Mitochondrial dysfunction and ME, Fibromyalgia and MCS

Discussion in 'Fibromyalgia and ME & Chronic Fatigue Syndrome' started by IanH, Jul 1, 2012.

  1. IanH

    IanH Active Member

    I posted this in another section but it was suggested I post it separately:

    The following study by Julian Ambrus et al is an interesting case study.
    http://www.jmedicalcasereports.com/content/6/1/55

    While the study treated fibromyalgia as mitochondrial myopathy, both ME and fibromyalgia have long since been thought of as having significant mitochondrial dysfunction, which can explain many of the varied symptoms. Eg. see also the work of Brad Chazotte,
    http://www.ncf-net.org/library/ChazotteCFSandMitochondria.pdf
    who found that the mitochondrial outer membrane is depolarized in people with ME, which means the permeability functions are impaired. Other work by Sarah Myhill and by David Bell have shown this dysfunction to be ubiquitous in ME.

    For those unfamiliar with the terminology , mitochondria are both the battery of cells as well as the organelle for toxin clearance from inside cells.

    What causes the dysfunction (myopathy) is not known. Of course there are several culprits which induce mitochondrial dysfunction. Viruses, which elevate IFNalpha and IFNgamma, various drugs and various Xenobiotic metabolites/toxins such as phthalates and the pesticide rotenone among many other pesticides and the endogenous toxins resulting mainly from oxidative metabolism (ROS or reactive oxygen species). In addition chronic vitamin D and magnesium deficiency cause mitochondrial dysfunction. (Hence the relationahip between vitamin D deficiency and MS, Autism and Schizophrenia) There is some evidence that continual psycho-social stress and sleep deprivation will also cause temporary mitochondrial dysfunction. The fMRI studies showing loss of brain shrinkage are better explained by a more general mitochondrial dysfunction.

    If the cause is a virus or external (xenobiotic) toxins then it will also be a ROS problem because once the mitochondria are dysfunctional the ROS cannot be cleared properly. In addition, once mitochondria are dysfunctional in highly dependent tissue such as neurons (which often require many mitochondria per cell) the required number of mitochondria are reduced.

    Ros are not helped by a glutathione deficiency, another deficiency shown almost universally in people with ME and Fibromyalgia. Glutathione is the main substance which clears ROS. Glutathione synthesis is highly impaired when mitochondria are dysfunctional:

    http://www.ncbi.nlm.nih.gov/pubmed/17936517

    There are some researchers who have demonstrated the glutathione dysfunction extensively, eg. Rich van Konynenberg (see his notes on Phoenix rising; http://forums.phoenixrising.me/index.php). I believe the glutathione depletion is due to mitochondrial dysfunction, at least it is an explanation for it.

    The consequence of mitochondrial dysfunction depends on the tissue/cells affected. Muscle cells will become shorter and fail to contract properly, lactic acid is not cleared properly and fatigue and pain build up. Cells of the spinal chord will no longer have their inhibitory function and pain is amplified without appropriate suppression. Cells of the immune system are mostly activated by signalling which is also faulty and pro-inflammatory cytokines are elevated and natural killer cells are not functional and fail to express their signalling receptors.

    In addition to all of this the vitamin D system is dysfunctional, possibly because the VDR (vitamin D receptor), a protein which allows vitamin D to communicate with genes is not being made in the required amounts. (The vitamin D system is already impaired in most people because of lack of sun exposure). When the vitamin D system is dysfunctional and the person has vitamin D deficiency. ie less than 35 ng/ml this contributes to muscle fatigue and pain. And as I stated above chronic vitamin D deficiency may be a cause of the mitochondrial dysfunction in the first place especially when combined with toxins and/or elevated viruses.

    The vitamin D system also controls/activates the "xenobiotic toxin removal system". When this is dysfunctional people have worse MCS (Multiple Chemical Sensitivity), the most perplexing set of symptoms of ME and those which invoke considerable medical skepticism - sadly!

    After discussing the case study with Julian Ambrus I tried a modified version of the treatment, which I have been on for six months. After three months my wife and daughter went onto the treatment. We are all responding very well. Dr. Ambrus is now following 400 patients in treatment.

    I have ME with fibromyalgia, my wife has ME with MCS and severe intermittent ataxia, my daughter has ME with severe MCS. We have all been diagnosed with ME by different specialists and our daughter is part of the research at Bond University in Queensland and this research has confirmed her dysfunction and immunological problems eg. low NKCbright cell function.

