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

Discussion in 'The Gut: De Meirleir & Maes; H2S; Leaky Gut' started by Ripley, Dec 11, 2013.

  1. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    How strange. I wondered whether my preferences had inadvertently become set to not show signatures, so I went into my preferences and it still showed that I wanted to see them. So I just clicked 'save changes' in there and they reappeared!
  2. Vegas

    Vegas Senior Member

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    Sorry, very long.

    I think you need to look at methylfolate as an immunomodulating agent that becomes particularly relevant to all humans with high oxidative stress burdens. In ME/CFS the processes whereby bioavailable folate is synthesized, made accessible to various tissues, and interconverted is inhibited by a number of different mechanisms, but I believe there is a very central role for conditions that exist in the colon in mediating an immune response. We speak of supplementation of this micronutrient without regard for the particular mechanisms in which folate is selectively transported to the lining of the cells in the colon, which is is distinct from any other tissues.

    The collapse of the population that provides folate synthesis and interconversion has enormous consequences on immunity, but the interrelationships between different organisms implies that all the key bacterial organisms need to be supported to restore an appropriate immune response. There is much more involved than getting reduced folate to our cells; the colon requires a continuous supply of reduced folate delivered to the epithelium, and there are multiple transport systems, which presumably control the accessibility to this nutrient when things go wrong. One of the most basic common denominators of this population of commensals that I think will soon be proven to have been compromised in ME/CFS is their high sensitivity to oxygen. This is true not just in speaking of microbial density and the species ability to withstand oxidation, but also includes the individual capacity of our microbes to reduce folate. The strength of association between "aerointolerance" and reduced folate synthesis may suggest that this evolved to inhibit the immune response when oxidative conditions predominated.

    I believe the high "response" rate in this patient population to more bioavailable forms of this vitamin not only suggests that there is poor bio-availability, but that there is a high priority to limit the availability of tetrahydrofolate and its more reduced forms simply because of the importance of folate to the immune response. When we orally supplement reduced folate, this may allow for enhanced availability of microbial synthesized reduced folate to the intestinal epithelium. We are, however, also, likely over-riding a natural process of moderating the immune response, so there may be a downside to this supplementation.

    We know that these reduced forms of folate are central in the metabolism of proteinogenic amino acids; which is certainly critical to the immune response, via countless mechanisms. The one most are familiar with is limiting methionine recycling, cysteine availability and the sulfur metabolism. This is one powerful means of suppressing the immune system, because it curtails the immune response stimulated by our intake and metabolism of amino acids. For example, while we think of glutathione as an antioxidant, which it it is, it also binds to nitric oxide, and plays a part in stimulating an immune cascade.

    While Methionine is just one amino acid, it is particularly significant because if you suppress methionine you suppress the synthesis of threonine and all proteins. Various immunocompromised conditions/diseases demonstrate not only glutathione depletion, but inhibition of protein synthesis, which has been specifically tied to the inhibition of synthesis of these amino acids. Methionine synthase is therefore a very powerful control point because it limits the regeneration of methionine, and hence threonine. Inhibition of methionine, threonione, and glutathione is seemingly a programmed consequence of oxidative stress. This inhibition of protein synthesis is also exactly the same way that most popular category of antibiotics used to treat gram-negative bacteria works, so the process may serve to hinder the growth and replication of these organisms.

    I suspect that with the multitude of human pathogens, such a central focus on gram-negative pathogens seems exaggerated, but I think their virulence is simply unparalleled, and their relationship with humans has evolved since our creation leading to countless regulatory measures to limit the harm they can cause. Our modern diets have clearly enhanced the threat that they present, as have antibiotics. The findings, such as 4-5x's the level of bacteria in the blood of those with type II diabetes is simply not getting enough attention. As far as I know, this can only be explained by bacterial translocation from the GIT. This also may underscore the power of polysaccharides that not only resist digestion, but as Ripley has discussed, are small enough to enter the circulatory system. This might represent another important means of sustaining the microbes that make their way into the extra-intestinal tissues and blood.

