1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
New Exercise Study Brings Both Illumination and Questions
Simon McGrath looks at new objective evidence of abnormal response to exercise in ME/CFS patients, and the questions that researchers are still trying to answer ...
Discuss the article on the Forums.

D-Lactic Acidosis in CFS

Discussion in 'Latest ME/CFS Research' started by Glynis Steele, Oct 9, 2010.

  1. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    I also thought I'd post these which state it is possible for d-lactic to occur without an increase in the anion gap.

    Clinical presentation, the plasma anion gap

    There are two major ways acidosis is defined from routine
    laboratory data. First, organic acids may be added to the body so
    quickly that both the H and the anion are retained; this results
    in metabolic acidosis and an elevated value for the plasma anion
    gap [64—66] (upper right portion of Fig. 6). Second, metabolic
    acidosis may be present without a rise in the plasma anion gap. In
    this latter setting, either the D-lactate anion was retained in the
    lumen of the GI tract (with the H being absorbed or titrated by
    bicarbonate in the lumen of the GI tract), or it was excreted in the
    urine, but in either case, the cation lost with it was Na and/or K
    ion [671 (not a H or NH4 ion, lower right portion of Fig. 6).
    This latter type of metabolic acidosis is akin to the over-production
    of hippuric acid in glue sniffers [68]. Since D-lactate anions
    are reabsorbed by the kidney much less readily than is L-lactate
    [54, 69, 70], as time progresses, the anion gap may decline without
    resulting in a rise in the plasma bicarbonate concentration-that is,
    D-Iactate is excreted as its Na or K salt (Fig. 6). Hence there
    are a number of mechanisms that may contribute to the presentation
    whereby the rise in the plasma anion gap might not match
    the fall in the plasma bicarbonate concentration. Not only might
    this lead to a diagnostic problem, it has implications for therapy
    because, once the organic anions are excreted as their Na or
    salts, these anions are no longer available for metabolism to
    regenerate bicarbonate, and the patient might have developed a
    deficit of Na and/or K4.


    And from another article about the anion gap:

    "There are, however, conditions in which the unmeasured anion is not reabsorbed. As a result, the anion will be rapidly eliminated from the plasma, potentially normalizing the anion gap. One example is D-lactic acidosis. This rare disorder is seen with jejunoileal bypass or a short-bowel syndrome; it is due to the combination of bacterial overgrowth and increased glucose and starch delivery into the colon (due to lack of normal absorption in the small intestine). As a result, dietary carbohydrate is converted to D-lactate, rather than the physiologically occurring L-lactate. (See "D-lactic acidosis"). The proximal sodium-L-lactate cotransporter is stereospecific and does not bind D-lactate. Thus, this anion is quickly excreted in the urine"

    Glynis
  2. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    439
    Raleigh, NC
    Interesting...I definitely do better for a short time when I fast - I feel lighter, I think more clearly - after a while though I tend to fall apart - but there is a definite improvement short term

    My symptoms with hot burning muscles after exercise or sometimes other forms of stress have always made me think of lactate and lactic acid
  3. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    The annoying thing is, only GI's are trained to recognise dla, and then only in short bowel patients. If it can occur without an increase in the anion gap, and therefore not seen in a routine blood test, what are the chances of it being picked up, without a specific test? And path labs do not normally have the test in, it has to be bought in. I think it can be tested for in urine, but again, who would bother to check, if they are not trained to recognise the symptoms?

    If a CFS patient were tested for dla, they would not allowed out of hospital until the dla levels were zero. At least after that, if there was a recurrance of dla, they would be seen immediately, and a treatmen plan put in place. The question is, would their CFS symptoms also be helped? Judging by their strikingly similar symptoms, you would have to think so.

    Best Wishes

    Glynis
  4. talumbaugh

    talumbaugh

    Messages:
    4
    Likes:
    0
    Oregon
    Through email with the Belgium reasearcher in the study, Dr. DeMeirlier, "We have to 95% complete remission of symptoms after 6 months of treatment with pulsed antibiotherapy." He also stated "I am sorry to say, but the US missed this." I hope this post will get NIH testing for this subgroup.
  5. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    D-Lactic acidosis, Lactobacilli Overgrowth and b12 Deficiency

    This paper talks about d-lactic acidosis, lactobacilli overgrowth and subsequent b12 deficiency, as a result of the bacterial overgrowth.