    I began the treatment in January 2012, a total of 6 months: I am functioning at about 85-90% of pre-morbidity, Working every day.
    The first thing I noted after about four weeks was the tremendous lift in energy. It took four months for most of the FM pain to subside and I am now walking about 3 Km daily. I believe the exercise is important but only after the treatment has reduced pain and fatigue. This treatment is a first step for those with severe fatigue.
    The following symptoms have also ceased for several months now:
    tremor, diarrhea, poor hearing, inability to find words, sleep improved from 3 hours to 6-7 hours and my morning stiffness has gone, I can type endlessly. Also my fingerprints are returning and the ridging of the fingernails is going.
    I still have some wrist pain and hot hands first thing in the morning although this is much less and possibly diminishing slowly.

    The treatment is unusually long and may have to go on for longer. I don't know yet. Becuase of my lifestyle I will be on the vitamin D for the rst of my life.

    My rationale for the improvement is that improved/normalised mitochondrial function increases cellular function to enable recovery of tissue, modulation of intra-cellular and immunological signalling in all affected systems, in addition the gut imbalances are reduced and the bacterial leakage through the digestive tract wall is reduced. Glutathione synthesis will be normalised.
    I am hoping/predicting that even if the cause is viral the re-establishement of proper homeostasis will bring the viral infection/activation under control. That it will also improve ROS/toxin clearance more permanently. That I will reach a state where normality of functions will continue.
    The basic treatment is as follows: a * indicates obligatory,

    *acetyl carnitine 500mg TD (For mitochondrial function)
    *CoQ10 200mg TD (For mitochondrial function)
    *B12, (methyl cobalamine or hydroxy cobalamine) 1mg TD (For mitochondrial function and glutathione increase)
    vitamin B6 30mg TD (For mitochondrial function and glutathione increase)
    *methyl folate or folinic acid 800mcg (or folic acid) TD (For mitochondrial function and glutathione increase)
    * magnesium citrate or magnesium malate 200mg TD (To support vitamin D and to reduce muscular cramps and pain)
    *vitamin D3 (cholecalciferol, not ergocalciferol and not calcitriol 120 mcg TD, also limit calcium to no more than 500 mg daily) After one month reduce vitamin D to 120 mcg once daily, smae with vitamin K
    *vitamin K2 (K4+_K7) 100mcg TD (To support vitamin D)
    vitamin P (PQQ) 10mg BD (For mitochondrial function, actually to increase mitochondrial biogenesis)
    niacinamide 50mg TD (For mitochondrial function)
    Optionally include NAC (N-acetyl-cysteine and curcumin 1mg TD and a multivite)

    TD = three times per day
    BD = twice daily
    note: If you take vitamin D you MUST take vitamin K2 and magnesium. This may seem to some a very high dose of vitamin D but recent evidence verifies it is safe. If you want to be sure then have your calcium levels tested during the treatment (1 month, then 6 months should suffice).

    It is a lot of supplements, so must be taken with meals.

    As soon as the wrist pain subsides completely I will go off the treatment to see if any symptoms return. So I have no idea how long I will need to be on this regime.
    Last edited: Jun 22, 2014
  2. IanH

    IanH Active Member

    I see this now posted on the PH news.
    This is a MUST READ study
    http://www.prohealth.com/library/showarticle.cfm?libid=17076
  3. simpsons

    simpsons Member

    this is the second study by this team of myhill booth and john maclaren howard

    we have discussed years ago the treatments for mitocondial function. in fact the last paper was included in the new international guidelines concensus.

    can you tell me the methods used by your chap please? is it the same method of testing as new study?

    if so this really is exciting to see

    they say that mitochondial is not a unique test for ME but also can be found in parkinsons autism and i think gws but i would need to read through again to see that.

    however they propose that one or two of the other tests they use can dx pwme.

    that would wipe me out for whole day so sorry will do if you can't see

    thanks too this is a very exciting area

    simpsons
  4. richvank

    richvank New Member

    Hi, IanH.