    The quantity of endotoxin in a single GIT could kill thousands of humans, but we are largely protected while the intestinal epithelium and mucosal barrier are preserved. The TLR-4 receptors, which initiate the inflammatory response are typically not accessible in the GIT, they are protected by the mucosal barrier. It is only with the changes in the microbially-maintained mucosal layer that these are exposed, and when permeability is enhanced, the extraintestinal tissues, which do have exposed TLR-4 receptors, precipitate such a potent immune response.

    Inhibition of protein synthesis via limiting threonine biosynthesis limits cellular proliferation, and this is is essentially what happens when tetrahydrofolate is limited at a molecular level. Inhibiting the synthesis of tetrahydrofolate suppresses the immune response because it is the principal co-factor required as part of the one carbon metabolism, which participates in the synthesis of RNA and DNA. Folic acid has to be reduced to 5,6,7,8-Tetrahydrofolic Acid. Limiting tetrahydrofolate has the power to dampen the immune response and protect us because it has the ability to affect DNA synthesis. This is the same method used to suppress cell growth in cancer cells, but in ME/CFS, I think it principally serves to dampen the synthesis of immune cells and limit the immune response.

    A robust responses to MTHF may simply imply that patients have energy deficits as ATP/NADPH is required for DHFR and MTHFR, In this respect, tetrahydrofolate and methyltetrahydrofolate synthesis can be inhibited simply by mitochondrial dysfunction. Mitochondrial function has to be coordinated with all the systems that have the potential to cause great harm. NADPH availability affects a lot of processes, including the detoxification system our uses to neutralize nearly every sort of toxin we encounter. In this regard, it's scarcity serves to limit the burden that we are subjected to, including the mobilization of toxins from all our tissues that is mediated by glutathione.

    As alluded to above though, very special circumstances exist in the colon, where there is a complex ecosystem involving the microbial synthesis and interconversion of folates. Some speak of the dietary intake obviating the need for this bacterial biosynthesis and interconversion, but I think this is unlikely when you look not just at the microbial folate synthesizing and conversion capabilities, but the complicated transport systems, which allow for these various forms of folates to saturate the tissues in the colonic intestinal epithelium. Folate availability to cells and uptake in the colon is distinctly different than in the small intestine where most folate is taken up for systemic distribution and supports the microbial organisms in the small intestine that are net consumers of folate.

    With uncontrolled oxidative stress, I think there is an obvious means to control the reduction of folate when energy metabolism falters. This impacts the processes of generating DNA via de novo synthesis (which requires tetrahydrofolate) and limits the extent of amino acid metabolism. These mechanisms that seem to downregulate the immune response seems to be paired to mechanisms that protect our cells. For example the primary cysteine synthesizing enzymes are directly linked to the creation of short chain fatty acids, butyrate and propionate. In other words, biochemically, there is a diversion of methionine metabolites to products that almost exclusively protect us from oxidative stress. Enhancement of the sulfur amino acid metabolism does not do this.

    In terms of the immune response, the effects of providing methylfolate to those with ME/CFS may relate to the creation of immune cells and the effects these create in the inflammatory cascade. I think this could be a deliberate regulatory mechanism that happens to inhibit the mobilization of endotoxins, because a robust immune response is what allows for cell wall destruction and the massive inflammatory response that would ensue if there was existing intestinal epithelial dysfunction. I also suspect that limiting cell turnover by suppressing tetrahydrofolate biosynthesis may also inhibit the exchange of the mucosal lining in other ways; I speculate that it basically preserves status quo so that the endotoxin is less accessible (physically) to stimulate an immune response.
    Last edited: May 30, 2014
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  3. Vegas

    Vegas Senior Member

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    Raw fava beans possess a very potent ability to stimulate innate immunity. Perhaps you have heard of favism? While I doubt you have G6PD, otherwise you would have symptoms of hemolysis, but those with ME/CFS have to be very careful with these because of the fact that these can act as a very powerful oxidant. I think they can cause hemolysis secondary to acquired Glucose-6-Phosphate Dehydrogenation deficiency, which is a part of ME/CFS. G6PD participates in the recycling of oxidized glutathione (via NADPH) that is produced by the pentose phosphate shunt. This is necessary to provide protection to our red blood cells, which don't have mitochondria and therefore lack other means of recycling this antioxidant and protecting our red blood cells from oxidation.

