Thiamine Reverses Diabetic Kidney Damage In Humans

Discussion in 'Scientific Studies' started by haidut, Oct 14, 2014.

  1. haidut

    haidut Member

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    The study used what they consider a "high" dose of 300mg thiamine and duration was 3 months. In 35% of the patients the damage disappeared completely.

    http://www.sciencedaily.com/releases/20 ... 092149.htm
    http://www.drwhitaker.com/benefits-of-v ... ur-kidneys

    "...In a double-blind, placebo-controlled study, researchers gave patients with early-stage diabetic kidney disease 300 mg of vitamin B1 (thiamine) or a placebo daily for three months. Those taking thiamine experienced many benefits of vitamin B1, including a 41 percent decrease in urinary albumin excretion. Even more impressive, in one-third of those taking the vitamin, the condition disappeared completely!"
     
  2. DrG

    DrG New Member

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    Hello Haidut,

    I am new to this board, but would like to connect with you a bit about thiamine based on some of your other posts.

    Regarding the paper relating thiamine effects to those of DCA, I looked into the pharmacokinetics to check the comparison. That paper takes the concentrations of both substances up to the mmol level (in vitro) and sees the strong effects at levels above 1 mmol. In checking some other papers about DCA pharmacokinetics, I see that it is possible to bring blood levels that high. In fact, the breakdown is dependent on GSTZ and can vary significantly from person to person. This is reason for some caution in people self medicating with DCA.

    Looking at the thiamine dosing paper, it appears that highest level they reach is a few hundred nmol using a 1500 mg dose. This is a big disappointment, because at least on the surface, reaching the mmol level would be very difficult or impossible. The authors of the thiamine vs DCA paper do not seem to recognize this disconnect.

    Just want to check my thinking and see if you have any further thoughts about this. I was hopeful that thiamine might be a substitute for the trickier DCA. Perhaps some kind of combination (high-dose thiamine with more moderated doses of DCA) could be interesting.
     
  3. OP
    haidut

    haidut Member

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    Yes, I noticed the same thing - even very high oral doses of thiamine (as hydrochloride or mononitrate) barely get close to the mmol range. However, based on a quick check there are thousands of older studies with thiamine in humans and I don't know if some of the managed to reach higher concentrations. I think there is a human study with thiamine for Alzheimers and that used up to 8g of thiamine daily, and it was an oral protocol as far as I remember. So, in some other studies higher concentrations may have been achieved. Finally, there are fat-soluble versions like the naturally occurring allithiamine which I think accumulates and can probably reach higher concentrations. Allithiamine (and also sulbutiamine) also very easily crosses the blood-brain barrier and as such is probably better suited for treating neurological conditions. There is also benfotiamine but I seem to remember reading something bad about it. In addition, benfotiamine apparently does not reach the brain or accumulate in it as per this study:
    http://www.ncbi.nlm.nih.gov/pubmed/18549472

    So, allithiamine and sulbutiamine seem like the ways to go to load up on thiamine and maybe reach mmol concentrations.
    This study discusses their use and also states that the allithiamine derivatives are the way to go for therapeutic purposes.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1375232

    The study above refers to this study claiming that it shows the superiority of the allithiamine derivatives.
    http://www.ncbi.nlm.nih.gov/pmc/article ... lassic#b99

    Anyways, feel free to PM me and we can discuss further.
     
  4. gummybear

    gummybear Guest

    When did 300mg became a high dose? I take 1500mg on a regular basis.
     
  5. aguilaroja

    aguilaroja Member

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    The Rabbani study this thread refers to was submitted in 2008 and in print by 2009. It did not have the perspective by Constantini and others of promising results in other conditions with larger thiamine amounts. The early Rabbani studied referenced animal studies by Babaei-Jadidi and collaborators which used thiamine doses of 70 mg/kg per day in rat studies. It is not clear browsing the references how the 300 mg amount in human subjects was decided on.
     
  6. aguilaroja

    aguilaroja Member

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    Interesting question. As Constantini's various cases series have shown, there can be pretty dramatic human clinical improvements at an amount of 600 mg to 1500 mg per day.

    http://www.ncbi.nlm.nih.gov/pubmed/23379830
    J Altern Complement Med. 2013 Aug;19(8):704-8. doi: 10.1089/acm.2011.0840.
    Thiamine and fatigue in inflammatory bowel diseases: an open-label pilot study.
    Costantini A1, Pala MI.