    This is a very nice protocol from my point of view, and I'm glad to hear that it is working for you:

    *acetyl carnitine 500mg TD (For mitochondrial function)
    *CoQ10 200mg TD (For mitochondrial function)
    *B12, (methyl cobalamine or hydroxy cobalamine) 1mg TD (For mitochondrial function and glutathione increase)
    vitamin B6 30mg TD (For mitochondrial function and glutathione increase)
    *folinic acid 800mcg (or folic acid) TD (For mitochondrial function and glutathione increase)
    * magnesium citrate or magnesium malate 200mg TD (To support vitamin D and to reduce muscular cramps and pain)
    *vitamin D3 (cholecalciferol, not ergocalciferol and not calcitriol 120 mcg TD, also limit calcium to no more than 500 mg daily) After one month reduce vitamin D to 120 mcg once daily, smae with vitamin K
    *vitamin K2 (K4+_K7) 100mcg TD (To support vitamin D)
    vitamin P (PQQ) 10mg BD (For mitochondrial function, actually to increase mitochondrial biogenesis)
    niacinamide 50mg TD (For mitochondrial function)
    Optionally include NAC (N-acetyl-cysteine and curcumin 1mg TD and a multivite)

    TD = three times per day
    BD = twice daily

    This protocol rolls together the essence of the methylation protocol I have suggested (high-dose B12 with a reduced folate (folinic acid), the Myhill mito support package (carnitine, Co Q10, magnesium and niacin), support for vitamin D, which has been found to be important for the immune system in particular, B6 to support the transsulfuration pathway, neurotransmitter synthesis and amino acids metabolism, the new PQQ for supporting formation of new mitochondria, NAC and curcumin to support glutathione synthesis, and a multi to take care of deficiencies.

    Is the B12 taken orally? If so, I think sublingual would be better.
    Folinic is O.K. for many people, but not all. Methylfolate might work better. I don't recommend folic acid.

    I note that you mentioned my work (thank you!), but I don't know if you are familiar with the GD-MCB hypothesis. This protocol meshes very well with it. There are a video and slides here (slides are available by clicking on the blue print below the video):

    http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/$%7Bweburl%7D

    I hope you will keep us posted on how things go for you and others on this protocol.

    Best regards,

    Rich Van Konynenburg
    [This Message was Edited on 07/02/2012]
    [This Message was Edited on 07/02/2012]
    [This Message was Edited on 07/02/2012]
  5. simpsons

    simpsons Member

    rich can you or ian explain how the different testing methods for measuring mitochondrial function compare please?

    i'm interested in how these studies could be replicated and become a test that we can use together with other tests to get to a dx.

    i may again try your part mixed in on top of myhill/booth/jmh protocol although i have tended to sometimes become v low on folic levels so i would need to start taking that again if it is again low

    Ian

    i've been following a basic myhill protocol for years now.
    i take tablets with b12 slow release and find them very good. it took me years to find good tablets as previoulsy the injections only worked for me.

    i would love to hear how you get on.

    thanks for the links

    simpsons

  6. FaithHopeCure

    FaithHopeCure New Member

    After doing a lot of my own research from several different sources, I took the best supplement and treatments that I felt was best for me. After 10 years of taking prescription pills and not getting any improvement I felt I wanted to cleanse myself of the toxins. I do believe that the above mentioned are the three reasons that cause ME/CFS and ME/FS (for me it was surgeries, chronic stress, and side effects from meds). After going off the meds and using supplements I have improved by 70%. The only vitamins that I do not take that are on the above list are: Acetyl Carnitine, Vita K2, Vita P and the Niacinamide. I will consider adding the above items for even more improvement. My energy is coming back and I am able to cook healthy meals with lots of vegetables and no gluetin. I am hoping the healthy eating will bring back more energy too.

    I have been taking nearly everything that is listed in the above protocal. I have a question about the Coq10. Do you think the Hydroxytyrosol Extreme is superior to the Ubiquinol Coq10?

  7. caledonia

    caledonia Member

    Vitamin D is typically measured in IU (international units). So do you mean IU, not mg or mcg?

    To clarify, if you say you're taking 500mg TD that means 500mg three times a day, i.e., 1500mg per day, not 500mg per day.
  8. MicheleK

    MicheleK Member

    This is very interesting research. I too take most of the supplements, but will have to add Vit K & P to my regimen. I have a severe energy issue. I am like a battery that will not hold a charge.