    But what you dealt with clearly involved an amplified immune response. Lectins are intricately involved in the immune response, and they are not going to be well-tolerated by many.

    You can get a general idea about what pathogens may be involved and what parts of the immune system were mobilized simply based upon the fact that the mannose-binding lectics in the fava bean have been correlated to specific toll-like receptors, which are activated by specific pathogens. They are in fact correlated to gram-positive organisms (like staph), fungal organisms, and mycoplasma. So while there are other compounds in the fava bean that stimulate an immune response, they seem to have particular specificity not to the gram-negative pathogens in the gut that I talk abou, but some of the organisms more likely to reside in places, like the sinus cavity.

    Of course essential oils like what is found in corriander and some of these other spices like the capsaicin cause me great pain as well. Some lectins put me in a stupor. Blood type may be significant as well. I don't think I could survive this recipe. :)
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  4. Asklipia

    Asklipia Senior Member

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    @Vegas,
    I am so sorry you cannot enjoy my recipe!:( Of course this was not a recommendation for anyone to try, just something I wanted to share in case it would be somehow useful.
    Many many thanks for the beautiful post you just provided about the relationship between folates and immunity. This is on my mind and has been for a very long time. You have helped me a lot, as usual :hug:

    Yes, it is true that we may indirectly find out what kind of organisms are creating trouble by trying various recipes.
    For the moment, all that we have been trying is helping. However, this morning we decided to go back to a little Riboflavin (12.5 mg) and manganese (10 mg) a day for the next week. 16 hours after having taken that, we both feel a little bit better (not feeling bad in the first place, but we felt we needed this little help).

    Tonight sauerkraut is on the menu! Ten years ago it would make us very sick, last week we tried a plate and there was not enough. Maybe the fava beans had prepared the way!
    Be well always :)
  5. Lou

    Lou Senior Member

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    Hi @Ripley

    I ordered Chaga extract from amazon. If it's your opinion that a tea is better will you please supply the brand name of the chaga you're using? Thanks.
  6. Ripley

    Ripley Senior Member

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    Lou. A dual chaga (alcohol and water) extract is the strongest and most effective way to obtain all the nutrients from chaga — particularly if it's Siberian chaga (the colder the temperature it was found in, the stronger it is). Most people just make a tea, which is technically a weak form of chaga, in terms of its full potential. Though, I think a weak tea is more than strong enough for most people. I suppose it's the people with cancer and HIV that really need the full dual extract.

    I don't use a brand. I got my chaga from a friend who finds it in the woods. Chaga can be quite expensive — and it's a very limited resource — so you have to learn to use it sparingly. I make my tea by grinding up the chunks into grounds and I treat it like loose tea (steep and strain). I keep re-using the grounds over and over again until the color is no longer showing in the tea. By re-using the grounds, 1 teaspoon of ground chaga can yield me 4 cups of tea (and I only drink 1 cup per day). So, I probably only go through 1.5 tsp per week.

    When you are done with the grounds, you dry them and throw them in some vodka for a few weeks to get the alcohol fractions. And then you can eat the grounds when you are done (sprinkle them on food for instance). Nothing gets wasted.

    The high cost of chaga and the fact that it's such a limited resource makes other more accessible mushrooms (Resihi, PSP-50/Turkey Tail, for instance) worth considering if you have specific issues you are targeting:

    [​IMG]
    I will likely try Reishi next. Very easy to find Reishi from local mushroom growers — they can literally grow them easily on special sawdust bags in a grow-room.