    "Depending upon the body weight of each patient, dosage ranged from 600 mg/day (60 kg) to 1,500 mg/day (90 kg)... RESULTS: Ten patients out of twelve showed complete regression of fatigue, while the remaining two patients showed nearly complete regression of fatigue compared to the chronic fatigue syndrome scale scores before therapy."

    As mentioned in other posts, there have been very few comparison studies either in distribution or clinical effect between the various thiamine forms. As usual, it is difficult to know how the serum level of thiamine reflects what is acting in the cells. Anecdotally, I have no clear indications about the utility of one form over another. "Regular" thiamine has a much longer track record of safety-there is just very small data about the other forms by comparison.

    viewtopic.php?t=4687

    It is interesting how thiamine transport and absorption are impaired at different stages in different processes of decline including kidney disease and alcohol excess:

    Am J Physiol Renal Physiol. Jul 2010; 299(1): F26–F27.
    Published online May 19, 2010. PMCID: PMC2904165
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904165/
    Unraveling the pathophysiology of alcohol-induced thiamin deficiency
    Pawel R. Kiela

    "In an issue of the American Journal of Physiology-Renal Physiology, Subramanian et al. (9) provide a novel and informative report that chronic alcohol consumption in rats fed a Lieber-DeCarli diet results in decreased carrier-mediated thiamin transport across the renal brush-border and basolateral membranes and in transcriptionally-mediated inhibition of the THTR1 and THTR2 expression. Moreover, the expression of thiamin pyrophosphokinase (TPKase), the rate-limiting enzyme in the synthesis of the coenzyme form of thiamin was modestly, albeit significantly reduced. This observation is consistent with the previously reported 27% decrease in the enzymatic activity of TPKase in the kidneys and other organs of rats chronically fed ethanol (4). The authors did not observe changes in the expression of the mitochondrial thiamin pyrophosphate carrier Slc25a19. In an article published in parallel in the American Journal of Physiology-Gastrointestinal and Liver Physiology, the same group provides additional evidence for detrimental effects of chronic alcohol administration on intestinal thiamin absorption, also accompanied by decreased transcription and expression of the Slc19a2 and Slc19a3 genes (10). While the transcriptional mechanisms at the level of Slc19a2 and Slc19a3 gene promoters remains to be determined, these two reports provide a significant advance in our understanding of alcohol-induced thiamin deficiency. In this case, the “two-hit” model is related not only to a simultaneous reduction of expression and activity of the two key thiamin carriers but also to the two affected sites of thiamin absorption. In alcoholic subjects, changes in thiamin supply combined with impaired epithelial thiamin transport and increased metabolic demand are likely the major factors contributing to alcohol-related brain damage."

    Diabetologia. 2010 Jul;53(7):1506-16. doi: 10.1007/s00125-010-1722-z. Epub 2010 Apr 6.
    Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes.
    Karachalias N1, Babaei-Jadidi R, Rabbani N, Thornalley PJ.
    "Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine."

    Am J Physiol Renal Physiol. Jul 2010; 299(1): F26–F27. PMCID: PMC2904165
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904165/
    Unraveling the pathophysiology of alcohol-induced thiamin deficiency. Pawel R. Kiela

    "In an issue of the American Journal of Physiology-Renal Physiology, Subramanian et al. (9) provide a novel and informative report that chronic alcohol consumption in rats fed a Lieber-DeCarli diet results in decreased carrier-mediated thiamin transport across the renal brush-border and basolateral membranes and in transcriptionally-mediated inhibition of the THTR1 and THTR2 expression. Moreover, the expression of thiamin pyrophosphokinase (TPKase), the rate-limiting enzyme in the synthesis of the coenzyme form of thiamin was modestly, albeit significantly reduced. This observation is consistent with the previously reported 27% decrease in the enzymatic activity of TPKase in the kidneys and other organs of rats chronically fed ethanol (4). The authors did not observe changes in the expression of the mitochondrial thiamin pyrophosphate carrier Slc25a19. In an article published in parallel in the American Journal of Physiology-Gastrointestinal and Liver Physiology, the same group provides additional evidence for detrimental effects of chronic alcohol administration on intestinal thiamin absorption, also accompanied by decreased transcription and expression of the Slc19a2 and Slc19a3 genes (10). While the transcriptional mechanisms at the level of Slc19a2 and Slc19a3 gene promoters remains to be determined, these two reports provide a significant advance in our understanding of alcohol-induced thiamin deficiency. In this case, the “two-hit” model is related not only to a simultaneous reduction of expression and activity of the two key thiamin carriers but also to the two affected sites of thiamin absorption. In alcoholic subjects, changes in thiamin supply combined with impaired epithelial thiamin transport and increased metabolic demand are likely the major factors contributing to alcohol-related brain damage."

