Thiamine Deficiency and Diabetes
by Jeffrey Dach MD
The Paradigm Shift
Pharmacist Stuart Lindsey Comes Clean – Stuart Lindsey is a pharmacist with a few observations about diabetic drug treatment written in a May 2012 article. (1A ) For many years, Stuart managed a neighborhood pharmacy observing his diabetic customers faithfully taking diabetic medications, yet they had little improvement in health: Here is a quote from his article:
“After prolonged consumption of their diabetic medications, their health did not improve. This was disturbing to me (1A)”
When Stuart Lindsey himself developed diabetes, presenting as painful neuropathy in his feet, he began researching diabetes, in a self-interested attempt to understand and cure his symptoms. While researching, Stuart discovered a 2005 paper by Dr. Thornalley detailing how many of the symptoms of diabetes are due to thiamine deficiency (Vitamin B1).(7)
Increased Renal Excretion of Thiamine
Thiamine (B1) levels are lower in diabetics, partly because the elevated blood sugar causes increased thiamine excretion by the kidney at a rate twenty-five times higher than normal. (1,2) This leads to an acute deficiency of thiamine, also called beri-beri.(1C) In addition, other B vitamins, vitamin C and Vitamin D supplementation may also be beneficial.[1B]
Thiamine Deficiency – Not On The Radar Screen
Stuart Lindsey reasoned that most of the symptoms of type 2 diabetes, the neuropathy, kidney damage, retinopathy (eye damage), and eventually heart failure are from thiamine deficiency (acute beriberi) (1A)(1C) Beri-Beri is thought to be rare in the US and the western world and merely of historical interest. After all, boxes of cereal at the grocery store are fortified with B vitamins to prevent beri-beri and pellagra (niacin deficiency). For the most part, thiamin deficiency in diabetes is not even on the radar screen for mainstream medical doctors. And it should be.
Above Image: 1920 photo of the People’s Drug Store located in Washington, D.C. United States Library of Congress’s Prints and Photographs division courtesy of wikimedia commons.
Stuart’s Vitamin Program
When Stuart Lindsey was diagnosed with type II diabetes, his doctor placed him on the standard diabetic drugs, statins, metformin and Byetta, all of which he refused to take. Instead, based on Dr. Thornalley’s theory of diabetes as an acute thiamine deficiency, Stuart Lindsey began a regimen of vitamin and mineral supplements. This is his list of supplements:
1) Source Naturals Benfotiamine -Thiamine 150mg tabs (2 tabs 3x/day)
2) Pyridoxal-5-phosphate 50 mg caps (2 caps, 100mg/day)
3) Magnesium Citrate 150 mg caps (2 caps with meals, 3x/ day)
4) Acetyl-l-carnitine 500 mg caps (2 caps between meals, 1000 mg/day)
5) Vitamin C 1000 mg caps buffered (2-3 caps per day with or between meals)
also recommended by others:
6) Alpha Lipoic Acid
7) Source Naturals Vanadium with Chromium, 180 Tablets
8) Dietary Fiber
9) Tocotrienol Vitamin E
10) Exercise and Weight Reduction Program (call my office for details)
Metformiin is a Good Drug !!!
I agree with Stuart Lindsey’s assessment and dim view of diabetic drug treatment, with the exception of Metformin, which is a good drug, and should be the first line of treatment for elevated blood sugar. Metformin has many health benefits outlined in my previous article. So, I think it was a mistake for Stuart, or any diabetic for that matter, to withhold Metformin.
Diabetic Neuropathy Cured With Vitamins !!
Upon starting his vitamin regimen, Stuart Lindsey reported the painful neuropathy in his feet subsided fairly quickly, within a week. The numbness and sensations of a “boot effect” in the feet were gone after three weeks. He noticed if he quit the vitamins the symptoms came back.
Thiamine is Found in Nerve Tissue
Thiamine modulates nerve impulse transmission, hence its usefulness in neuropathy and nerve pain syndromes.(4) Thiamine is an integral component of synaptic membranes in brain and neural tissue. (link)(link)(link)
Diabetics Are Thiamine Deficient
In 1987, Dr Saito from Japan measured blood thiamin levels in diabetics and found thiamine deficiency. Average blood thiamin level in 46 diabetics was only 47 ng/ml, slightly below the 50 ng/ml lower limit of normal.(2) In 2007, Dr. Thornalley from the UK found plasma thiamine levels in diabetics were only one fourth that of normal controls.(1)
Thiamine Supplementation helps Control Blood Sugar in Diabetics
In an animal model of diabetes, thiamine treated diabetic mice had blood sugars reduced to 111 ng/dl compared 132 ng/dl in diabetic controls (3). This indicated that thiamine was useful in controlling blood sugar. I would add here that Metformin is a very beneficial and useful drug that should should not be withheld from the diabetic with elevated blood sugar.
Thiamine prevents Diabetic Complications
Biochemistry of Thiamine and Glucose Utilization
A 2008 report by Dr Beltarno from Turin Italy, published in Acta Diabetol, explains the effects of thiamine on intracellular glucose metabolism, and prevention of diabetic complications. (4) Dr. Beltarno explains that Thiamine (vitamin B1) is an essential cofactor in most organisms required for intracellular glucose metabolism. Dr Beltarno writes:
“Diabetes might be considered a thiamine-deficient state”
Some Boring Biochemistry – For Health Care Professionals
If you are not a technical person, you might want to skip this section.
What is Thiamine ?
Left Image: Chemical structure of Thiamine Triphosphate (TPP) courtesy of wikimedia commons.
Thiamine acts as a coenzyme for the transketolase enzyme (TK) which shifts excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cell. An excellent description of this pathway can be found here .
Thiamine is a cofactor for two important enzymes, the pyruvate dehydrogenase complex (PDC) and alpha-ketoglutarate dehydrogenase (AKGD) enzymes which are fundamental for intracellular glucose metabolism. (4)
The first enzyme, the PDC converts pyruvate to acetyl CoA which can then be utilized by the Citric Acid Cycle (Krebs Cycle) to make energy in an oxidative reaction that burns carbon to Carbon Dioxide (CO2). By the way, Co-Enzyme-A is also a co-factor for the PDC enzyme.
The second enzyme resides in the mitochondria, is called the alpha-ketoglutarate-dehydrogenase complex (AKGD). The AKGD enzyme is a key and rate-limiting step of the Krebs Citric Acid (tricarboxylic acid) cycle. An excellent description of the AKDG enzyme can be found here .
For those who forgot their medical school biochemistry, an excellent description of Citric Acid cycle can be found Here. Another good explanation of the Citric Acid Cycle
Thiamine Reverses Renal Complications of Diabetes (5)
“Thiamine supplementation may prevent and reverse early-stage diabetic nephropathy.”
Thiamine supplementation prevented the development of early-stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials.”(5)
A 2009 Double Blind Clinical Trial of High Dose Thiamine
In a 2009 study published in Diabetologia by Dr Rabbani from Warwick Medical Center, 300 mg thiamine per day in diabetic patients produced regression of micro-albuminuria (early diabetic renal disease) . This was a pilot study of 40 patients with type 2 diabetes over 12 weeks(6). A later study from the Netherlands using Benfotiamine, a lipid soluble form of thiamine, did not find any improvement in proteinuria in spite of higher blood thiamin levels.(6A) Whole blood thiamine levels in 40 patients increased from 126 (baseline) to 300 nmol/L after 12 weeks of Benfotiamine.(6A)
Review Articles on Thiamin Preventing Diabetic Complications
An excellent review article by Dr Page was published in the 2011 issue of the International Journal of Clinical Practice, entitled “Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease”(10) Dr Page clearly links thiamine deficiency with the progressive atherosclerosis disease commonly found in diabetic patients with “metabolic syndrome”. Dr Page writes:
“Individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction…
Thiamine deficiency occurs in individuals with diabetes, which leads to hyperglycaemic-induced damage…Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long-term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.”
A review article from 2012 in the Journal of Clinical Medicine by Dr Luong (9) discusses the mechanisms by which thiamin prevents the complications of diabetes. He writes:
“Thiamine definitively has a role in the diabetic endothelial vascular diseases (micro and macroangiopathy), lipid profile, retinopathy, nephropathy, cardiopathy, and neuropathy.”(9)
Thiamine Treats Elevated Cholesterol and Triglycerides of Diabetes
Thiamine prevents diabetes-induced increases in plasma cholesterol and triglycerides in an animal model (12,13) High-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis in the same animal model. (14)
Left image: Typical changes of diabetic foot and toes caused by combined sensory neuropathy and vascular disease of diabetes. Courtesy of wikimedia commons.