    I am on the methylation protocol but will be adding B-12 shots instead of sublingal B-12 to see if that will work better for me now that i am on the methylation protocol. Previously the B-12 shots were limited in their success, but Rich V. has said that those who have problems with the methylation process and who are now on the protocol might benefit more from tryng the shots again. I plan to do just that. Will report any progress.
  9. IanH

    IanH Active Member

    vitamin d is commonly measured in IU. However the correct way to measure for scientific research is in mcg (micrograms) within the body it converts to its active form, commonly called calcitriol which is measured in pcg (picograms).
    1000IU is equal to 50 mcg of vitamin D. The reason why IU is not used scientifically is because it is not standardised or easily used in chemical reactions. For example 1000IU vitamin D is 50 mcg but 1000IU of vitamn A and that is approx 0.3mg (300mcg) but if you took 300mcg vitamin D it would be too high. That is, IU can be confusing.
  10. IanH

    IanH Active Member

    I look forward to your progress reports.
  11. IanH

    IanH Active Member

    This was the testing done. Different from the Myhill study. Myhill more advanced research level testing.

    Significant laboratory results included creatine kinase (CK) = 325 U/L (normal range 0 to 150 U/L), normal comprehensive metabolic panel (CMP) and complete blood count (CBC), liver function tests and thyroid functions tests. A six-minute walk test revealed a normal resting lactic acid = 1.6 mmol/L, and an elevated post-six-minute-walk lactic acid = 5 mmol/L (normal result < 2 mmol/L). Her ammonia levels were normal at rest and after six-minute walk (14 ?mol/L and 38 ?mol/L respectively; normal 0 to 40 ?mol/L). A muscle biopsy was performed for biochemical evaluation, which revealed several abnormalities including decreased levels of citric acid synthase (49% of normal), cytochrome c oxidase (53% of normal), succinate dehydrogenase (72% of normal), and nicotinamide adenine dinucleotide (NADH) dehydrogenase (73% of normal), thereby demonstrating a defect in the mitochondrial respiratory chain. Genome sequencing was performed, which revealed multiple POLG1 polymorphisms (C-T polymorphism at 2254, and G-T polymorphism at 3708) and several mitochondrial genome polymorphisms (1438 A-G, 3992 C-T, 14365 C-T, 14582 A-G, and 4042 A-G).
  12. IanH

    IanH Active Member

    These were the enzymes deficient:

    decreased levels of citric acid synthase (49% of normal), cytochrome c oxidase (53% of normal), succinate dehydrogenase (72% of normal), and nicotinamide adenine dinucleotide (NADH) dehydrogenase (73% of normal).

    These deficiencies are complex and it would be difficult to know what is causing each one.

    For example NADH dehydrogenase could be 73% because of accumulation of AMP (adenosine monophosphate) which inhibits NADH dehydrogenase.

    Similarly succinate dehydrogenase could be affected by a build up of oxaloacetic acid.

    Citric acid synthase may not be getting into the mitochondria. It is sythesised by a nuclear gene and transferred into the mitochondrion. However it has been shown that the mitochondrial membrane is seriously dysfunctional in ME. (see Brad Chazotte's work)
  13. richvank

    richvank New Member

    Hi, simpsons.

    There are two general categories of mito problems. One is mito disease, and the other is mito dysfunction.

    Mito disease is a recognized category in conventional medicine, and there are physicians who specialize in it. It involves inherited genetic mutations in genes that code for proteins in the mitochondria. The kinds of tests that are run include activities of certain enzymes, and genomic tests, looking for mutations.

    Mito dysfunction is a disorder in which there are biochemical problems with the function of the mitos, but not genetic problems. This is what occurs in ME/CFS.

    It's possible that there is some overlap of these two categories, and in fact some of the treatments, such as coenzyme Q10, are the same. In principle, it should be possible to correct mito dysfunction, while at least some of the mito diseases, such as MELAS, are not really very treatable.

    The testing that Dr. Myhill and her coauthors have reported is used to quantify mito dysfunction. Dr. McLaren Howard, her coauthor, is the person who developed these tests, and I think he is still the only one who performs them. I think they do a good job of separating the various phases of operation of the mitochondria and quantifying how serious the dysfunction is in each one.

    They don't determine the root causes of the mito dysfunction, however. In my opinion, the root causes can be traced back to the vicious cycle mechanism that involves glutathione depletion and a partial block of methionine synthase.

