Super Carnosine 500 mg by Life Extension

POSSIBLY EFFECTIVE

• Diabetic neuropathy. Oral benfotiamine might improve symptoms of diabetic neuropathy. Details: Clinical trials in patients with diabetic neuropathy show that taking benfotiamine (Benfogamma, Worwag Pharma) 300-600 mg in divided doses daily for 3-6 weeks and for up to 6 months, might modestly improve neuropathic symptoms when compared with baseline or placebo. Benefit seems to be most notable with the 600 mg daily dose (98030,98032,105468). However, benfotiamine does not seem to improve peripheral nerve function as measured by nerve conduction and vibrational perception in patients with diabetic neuropathy when compared with control (98030,98032,98037). Many of these studies are limited by small sample sizes, lack of intention-to-treat analysis, and a short duration of follow-up, in some cases due to early termination of the clinical trial. Furthermore, many of these studies were funded by the supplement manufacturer. Benfotiamine has also shown symptomatic benefit for diabetic neuropathy when used in combination with other B vitamins. These combination products have combined benfotiamine 50 mg with vitamin B12 250 mcg (Milgamma, Worwag Pharma) (98024); and benfotiamine 40 mg with vitamin B6 90 mg and vitamin B12 250 mcg (Milgamma N, Worwag Pharma) (82799).

POSSIBLY INEFFECTIVE

• Diabetic nephropathy. Oral benfotiamine does not seem to improve markers of diabetic nephropathy. Details: Some clinical research shows that taking benfotiamine (Benfogamma, Worwag Pharma) 300 mg three times daily for 12 weeks does not reduce urinary albumin excretion or improve markers of kidney injury, endothelial dysfunction, or inflammation when compared with placebo in patients with diabetic nephropathy (98035,98039).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Small clinical studies suggest that oral benfotiamine may modestly improve symptoms and reduce alcohol consumption in some patients with alcohol use disorder. Details: One clinical trial in alcohol-dependent adults not seeking to quit drinking shows that taking benfotiamine 600 mg daily for 24 weeks decreases total alcohol consumption when compared to baseline; however, there was no difference between treatment and placebo groups. A greater benefit was found in female versus male participants (98046). A follow-up clinical trial in males with severe alcohol use disorder shows that taking benfotiamine 600 mg daily for 6 months does not improve overall psychiatric symptoms associated with alcohol use disorder; however, it might improve obsessive-compulsive and phobic anxiety symptom scores when compared with placebo (98048). Both studies had a drop-out rate above 40%, which is said to be expected in this patient population.
• Alzheimer disease. It is unclear if oral benfotiamine helps to prevent Alzheimer disease onset or progression. Details: One small clinical study in patients with mild Alzheimer disease or amnestic mild cognitive impairment (aMCI) shows that taking benfotiamine 300 mg twice daily for 12 months seems to improve cognition, measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the clinical dementia rating (CDR) score, when compared with placebo. The benefit was especially prevalent in patients without the APOE4 genotype. There were no improvements in activities of daily living or neuropsychiatric symptoms (105466). This study was limited by its small size and the lack of certainty that amyloid plaques were the primary cause of cognitive impairment.
• Osteoarthritis. Oral benfotiamine has only been evaluated in combination with other B vitamins; its effect when used alone is unclear. Details: One small clinical trial in adults with osteoarthritis shows that taking a specific combination product containing benfotiamine 50 mg, vitamin B6 50 mg, and vitamin B12 500 mcg (Vonder, Cosme Farma Laboratories) three times daily for 24 weeks modestly decreases pain and stiffness, improves functional ability, and reduces markers of inflammation when compared to baseline (98045). The validity of these findings is limited by the lack of a comparator group. Additionally, the effect of benfotiamine alone in patients with osteoarthritis is unclear.
• Peripheral neuropathy. It is unclear if oral benfotiamine is beneficial in patients with alcohol-induced peripheral neuropathy. Details: One small clinical study in patients with alcohol-induced peripheral neuropathy shows that taking benfotiamine (Benfogamma, Worwag Pharma) 320 mg daily for 4 weeks, followed by 120 mg daily for 4 weeks, improves overall neuropathy symptom scores when compared with placebo or a specific combination product (Milgamma N, Worwag Pharma) containing benfotiamine, vitamin B6, and vitamin B12. However, benfotiamine does not improve pain intensity, coordination, sensory function, or reflexes when compared with placebo or the combination product (98025). It is unclear why benfotiamine alone demonstrated some benefit while the combination product containing the same dose of benfotiamine did not. Further research is needed to determine the effects of benfotiamine, if any, for alcohol-induced peripheral neuropathy.
• Rheumatoid arthritis (RA). Oral benfotiamine has only been evaluated in combination with other B vitamins; its effect when used alone is unclear. Details: One small clinical trial in adults with RA receiving conventional disease-modifying antirheumatic drugs shows that taking a specific combination product containing benfotiamine 50 mg, vitamin B6 50 mg, and vitamin B12 500 mcg (Vonder, ACME Lifescience) twice daily for 12 weeks decreases inflammatory disease activity, improves markers of endothelial dysfunction, and reduces patient-rated disability scores when compared to baseline (98042). The lack of a control group limits the validity of these findings. Additionally, the effect of benfotiamine alone is unclear. More evidence is needed to rate benfotiamine for these uses.