    Abnormal Fecal Lactobacillus Flora and Vitamin B12 Deficiency in a Patient With Short Bowel Syndrome
    Hojo, Kenichi*; Bando, Yuki†; Itoh, Yoko†; Taketomo, Naoki*; Ishii, Masahiro†

    Free AccessArticle Outline
    Author Information*Food Science Institute, Meiji Dairies Corporation, Odawara, Japan

    †Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

    Received October 10, 2006; accepted May 23, 2007.

    Address correspondence and reprint requests to Kenichi Hojo, Food Science Institute, Meiji Dairies Corp, 540 Naruda, Odawara, Kanagawa 250-0862, Japan (e-mail: kenichi_houjou@meiji-milk.com).

    The authors report no conflicts of interest.
    Lactobacillus overgrowth has been reported in patients with short bowel syndrome (SBS) (1-4). We previously reported D-lactic acidosis that Lactobacillus overgrowth caused in a male SBS patient (5). He had severe anemia related to vitamin B12 deficiency 9 years later. It has been generally accepted that B12 deficiency in SBS patients results from the inadequate absorption of B12 and/or the bacteria-host competition for uptake of B12 (6). In the present study, we suspected the recurrence of Lactobacillus overgrowth as a possible cause, because some lactobacilli require B12 for growth. Therefore, we analyzed the fecal flora and the B12 auxotrophy of Lactobacillus isolates.
    Back to Top | Article Outline
    CASE REPORT
    A 14-year-old boy presented in June 2005 with severe anemia and complaints of general fatigue. His medical history included an extensive small-bowel resection to treat obstructive ileus in September 1995. Subsequent malabsorption was treated with intravenous hyperalimentation and elemental diet for 2 months. The first attack of D-lactic acidosis was observed in this patient in early 1996. Similar attacks were observed 6 times in 5 months. Bacterial analyses revealed an increase of D-lactate producers, namely Lactobacillus delbrueckii subsp. lactis. We concluded that this increase was responsible for the D-lactic acidosis attack (5). Before the June 2005 presentation, he had been free from D-lactic acidosis for 9 years.
    The laboratory findings on admission suggested megaloblastic anemia with pancytopemia. The serum B12 level was <50 pg/mL (reference range 180-914 pg/mL), unsaturated B12-binding capacity 2351 pg/mL (650-1340 pg/mL), serum folate 6.5 ng/mL (>3.1 ng/mL), serum iron 83 μg/dL (48-154 μg/dL), hemoglobin 4.2 g/dL (14-18 g/dL), and red blood cells 149 104 cells/mm3 (410 104-530 104 cells/mm3). The levels of other vitamins such as B1, B6, A, and E were normal. Bone marrow aspirates showed megaloblastic erythropoiesis; therefore, megaloblastic anemia due to B12 deficiency was diagnosed. He was treated with physiological doses (1000 μg/day) of B12 (Methycobal, Eisai, Tokyo, Japan) by intramuscular injection. Given 5 days of treatment, serum B12 level recovered within 2 weeks and the other hematological parameters normalized within 1 month. Subsequently, he was treated with B12 by mouth for 6 months without any other complication.
    Back to Top | Article Outline
    MICROBIOLOGICAL STUDIES
    Fecal samples were obtained in September 2001 at a periodical medical checkup (during normal conditions) and in July 2005, when the patient was hospitalized (during B12 deficiency). Bacteriological analyses were carried out using methods described in a previous study (5,7). As shown in Table 1, the number of lactobacilli and the percentage of lactobacilli in the total bacteria count during B12 deficiency (9.45 log10 CFU/g and 45.2%) were higher than during the normal conditions (9.16 log10 CFU/g and 8.6%). During B12 deficiency, the number of bacteroidaceae, eubacteria, clostridia, and anaerobic cocci was <107/g in the fecal sample (Table 1).
    Table 1
    Image ToolsWe obtained 35 Lactobacillus isolates from the feces sampled during normal conditions, and 45 isolates from the B12-deficient sample. Lactobacillus isolates were identified by 16S rDNA sequence similarity (>98%) and a species-specific polymerase chain reaction method described by Torriani et al (8). The 16S rDNA sequence analysis could not discriminate clearly between L pentosus and L plantarum, or between L gasseri and L johnsonii. Table 2 shows that L fermentum was the predominant species, followed by L pentosus/plantarum and L gasseri/johnsonii, during the normal conditions. During B12 deficiency, L gasseri/johnsonii was predominant, followed by L mucosae and L delbrueckii subsp. lactis. We explored whether L delbrueckii subsp. lactis isolates in this study were the same strains that caused D-lactic acidosis in our previous study (5). Randomly amplified polymorphic DNA analysis (9) revealed that the isolates obtained in the present study were different from the previous isolates.
    Table 2
    Image ToolsTo determine the B12 auxotrophy of Lactobacillus isolates, each isolate was anaerobically inoculated in a chemically defined medium (10) with or without B12 (40 μg/L) for 24 hours at 37C. As shown in Table 2, all of the isolates of L gasseri/johnsonii and L delbrueckii subsp. lactis required B12. During the normal conditions, the ratio of these B12 auxotrophs to the total bacteria was only 1% in the feces (Table 2). Surprisingly, the population of B12 auxotrophs was one fourth (25.8%) of the total fecal flora during B12 deficiency.