    Int J Clin Pract. 2011 Jun;65(6):684-90. doi: 10.1111/j.1742-1241.2011.02680.x.
    Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Page GL1, Laight D, Cummings MH.
    "Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function"

    Indian J Pharmacol. 2013 Jul-Aug;45(4):339-43. doi: 10.4103/0253-7613.115005.
    Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney. Altuner D1, Cetin N, Suleyman B, Aslan Z, Hacimuftuoglu A, Gulaboglu M, Isaoglu N, Demiryilmaz I, Suleyman H.

    J Endocrinol Invest. 2012 Dec;35(11):951-6. doi: 10.3275/8126. Epub 2011 Nov 22.
    Blood thiamine and its phosphate esters as measured by high-performance liquid chromatography: levels and associations in diabetes mellitus patients with varying degrees of microalbuminuria. Al-Attas OS1, Al-Daghri NM, Alfadda AA, Abd-Alrahman SH, Sabico S.

    "DMT1 and DMT2 patients with micro- albuminuria on the other hand had 2.5- and 3.4-fold increase in urinary excretion of thiamine compared to controls.
    CONCLUSION: Low levels of blood thiamine are present in patients with DMT1 and DMT2, and are associated with increased thiamine clearance."

    PLoS One. 2012;7(12):e53175. doi: 10.1371/journal.pone.0053175. Epub 2012 Dec 28.
    Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes.
    Larkin JR1, Zhang F, Godfrey L, Molostvov G, Zehnder D, Rabbani N, Thornalley PJ.
    "...glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy."

    Nephrol Dial Transplant. 2011 Jul;26(7):2137-44. doi: 10.1093/ndt/gfq675. Epub 2010 Dec 13.
    Effect of chronic kidney disease on the expression of thiamin and folic acid transporters.
    Bukhari FJ1, Moradi H, Gollapudi P, Ju Kim H, Vaziri ND, Said HM.
    "CONCLUSIONS: CKD results in marked down-regulation in the expression of folate and thiamin transporters in the intestine, heart, liver and brain. These events can lead to reduced intestinal absorption and impaired cellular homeostasis of these essential micronutrients despite their normal plasma levels."

    J Biochem Mol Toxicol. 2013 Aug;27(8):398-405. doi: 10.1002/jbt.21501. Epub 2013 May 28.
    Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats. Harisa GI.
    "This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen."

    Biometals. 2010 Apr;23(2):247-53. doi: 10.1007/s10534-009-9282-8. Epub 2009 Dec 10.
    Thiamine reduces tissue lead levels in rats: mechanism of interaction.
    Reddy SY1, Pullakhandam R, Dinesh Kumar B.
    "Further, thiamine reduced the Pb levels in blood, kidney and bone during both simultaneous and post-exposure Pb treatment. Interestingly, thiamine appears to prevent the accumulation of Pb in bone during simultaneous treatment. Together these results suggest that pyrimidine ring of thiamine mediates its interaction with Pb, leading to the prevention of its accumulation and/or increased clearance from tissues."
     
  7. DrG

    DrG New Member

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    Thanks for sharing your thoughts on all this, Haidut. Thanks also to aguilaroja.

    I found a Japanese paper with some pharmacokinetics data for allithiamine and just reviewing it now. Happy to share anything I find and will send a PM to make the connection.

    According to the Japanese paper I am looking at, the subjects reached around 1.1 micro molar blood level after a single 100 mg dose of allithiamine. This is pretty good, as it beats the 1500 mg dose of regular water soluble thiamine by around a factor of 3.

    Still, on the surface, it appears that one would need around 100 grams of allithiamine to reach a mmol level, or around 2000 of the 50 mg capsules.