A study by Dr Gadau in Italy published in Diabetologia in 2006 using diabetic mice showed that a lipid soluble form of thiamine called Benfotiamine accelerates healing of diabetic wounds (left image) produced by hindlimb ischemia. (15) The authors found that
“benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation. (15)”
The thiamine treated animals had improved growth of new blood vessels and reduced cell death in the ischemic areas. Reduced EPC’s (endothelial progenitor cells) in the control animals was restored to normal in thiamine treated animals. This is beneficial for healing since the EPC’s are the stem cells that heal the vessel walls and help to form collateral vessel formation in healing tissues.(15)
More on Benfotiamine
Benfotiamine (Thiamine) prevents diabetic retinopathy (16), polyneuropathy (17), and since it is lipid soluble and highly absorbable, may be the most effective of thiamine compounds. Benfotiamine produces beneficial effects on general nerve health, sciatica, neuropathy, retinopathy, nephropathy, polyneuropathy, peripheral neuropathy (PN), shingles, herpes zoster, vascular health for diabetics and non-diabetics alike. (18)(19)
Diabetes Drugs: More Is Not Always Better.
The ACCORD trial was devised to test the theory that reducing blood sugar and HgbA1C in Diabetics to near normal levels would decrease the incidence of cardiovascular disease.(1E) However, they found the exact opposite.
The large NIH Diabetes study, ACCORD, was halted early because of higher mortality in the lower blood sugar groups, (the intensive treatment group), as reported in a New York Times article by Gina Kolata. This shocked and stunned the medical community because it has always been believed that the closely or “tightly controlled” blood sugar had the best clinical results for diabetes. This was proven wrong.
Dr RW Donnell concludes from the ACCORD study:
1) Intensive glycemic control in Type Two Diabetes does not prevent vascular disease.
2) Diabetic Drugs, including insulin, have the potential for macrovascular harm.
The ACCORD Study Did Not Give Thiamine to The Diabetic Patients
Why did this happen? The answer is obvious. Using high dose insulin to drive blood sugar into thiamine deficient cells can be harmful. The cells are pumped full of glucose which they cannot metabolize because of thiamine deficiency. Instead, the glucose is shunted into alternate pathways creating harmful and damaging metabolites which cause accelerated vascular disease.
Conclusion – Overwhelming Evidence
I was taught in medical school that diabetes was caused by either inadequate insulin production (Type I) or insensitivity to insulin (type II Diabetes). This is not the complete story, and a paradigm shift has occurred in thinking about the underlying mechanism of diabetes. Current research reveals that diabetes is a thiamine deficiency state, which is the primary cause of diabetic complications. The evidence is now overwhelming that treatment of the diabetic patient should include thiamine supplementation, preferably in the form of benfotiamine which is inexpensive, readily available, and has no adverse effects.
To Buy Benfotiamine, click on link:
Source Naturals Benfotiaminefrom Source Naturals on Amazon
Articles With Related Interest:
Jeffrey Dach MD
7450 Griffin Road, Suite 190
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Links and References
2007 – Low Plasma Thiamine in Diabetics
Diabetologia. 2007 October; 50(10): 2164–2170.
High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease P. J. Thornalley,corresponding author1,2 R. Babaei-Jadidi,1 H. Al Ali,1 N. Rabbani,1,2 A. Antonysunil,1,2 J. Larkin,1,2 A. Ahmed,3 G. Rayman,4 and C. W. Bodmer
Surveying the thiamine status in the study patients and normal volunteer groups, we found the plasma concentration of thiamine was decreased 76% and 75% in type 1 and type 2 diabetic patients, respectively.
The plasma concentration of thiamine (mean ± SD) was:
normal volunteers 64.1 ± 12.0 nmol/l,
type 1 diabetes 15.3 ± 9.6 nmol/l
type 2 diabetes 16.3 ± 11.5 nmol/l,
Orthomolecular Medicine News Service, May 28, 2012
Substituting Vitamins and Supplements for Pharmaceuticals
in Type 2 Diabetes Commentary by Stuart Lindsey, PharmD
(1/B/) // The Vitamin Cure for Diabetes: Prevent and Treat Diabetes Using Nutrition and Vitamin Supplementation Brighthope IE (2012) . Basic Health Publications ISBN-13: 978-1591202905.
Med Hist. 2010 July; 54(3): 295–314.
British India and the “Beriberi Problem”, 1798–1942
David Arnold, BA, DPhil, Department of History, University of Warwick, Coventry
Mol Neurobiol. 2005;31(1-3):43-63.
The alpha-ketoglutarate-dehydrogenase complex: a mediator between mitochondria and oxidative stress in neurodegeneration.
Gibson GE, Blass JP, Beal MF, Bunik V. Source Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA.
Damage from oxidative stress and mitochondrial dysfunction occur together in many common neurodegenerative diseases. The enzymes that form the mitochondrial alpha-ketoglutarate- dehydrogenase complex (KGDHC), a key and arguably rate-limiting enzyme system of the tricarboxylic acid cycle, might mediate the interaction of these processes. KGDHC activity is reduced in numerous age-related neurodegenerative diseases and is diminished by oxidative stress. In Alzheimer’s disease (AD), the reduction correlates highly to diminished mental performance. Thus, research has focused on the mechanisms by which select oxidants reduce KGDHC and the consequences of such a reduction.
Diminished KGDHC in cells is associated with apoptosis without changes in the mitochondrial membrane potential.
Studies of isolated mitochondria and of animal models suggest that a reduction in KGDHC can predispose to damage by other toxins that promote neurodegeneration. Diminished oxidative metabolism can be plausibly linked to pathological features of neurodegenerative diseases (e.g., reduced mental function, the plaques and tangles in AD). Thus, reductions in KGDHC might be central to the pathophysiology of these diseases. Studies of proteins, cells, animal models, and humans suggest that treatments to diminish, or bypass, the reduction in KGDHC might be beneficial in age-related neurodegenerative disorders.
Am J Cardiol. 2007 Jun 18;99(12A):21i-33i. Epub 2007 Apr 16.
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods.
ACCORD Study Group, Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD.
Source Division of Endocrinology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7172, USA.
Abstract Most patients with type 2 diabetes mellitus develop cardiovascular disease (CVD), with substantial loss of life expectancy. Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes. The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge. Despite the importance of this health problem, there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors. ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality. All participants are in the glycemia trial, which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin (HbA1c) level of <6.0% will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9%.
The lipid trial includes 5,518 of the participants, who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether, in the context of good glycemic control, a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo. The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of <120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of <140 mm Hg.
The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Upon the expected completion of participant follow-up in 2009, the ACCORD trial should document for the first time the benefits and risks of intensive glucose control, intensive blood pressure control, and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes.
Blood thiamine is lower in Diabetics
J Nutr Sci Vitaminol (Tokyo). 1987 Dec;33(6):421-30.
Blood thiamine levels in outpatients with diabetes mellitus.
Saito N, Kimura M, Kuchiba A, Itokawa Y. Source Department of Geriatrics, Kochi Medical University, Japan.
In 46 diabetic outpatients consisting of 20 males and 26 females not given thiamine treatment, the blood thiamine level was 46.9 +/- 28.5 ng/ml (mean +/- SD) and only 23.9% of all cases had a value of more than the normal lower limit (50 ng/ml).
Erythrocyte transketolase activity was 443.8 +/- 107.7 micrograms/ml/h and only 20.9% had a value of more than the normal lower limit (50 micrograms/ml/h), and the erythrocyte TPP effect was 16.6 +/- 13.2%. Moreover, there was a significant positive correlation (r = 0.97) between the blood thiamine level and erythrocyte transketolase activity, and a significant inverse correlation (r = -0.525, r = -0.576) between blood thiamine level and/or erythrocyte transketolase activity and the erythrocyte TPP effect.