    Short-chain fatty acids in feces, urine, and serum samples were identified using a high-pressure liquid chromatography system (Shimadzu, Kyoto, Japan) (11). D- and L-lactate concentrations in the samples were identified by an enzymatic method (Boehringer, Mannheim, Germany). The serum lactate levels during B12 deficiency (D-lactate, 0.93 mmol/L; L-lactate, 2.82 mmol/L) were excessively higher than those during the normal condition (D-lactate, 0.04 mmol/L; L-lactate, 1.51 mmol/L) (Table 3). Moreover, the fecal D- and L-lactate levels during B12 deficiency were 23.82 mmol/kg and 37.13 mmol/kg, respectively; these levels were higher than those during the normal conditions (1.13 and 2.18 mmol/kg, respectively). The pH of fecal samples during the normal conditions and B12 deficiency was 5.6 and 4.5, respectively.
    Table 3
    Image ToolsBack to Top | Article Outline
    DISCUSSION
    Valman and Roberts (12) measured B12 absorption in SBS patients who underwent ileal resections in childhood. They found normal B12 absorption in infants in whom the residual terminal ileum was ≥15 cm in length. In our patient, the residual terminal ileum with an intact ileocecal valve was about 52 cm in length when he was operated on for intestinal volvulus. In light of the previous article (12), the length and segment of the residual terminal ileum are sufficient for normal B12 absorption. In the present study, therefore, we examined whether intestinal bacteria were associated with B12 deficiency in our patient. Bacteriological analyses in feces revealed that the ratio of fecal lactobacilli to total bacteria during B12 deficiency (45.2%) was higher than that during normal conditions (8.6%) (Table 1). The number of bacteroidaceae, eubacteria, and clostridia, which are usually predominant in human feces (7), was <107/g. This may be related to the lactobacilli overgrowth because the overproduced lactate would suppress the other bacteria. In fact, the fecal pH during B12 deficiency was extremely low, and total lactate concentration in the feces during B12 deficiency was extremely high. From these results, we presume that Lactobacillus overgrowth recurred in this patient.
    In humans, the relation between the microorganisms that constitute the intestinal microflora and B12 metabolism has been discussed. From this viewpoint, the ratio of B12 producer/consumer may be crucial for B12 uptake. In this report, L gasseri/johnsonii and L delbrueckii subsp. lactis required B12. Surprisingly, the ratio of these B12 auxotrophs during B12 deficiency (25.8%) was much higher than that during normal conditions (1.0%) (Table 2). It is known that patients with SBS have a predisposition to B12 malabsorption because of ileal resection and bacterial overgrowth (6). In the present study, we cannot rule out possible causes other than bacterial competition for uptake of B12, especially the inadequate absorption of B12, because we did not carry out a Schilling test for the determination of B12 absorption ability. Moreover, because our patient went through pubertal growth at about 11 years of age, it is not evident whether B12 deficiency was under the influence of pubertal growth. However, the possibility that lactobacilli may compete with the host for the uptake of B12 was implied by the finding that predominant Lactobacillus species required B12. The B12 auxotrophic lactobacilli apparently competed for uptake of B12 with our patient. To our knowledge, this is the first case indicating that B12 deficiency may be attributable to the overgrowth of the Lactobacillus strains.
    Here, we would like to address a question: Why did our patient evade D-lactic acidosis despite the recurrence of Lactobacillus overgrowth? The serum D-lactate level during B12 deficiency (0.93 mmol/L) was higher than that during normal conditions (0.04 mmol/L) (Table 3); however, it was lower than that observed at 1 day after the attack of D-lactic acidosis in our previous study (2.32 mmol/L) (5). Before and during the episode of anemia, our patient had no typical D-lactic acidosis symptoms such as confusion, speech disturbance, and unusual behavior. We can suggest at least 2 possible explanations. One is dietary management, including carbohydrates, with related changes in the bacterial cell counts of D-lactate producers. Mayne et al (13) suggested that manipulation of carbohydrate intake may be used to treat severe, recurrent D-lactic acidosis in a patient with SBS. We had instructed our patient to avoid large amounts of simple carbohydrates after the onset of D-lactic acidosis (5). Therefore, restricted sugar administration probably contributed to the prevention of D-lactic acidosis. The second possible explanation is the difference in the bacterial cell counts of D-lactate producers. The number of lactobacilli that produced D-lactate was 9.0 log10 CFU/g in our previous study (5), whereas the number of D-lactate producers, namely, the isolates of L delbrueckii subsp. lactis, was 8.3 log10 CFU/g in the present study (Table 2).
    In conclusion, it is evident that lactobacilli overgrowth recurred in our patient. Moreover, B12 auxotrophic Lactobacillus species increased during B12 deficiency. We believe that the overgrowth of these B12 auxotrophs may be implicated in B12 deficiency, although other causes were not excluded, such as the inadequate absorption of B12. From the results presented in this study, our patient seems to be predisposed to lactobacilli overgrowth; therefore, the lifelong control of intestinal flora would be required for the patient with SBS. Restricted intake of simple carbohydrates seems promising to improve and/or prevent abnormal intestinal Lactobacillus flora. In addition, routine hematological analyses, including minerals and vitamins, are needed for the detection of nutritional deficiencies before clinical symptoms occur.

