in the displacement of pathogenic organisms that are net producers of ammonia (or other nitrogenous products that contribute to this). While I see individual variances in organisms that predominate in many different inflammatory diseases down to something as specific as ME/CFS, the broadest classification of organisms creating the dysbiosis is the predominance of PROTEOBACTERIA. These gram-positive, largely anaerobic species need to be displaced from the lower intestinal tract; the void needs to be filled with organisms that can reside there. This means you need competing species that will fill this largely anaerobic niche. Like proteobacteria, bifidus species, will occupy that niche. They are obligatively or facultatively, anaerobic, like most proteobacteria, yet they are gram positive and non-pathogenic.
(Other aerobic organisms and the deamination of proteins and other nitrogenous compounds also contribute to this, but I don't want to get too complicated).

The second, method whereby the Bifidum will decrease plasma ammonia is through it's ability to alter pH. Lower pH reduces the production of ammonia by intestinal organisms. What I think is more consequential though is that a lower, and more acidic pH will enhance hydrolysis. In the lower pH of the large intestine ammonia (NH3) can more readily bond with Hydrogen, creating ammonium (NH4). The importance of this reaction is that ammonium cannot pass through the bowel wall into the blood. Reducing pH in the colon thus allows for ammonia to be converted to a less toxic form, and one that does not diffuse into the blood.

The nitrogenous compounds that will create problems don't just include ammonia. Protein catabolism and the one's metabolism and disassimilation of amino acids can create a number of toxic byproducts. I think that some people who take enzymes do poorly because they are freeing compounds that cannot be readily metabolized. Perhaps the failure to fully breakdown proteins that is nearly universal in ME/CFS has a protective purpose. These toxic compounds include, cresols, phenols, indoles, hydrogen sufide, amines, etc. Purine alkaloids from plants are simply amines. Another problematic category is threonine, which is metabolized into aldehydes. (Check out foods high in threonine to see if you have trouble with any of these) Threonine is toxic to me, yet it is an important molecule in maintaining the integrity of the intestinal lining. For those who use GcMAF, it is a sugar attached to the threonine amino acid that makes the Gc protein “glycosylated.”

In vivo and vitro studies do show that these organism can lower plasma ammonia, and other toxic compounds like phenols. Sure, an "upregulated" enzyme involved in cysteine biosynthesis might make you a bit more symptomatic, but this is not the underlying cause of the disordered metabolism. Adults have 10x's higher plasma ammonia than children, and they have, by proportion, about 1/4 to 1/5 the number of bifidus organisms. I see many with ME/CFS who have 10 x's the concentration of plasma ammonia than the average adult. What I think many people don't realize though, and I believe I mentioned this, but many pathogenic organisms are involved in nitrogen fixation and denitrification, so while all must go, their diminishment can make matters worse unless the appropriate organisms are left in their place.

I read where Dr. Ruggiero said that his GcMAF "yogurt" formulation was dominated by bacterial organisms that predominate in infants. This is exactly what I am suggesting, re-populate with those human strains that healthy infants possess. I do, however, believe many strains, particularly homofermentative LAB are to be initially avoided, i think the full ability to synthesize and convert all forms of folate should be incorporated, and I also believe that one needs to concentrate on repopulating with COLONIZING strains.

Unfortunately, gram-positive bacteria are, by nature, extremely hostile. They have tough outer layers of lipopolysaccharide (LPS) that make them resilient to many antibiotics. (Conversely, many of the commensal organisms, like those most should receive at birth, are highly sensitive to these antibiotics..thanks Fleming.) Lipid A takes no prisoners, and it's antigenic friend O-antigen will help stimulate some more unwanted symptoms. Bifidobacteria can neutralize some of this, but once you start displacing organisms these components of the dead bacterial cell walls will elicit a powerful immune response and cause huge amounts of ROS and NOS, which will call upon your GSH stores and occupy the lympathic networks as they make their way to the liver. Go too quickly, and your symptoms will tell you. Modifying the human intestinal microbiome takes time, but it seems to be worth it. Like others who have made very pronounced recoveries from ME/CFS, I always considered the GI component a secondary complication, but I know feel confident that it was primary in the pathogenesis of my illness.

 

[MeSci]

I am reposting @Vegas posts on ammonia since they clearly articulate how ammonia is decreased by increased bifido populations which can be done with RS. He uses a cultured milk method instead.

This is interesting, but I wonder whether it generalises too much, as 'ME/CFS' is likely to be a range of conditions with a range of biochemical abnormalities.

For example, some of us seem to be prone to intestinal acidosis rather than too high a pH. Some of us seem to benefit from taking alkalising agents like sodium bicarbonate, others from acidifying agents like betaine HCl.

I'm not aware of research finding low uric acid in ME/CFS. I searched the large database of papers downloaded from ME Research UK, and the only abstract referring to uric acid reports normal levels.

What is LAB, by the way?

 

[Gestalt]

What is LAB, by the way?

I think it is Lactic Acid Bacteria. If you re-read it Vegas addresses your concerns about lactic acid and why bifido needs to be distinguished from LAB precisely because of your concerns.

 

[xjhuez]

Thank you for reposting these, Gestalt. I had not seen them.

Frankly, I'm at a loss right now. That is a lot of info to process.

I try to stick with prebiotics, as mixed probiotics like the Jarrow and Ultimate Flora make me feel awful, like I've been poisoned. (gut permeability issues, perhaps) I wonder if I need to try one strain at a time.

 

[Gestalt]

Been doing some research on how gut bacteria affect the brain. I am trying to hunt down the most beneficial species and strains to ingest as seeds for my RS. Here are some interesting snippets:

The following are from: Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour

​

the Bacteroides spp. enterotype​

has been associated with diets that are high in fat or
protein, whereas the Prevotella spp. enterotype has been
associated with high-carbohydrate diets 29

Specifically,
exposure to chronic psychosocial stress decreased and
increased the relative abundance of Bacteroides spp.
and Clostridium spp., respectively, in the caecum.