    Chaga isn't something I would go around telling everyone in the world about. If everyone used it, there wouldn't be any left, and there are plenty of other mushrooms that do a good job.
    Last edited: May 30, 2014
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  7. South

    South Senior Member

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    quote="Vegas, post: 465394, member: 1661"] "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."

    @Vegas, chitin also stimulates many other types of bacteria, for example bifidobacteria (link at end of my post). I have never seen a way to encourage one type of bacteria while avoiding feeding the others who eat that same substance - lab scientists using sterile gut rats may be able to "prove" something, but in a real human gut? How would you attempt to stimulate only your favorite kind of bacteria simply by eating chitin?

    And B-glucan has always worried me due to it's role in building yet more biofilm in the gut.

    So, I'm not as brave as you, or some people here, I guess.

    Links:

    http://www.ncbi.nlm.nih.gov/pubmed/7221561

    http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002848
  8. South

    South Senior Member

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    Don't be surprised that PGX was in a study. The company that makes PGX paid for the study. I work in a health food store that sells it. Lots of "patented, our blend is unmatched by anything in the world" supplements will pay for a study on their own product.

    My guess is that it's a useful fiber blend (I haven't tried it), but the company is charging a fortune for what is simply a certain ratio of about 3 kinds of fibers, in my opinion. Highway robbery, also in my opinion.
  9. Violeta

    Violeta Senior Member

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    @Lou, which chaga extract did you order?
  10. Lou

    Lou Senior Member

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    @Violeta Chaga extract, 90 vegi caps, by Mushroom Science. Ordered from Amazon, delivered today. If helpful, it'll be a first for mushrooms and me.

    Think I'd try anything to lift this Lyme brain fog, and it was Ripley's comment about its effect on his brain fog that prompted my interest. The me/cfs, Lyme moment of this is that friggin brain fog has always been what mushrooms do for me.:)

    Haven't tried the chaga before, or any mushrooms since taking ps, hopefully I'll get a different result.
    Last edited: Jun 2, 2014
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  11. Vegas

    Vegas Senior Member

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    While you are correct that some bifidiobacterial species are also able to ferment this substrate, this is about preferential access, and a particular species' superior enzymatic capabilities. True, some bifidobacteria can access the chitin but not as well as specific commensal clostridial species. The converse is true for beta glucan (with qualifications). This is presumably the way it is supposed to be because there is such a strong mutualistic relationship. These polysaccharides escape digestion from human digestive enzymes, and most bacterial organisms, with only a select number of organisms able to take advantage of these compounds.

    Of course, there is no practical way to microengineer a solution, I am simply trying to steer the microbiome in a particular direction. It is evident to me that this is practicable. I have a growing number of reasons to believe what specific organisms are most likely to provide benefits, and this particular species of acetate utilizing butyrate synthesizing organism is very high on my list of priorities for stimulating expansion. The in vivo effects in this human have proven to be very encouraging. I also have renewed interest in some soil based organisms as I overlooked a particular capacity. This is a work in progress.

    But let's be honest, there is tremendous speculation that is taking place. I know many are completely dismissive of anecdote, but I believe, without any semblance of hyperbole, that personal observations largely led to my own survival. I think that perhaps the only redeeming thing about ME/CFS is that it affords one the ability to experience "symptoms" that most humans will never experience. This leaves the question about whether or not we can interpret the significance of these symptoms and act on this information. I feel increasingly confident that these observations are reliable, but I don't expect anyone else to share this optimism.

    I will let each draw their own conclusions about the ability of prebiotics to effectuate changes in their condition and the risk taking these presents. I certainly don't fault anyone for not wanting to try these compounds. My latest foray has paid dividends, but it has been yet another bitter pill to swallow. I am finally and stubbornly learning to heed my own warnings. I've learned to stop taking things that no longer provide benefit, and to avoid the compulsion of sticking to a strict schedule of "administration." I think the benefits of the prebiotics can be disguised by the symptomatic features of endotoxins and associated immune response, and one needs to become familiar with this, or if they don't believe the endotoxin/inflammatory hypothesis, try to otherwise establish explanations for these symptoms. If you can't discriminate the good and bad, the psychological impact itself can be defeating.