    I also believe that in order to correct the mito dysfunction in ME/CFS, it is necessary to lift the partial block of methionine synthase, which allows glutathione to rise. That's why I like the protocol that Ian has posted. He is supporting the mitochondria with the supplements it uses, but he is also treating the methioinine synthase problem at the same time.

    Best regards,

    Rich
  14. simpsons

    simpsons Member

    thanks Rich for answering my question and more in such a clear way to understand. wish you would blog more.

    I'm very interested in the pos overlap of the two types of mito illness that you describe.

    i believe they speak of the other illness types that have mito probs that this test may pick up. autism and parkinsons i believe with mito problems. though they are not i don't believe the other type of mito illness you are speaking of? I think it is thought that parkinsons may be linked to chemical pollution too?

    I did have the tests done by dr howard some years ago now. He did a range of tests, and said he could see that the production of energy was blocked by both chemicals and viral infection. My UK dr refused to take anymore blood at that stage so i couldn't find out more.

    What he said to me was that chemicals I used in the house such as toilet cleaners air fresh sprays shampoo perfume etc had chemicals in that blocked the energy production of mitochondia.

    so thats something that can also be looked at in the picture of mito dysfunction and the process you speak of.

    How would that fit in with your further work into the glutathione depletion a partial block of methionine synthase? Can that be chemicals from household items ie cleaning fluids etc?

    I stopped eating wheat as advised by dr myhill, and that helped clear the tinnitus and muscle pain. Cleared out the chemicals and started on the basic myhill plan. Along with the stoneage diet, so i was getting the correct vits out of the food and no chemical addtives.

    It took time but i couldn't believe how fast the b12 shots worked, couldn't believe how good and helpful they were in combination with the magnesium and co q10 and other supps. though the process took time it really worked v well.

    Now as soon as i went back to anywhere with chemicals or took wheat into my system, back came the symptoms hard and fast.

    now i'm not saying i'm cured far from it. However I slowly improved to a point where i didn't want to die to get away from the pain, and energy improved considerably.

    Thank you Rich for making such a complex subject so clear to understand.

    Pro health used to do the drop in sessions in chat with leading Dr's I miss that. Wish you could do it again.

    I find pr so complex and hard to get around so its good to be able to talk to you here.

    warm regards
    simpsons





  15. MicheleK

    MicheleK Member

    Thanks for the extra information. It is so interesting. For myself I did not find eliminating wheat from my diet to make any difference in my symptoms. I don't have a lot of pain. I have mostly deep exhaustion and orthostatic issues. LDN has been really helping my orthostatic issues and I am down from 2 liters of saline fluids a week to 2 liters every 3 weeks. It is quite striking, the difference LDN has made for me in that area.

    If I could now get a 20% boost in energy minumum, I think I could have a regular social life. That would be nice!
  16. IanH

    IanH Active Member

    Hi Simpsons,
    Chemical hypersensitivity (MCS) is a symptom set of ME. Both my daughter and wife have significant MCS (both diagnosed with ME) My daughter is part of the research at Bond University in Australia and has very significant immunological dysfunction. Both have been on the above regime for nearly three months. Their reactions to chemical exposure (petrochems, pesticides and some household cleaners, particularly those with antibacterials like triclosan) are of shorter duration (down from 3 days disability to half to one day) but they still react. Each with different symptoms. My wife suffers mainly ataxia and tremor (Parkinsonism) incidentally my wife showed several brain "scars" after a scan suggestive of MS but she does not have MS. My daughter suffers mainly cognitive dullness and nausea (Same chemical trigger though!) She has not had a scan.

    I too have had the chemical sensitivity, mainly to perfumes and deodorants. That has gone on this treatment but it took the full six months to go. I still have a slight flushing reaction to them but no other symptoms (vertigo, nausea and pain)

    Martin Pall has a good expose of MCS. Also check out the work of Chiara deLuca

    eg. http://www.ncbi.nlm.nih.gov/pubmed/20430047
    and http://www.national-toxic-encephalopathy-foundation.org/needbio.pdf
  17. ljimbo42

    ljimbo42 Member

    That's great info! Thank you. Could you help me understand how your protocol helps to correct gut imbalances and bacterial leakage through the digestive tract wall.
    I am on a protocol for gut dysbiosis and leaky gut. I have made good progress but would like to add a mitochondria protocol. Any info you can give me would be greatly appreciated. Jim...
  18. simpsons

    simpsons Member

    good links thank you so much Ian very interesting. the whole gws ME FM overlap with MCS is very interesting.