In 24 diabetic outpatients consisting of 14 males and 10 females given thiamine treatment, the blood thiamine level was 96.5 +/- 44.5 ng/ml/h excluding one case (621.7 ng/ml), and it was higher than the normal lower limit in 83% of all cases. Erythrocyte transketolase activity was 513.9 +/- 133.4 micrograms/ml/h and it was higher than the normal lower limit in 58.3%. Erythrocyte TPP effect was 5.84 +/- 8.39%. There was also a significant positive correlation (r = 0.663) between blood thiamine level and erythrocyte transketolase activity, and a significant inverse correlation (r = 0.0668, r = 0.834) between blood thiamine level and/or erythrocyte transketolase activity and erythrocyte TPP effect.
Blood thiamine level and erythrocyte transketolase activity were significantly higher in diabetic outpatients given thiamine treatment than in diabetic outpatients not given thiamine treatment, while the erythrocyte TPP effect was significantly lower in diabetic outpatients given thiamine treatment than in diabetic outpatients not given thiamine treatment. There was no direct relationship between the lowered response of patellar tendon reflex and the biochemical status of thiamine.
From the above findings it was concluded that diabetic outpatients tend to have a low blood thiamine level, with low erythrocyte transketolase activity and high erythrocyte TPP effect, and showed marginal thiamine deficiency.
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 GL, Laight D, Cummings MH.
Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth, UK. firstname.lastname@example.org
Despite the targeting of traditional risk factors for cardiovascular disease, disease burden has not been completely eliminated. Thiamine is an essential cofactor in carbohydrate metabolism and individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction. This review examines the mechanisms by which thiamine deficiency occurs in individuals with diabetes, how this deficiency leads to hyperglycaemic-induced damage, and the effect of thiamine replacement on vascular disease, endothelial function and oxidative stress. Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long-term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.
Thiamin helps control blood sugar in Diabetes
Effect of Thiamine on Glycemic Control in Diabetic Rats
S Saleem – Ann. Pak. Inst. Med. Sci, 2011 – apims.net
Objectives: To evaluate the effect of high dose thiamine on blood glucose level in diabetic rats.
Study Design: Experimental Interventional study.
Place and duration: Animal House/Laboratory of the National Reference Laboratory for Poultry Diseases (NRLPD) /Biochemistry
Objectives: To evaluate the effect of high dose thiamine on blood glucose level in diabetic rats.
Study Design: Experimental Interventional study.
Place and duration: Animal House/Laboratory of the National Reference Laboratory for Poultry Diseases (NRLPD) /Biochemistry Department, Army Medical College. Rawalpindi, from December 2006 to January 2007.
Materials and Methods:
The study was conducted on 120, 12 weeks old male albino rats of Sprague Dawley Strains randomly divided into 4 groups of 30 rats each.
Group I comprised of 30 normal rats, on normal (regular) diet.
Group II comprised of 30 normal rats, on thiamine supplemented diet.
Group III comprised of 30 diabetic rats, on normal (regular) diet.
Group IV comprised of 30 diabetic rats, on thiamine supplemented diet.
Out of 120 rats, 60 were made diabetic by injecting Alloxan.
Blood glucose levels were measured by applying glucose oxidase method. Determination of total HbA1c was performed by diagnostic Kits.
Results: Significant difference was found in the blood glucose levels (P<0.05) but no significant difference was noticed in the value of glycosylated Hb (HbA1c) (P>0.05) of all the 4 groups.
Conclusion: Thiamine has very important role in glucose metabolism in diabetics therefore it can be used as adjuvant but cannot be used as a substitute for standard anti diabetic drugs.
Thiamin prevents complications
Acta Diabetol. 2008 Sep;45(3):131-41. Epub 2008 Jun 26. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications.
Beltramo E, Berrone E, Tarallo S, Porta M. Source
Department of Internal Medicine, University of Turin, Corso AM Dogliotti, 14, 10126, Turin, Italy.
Thiamine (vitamin B1) is an essential cofactor in most organisms and is required at several stages of anabolic and catabolic intermediary metabolism, such as intracellular glucose metabolism, and is also a modulator of neuronal and neuro-muscular transmission.
Lack of thiamine or defects in its intracellular transport can cause a number of severe disorders. Thiamine acts as a coenzyme for transketolase (TK) and for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism.
In particular, TK is able to shift excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cytosol.
Diabetes might be considered a thiamine-deficient state, if not in absolute terms at least relative to the increased requirements deriving from accelerated and amplified glucose metabolism in non-insulin dependent tissues that, like the vessel wall, are prone to complications.
A thiamine/TK activity deficiency has been described in diabetic patients, the correction of which by thiamine and/or its lipophilic derivative, benfotiamine, has been demonstrated in vitro to counteract the damaging effects of hyperglycaemia on vascular cells. Little is known, however, on the positive effects of thiamine/benfotiamine administration in diabetic patients, apart from the possible amelioration of neuropathic symptoms. Clinical trials on diabetic patients would be necessary to test this vitamin as a potential and inexpensive approach to the prevention and/or treatment of diabetic vascular complications.
2011 Thiamine Prevents Diabetic Nephropathy
Increased renal clearance of Thiamine by diabetic kidney
Diabetes Obes Metab. 2011 Jul;13(7):577-83.
Emerging role of thiamine therapy for prevention and treatment of early-stage diabetic nephropathy. Rabbani N, Thornalley PJ.Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK.
Thiamine supplementation may prevent and reverse early-stage diabetic nephropathy. This probably occurs by correcting diabetes-linked increased clearance of thiamine, maintaining activity and expression of thiamine pyrophosphate-dependent enzymes that help counter the adverse effects of high glucose concentrations-particularly transketolase.
Evidence from experimental and clinical studies suggests that metabolism and clearance of thiamine is disturbed in diabetes leading to tissue-specific thiamine deficiency in the kidney and other sites of development of vascular complications.
Thiamine supplementation prevented the development of early-stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials.
The thiamine monophosphate prodrug, Benfotiamine, whilst preventing early-stage development of diabetic nephropathy experimentally, has failed to produce similar clinical effect. The probable explanations for this are discussed. Further definitive trials for prevention of progression of early-stage diabetic nephropathy by thiamine are now required.
2009 – Double Blind Clinical Trial of High Dose Thiamin prevents Diabetic nephropathy, reduces proteinuria.
300 mg thiamin per day in diabetics produced regression of micro-albuminuria (early diabetic renal disease)
6) Diabetologia. 2009 Feb;52(2):208-12. Epub 2008 Dec 5.
High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study.
Rabbani N, Alam SS, Riaz S, Larkin JR, Akhtar MW, Shafi T, Thornalley PJ.
Source Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Clifford Bridge Road, Coventry CV2 2DX, UK.
Abstract AIMS/HYPOTHESIS: High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes.
METHODS: Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 x 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined.
RESULTS: UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median -17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy.
CONCLUSIONS/INTERPRETATION: In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy.
Diabetes Care. 2010 Jul;33(7):1598-601. Epub 2010 Apr 22.
A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Alkhalaf A, Klooster A, van Oeveren W, Achenbach U, Kleefstra N, Slingerland RJ, Mijnhout GS, Bilo HJ, Gans RO, Navis GJ, Bakker SJ.
Source Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands
2005- Thiamine Prevents complications of Diabetes
Curr Diabetes Rev. 2005 Aug;1(3):287-98.
The potential role of thiamine (vitamin B1) in diabetic complications.
Thornalley PJ. Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom.
Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is one likely or potential trigger for biochemical dysfunction leading to the development of diabetic complications. This may be prevented by disposal of excess triosephosphates via the reductive pentosephosphate pathway. This pathway is impaired in experimental and clinical diabetes by mild thiamine deficiency.
The expression and activity of the thiamine-dependent enzyme, transketolase–the pacemaking enzyme of the reductive pentosephosphate pathway, is consequently decreased. Correction of thiamine deficiency in experimental diabetes by high dose therapy with thiamine and the thiamine monophosphate prodrug, Benfotiamine, restores disposal of triosephosphates by the reductive pentosephosphate pathway in hyperglycemia.
This prevented multiple mechanisms of biochemical dysfunction: activation of protein kinase C, activation of the hexosamine pathway, increased glycation and oxidative stress.
Consequently, the development of incipient diabetic nephropathy, neuropathy and retinopathy were prevented.
Both thiamine and Benfotiamine produced other remarkable effects in experimental diabetes: marked reversals of increased diuresis and glucosuria without change in glycemic status. High dose thiamine also corrected dyslipidemia in experimental diabetes–normalizing cholesterol and triglycerides.