    The biochemical basis for why I am captivated with micro-organisms which can synthesize SCFA's like acetate and butyrate, metabolize acetylated glucosamine and galactose, assimilate protein, reduce lactate concentrations, etc. probably extends beyond most people's interest levels, but I should say that chitin and b-glucan are not just ordinary compounds that are left for Bifidobacteria and Clostridial species to use. Chitin is a polymer of n-acetylglucosamine, and it comprises a large percentage of the mucusoal layer which lines the intestinal tract. Specific bifidobacterial strains possess the unique enzymatic capacity to synthesize other chemicals that are combined to manufacturer this lining as well as to provide chemical/immunological defenses against pathogens, and a host of other interdependent relationships. The exopolysaccharidic enzymes of bifidobacterial species dominate the intestinal environment: these chemicals that our bacterial organisms secrete are likely more important than our own, but they are of no particular value without their closest microbiomic partners. N-acetylglucosamine also happens to be necessary for the synthesis for lipopolysaccharide, but this is another story.

    Sorry, I don't recall your condition or experience. Have you had any luck with any of the prebiotics?
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  12. Vegas

    Vegas Senior Member

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    Definitely be careful with the mushrooms. Consider this a longer-term investment in the resolution of brain fog. In other words, you may have to take tiny doses, and it may get worse before it gets better. I feel like I am drunk today, without the pleasurable part. While I am using something a bit different, there are similarities in compounds and the effects it would produce, I think.

    I am going to be very interested to see how these compounds affect airborne allergies, histamine, and even sympathetic nervous response.
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  13. Lou

    Lou Senior Member

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    Thanks, Vegas, I've already taken 1 capsule (suggested dose is 1-3 twice daily) and I'll heed your timely advice. The fog seems to be rolling in as we speak, so to speak.

    We'll see if tiny doses over the long haul help, that would be wonderful.
  14. Vegas

    Vegas Senior Member

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    Yes, I know you were not advocating general use. Traditional recipes are interesting, but this one has unbelievable "potential" to influence the innate immunity, which makes me wonder from what part of the world this originated. I'm curious if it comes from a high malarial risk region.

    I still take riboflavin, with the only apparent effect today relating to its prophylactic ability to prevent aphthous ulcers. ...along with a little MTHF, but I'm guessing this is not a problem for you and your husband.

    I nearly memorized the principal managanese enzymes a few years back and suspect that it can be rate limiting in the creation of uridine diphosphate by way of its role as a cofactor in galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase. Say that one real fast 10 times. There are lots of tie-ins with liver detoxification, maintaining the intestinal epithelium, and joints. The big problem that I see in ME/CFS is 1. uridine is necessary (combined with omega 3 fatty acids and choline) to form phospholipids, but we are damaging these faster than the special lipids can be synthesized and purine synthesis is already inhibited. I'm never quite sure if Mn supplementation represents a good or a bad idea, but in your case, having improved so much, it is probably fine. 2.
    Humans also have an inability to break down galactose directly, it has to be converted to glucose, and this burdens an already impaired process of glycolysis in ME/CFS. To me this strongly suggests that a microbial capacity to directly metabolize galactose is of great importance. I really like the larch arabinogalactan, and I suspect you might want to try this, if you haven't.