    Glynis
  6. talumbaugh

    talumbaugh

    Messages:
    4
    Likes:
    0
    Oregon
    Dear Glynis,

    Are you had any improvement getting tested in dla? I am from the US so, from 1992 to date, no one beleives dla without short bowel. The paper from Austrailia was the first acknowledgement that what I was presenting was at least possible.

    I feel so bad for your daughter. As is apparent in your blogs, you realize how much she suffers. If you would like to here some tricks that will help her cope, I would be glad to provide some based on my 20 years experiernce.

    Terry
  7. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    746
    Hi, Glynis.

    I appreciate your posting the paper about B12 utilization by Lactobacillus species that overgrew in this case of short bowel syndrome.

    I think there are beginning to be some clues as to how Dr. de Meirleir's gut-based pathogenesis thinking for ME/CFS might mesh with the Glutathione Depletion--Methylation Cycle Block hypothesis that I have proposed.

    On another thread, we have been discussing how gluten and caffeine sensitivity can result in poor absorption of cysteine by the gut, so that bacteria that are able to ferment cysteine to form hydrogen sulfide may multiply. This process would have the dual effect of making it more difficult for the host to produce glutathione (since cysteine is usually the rate-limiting amino acid for doing that), and producing hydrogen sulfide, which in large enough amounts can overwhelm the guts sulfide oxidase capacity and enter the blood stream, to produce toxic effects on the cells.

    Now, in this paper, we see evidence that overgrowth of certain B12-consuming bacteria may result in B12 deficiency in the host.

    Both glutathione depletion and B12 deficiency would act in the direction of producing CFS onset, according to the GD-MCB hypothesis.

    In addition, lack of certain bacteria would lower the bacterial production of folate in the gut as well, which would also impact the GD-MCB mechanism.

    On top of all that is the D-lactate that you have been emphasizing, also produced by dysbiotic bacteria, and also having deleterious effects on the host.

    The more I learn about these things, the more I believe that Dr. de Meirleir has been on the right track for a long time. There may be, and probably are, routes into CFS that do not involve the gut initially, but it looks as though there are also many cases in which gut problems start things off. And whether the problems start in the gut or not, there is usually eventually gut involvement in CFS.

    Thanks very much.

    Rich
  8. talumbaugh

    talumbaugh

    Messages:
    4
    Likes:
    0
    Oregon
    Rich,

    Do you have a link for the GD-MCB paper?

    Terry
  9. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    746
    Hi, Terry.