Dysfunction of beta-cells and impaired glucose tolerance in thiamine deficiency and suggestion of a link of impaired glucose tolerance with dietary thiamine indicates that thiamine therapy may have a future role in prevention of type 2 diabetes.
More immediately, given the emerging multiple benefits of thiamine repletion, even mild thiamine deficiency in diabetes should be avoided and thiamine supplementation to high dose should be considered as adjunct nutritional therapy to prevent dyslipidemia and the development of vascular complications in clinical diabetes.
2003 Thiamine prevents diabetic nephropathy
8) diabetes.diabetesjournals.org/content/52/8/2110.long www.ncbi.nlm.nih.gov/pubmed/12882930?dopt=Abstract
Diabetes. 2003 Aug;52(8):2110-20.
Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley PJ.
Source epartment of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex, UK.
Abstract Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy.
High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. T
his was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.
9) www.jocmr.org/index.php/JOCMR/article/viewArticle/890/463 www.jocmr.org/index.php/JOCMR/article/viewFile/890/464
J Clin Med Res. 2012 June; 4(3): 153–160.
The Impact of Thiamine Treatment in the Diabetes Mellitus
Khanh vinh quoc Luonga,b and Lan Thi Hoang Nguyena
Thiamine acts as a coenzyme for transketolase (Tk) and for the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. The relationship between thiamine and diabetes mellitus (DM) has been reported in the literature.
Thiamine levels and thiamine-dependent enzyme activities have been reduced in DM.
Genetic studies provide opportunity to link the relationship between thiamine and DM (such as Tk, SLC19A2 gene, transcription factor Sp1, α-1-antitrypsin, and p53). Thiamine and its derivatives have been demonstrated to prevent the activation of the biochemical pathways (increased flux through the polyol pathway, formation of advanced glycation end-products, activation of protein kinase C, and increased flux through the hexosamine biosynthesis pathway) induced by hyperglycemia in DM.
Thiamine definitively has a role in the diabetic endothelial vascular diseases (micro and macroangiopathy), lipid profile, retinopathy, nephropathy, cardiopathy, and neuropathy.
2011 – Review Article
International Journal of Clinical Practice
Volume 65, Issue 6, pages 684–690, June 2011 REVIEW ARTICLE
Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease
G. L. J. Page1, D. Laight2, M. H. Cummings1
Article first published online: 12 MAY 2011
Measuring Thiamine in whole blood – 125 (75-194) nmol/L
Rapid HPLC measurement of thiamine and its phosphate esters in whole blood.
Lu J, Frank EL. Clin Chem 2008; 54: 901–6.
The means (ranges) for an apparently healthy population were
114 (70-179) nmol/L for TDP and 125 (75-194) nmol/L for total thiamine.
Thiamine corrects dyslipidemia of diabetes in mouse model of diabetes.
Diabetologia. 2004 Dec;47(12):2235-46. Epub 2004 Dec 11.
High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. by Babaei-Jadidi R, Karachalias N, Kupich C, Ahmed N, Thornalley PJ. Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex, CO4 3SQ, UK.
Cardiovascular disease in diabetes is linked to increased risk of atherosclerosis, increased levels of triglyceride-rich lipoproteins and enhanced hepatic lipogenesis. The hepatic hexosamine pathway has been implicated in signalling for de novo lipogenesis by the liver. In this study, we assessed if decrease of flux through the hexosamine pathway induced by high-dose thiamine therapy counters diabetic dyslipidaemia.
METHODS:The model of diabetes used was the streptozotocin-induced diabetic rat with maintenance insulin therapy. Normal control and diabetic rats were studied for 24 weeks with and without oral high-dose therapy (7 and 70 mg/kg) with thiamine and benfotiamine. Plasma total cholesterol, HDL cholesterol and triglycerides were determined at 6-week intervals and hepatic metabolites and transketolase activity after death of the rats at 24 weeks.
RESULTS:We found that thiamine therapy (70 mg/kg) prevented diabetes-induced increases in plasma cholesterol and triglycerides in diabetic rats but did not reverse the diabetes-induced decrease of HDL. This was achieved by prevention of thiamine depletion and decreased transketolase activity in the liver of diabetic rats. There was a concomitant decrease in hepatic UDP-N-acetylglucosamine and fatty acid synthase activity. Thiamine also normalised food intake of diabetic rats. A lower dose of thiamine (7 mg/kg) and the thiamine monophosphate prodrug benfotiamine (7 and 70 mg/kg) were ineffective.
CONCLUSIONS/INTERPRETATION:High-dose thiamine therapy prevented diabetic dyslipidaemia in experimental diabetes probably by suppression of food intake and hexosamine pathway signalling but other factors may also be involved.
Ann N Y Acad Sci. 2005 Jun;1043:777-83.
High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats. Karachalias N, Babaei-Jadidi R, Kupich C, Ahmed N, Thornalley PJ. Source Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
Abstract The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy.
Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only.
The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.
Thiamin prevents cardiomyopthy in diabetics
J Toxicol Sci. 2008 Oct;33(4):459-72.
Prevention of incipient diabetic cardiomyopathy by high-dose thiamine.
Kohda Y, Shirakawa H, Yamane K, Otsuka K, Kono T, Terasaki F, Tanaka T. Source Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B(1)) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-beta1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.
Healing of diabetic ischemic wounds
Diabetic Wounds- Benfotiamine
Diabetologia. 2006 Feb;49(2):405-20. Epub 2006 Jan 17.
Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis.
Gadau S, Emanueli C, Van Linthout S, Graiani G, Todaro M, Meloni M, Campesi I, Invernici G, Spillmann F, Ward K, Madeddu P. Source Experimental Medicine and Gene Therapy, National Institute of Biostructures and Biosystems (INB, Osilo, Italy. Benfotiamine, a vitamin B1 analogue, reportedly prevents diabetic microangiopathy.
The aim of this study was to evaluate whether benfotiamine is of benefit in reparative neovascularisation using a type I diabetes model of hindlimb ischaemia. We also investigated the involvement of protein kinase B (PK/Akt in the therapeutic effects of benfotiamine. Streptozotocin-induced diabetic mice, given oral benfotiamine or vehicle, were subjected to unilateral limb ischaemia. Reparative neovascularisation was analysed by histology. The expression of Nos3 and Casp3 was evaluated by real-time PCR, and the activation state of PKB/Akt was assessed by western blot analysis and immunohistochemistry. The functional importance of PKB/Akt in benfotiamine-induced effects was investigated using a dominant-negative construct. Diabetic muscles showed reduced transketolase activity, which was corrected by benfotiamine. Importantly, benfotiamine prevented ischaemia-induced toe necrosis, improved hindlimb perfusion and oxygenation, and restored endothelium-dependent vasodilation. Histological studies revealed the improvement of reparative neovascularisation and the inhibition of endothelial and skeletal muscle cell apoptosis. In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles. The benefits of benfotiamine were nullified by dominant-negative PKB/Akt. In vitro, benfotiamine stimulated the proliferation of human EPCs, while inhibiting apoptosis induced by high glucose. In diabetic mice, the number of circulating EPCs was reduced, with the deficit being corrected by benfotiamine.
CONCLUSIONS/INTERPRETATION: We have demonstrated, for the first time, that benfotiamine aids the post-ischaemic healing of diabetic animals via PKB/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. In addition, benfotiamine combats the diabetes-induced deficit in endothelial progenitor cells.
Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18.
Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M. Source Medical Clinic V, School of Clinical Medicine, Mannheim, Germany.
Abstract Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. We have discovered that the lipid-soluble thiamine derivative benfotiamine can inhibit these three pathways, as well as hyperglycemia-associated NF-kappaB activation, by activating the pentose phosphate pathway enzyme transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate into pentose-5-phosphates and other sugars. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy. The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications.
Exp Clin Endocrinol Diabetes. 2008 Nov;116(10):600-5. Epub 2008 May 13.
Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.
Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Medical Clinic und Policlinic III, University Hospital Giessen and Marburg, Location Giessen, Germany.
Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom “pain”. Treatment was well tolerated in all groups.
CONCLUSION:Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.
19) Pharmacol Res. 2010 Jun;61(6):482-8. Epub 2010 Feb 25.
The multifaceted therapeutic potential of benfotiamine.Balakumar P, Rohilla A, Krishan P, Solairaj P, Thangathirupathi A. Source Department of Pharmacology, SB College of Pharmacy, Sivakasi 626130, India.