    The idea is to provide the substrate that supports the organisms and you will gain the enzymatic capacity that they possess, and in doing so you may bolster your own microbially supplemented energy metabolism and make Mn supplementation irrelevant. I apologize in advance, as I am still "drunk" from the prebiotic intoxication.
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  15. Vegas

    Vegas Senior Member

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    Yes, you may be cool with that, or it may catch up with you very fast. There's no way I can predict your response, just throwing it out there that these compounds are as "potent" prebiotics as you can find.
  16. Ripley

    Ripley Senior Member

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    Wow... Came across this fantastic thread, from December, on Dr. Grace's blog with Kieth Bell:

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  17. Asklipia

    Asklipia Senior Member

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    I am not sure it comes from a high malarial risk region but it could well be. It is a recipe used all around the Mediterranean, which was a very malarial region until recently, not only malaria but different types of dengue fever too. Do you think my salad could be useful against malaria and dengue? The recipe I gave is from Tunisia, in Egypt they do not use coriander leaves, but instead flat parsley and mint, and there is no cumin, in Lebanon there is mint and coriander, no cumin.
    I think the one that you could not possibly survive is from Morocco : raw garlic cloves crushed instead of spring onion, lemon peels and olives, the rest is like the Tunisian recipe.
    Everyone recommends though that you pick your fava beans in the morning for making a salad during the day, so something must be disappearing as time goes on. Or it could mean that as time passes it becomes more and more difficult to peel the beans.
    As for favism I thought it was only for boys and girls never have the problem. :)

    Maybe eating lamb brains twice a week for breakfast is helping with this phospholipids problem?

    We are trying this at the moment, by small amounts (about 3 g every few days). Don't want to go too fast. We feel the immune system waking up with whatever we do!!!!

    Please don't apologize, otherwise I shall apologize too :). You are helping me so much. May all this help come back to you a thousand times every day and every night. And in the twilights dawn and evening when the truth is visible may you find the solutions to all of this. I believe that only in these twilights, on the edges of the known, where you may go armed with the knowledge you have acquired, you will catch the glimpses of what is real and hiding.
    Good luck @Vegas! :)
    May I offer a traditional chitin recipe, actually what is on my fire today?
    Monkfish a l'Armoricaine.
    For 2 : 2 lbs monkfish in thick slices.
    In a hot pan with butter, turn around the slices to get the water out of the fish. Throw away that water. Keep the fish on the side.
    Prepare the sauce in the same pan (saving on washing-up) and fry in half butter/half olive oil : 1 big onion, 2 small shallots, 2 bay leaves, 2 cloves of garlic, 1 sprig of thyme, 3 big handfuls of small shrimps in their shells with their heads still on, 2 small chillies, a few turns of the mill of nice white pepper (Vietnamese is best), a glass of white wine or a shot of cognac/whisky/bourbon whatever. Then add 2 big tomatoes in chunks. When this is cooked, fish out the bay leaves and you can grind it all.
    Back on the fire. Taste for salt, add a little sugar if needed (all depends on how ripe the tomatoes were). Then you can finish cooking the fish in the sauce. You may need to add water at some point, but careful not to make it too watery.
    Serve with arepas.
    I hope you can survive this. Maybe just the thought will bolster the will to live of many, hence helping with their healing.:hug:
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I wonder whether taking something to dampen down the immune system would help to mitigate some of the adverse symptoms of taking resistant starch? I have been taking 5-HTP to improve my mood, but it also raises cortisol levels, which would dampen down some immune activity.

    I used to have swollen neck glands almost every day when I woke up, but this has decreased greatly in the past few weeks, which I am guessing is due to the cortisol-raising effects of the 5-HTP. I think I forgot to take it last night, and my glands are swollen for the first time in weeks.

    I can't be sure that this is the reason, but it will be interesting to see if the gland problem disappears/decreases again, assuming that I remember to take my 5-HTP!

    Some sources say that melatonin also boosts cortisol, but it may be only in some people and not others. I have posted details of this on another thread (no time to search but you may be able to find it through a search for 'melatonin' and my username).
  19. adreno

    adreno 3% neanderthal

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    According to studies I have seen, lower doses of melatonin (0.5mg) raises cortisol, whereas higher dose (5mg) lowers it.
  20. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    OK, you've made me search now, when I should be doing other things. :D

    http://examine.com/supplements/Melatonin/

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