    Yes. All but my most recent things are here: http://www.aboutmecfs.org/Trt/TrtGSHIntro.aspx

    Cort is planning to update this site with my newer things soon, but the GD-MCB hypothesis is there, in the poster paper dated 2007. There are also some others after that that may be helpful in explaining it.

    Best regards,

    Rich
  10. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    Hi Terry,

    Thank you for your post. My daughter also has severe hypoglycaemia issue, which is why I cannot implement a low carb diet for her. She was once poorly and did not eat for 2 days. She then fell into a hypo coma and was bluelighted to hospital. On testing her blood sugar was 0.9 (UK measurement), the look of shock on the doc's face was one I will never forget. However if you have any info which might benefit, I'd love to hear it, thanks. My daughter was allowed to trial abx by the GI, and this was made a permanent regime, after the school wrote letters of support when the staff noticed a sudden improvement in her behaviours, which stopped when the abx were discontinued. She takes metronidazole, 2 weeks on, 2 weeks off.

    There is to be a follow up of KDM's d-lactic/CFS paper, which is due to start soon, blood, stool and urine of CFS patients will be analysed, and compared to healthy controls, to see whether the levels are higher in CFS. I can't wait for this study to be completed. Would love to be able to show the GI that d-lactate can occur in patients with a complete bowel, lol. I know of about 3 people, 2 from this forum who have tested high for d-lactate in their urine, however they are not under the care of a GI, so I presume their doctor's are unaware of the implications of high d-lactate, or that these patients should be referred on.

    Best Wishes

    Glynis x
  11. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    Hi Rich,

    Thanks for your reply. Not sure if you are aware, but there is a study just starting in Australia, by Prof Paul Gooley who collaborated on the KDM/Sheedy CFSF/d-lactic paper, taking this research further. Testing on blood, urine and stools of CFS patients, to see whether d-lactate is higher than in healthy controls. D-lactate should barely be detectable so this will give a valuable insight into CFS, seeing as symptoms of d-lactate are said to be strikingly similar to CFS.

    Best Wishes

    Glynis x
  12. talumbaugh

    talumbaugh

    Messages:
    4
    Likes:
    0
    Oregon
    Glynis,

    Happy for the news KDM is starting a follow-up. He mentioned a year ago that he was going to publish the success of their treatment this last fall, but never did.

    I also tested urine for dla and presented to various doctors, including my experience of a one-week elimination of symptoms after treatment of the antibiotic Floxin, only with the end statement being "Why are you so acid?" The US armed services are also doing a study for Gulf War Syndrome (GWS) with CFS. The study purpose states "the investigators propose to investigate the hypothesis that gut bateria may be responsible for symptoms associated with GWS." They just don't sound like they think it is possible. They are testing with the Lactulose Breath Test, which I do not think will reveal adequate results. KDM stated "Feceal microbial analysis, to identify the right H2S producing bacteria, is key to changing the situation."

    You can test urine with pH paper after every urination to determine dla. If your daughter has dla, you will begin to notice that each test gets more and more acid until, what I beleive to be recurring metabolic acidosis, ammonia is dumped into the bladder and the pH at the next urination will be very alkaline. The ammonia protects the urethra much the same way as mucus protects the colon. This can occur several times a day and is very fatiguing. You will know that it is dla and I hope that is enough, because this will not help convince your GI.

    The most notible treatment for me was Provigil. It does not work for CFS patients very often, but I feel the ones that benefit from the durg probably have dla. And I am sure that some gave up before discovering how to make it work. First, early Monday morning, take as little as 50mg and wait for the drug-induced BM that reduces the bacterial overgrowth. Then take one tablet and adjust dose over time. The key is the 80 hour cycle, because proper diet (for me means no Milk) will result in 80 hours inprovement of symptoms, of up to 5 points on the pain scale. There will generally be no BM for the four days, and reducing your sleep drugs by 50% will help your success. You will also want to keep this feeling as long as possible and sleep less, and this also seems to help the effectiveness of the Provigil if you are sleepy, since it is for narcalepsy. After the 80 hours is up the Provigil becomes less effective. I discontinue the Provigil and try to sleep as much as possible the next 3 days to get ready for the next 80 hour cycle.

    I have varied the above plan several times with some good results, but 80 hours is all I can get and have scheduled my weekly activities accordingly. I was able to work the weekend shift at a Motel for five years. Even though this is about a quarter-life, it is much better than zero.

    I also have some minor treatments, and will finish this blog when I get a chance. Hope this helps.