    Digging one level deeper, a direct equivalence is probably not reasonable as allithiamine is claimed to penetrate the plasma membrane far more efficiently.
     
  8. lexis

    lexis Member

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  9. DrG

    DrG New Member

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    Cool story:

    "In a 24-hour period she received 100 milligrams of crushed tablets every 4 hours by stomach tube and 150 milligrams intravenously, a total dose of 750 milligrams a day, an incredibly large dose."

    That is in a 18 month old. Would represent several grams in an adult.
     
  10. Sheila

    Sheila Member

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    In my experience the key here might be 'early stage' kidney disease, this is not what I am dealing with (20 eGFR and below) and results are not as above.
    As I mentioned in PD thread on B1, viewtopic.php?f=213&t=8305 using high (300+) doses of thiamine within this context is not as simple as hoped.
    Or at least, if it is, I AM missing something. If anyone else has any experience/thoughts, do let me know. Thiamine seems to help in one way then smacks you around with gout in the other.
    There are other factors here (lowered kidney function tends to lower appetite, dietary issues with potassium etc) so thiamine probably pushes fuel availability so maybe smaller, more divided doses (6x a day) would help.
    Thanks
    Sheila
     
  11. OP
    haidut

    haidut Member

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    Charcoal is approved for more serious stages of kidney disease and can reliably lower creatinine in many cases.
    http://www.diabetesresearchclinicalprac ... 3/abstract
    http://care.diabetesjournals.org/conten ... /2590.full
    http://www.eurekalert.org/pub_releases/ ... 102009.php
    http://ndt.oxfordjournals.org/content/24/7/2089.full
    http://www.ncbi.nlm.nih.gov/pubmed/23689670
    Much of kidney damage is done by PUFA passing through the kidney together with albumin. So, lowering PUFA in blood or reducing the PUFA stores in the body would also be beneficial.
     
  12. Renaiscience_Man

    Renaiscience_Man Member

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    Aspirin sounds like a good option to block PUFA release from the tissues. However, people with gout should stay away from it, right?
     
  13. OP
    haidut

    haidut Member

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    Gout is yet another symptom of hypothyroidism, so a little aspirin (1-2 tablets) should block PUFA release, improve metabolism and not have much effect on uric acid. Sugar and caffeine raise uric acid more than aspirin.
     
  14. Peata

    Peata Member

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    bump for Ewlevy1
     
  15. robknob

    robknob Member

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    In Ray's article on caffeine, he writes... " Coffee drinking, which lowers uric acid levels, nevertheless appeared to be much more strongly protective against Parkinson’s disease than uric acid."
    He didn't specify but I think it's caffeine that lowers it because they are both very similar chemicals and the body would probably lower its production of uric acid if it sensed a lot of caffeine floating around. Of course he says right there that caffeine is better than uric acid anyway.
    Would sugar on it's own raise it uric acid?
    BTW thanks for making all your threads haidut, I think they are really well done and I enjoy reading them alot.
     
  16. OP
    haidut

    haidut Member

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    Thanks!
    Caffeine is a purine and it raises uric acid. Coffee, which contains a lot more than just caffeine, lowers uric acid. Google it for more info.
    Eating a lot of fructose in theory should raise uric acid but since it increases the metabolism by so much in the end may be a net nil effect.
     
  17. TreasureVibe

    TreasureVibe Member

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    Hey how did the thiamine work out for you? Did it do something for your kidney damage? Thanks!
     
  18. Bart1

    Bart1 Member

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    Yes I also have slightly elevated creatinine. I also have other worrying signs that my kidneys are under pressure. I keep getting elevated FFA by high stress hormones and insulin resistance.

    I’m also using 300mg per day now, as well as niacinamide.
     
  19. Bart1

    Bart1 Member

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    Effects of Coffee Intake on Incident Chronic Kidney Disease: A Community-Based Prospective Cohort Study.

    Effects of Coffee Intake on Incident Chronic Kidney Disease: A Community-Based Prospective Cohort Study. - PubMed - NCBI

    "Our findings suggest that daily coffee intake is associated with decreased risk of the development of chronic kidney disease."

    So indeed coffee is (even) protective for kidney disease.
     
  20. Momado965

    Momado965 Member

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    Did you figure out how to heal your kidneys and did thiamine help?
     
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