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POSSIBLY INEFFECTIVE

• Autism spectrum disorder. Oral carnosine does not seem to improve symptoms of autism spectrum disorder. Details: A meta-analysis of three clinical trials in children aged 3-16 years with autism shows that taking carnosine does not improve symptoms of autism, including socialization, behavior, and communication, when compared with placebo (106082). Studies included in the analysis were small to moderate in size and used carnosine 500-800 mg, or 10-15 mg/kg, daily for 8 weeks (39926,100483,106081).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral carnosine has only been evaluated in combination with anserine; its effect when used alone is unclear. Details: Meta-analyses of a few small clinical studies suggest that taking a combination of carnosine and anserine 1 gram daily in a 1:2 or 1:3 ratio for 3 months improves some, but not all, measures of cognitive function and memory when compared with placebo (106086,111263). It is unclear if these findings are due to carnosine, anserine, or the combination.
• Alzheimer disease. Although there is interest in using oral carnosine for Alzheimer disease, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Athletic performance. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some research has evaluated carnosine in combination with beta-alanine. One small clinical study in muscle-fatigued healthy males shows that taking a combination of carnosine 2 grams plus beta-alanine 2 grams as a single dose 4 hours prior to testing increases maximal voluntary muscle contractions during knee extensions by 15% and jump height by 6% when compared with placebo. However, muscle pain was increased after 24 hours following use of carnosine and beta-alanine (94232). In another small clinical trial in healthy males, taking a single dose of carnosine 2.5 grams plus beta-alanine 2.5 grams (DDM Carnosina, Omeopiacenza Srl, Pontenure) does not affect most measures of athletic performance, including perceived exertion, work rate, maximum workload, and oxygen use, when compared with placebo. However, there was a small benefit on the ventilatory threshold during one test (106079). Other research has evaluated carnosine in combination with anserine. One small clinical study shows that taking a single dose of a specific chicken breast extract (CBEX) 40 grams containing 1.5 grams of carnosine and anserine orally does not affect power during maximal cycle ergometer sprints when compared with placebo in healthy active males (39938). However, a very small study shows that taking a single dose of pure carnosine and anserine 20 mg/kg each improves power by 6.1% in the first 5 seconds of a cycling performance test following 6-minutes of high intensity cycling. There was no effect on mean power, time to peak power, or time to power drop during the performance test. When power was measured over three consecutive cycling performance tests, peak power was increased by 2.5% when compared with placebo (106085).
• Cataracts. Although there is interest in using oral carnosine for cataracts, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Cognitive impairment. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of three clinical trials shows that taking a combination of carnosine and anserine 1 gram daily in a 1:2 or 1:3 ratio for 12 weeks modestly improves global cognitive function when compared with placebo (106086). However, there was no evidence of benefit in any of the individual small studies included in the analysis. Also, only one study was limited to patients with mild cognitive impairment.
• Corneal ulceration. Although there is interest in using topical carnosine for corneal ulceration, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Depression. It is unclear if oral carnosine is beneficial for depression. Details: Preliminary clinical research in patients with major depressive disorder shows that taking carnosine 400 mg twice daily while initiating treatment with citalopram, titrated up to a dose of 40 mg daily, for 6 weeks improves symptoms of depression, as measured on the Hamilton Depression Rating Scale (HAM-D), when compared with placebo plus citalopram (103289). It is unclear whether carnosine is beneficial as an adjunct treatment in patients who have already been treated with antidepressants.
• Diabetes. It is unclear if oral carnosine is beneficial for diabetes. Details: A meta-analysis of three small clinical studies in patients with type 2 diabetes shows that taking carnosine 1 gram two or three times daily for 12 weeks or 6 mg/kg three times daily for 8 weeks reduces glycated hemoglobin (HbA1c) by 1.5% and fasting blood glucose by 12.4 mg/dL when compared with placebo (111263). However, one of the studies included in this analysis evaluated carnosine in combination with alpha-lipoic acid 7 mg/kg and thiamine 1 mg/kg (98682).
• Diabetic nephropathy. It is unclear if oral carnosine is beneficial for diabetic nephropathy. Details: A small clinical trial in patients with type 2 diabetes and diabetic nephropathy shows that taking carnosine (Tokai Bussan Co., Ltd) 1 gram twice daily for 12 weeks does not improve levels of blood urea nitrogen or serum creatinine, or improve glomerular filtration rate, when compared with placebo. However, there is a small improvement in urinary levels of transforming growth factor (TGF)-beta, a marker of renal injury in these patients (106083).