    Terry
  13. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    746
    Hi, Glynis.

    Thanks for this news. Sounds good!

    Best wishes,

    Rich
  14. Francelle

    Francelle Senior Member

    Messages:
    444
    Likes:
    15
    Victoria, Australia
    I have just been recruited to this study mentioned by Glynis. Yesterday the first of my samples were sent in.

    I think I read somewhere that it is hoped that the preliminary results of the study will be out by about September 2011, but another year or so 'til the full findings are published.

    This is a link for a study which sounds very like the one I am in "Biomarkers in Chronic Fatigue Syndrome" except there are some anomalies such as the number of subjects in the study and there is no mention of the Melbourne recruitment of subjects. Perhaps the study has been expanded upon and this was an earlier application. http://sacfs.asn.au/download/Lactic acid study 2008 - Ethics Application.pdf
  15. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    Thanks for letting us know this, Francelle. When you have had the d-lactic blood test, and have been given the results, would you be able to let us know what they are? Try and have the test as late in the day as possible, as d-lactate has a circidian (day and night) rhythm, and builds up after each carb rich meal. It reaches a peak in early evening, and lowers through the night, as long as a person is not eating carbs through the night, lol.

    If you do test for high d-lactate, your GP should refer you to a GI, as they are the specialist's dealing with this condition.

    HTH and thanks again for the info.

    Glynis x
  16. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
  17. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    Here is a study in a rat model about lactic acid causing anxiety and aggression, and some other studies regarding carb malabsorption and depression

    Anxiety and Aggression Associated with the Fermentation of Carbohydrates in the Hindgut of Rat

    Authors: Hanstock TL, Clayton EH, Li KM, Mallet PE.

    Institution: School of Psychology, University of New England, Armidale, NSW 2351, Australia.

    Summary:Lactic acid accumulation in the caecum and colon resulting from the fermentation of carbohydrates can lead to deleterious effects in ruminant and monogastric animals, including humans.
    In the present study, we examined the behavioural effects of two types of commonly consumed foods: soluble and fermentable carbohydrates (FCs). Thirty-six male Wistar rats were fed either a commercial rat and mouse chow, a soluble carbohydrate (SC)-based diet or an FC-based diet. Social interaction, anxiety, aggression and locomotor activity were examined by employing a social interaction test and a light/dark emergence test, while physical parameters of hindgut fermentation were examined after sacrifice, either 3 or 21 h after feeding.

    Results showed that anxiety (spending less time in the light compartment during the light/dark emergence test) and aggression (increased fighting during the social interaction test) were increased following raised concentrations of fermentation end products, such as lactic acid and volatile fatty acids (VFAs) in the caecum of rats.

    These associations occurred regardless of dopamine and 5-HT concentrations in the prefrontal cortex (PFC) and provide evidence supporting a general effect of FCs on behaviour. Possible mechanisms of action along with similarities between a rat and human model of acidosis are discussed.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...dopt=Abstract&list_uids=15276799&query_hl=143

    Anxiety Following Increased Hind-Gut Fermentation
    Authors: Hanstock TL, Claytons EH, Mallet PE.

    Institution: School of Psychology, University of New England, Armidale NSW 2351.

    Background: Previous investigations into the effects of carbohydrate on behaviour have focussed on behavioural changes 2-4 hrs after consumption of the diet and have not considered the effect of site of digestion. Fermentation and lactic acid production in the caecum and colon can lead to detrimental effects in several animal models, including adverse behaviour in horses.
    Objective: To determine changes in anxiety promoted by the consumption of fermentable carbohydrate and increased fermentation in the hind-gut of rats. Design - Randomised control trial with 3 iso-energetic dietary treatment groups, a soluble carbohydrate diet containing wheat (n=12), a fermentable carbohydrate diet based on cooked and cooled rice (n=12) and a basal control rat and mouse Chow diet (n= 12). Behaviour was assessed 3 and 21 hrs after dietary consumption by the light dark emergence test.

    Outcomes: The 3 diets promoted different fermentation patterns in terms of pH and lactic acid concentrations in the caecum of rats 3 or 21 hrs after consumption. The length of time spent in the dark compartment of the light dark emergence test, indicating increased anxiety, was associated with increased concentrations of D- and L-lactic acid in the caecum (r(2)= 0.97 and 0.96 respectively; P <0.01) irrespective of dietary group.