Abstract Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine.
Mol Cell Neurosci. 2012 Sep 13. pii: S1044-7431(12)00177-7. doi: 10.1016/j.mcn.2012.09.001. [Epub ahead of print]
Abnormal thiamine-dependent processes in Alzheimer’s Disease. Lessons from diabetes. Gibson GE, Hirsch JA, Cirio RT, Jordan BD, Fonzetti P, Elder J. Source Department of Neurology and Neuroscience, Weill Cornell Medical College, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605. Electronic address: email@example.com.
Abstract Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine- dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression.
This article is part of a Special Issue entitled ‘Mitochondrial function’.
Thiamin deficiency in non-alcoholics
Eur Neurol. 2001;45(1):34-7.
Thiamine-responsive acute neurological disorders in nonalcoholic patients.
Merkin–Zaborsky H, Ifergane G, Frisher S, Valdman S, Herishanu Y, Wirguin I. Source Department of Neurology, Soroka University Medical Center, Goldman Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Abstract Wernicke’s encephalopathy (WE) is most commonly associated with alcoholism, although other causes have also been implicated. In the years 1994-1997, 9 patients with no history of alcohol abuse presented with acute signs of ophthalmoplegia or nystagmus and ataxia which resolved within 48 h after intravenous thiamine. There were 7 women and 2 men aged 17-57 (7 below the age of 30). Precipitating events included vomiting 2, drastic weight-reducing diet 2, renal colic in a postpartum woman 1, colonic surgery 2 and chronic hemodialysis 1. In 2 patients there was no obvious precipitating event but their history was suggestive of a genetic predisposition. Mental changes were slight or absent in all patients and all of them made good functional recovery. These cases suggest that the diagnosis of WE should be considered more often in nonalcoholics in various clinical settings.
Thiamin Deficient Infant Feeding Formula
Ann Nutr Metab. 2012;60(3):185-7. Epub 2012 Jun 6.
Thiamine-deficient infant formula: what happened and what have we learned?
Shamir R.Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children’s Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
INTRODUCTION:In 2003, a thiamine-deficient soy infant formula was produced in Germany and marketed exclusively in Israel. Between October and November 2003, infants with encephalopathy were admitted to several intensive care units in Israel and were later diagnosed as suffering from thiamine deficiency. The soy formula consumed by these children was found to be the cause of these admissions.
METHODS:A Medline search using the terms ‘thiamine deficiency’ and ‘formula’ or ‘feeding’ without year limit identified relevant published data on that event. Newspapers from Israel were screened from November 2003 until April 2011.
RESULTS:On November 2003, 2-6% of infants in Israel consumed this formula. The consumption of this thiamine-deficient formula was associated with the death of 3 infants and with more than 20 infants manifesting neurologic damage. In this report, we summarize the chain of events, the neurologic outcome, and discuss the lessons needed to be learned from this sad event. CONCLUSIONS:Based on difficulties in diagnosis of subtle deficiencies, we suggest that apparent history of safe use is not a reliable source for establishing adequate intake. Infant formulae can be produced or imported only under stringent criteria with the manufacturer/importer having total responsibility for the product.
Pediatrics. 2005 Feb;115(2):e233-8.
Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. Fattal–Valevski A, Kesler A, Sela BA, Nitzan–Kaluski D, Rotstein M, Mesterman R, Toledano–Alhadef H, Stolovitch C, Hoffmann C, Globus O, Eshel G. Institute for Child Development and Pediatric Neurology Unit, Dana Children’s Hospital, Sourasky Medical Center, Tel Aviv, Israel. firstname.lastname@example.org
Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernicke’s encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable (<0.5 microg/g). The product was pulled from the shelves, and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis, clinical course, and outcome of 9 affected infants in our care.
J Neuroophthalmol. 2005 Sep;25(3):169-72.
Acute ophthalmoplegia and nystagmus in infants fed a thiamine-deficient formula: an epidemic of Wernicke encephalopathy.
Kesler A, Stolovitch C, Hoffmann C, Avni I, Morad Y. Neuro-ophthalmology Unit (AK) and the Department of Ophthalmology (AK,CS), Tel Aviv Medical Center, and the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. email@example.com In 2003, an epidemic of Wernicke encephalopathy (WE) developed in Israeli infants fed a thiamine-deficient soy-based formula. Approximately 20 infants were affected out of an estimated 3500 fed the vitamin-deficient formula. The finding of gaze abnormalities in a single infant by neuro-ophthalmologists led to the unraveling of the epidemic. In this report, the findings in three infants are described. Early diagnosis and treatment with parenteral thiamine led to complete neurologic recovery in two infants; in the third infant, delayed diagnosis may have been responsible for severe lingering deficits. This is the first reported epidemic of WE secondary to thiamine-deficient infant formula. Early diagnosis and treatment are critical to avoid persistent neurologic impairment.
Thiamine Deficiency from Alcohol USe
Neuropsychol Rev. 2012 Jun;22(2):81-92. Epub 2012 May 9.
The evolution and treatment of Korsakoff’s syndrome: out of sight, out of mind? Thomson AD, Guerrini I, Marshall EJ. Source Molecular Psychiatry Laboratory, Rockefeller Building, University College London, 21 University Street, London, UK.
Abstract Wernicke’s Encephalopathy is an acute neuro-psychiatric condition caused by an insufficient supply of thiamine (Vitamin B1) to the brain. If undiagnosed or inadequately treated, it is likely to proceed to Korsakoff’s Syndrome. Wernicke’s Encephalopathy can result from dietary deficiency alone and this form is usually successfully treated, with little chance of Korsakoff’s Syndrome supervening. On the other hand, thiamine deficiency associated with alcohol misuse/dependence may require up to 1 gram of thiamine IV in the first 24 hours to be treated successfully. The reasons for this difference in treatment will be discussed. Thiamine diphosphate acts as a co-factor for a number of thiamine-dependent enzymes. Thiamine deficiency leads to a reduction in the activity of these enzymes, and this leads to alterations in mitochondrial activity, impairment of oxidative metabolism, decreased energy status and eventually selective neuronal death. The damage caused by the combination of thiamine deficiency and alcohol metabolism probably interferes with adequate thiamine transport at a number of sites in the body, including the blood-brain barrier, as well as causing damage to the apoenzymes which then require higher concentrations of thiamine to work normally. The accumulated damage is likely to render the use of oral thiamine therapeutically inadequate since the body is unable to produce high enough concentrations of thiamine in the blood to traverse the blood-brain barrier. Some individuals are probably genetically predisposed to develop Wernicke’s. Long before individuals with alcohol misuse or dependence develop Wernicke’s Encephalopathy the neurons and other cells of the body are functioning sub-optimally because of the inadequate supply of thiamine and the neurotoxic effect of alcohol. This relative deficiency initiates a series of pathological changes which accumulate and further interfere with the supply of thiamine and its utilisation at a time when the requirements are increased. The best treatment for Korsakoff’s Syndrome is timely recognition of Wernicke’s Encephalopathy and appropriate intervention and prevention.
THE TREATMENT OF PATIENTS AT RISK OF DEVELOPING WERNICKE’S ENCEPHALOPATHY IN THE COMMUNITY ALLAN D. THOMSON1,2 and E. JANE MARSHALL3,* 1Molecular Psychiatry Laboratory, Windeyer Institute of Medical Science, Department of Mental Health Sciences, Royal Free and University College London, Medical School, 46 Cleveland Street, London W1T 4JF, UK, 2Kent Institute of Medicine and Health Science, University of Kent at Canterbury, UK and 3National Addiction Centre, Box 048, Institute of Psychiatry, Kings College London, De Crespigny Park, London SE5 8AF, UK thiamin on Diuretics
Diuretics and thiamine deficiency
Nutr Rev. 2000 Oct;58(10):319-23.
Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition?
Suter PM, Vetter W. Source Medical Policlinic, University Hospital, Zürich, Switzerland. Abstract Despite modern pharmacologic agents in the therapy of heart failure, the prevalence of heart failure is increasing worldwide. In the vitamin B1 deficiency disease beriberi, cardiac symptoms may represent the central feature. Two new studies confirmed that all diuretics lead to increased urinary thiamin excretion depending on the urinary flow rate. In a subject at risk, such as an elderly patient, chronic diuretic treatment may lead to a subclinical thiamin deficiency. Whether subclinical thiamin nutriture is a modulator of the prevalence and/or severity of heart failure is not known; however, it seems to be plausible from the metabolic point of view.