    I appreciate the technical data, but my foggy brain needs time to learn and take it all in. However I'm very interested in this area, and very pleased to see the research being done. just brilliant :)

    What do the bond group say about mito testing re myhill paper? are they interested in replication of this study and comparing it to their own tests and patients?

    This would be key to disproving the whole cbt and get belief that we can positive think ourselves well, vs our cells are not reproducing the energy even in a test tube not connected to our brains.

    I've spoken to miss crawley face to face and she couldn't answer this question on how our cells in a test tube were not connected to our brains and couldn't reproduce energy.

    be it because of chemicals or viral infections this is going to be key to avoiding damaging cbt get beliefs being forced on patients.



  19. IanH

    IanH Active Member

    You know, I believe the biomarkers of "ME" are available but the cost of using them is prohibitive in a clinical setting. I doubt there will be a single cheap biomarker because the illness is heterogeneous and too complex to come up with a single test. It will never happen! The best we will do is a conglomerate of tests.
    All the available biomarkers are not exclusive to ME but when you combine an exclusion diagnosis with several of these biomarkers you can, with good reliability diagnose ME. The issue of "cause" is not dealt with. In theory you can have significant immunological, endocrinological and neurological dysfunction and still say the cause is psycho-social stress. There is plenty of evidence for psycho-social stress causing disturbances in the these systems. So what I am saying is, by having a biomarker, even an exclusive one, will not silence a Psychiatrist. It does however silence those who say the cause is faulty illness beliefs.

    I am a Psychologist also with a biochemistry background. I used to treat people with CFS/ME. At the time, I applied CBT and encouraged exercise, just as your Health Dept. do in Britain. When I got the illness I was shocked how sudden and intensely the symptoms came on. I changed my opinion quickly, however I do still believe that prolonged psycho-social stress can be a contributor but only one of many contributors.

    There will be different contributors for different people:
    psycho-social stress
    Chronically low vitamin D (or sun exposure)
    Accumulated Xenobiotic toxins
    Single nucleotide polymorphisms especially those which impair mitochondrial enzymes such as glucose-6-phosphate dehydrogenase or glutathione reductase, etc
    viral infection
    chronic gut dysbiosis, especially from mycobacterial infection

    Chronic pain from duodenal ulcer or neurological/spinal trauma

    Whether these trigger the ME symptom set will depend on the immunological and mitochondrial status. I believe that the mitochondrial status/health of people varies considerably depending on diet, xenobiotic toxins and fitness. If you could test everyone's mitochondria I am sure you would find great variation but "symptoms" (mainly energy symptoms) would vary but not necessarily be noticed by the individual unless they exerted or stressed themselves.

    When a significant drop in mitochondrial function occurs there is insufficient energy and high oxidative stress causing epigenetic abnormality with the re-activation of viruses and possibly bacteria, especially in the gut. Re- or trans- activated viruses will cause elevated cytokines such as INF-alpha which then causes a catastrophic drop in mitochondrial function further contributing to the illness.
    [This Message was Edited on 07/08/2012]
  20. IanH

    IanH Active Member

    I have treated our/and others "leaky gut" with the following:
    Bovine colostrum (1 heaped teaspoon before any food or drink in the morning)
    Melatonin 1 mg taken with the colostrum and again at night.
    Acidophilus probiotics taken also with the colostrum.
    Magnesium 400 mg daily
    vitamin D 5000 IU daily
    vitamin A 10000 IU weekly

    note melatonin is sometimes taken to aid sleep, however melatonin taken in the morning will not affect your sleep because it actually does not get to your brain. That melatonin is secreted by your pineal gland triggered by darkness.
    Melatonin is mostly found in the gut. It is the guts main healing hormone and secreted by the chromafin cells. Hopefully you can buy melatonin where you are. We cannot buy it in NZ.

    http://www.ncbi.nlm.nih.gov/pubmed/9921037
    http://www.ncbi.nlm.nih.gov/pubmed/17233075
    http://www.needs.com/product/NDNL-1106-01/a_Digestive_Health/?r=K06NDNL
    http://www.jpp.krakow.pl/journal/archive/08_08_s2/pdf/33_08_08_s2_article.pdf

    It is important to also reduce sugar in the diet.
    [This Message was Edited on 07/10/2012]