A growing body of evidence points to dysregulation of the often-overlooked
kynurenine arm of the tryptophan metabolic pathway — which accounts for over 95% of the available peripheral tryptophan in mammals130 — in many disorders of both the brain and gastrointestinal tract. This initial rate-limiting step in the kynurenine metabolic cascade is catalysed by either indoleamine‑2,3‑dioxygenase or the largely hepatic-based tryptophan 2,3‑dioxygenase. The activity of both enzymes can be induced by inflammatory mediators and by corticosteroids129. There is some evidence to suggest that a probiotic bacterium (Bifidobacterium infantis) can alter concentrations of kynurenine82. However, this is not a universal property of all Bifidobacterium strains, as Bifidobacterium longum administration had no effect on kynurenine levels61.


Microbial neurometabolites. Bacteria have the capacity to generate many neurotransmitters and neuromodulators. It has been determined that Lactobacillus spp. and Bifidobacterium spp. produce GABA; Escherichia spp., Bacillus spp. and Saccharomyces spp. produce noradrenalin; Candida spp., Streptococcus spp., Escherichia spp. and Enterococcus spp. produce serotonin; Bacillus spp. produce dopamine; and Lactobacillus spp. produce acetylcholine133–135.


Recently, a study assessing
the effect of a combination of Lactobacillus helveticus
and B. longum demonstrated that this probiotic cocktail
reduced anxiety-like behaviour in animals, and had beneficial
psychological effects and decreased serum cortisol
levels in humans73

In a recent study, ingestion of Lactobacillus rhamnosus
(JB‑1) decreased anxiety and despair-like behaviour
and reduced the stress-induced increase of plasma
corticosterone levels in mice75

probiotic agent B. infantis had antidepressant-like
effects and normalized peripheral pro-inflammatory
cytokine and tryptophan concentrations, both of which
have been implicated in depression80 and in a maternal
separation model of depression81,82


fatty acid concentrations in the brain
(including arachidonic acid and docosahexaenoic acid)
are elevated in mice whose diets were supplemented with
the Bifidobacterium breve strain NCIMB 702258 (REF. 83).
Interestingly, this effect was bacterial strain-dependent
as it was not induced by the B. breve strain DPC 6330.
Arachadonic acid and docosahexaenoic acid are known
to play important roles in neurodevelopmental processes,
including neurogenesis, can alter neurotransmission
and protect against oxidative stress84,85. Moreover,
their concentrations in the brain influence anxiety,
depression and learning and memory85,86.

http://www.ncbi.nlm.nih.gov/pubmed/22612585

"The production of GABA by bifidobacteria exhibited considerable interspecies variation. Lactobacillus brevis and Bifidobacterium dentium were the most efficient GABA producers among the range of strains tested. The addition of Lact. brevis DPC6108 to the culturable gut microbiota increased the GABA concentration in fermented faecal slurry at physiological pH."​

 

[Gestalt]

As per Vegas recommendations and the above, I was trying to find products that contain the single strains of B.Infantis (to influence my serotonin levels) and B.Bifidum (to decrease ammonia).

B.Infantis is pretty hard to find and it seems 90%+ of probiotics on the market do not contain it. So check your bottles.

I did find that Natren does carry those two species and you can buy them individually. Luckily I found both locally yesterday.

• Bifido Factor (for B.Bifidum)
• Life Start or Life Start 2 (For B.Infantis)

I am now taking those two species mixed with my RS, as RS seems to primarily be the food for bifido bacteria as opposed to the Lactic Acid Bacteria populations based on the anecdotal results of Tim Steele.

I will still periodically take many other probiotics (such as SBO's Prescript Assist) as species variation is probably ideal and we don't know what all the possible beneficial effects of all the various strains and species are. I just didn't want to be missing an important one that we know works. Like B.Infantis which seems to be pretty rare and highly beneficial.

 

[Beyond]

Hmm isn´t trying to influence serotonin (increase? affect the receptors or related genes?) with probiotics a bit far fetched? If I was to try to something for serotonin I would not go that route. I would try herbs probably, maybe supplements and rarely medication.

Yes RS is pretty bifidogenic based in the studies I´ve seen.

Any positive results from RS yet, Gestalt? We have to keep in mind that RS is beneficial for the colon, and if it is beneficial for the small bowel (in my opinion what most people here have worst) I haven´t yet found proof of that.

 

[MeSci]

The findings of anxiolytic effects and effects on GABA from probiotics support the anecdotal observations by several of us on PR that an appropriate leaky-gut regime reduces anxiety and improves sleep. I haven't taken any probiotics, but just changed my diet and also take some gut-relevant supplements, and I observed a dramatic reduction of anxiety and improvement in sleep. Having a slight relapse at the moment, maybe due to some dietary errors which I am trying to correct.

I see no reason why diet or probiotics/prebiotics can't increase serotonin.

 

[Beyond]

Well I am not saying that gut microbes do not affect neurotransmitters, I am just saying that I find odd using them as a primary way to treat neurology, honestly. If it works significantly, hey, that´s great and I would do it then.

 

[xjhuez]

Today will be my 3rd day of "bolus" RS - 3 tsp with psyllium on an empty stomach. Impossible to attribute it to the RS, of course, but I did sleep very well last night. This is a rare occurrence, as I suffer from highly fragmented sleep.

I did find that Natren does carry those two species and you can buy them individually. Luckily I found both locally yesterday.

Please let us know how that goes for you. I'm eager to try them myself, but I know I'm better off waiting a few weeks - learned awhile back to try new things separately.