Thiamine Deficiency in CHF pts on Lasix
Can J Clin Pharmacol. 2003 Winter;10(4):184-8.
Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Zenuk C, Healey J, Donnelly J, Vaillancourt R, Almalki Y, Smith S. Ottawa Hospital, Civic Campus Pharmacy Department.
To assess the presence of thiamine deficiency in congestive heart failure patients receiving furosemide therapy.
DESIGN: Prospective, biochemical analysis of thiamine status was performed in outpatients and inpatients of the University of Ottawa Heart Institute.
SUBJECTS: Thirty-two patients with congestive heart failure who received at least 40 mg/day of furosemide were included. Patients were then separated into two groups depending on whether the dose of furosemide was greater than or equal to 80 mg/day. METHODS:The primary measure was actual thiamine status as assessed by the erythrocyte transketolase enzyme activity and the degree of thiamine pyrophosphate effect.
RESULTS:Biochemical evidence of severe thiamine deficiency was found in 98% (24 of 25) patients receiving at least 80 mg/day of furosemide and in 57% (four of seven) of patients taking 40 mg furosemide daily, odds ratio (OR) 19.0 (1.13
Ann Cardiol Angeiol (Paris). 2001 Apr;50(3):160-8.
[Is thiamine supplementation necessary in patient with cardiac insufficiency?].
Blanc P, Boussuges A. Service de réanimation polyvalente, service de cardiologie, CHD Félix Guyon, 97405 Saint-Denis, La Réunion, France. ph-blanc@chd–fguyon.fr
Interest has recently risen regarding thiamine deficiency in patients with cardiac deficiency who are receiving long-term diuretic therapy. Thiamine deficiency can lead biventricular myocardial failure (cardiac beriberi), and treatment consists of thiamine administration. Studies have shown that long-term furosemide use may be associated with thiamine deficiency through urinary loss, contributing to cardiac insufficiency in patients with congestive heart failure. Thiamine supplementation could improved left ventricular function. However, the results of those studies are controversial, and none study have till proved the clinical impact of a systematic administration of thiamine in a cohort of patients with cardiac insufficiency. To date, and waiting for available literature, thiamine administration should be consider in patients at risk for thiamine deficiency (elderly, malnourished, alcoholic), and in patients receiving very large doses of diuretics.
J Cardiovasc Pharmacol Ther. 2003 Dec;8(4):313-6.
Reversal of refractory congestive heart failure after thiamine supplementation: report of a case and review of literature.
Mendoza CE, Rodriguez F, Rosenberg DG. Source Division of Cardiology, University of Miami School of Medicine, Miami, Florida 33136, USA.
Abstract Patients with refractory heart failure comprise a very important subgroup of patients with congestive heart failure. Before assuming that this condition simply reflects advanced, perhaps terminal, myocardial dysfunction, potentially reversible factors should be sought carefully. We describe a 58-year-old Hispanic man with a diagnosis of idiopathic dilated cardiomyopathy who presented with symptoms of severe congestive heart failure, glossitis, and peripheral neuropathy. His hemodynamic profile was characterized by refractory low-output cardiac failure and decreased vascular resistance. Thiamine deficiency was documented by a high thiamine pyrophosphate effect. His clinical condition was quickly reversed with thiamine administration. This response to thiamine administration supports the diagnosis and indicates that thiamine deficiency may play an important etiologic role in the deterioration of cardiac function in some patients with congestive heart failure.
Carbonated Drinks-High CAlorie Malnutrition
Scott Med J. 1987 Oct;32(5):137-8.
Carbonated drinks, thiamine deficiency and right ventricular failure.
Bell D, Robertson CE, Muir AL. Department of Medicine, Royal Infirmary, Edinburgh.
A 69 year old male presented with clinical features of right ventricular failure. A dilated poorly contracting right ventricle was confirmed by echocardiography and radionuclide ventriculography, with subsequent improvement following thiamine replacement. Wet beriberi is a result of thiamine deficiency and is uncommon in Europe and North America except in association with chronic alcohol abuse. We report a patient with beriberi presenting unusually with severe right-sided cardiac failure, with documented impairment of right ventricular function, which improved with thiamine replacement. His dietary intake of thiamine was low because of excess intake of carbonated drinks and carbohydrates.
Thiamin deficieny in Bariatric Surgery
J Obes. 2012; 2012: 608534.
The Neurological Complications of Nutritional Deficiency following Bariatric Surgery Danielle A. Becker, 1 Laura J. Balcer, 1 , 2 , 3 and Steven L. Galetta 1 , 2 ,* 1Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3 W. Gates Building, 3400 Spruce Street, Philadelphia, PA 19104, USA Neurologic complications of bariatric surgery have become increasingly recognized with the rising numbers of procedures and the increasing prevalence of obesity in the US. Deficits are most commonly seen with thiamine, vitamin B12, folate, vitamin D, vitamin E, and copper deficiencies. The neurological findings observed with these nutritional deficiencies are variable and include encephalopathy, optic neuropathy, myelopathy, polyradiculoneuropathy, and polyneuropathy. We review the neurological complications of bariatric surgery and emphasize that these findings may vary based on the specific type of bariatric surgery and time elapsed from the procedure.
Curr Gastroenterol Rep. 2012 Aug;14(4):367-72.
Neurologic complications of bariatric surgery: involvement of central, peripheral, and enteric nervous systems. Frantz DJ.Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, 27599-7080, USA. firstname.lastname@example.org
Approximately one in three Americans is obese. Current society guidelines recommend bariatric surgery after conservative measures at weight loss have failed. The frequency of bariatric surgeries has increased significantly over the past decade. While considered both safe and effective, bariatric surgery presents a distinct set of risks. This review focuses on the neurological complications of bariatric surgery. Injuries have been reported at all levels of the nervous system, including the central, peripheral, and enteric nervous system. Injury can be classified according to time of presentation and location. The two main mechanisms of nerve injury are from mechanical injury or as a consequence of malnutrition. Encephalopathy, peripheral neuropathies, myelopathies, and radiculoneuropathies have all been reported. Mechanical injuries likely occur from mechanical compression. Malnutrition injuries result from multi-micronutrient deficiencies. The most likely candidates are vitamin B12, folate, zinc, thiamin, copper, vitamin A, and vitamin E deficiencies.
Arch Neurol. 1981 Nov;38(11):710-2.
Benign coital cephalalgia. Differential diagnosis and treatment. Porter M, Jankovic J. Abstract Benign coital cephalalgia is an acute headache that is time related to sexual intercourse. It is often confused with more serious conditions such as subarachnoid hemorrhage due to ruptured intracranial aneurysm. We describe eight patients with benign coital cephalalgia who were successfully treated with propranolol hydrochloride. We suggest that these patients have a variant of migraine.
Ginekol Pol. 2005 Dec;76(12):995-9. [Primary headache associated with sexual activity]. [Article in Polish] Domitrz I. Klinika Neurologii, Akademia Medyczna, Warszawa. email@example.com Benign coital headache is known as a rare type of primary headache related to sexual activity. The pathogenesis of this type of headache remains unknown. Clinical manifestation is typical and connected with three phases of sexual activity. Coital cephalalgia is divided into two subtypes: preorgasmic and orgasmic headache. Some authors specifie the third type–postural type. Preorgasmic headache starts as a dull bilateral ache and increases with sexual excitement. Orgasmic headache has sudden, intense character and occurs at orgasm. Postural headache has been reported to develop after coitus. The author describes four cases of different types of sexual headache, which were effectively treated. Indomethacin was effective in all patients as direct treatment and propranolol was effective in patients to whom it was administrated as preventive treatment.
Primary headache associated with sexual activity Anand K S, Dhikav V Singapore Med J 2009; 50(5): e176–e177 A rare case of primary headache associated with sexual activity in a 40-year-old married Indian man who had coital and postcoital headaches responsive to indomethacin is reported. Keywords: coital headache, postcoital headache, sex-related headache, sexual activity-associated headache A diagnosis of primary HSA was made, and he was started on indomethacin 25 mg/ day to be taken 30 minutes before intercourse, following which he noted a dramatic improvement.
Arch Neurol. 1975 Oct;32(10):649-52.