    Conclusions: Fermentation of carbohydrate leading to increased concentrations of lactic acid in the caecum of rats was associated with increased anxiety in rats. This has important implications in terms of those diets promoting increased fermentation (eg. with a high intake of resistant starch) without considering any possible detrimental effects.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...dopt=Abstract&list_uids=15023601&query_hl=141

    Malabsorption of Carbohydrates and Depression in Children and Adolescents
    Authors: Varea V, de Carpi JM, Puig C, Alda JA, Camacho E, Ormazabal A, Artuch R, Gomez L.

    Institution: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Deu, Barcelona, Spain. varea@hsjdbcn.org

    Background: Previous studies have shown an association between sugar malabsorption and depressive symptoms in adult women. Incompletely absorbed sugars may form nonabsorbable complexes with tryptophan, an amino acid precursor of serotonin, decreasing its availability. As serotonin is the most important neurotransmitter involved in depressive disorders, its depletion could lead to the onset of depression.
    Results: In the group with sugar malabsorption, there was a 28.5% prevalence of depressive symptoms that was higher than expected in our population. In the group with depression, the authors found a higher than expected prevalence of sugar intolerance (71.42% versus 15% in controls).

    Conclusions: The unexpected prevalences obtained for the groups studied suggest that there may be an association between sugar intolerance and depressive symptoms during adolescence.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...&dopt=Abstract&list_uids=15861016&query_hl=72

    Carbohydrate Malabsorption Syndromes and Early Signs of Mental Depression in Females

    Authors: Ledochowski M, Widner B, Sperner-Unterweger B, Propst T, Vogel W, Fuchs D.

    Institution: Department of Clinical Nutrition, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.

    Summary: Fructose and lactose malabsorption are characterized by impaired duodenal fructose transport or by the deficiency of mucosal lactase, respectively. As a consequence, the nonabsorbed saccharides reach the colon, where they are broken down by bacteria to short fatty acids, CO2, and H2.
    Bloating, cramps, osmotic diarrhea, and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of carbohydrate malabsorbers. We have previously shown that fructose as well as lactose malabsorption were associated with signs of mental depression. It was therefore of interest to investigate possible interactions between fructose and lactose malabsorption and their influence on the development of signs of depression. In all, 111 otherwise healthy volunteers (81 females and 30 males) with gastrointestinal complaints were analyzed by measuring breath H2 concentrations after an oral dose of 50 g lactose and of 50 g fructose one week apart…

    Further analysis of the data show that this association was strong in females (P < 0.01), but there was no such association between carbohydrate malabsorption and early signs of depression in males. In conclusion, the data confirm that fructose malabsorption may play a role in the development of mental depression in females and additional lactose malabsorption seems to further increase the risk for development of mental depression.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...&dopt=Abstract&list_uids=10961700&query_hl=61

    Fructose Malabsorption is Associated with Early Signs of Mental Depression
    Authors: Ledochowski M, Sperner-Unterweger B, Widner B, Fuchs D.

    Institution: Universitatsklinik Innsbruck, Arztliche Direktion, Anichstrasse 35, A-6020 Innsbruck, Austria.

    Summary: Fructose malabsorption is characterized by the inability to absorb fructose efficiently. As a consequence fructose reaches the colon were it is broken down by bacteria to short fatty acids, CO2 and H2.
    Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequence and can be seen in about 50% of fructose malabsorbers. Having made the observation that persons with fructose malabsorption very often seem to present not only with signs of irritable bowel syndrome but also with signs of pre-menstrual syndrome and mental depression, it was of interest to establish whether such an association could be demonstrated in patients.

    Fifty-five adults with gastrointestinal complaints of unknown origin (12 males, 43 females) were analyzed by measuring breath hydrogen concentrations after an oral dose of 50 g fructose and were classified as normals or fructose malabsorbers according to their breath H2 concentrations.

    All patients filled out a Beck s depression inventory - questionnaire. Fructose malabsorption was detected in 36 of 55 individuals (65.5%). Subjects with fructose malabsorption (DeltaH2 concentrations >10 p.p.m. after fructose load) showed a significantly higher score in the Beck s depression inventory than normal fructose absorbers. This was true especially for females. Fructose malabsorption may play a role in the development of depressed mood.