Posttraumatic dysautonomic cephalalgia. Clinical observations and treatment.
Vijayan N, Dreyfus PM. Abstract
Five patients developed posttraumatic vascular headaches associated with autonomic dysfunction. The precipitating injury affected the anterior triangle of the neck, presumably involving the region of the carotid artery sheath. Disturbance of sympathetic function, characterized by excessive sweating and pupillary dilation associated with headache, was noted. Appropriate pharmacologic studies revealed evidence of partial sympathetic devervation. While headache was resistant to ergotamine preparations, prompt relief was obtained with propranolol hydrochloride, and adrenergic beta-receptor blocking agent.
Dysautonia by Derrick Lonsdale
Dysautonomia, A Heuristic Approach to a Revised Model for Etiology of Disease. Derrick Lonsdale. Dysautonomia A Heuristic Approach to a Revised Model for Etiology of Disease Lonsdale Derrick eCAM 2009
Reversible autonomic dysfunction associated with high calorie malnutrition has been reported (60). The clinical presentation can be asymmetric (61). Sweating, tachycardia, dermographia, both wide and narrow unstable pulse pressure, attention deficit and other dysautonomic symptoms in children have been published (62). These symptoms have been shown to respond to dietary instruction, with particular reference to removal of sugar in all its commercial forms together with dietary supplements that always include thiamin and magnesium. It is suggested that high caloric malnutrition, particularly in the form of simple carbohydrates, is a common cause of defective autonomic control mechanisms in the lower brain that can be likened to the early stages of classic beriberi.
!!!!!!!!!!!!! KEY ARTICLE
Evid Based Complement Alternat Med. 2006 March; 3(1): 49–59. A Review of the Biochemistry, Metabolism and Clinical Benefits of Thiamin(e) and Its Derivatives by Derrick Lonsdale
The role of allithiamine and its synthetic derivatives is discussed.Thiamine plays a vital role in metabolism of glucose. Thus, emphasis is placed on the fact that ingestion of excessive simple carbohydrates automatically increases the need for this vitamin. This is referred to as high calorie malnutrition. In 1965, the morbidity from beriberi was not accurately known. A study of 375 patients seen in Tokyo Medical and Dental College Hospital revealed that 109 (29%) had at least two of the major beriberi signs of hyporeflexia, hypesthesia, edema, lowered diastolic pressure and tenderness by grasping the calf muscles. The fourth important enzyme requiring TPP is transketolase, an enzyme that occurs twice in the pentose shunt. The functions of this pathway are to provide pentose phosphate for nucleotide synthesis and to supply reduced NADP for various synthetic pathways. Activity of this enzyme has been used for many years as the best functional test for evidence of thiamine deficiency (7). Since the pentose shunt occurs in erythrocytes, these cells become convenient for performing the study as a routine method of detecting deficiency. dysfunction in the autonomic system was a prominent part of the clinical expression of beriberi (21) and reversible autonomic dysfunction, associated with evidence of high calorie malnutrition, has been reported in recent times in the United States (22,23). Sweating, tachycardia, dermographia, wide unstable pulse pressure, attention deficit and other symptoms of autonomic dysfunction in children have been reported as functional dysautonomia (24). Generally speaking, the deficiency is marginal and this might be defined as a thiamine pyrophosphate effect (TPPE) of between 15 and 25% in measuring erythrocyte transketolase Thiamin(e), also known as vitamin B1, is now known to play a fundamental role in energy metabolism. Its discovery followed from the original early research on the ‘anti-beriberi factor’ found in rice polishings. After its synthesis in 1936, it led to many years of research to find its action in treating beriberi, a lethal scourge known for thousands of years, particularly in cultures dependent on rice as a staple. This paper refers to the previously described symptomatology of beriberi, emphasizing that it differs from that in pure, experimentally induced thiamine deficiency in human subjects. Emphasis is placed on some of the more unusual manifestations of thiamine deficiency and its potential role in modern nutrition. Its biochemistry and pathophysiology are discussed and some of the less common conditions associated with thiamine deficiency are reviewed. An understanding of the role of thiamine in modern nutrition is crucial in the rapidly advancing knowledge applicable to Complementary Alternative Medicine. References are given that provide insight into the use of this vitamin in clinical conditions that are not usually associated with nutritional deficiency. The role of allithiamine and its synthetic derivatives is discussed. Thiamine plays a vital role in metabolism of glucose. Thus, emphasis is placed on the fact that ingestion of excessive simple carbohydrates automatically increases the need for this vitamin. This is referred to as high calorie malnutrition. It is, however, important to state that dysfunction in the autonomic system was a prominent part of the clinical expression of beriberi (21) and reversible autonomic dysfunction, associated with evidence of high calorie malnutrition, has been reported in recent times in the United States (22,23). Sweating, tachycardia, dermographia, wide unstable pulse pressure, attention deficit and other symptoms of autonomic dysfunction in children have been reported as functional dysautonomia (24). TD has been reported in refractory heart failure (36) and has occurred in epidemic form in Cuba involving 50 862 (461.4 per 100 000) people. Lesions included peripheral neuropathy, retrobulbar optic neuropathy, sensory and dysautonomic peripheral neuropathy, sensorineural deafness, dysphonia, dysphagia and spastic paraparesis (37,38). TD ataxia (39), post-gastrectomy polyneuropathy (40) and reversible autonomic neuropathy involving bladder dysfunction (41) have been described. Could fibromyalgia be a thiamine deficiency ? — All fibromyalgia patients should be given benfotiamine. In 1965, the morbidity from beriberi was not accurately known. A study of 375 patients seen in Tokyo Medical and Dental College Hospital revealed that 109 (29%) had at least two of the major beriberi signs of hyporeflexia, hypesthesia, edema, lowered diastolic pressure and tenderness by grasping the calf muscles. SWEATING – Dysautonomia It is, however, important to state that dysfunction in the autonomic system was a prominent part of the clinical expression of beriberi (21) and reversible autonomic dysfunction, associated with evidence of high calorie malnutrition, has been reported in recent times in the United States (22,23). Sweating, tachycardia, dermographia, wide unstable pulse pressure, attention deficit and other symptoms of autonomic dysfunction in children have been reported as functional dysautonomia (24).
Med Sci Monit. 2004 Sep;10(9):RA199-203. Epub 2004 Aug 20.
Thiamine tetrahydrofurfuryl disulfide: a little known therapeutic agent.Lonsdale D. Preventive Medicine Group, Westlake, Ohio, USA.
Abstract Thiamine tetrahydrofurfuryl disulfide (TTFD) is the synthetic counterpart of allithiamine, occurring naturally in garlic. Allithiamine was discovered in Japan in 1951. Its extensive research was reported by a group known as the Vitamin B Research Committee of Japan, and given this name because of its existence in the bulbs of many of the allium species of plants. It was found to be a disulfide derivative of thiamine, produced as a result of enzymatic action on the thiamine molecule in garlic bulbs when the bulb is cut or crushed. Subsequent experimental work in both animals and human subjects revealed that its metabolic effect was much more powerful than the thiamine from which it was derived. Japanese investigators created a number of synthetic forms and investigated their use in a number of human disease conditions. Although some derivatives have been synthesized without a disulfide bond in the molecule, these investigators emphasized that the disulfide was an extremely important part of its biologic action and TTFD is the most modern of the disulfide derivatives. Because at least part of its beneficial effects are the same as water soluble thiamine salts, this review deals first with the clinical uses of thiamine (vitamin B1) in medicine.
Lipid-soluble thiamine derivatives in the treatment of autism
Derrick Lonsdale et al
Introduction and Overview Thiamine pyrophosphate Assay for thiamine deficiency
Clinical presentations References Measurement of Thiamine in WHole Blood
Since erythrocyte thiamine stores deplete at a similar rate to other major organs (11) and since the erythrocyte contains approximately 80% of the total thiamine content of whole blood (12), mainly as the pyrophosphate, the analysis of thiamine pyrophosphate in whole blood or erythrocytes is the most appropriate measurement to assess thiamine status. ————————————————————————————————- Articles on Thiamine
Psychogenic erectile dysfunction
Twenty patients with psychogenic erectile dysfunction received the drug . After a 30-day course of enerion erectile function improved in 16 of the above patients. A mean value of the international index of erectile function (IIEF) increased in them from 17.5 to 24.8 points. Improvement of cavernous arterial blood flow after the treatment was seen in 3 of 6 patients with arterial disorders.
Thiamin, Pyridoxine and other B vit Deficiencies in Agoraphobia, Anxiery Diorders
mega-vitamin therapy in the treatment of agoraphobia.
Agoraphobia Laraine C. Abbey, R.N., M.S.1
ORTHOMOLECULAR PSYCHIATRY, VOLUME 11, NUMBER 4, 1982 Pp. 243-259
Testing – Disturbed thiamine metabolism was the most frequent abnormality with pyridoxine running a close second.
ANxiety – Alterations in blood lactate, pyruvate, ATP and the L/P ratio indicate a profound disturbance in transformation of chemical to kinetic energy in the anxiety prone patients. (Pauling and Hawkins, 1973., p. 295)
In such patients symptoms of anxiety may occur when there is a requirement to mobilize energy rapidly. Since these patients exhibit a marked shift from aerobic to anaerobic metabolism, their production of energy is markedly reduced. The chief symptoms of anxiety neurosis, as noted by Cohen and White, are breathlessness, palpitations, nervousness, fatigability, headaches, irritability, dizziness, chest pain, paresthesias and episodes of extreme tearfulness referred to as anxiety attacks. The disorder is characterized by the appearance of many symptoms but few signs (Cohen and White, p. 834). Blood lactate was found to be twice as high in neurocirculatory asthenia as in controls. (Cohen and White, p. 847). Cohen and White found many measurable abnormalities in the response of the anxiety patients to muscular work. These abnormalities which included low oxygen consumption are consistent with a defect in aerobic metabolism and a high anaerobic metabolism. (Cohen and White, p. 847). Lacticacidemia following PDH (pyruvate dehydrogenase) underactivity as a result of thiamine dependency was reported by Schweizer and Baumgart–ner in 1977.
Hills JI, et al, The effect of thiamin tetrahydrofurfuryl disul!de on behavior of juvenile DBA/2J mice, Neurotoxicol Teratol (2011), Researchers (Lonsdale, 1987a, 1982b, 1990, 2006) have reported other multifaceted behavioral and somatic disorders in children that have responded to thiamin or lipophilic thiamin precursor administration. In adults, lipophilic forms of thiamin have been used to treat psychobe– behavioral inhibition and asthenia, enhance memory in elderly patients, and improve cognitive function and reduce anxiety in university students with severe psychosomatic fatigue (reviewed by (Van Reeth, 1999)), as well as a number of other disorders which will be reviewed below in Section 4.4.
Thiamine deficiency and psychosis
ROBINSON, A JONES – Am J Psychiatry, 1987 – Am Psychiatric Assoc SIR:
We would like to report on a patient with psychosis related to thiamine deficiency; she responded to intramuscular administration of thiamine, with complete resolution of symptoms in 48 hours. Thiamine deficiency is known to cause Wernicke-Korsakoff
[A case of thiamine deficiency with psychotic symptoms–blood concentration of thiamine and response to therapy]. [Article in Japanese] Source Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School. Abstract We report the case of a 63-year-old woman with thiamine deficiency who showed auditory hallucinations, a delusion of persecution, catatonic stupor, and catalepsy but no neurological symptoms including oculomotor or gait disturbance. Brain MRI did not show high-intensity T2 signals in regions including the thalami, mamillary bodies, or periaqueductal area. Her thiamine concentration was 19 ng/mL, only slightly less than the reference range of 20-50 ng/mL. Her psychosis was unresponsive to antipsychotics or electroconvulsive therapy, but was ameliorated by repetitive intravenous thiamine administrations at 100-200 mg per day. However, one month after completing intravenous treatment, her psychosis recurred, even though she was given 150 mg of thiamine per day orally and her blood concentration of thiamine was maintained at far higher than the reference range. Again, intravenous thiamine administration was necessary to ameliorate her symptoms. The present patient indicates that the possibility of thiamine deficiency should be considered in cases of psychosis without neurological disturbance and high-intensity T2 MRI lesions. Also, this case suggests that a high blood thiamine concentration does not necessarily correspond to sufficient thiamine levels in the brain. Based on this, we must reconsider the importance of a high dose of thiamine administration as a therapy for thiamine deficiency. The validity of the reference range of the thiamine concentration, 20-50 ng/mL, is critically reviewed.
Their ages ranged from 57 to 83 years old (mean—72.8 ± 2.9 years). All of the patients had low blood thiamine levels (mean, 25.06 nmol/L ± 6.0 nmol/L; normal level—70 nmol/L – 180 nmol/L).
Thaimine Low in pediatric ICU-blood thiamin values
de Lima, Lúcio Flávio Peixoto, Heitor Pons Leite, and José Augusto de AC Taddei. “Low blood thiamine concentrations in children upon admission to the intensive care unit: risk factors and prognostic significance.” The American journal of clinical nutrition 93.1 (2011): 57-61.
Low blood thiamine in children upon admission to intensive care unit de Lima Am j clin nut 2011
BACKGROUND: Thiamine deficiency has been associated with poorer clinical outcomes. Early recognition of thiamine deficiency is difficult in critically ill patients because clinical signs are nonspecific.
OBJECTIVE: We determined the prevalence of and identified risk factors associated with low blood thiamine concentrations upon admission of children to a pediatric intensive care unit and evaluated this condition as a predictor of clinical outcomes. DESIGN: A prospective cohort study was conducted in 202 children who had whole-blood thiamin concentrations assessed by HPLC upon admission to the intensive care unit. The following independent variables for thiamine deficiency were analyzed: age, sex, nutritional status, clinical severity scores upon admission (ie, the revised Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction score), systemic inflammatory response measured by C-reactive protein serum concentrations, severe sepsis or septic shock, heart failure, and cardiac surgery. The dependent variables in the outcome analyses were mortality, length of stay, and time on mechanical ventilation.
RESULTS: Low blood thiamine concentrations upon admission were detected in 57 patients (28.2%) and were shown to be independently associated with C-reactive protein concentrations >20 mg/dL (odds ratio: 2.17; 95% CI: 1.13, 4.17; P = 0.02) but not with malnutrition. No significant association was shown between low blood thiamine concentrations upon admission and outcome variables.
CONCLUSIONS: The incidence of low blood thiamine concentrations upon admission was high. Of the risk factors examined, only the magnitude of the systemic inflammatory response showed an independent association with this event. The association between thiamine deficiency upon admission and prognosis requires further investigation.
Thiamin in Cambodia infants low
J Pediatr. 2012 Jun 13. [Epub ahead of print] Thiamine Deficiency in Cambodian Infants with and without Beriberi. Coats D, Shelton-Dodge K, Ou K, Khun V, Seab S, Sok K, Prou C, Tortorelli S, Moyer TP, Cooper LE, Begley TP, Enders F, Fischer PR, Topazian M. Eastern Mennonite Mission, Prey Veng, Cambodia.
OBJECTIVES:To test the hypothesis that heavy metal toxicity and consumption of thiaminase-containing foods predispose to symptomatic thiamine deficiency. STUDY DESIGN:In a case-control study, thiamine diphosphate (TDP) blood concentrations were measured in 27 infants diagnosed with beriberi at a rural clinic, as well as their mothers and healthy Cambodian and American controls. Blood and urine levels of lead, arsenic, cadmium, mercury, and thallium were measured. Local food samples were analyzed for thiaminase activity.
RESULTS:Mean TDP level among cases and Cambodian controls was 48 and 56 nmol/L, respectively (P = .08) and was 132 nmol/L in American controls (P < .0001 compared with both Cambodian groups). Mean TDP level of mothers of cases and Cambodian controls was 57 and 57 nmol/L (P = .92), and was 126 nmol/L in American mothers (P < .0001 compared with both Cambodian groups). Cases (but not controls) had lower blood TDP levels than their mothers (P = .02). Infant TDP level decreased with infant age and was positively associated with maternal TDP level. Specific diagnostic criteria for beriberi did not correlate with TDP level. There was no correlation between heavy metal levels and either TDP level or case/control status. No thiaminase activity was observed in food samples.
CONCLUSIONS:Thiamine deficiency is endemic among infants and nursing mothers in rural southeastern Cambodia and is often clinically inapparent. Neither heavy metal toxicity nor consumption of thiaminase-containing foods account for thiamine deficiency in this region.
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