    Fructose malabsorption should be considered in patients with symptoms of major depression or pre-menstrual syndrome. Further studies are needed to clarify the background of this association.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...d&dopt=Abstract&list_uids=9620891&query_hl=61

    Fructose- and Sorbitol-Reduced Diet Improves Mood and Gastrointestinal Disturbances in Fructose Malabsorbers
    Authors: Ledochowski M, Widner B, Bair H, Probst T, Fuchs D.

    Institution: Dept. of Clinical Nutrition, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.

    Background: Fructose malabsorption is characterized by the inability to absorb fructose efficiently. As a consequence fructose reaches the colon where it is broken down by bacteria to short fatty acids, CO2 and H2. Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequences and can be seen in about 50% of fructose malabsorbers. We have previously shown that fructose malabsorption is associated with early signs of mental depression and low serum tryptophan concentrations.
    Results: Depression scores were reduced by 65.2% after 4 weeks of diet (P < 0.0001), and there was a significant reduction of meteorism (P < 0.0001) and stool frequency (P < 0.01). Improvement of signs of depression and of meteorism was more pronounced in females than in males.

    Conclusion: Fructose- and sorbitol-reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression.


    Study link: http://www.ncbi.nlm.nih.gov/entrez/...ubmed&dopt=Abstract&list_uids=11099057&query_

    Glynis
  18. Glynis Steele

    Glynis Steele Senior Member

    Messages:
    400
    Likes:
    84
    Newcastle upon Tyne UK
    I found this link, which talks about cardiac irregularities, when d-lactate is high, in rat models, and thought I would add it to this thread.

    Glynis

    http://www.biomedsearch.com/nih/Neurocardiac-toxicity-racemic-DL-lactate/7696135.html

    Racemic D,L-lactate has long been used in burn therapy as Ringer's lactate and in peritoneal dialysis fluid for treatment of renal failure. The D-lactate component of this racemic mixture is known to cause two forms of neurological toxicity in patients: encephalopathy and, in a subset of the population, panic reaction. Here we demonstrate that coma, similar in degree to that produced by blood levels of 75 mM ethanol was induced in rats by the intraperitoneal infusion of sodium D-lactate sufficient to raise serum D-lactate concentration to 25 mM, whereas infusion of equal quantities of sodium L-lactate produced no observable neurological effect. We further demonstrate that the intravenous infusion of racemic D,L-lactic acid into 48-hour fasted rats produced serious disturbances of cardiac rate and rhythm leading to death. When serum D-lactate concentration had reached 1-2 mM there was bradycardia, at 2-3 mM prolongation of QT interval, at 6-7 mM AV block with ectopic escape rhythms, and at 11 mM death in ventricular standstill or fibrillation. In contrast, intravenous infusion of L-lactic acid to blood levels of 25 mM failed to produce any change in cardiac rhythm. On the other hand, the isolated working heart, free of influence from the central nervous system, displayed no change of cardiac rhythm or physiological function when perfused with 25 mM sodium D,L-lactate.
  19. MeSci

    MeSci ME/CFS since 1995; activity level 6

    Messages:
    3,496
    Likes:
    4,095
    Cornwall, UK
    Hi, Folks. This is my first post here. I have been very impressed by the knowledge and level of discussion here so decided to join!

    Due to the M.E. I can't do a comprehensive search of posts, etc., as I am sure is the case for most or all of you, but I wondered what were people's views/experiences of grapefruit seed extract to improve the gut flora balance, rather than using pharmaceutical antibiotics? I know that GSE (aka Citricidal) is quite broad-spectrum, but I recall that my digestion seemed to improve when I used it before. It would of course be great if there were some proper research into this, but if this is not yet available, a few anecdotes would be welcome!

    I have become strongly convinced of the likelihood that d-lactic acidosis is behind a lot of our problems and am taking steps to modify my diet accordingly. I went gluten-free in January, and haven't noticed an improvement in symptoms but have lost 5 kg in weight, which I needed to do, and it was mostly around my middle, which must be a good thing. I'm now further reducing the proportion of my diet that comes from carbs, including by increasing protein and fat in meals that contain carbs, although I am a vegan and am not planning to reduce veg intake except for starchy root veg. I'm also planning to get some xylitol to replace sugar.
  20. nanonug

    nanonug Senior Member

    Messages:
    1,248
    Likes:
    384
    Virginia, USA
    I tried it in the past to address a very specific gut infection: it didn't do anything. Research on Pubmed strongly suggested that the GSE that works is tainted with real antibiotics.

    Have you done any kind of testing for you gut issues?

See more popular forum discussions.

Share This Page