• Diabetic neuropathy. Although there is interest in using oral carnosine for diabetic neuropathy, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Dry mouth. Topical carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with dry mouth shows that use of a specific mucoadhesive tablet (Aqualief, Helsinn Healthcare SA), containing a combination of carnosine and Hibiscus sabdariffa calyces, 400 mg three times daily after meals for 6 days increases saliva production and improves symptoms of dry mouth when compared to baseline. While saliva production was also increased in patients taking placebo, the increase was 3-fold greater with the combination product, and significant improvements in dry mouth symptoms were lacking in the placebo group (103288). In another small trial in patients with radiation-induced dry mouth, taking the same tablets (marketed as Salifluss, Metis Healthcare srl) for 8 days increases saliva production by about 30% when compared with placebo. However, symptoms of dry mouth were not improved (106087). It is unclear if these findings are due to carnosine, Hibiscus sabdariffa, or the combination.
• Dry skin. Topical carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with diabetes and severe dry skin of the foot shows that using a cream containing urea 5%, arginine 0.5%, and carnosine 0.01% (Ureadin Podos Db cream) twice daily for 8 months improves skin hydration and reduces xerosis when compared with a control emollient cream. The carnosine cream reduced xerosis by 91% over baseline, compared with a 23% reduction with the control cream (93999).
• Glaucoma. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with primary open angle glaucoma shows that taking a specific combination supplement (Gangliolife, SOOFT Italia) as two tablets twice daily for 1 year in addition to standard topical therapy results in a decrease in intraocular pressure when compared with standard therapy alone. One tablet of the supplement contains carnosine 50 mg, coleus extract 150 mg (standardized to 10% forskolin), homotaurine 100 mg, vitamin B1 1.1 mg, vitamin B2 1.4 mg, vitamin B6 1.4 mg, folic acid 0.2 mg, and magnesium 150 mg (91886). It is not clear if this effect is due to carnosine, the other ingredients, or the combination.
• Gulf war syndrome. It is unclear if oral carnosine is beneficial in patients with Gulf war syndrome. Details: In patients with Gulf war syndrome, preliminary clinical research shows that taking carnosine 500 mg, 1000 mg, or 1500 mg daily as add-on therapy for 4 weeks each, and then tapered over 2 weeks, has little benefit on symptoms associated with this illness. Taking carnosine modestly reduces the number of patients with diarrhea and also modestly improves some scores on specific cognitive tests. However, other symptoms of the illness, such as fatigue, pain, and reduced activity, were not improved (93996).
• Heart failure. It is unclear if oral carnosine is beneficial for heart failure. Details: Preliminary clinical research in patients using standard treatment shows that taking carnosine 500 mg daily for 6 months might improve the peak oxygen uptake by 4.5% during a cardiopulmonary stress test, compared to a decrease of 3.8% in patients not using carnosine. This change resulted in improvements in maximal workload and a 59.4-meter increase in 6-minute walking distance, compared to a decrease of 10.6 meters in the control group (94235).
• Hyperlipidemia. It is unclear if oral carnosine is beneficial in patients with hyperlipidemia. Details: Meta-analyses of mostly small clinical trials show that taking carnosine 1-3 grams daily for up to 12 weeks does not improve total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides when compared with placebo. (103287,111263). However, it is unclear if these findings can be generalized to patients with hyperlipidemia; the studies included in this analysis focused on patients who were obese or had diabetes or impaired glucose tolerance.
• Metabolic syndrome. It is unclear if oral carnosine is beneficial for patients with metabolic syndrome. Details: Observational research in adults at risk for metabolic syndrome has found that taking carcinine, a metabolite of carnosine, 60 mg daily for 8 weeks is associated with improvements in blood glucose, glycated hemoglobin, serum insulin, insulin resistance, and total cholesterol when compared with a control group (111265). The validity of these findings is limited the retrospective nature of the study, which includes a lack of randomization, blinding, and placebo control.
• Obesity. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that taking a specific product containing cinnamon extract 456 mg, chromium guanylate 2.5 mg, and carnosine 400 mg (Glycabiane, PiLeJe) daily for 4 months reduces fasting blood glucose levels and fat-free mass when compared with placebo. However, there were no changes in glycated hemoglobin, insulin sensitivity, or body weight (94234). It is not clear if these effects are due to carnosine, the other ingredients, or the combination.
• Obsessive-Compulsive Disorder (OCD). It is unclear if oral carnosine is beneficial for OCD. Details: Preliminary clinical research shows that taking carnosine 500 mg twice daily in combination with fluvoxamine for 10 weeks reduces compulsive symptoms, but not obsessive symptoms, in adults with moderate to severe OCD when compared with fluvoxamine alone. However, the degree of symptom reduction might not be considered clinically meaningful (97338).
• Peptic ulcers. Although there is interest in using oral carnosine for peptic ulcers, there is insufficient reliable information about the clinical effects of carnosine for this use.
• Pressure ulcers. It is unclear if oral carnosine is beneficial for pressure ulcer healing. Details: Preliminary clinical research shows that taking carnosine might help with the healing of pressure ulcers in patients also treated with standard care. Taking carnosine 116 mg for 4 weeks increased the rate of healing by approximately 50% when compared with a control group receiving standard care alone (97601).
• Schizophrenia. Small clinical studies suggest that oral carnosine does not improve symptoms of schizophrenia. Details: One small clinical study of patients with schizophrenia or schizoaffective disorder who are on stable doses of antipsychotics shows that taking carnosine titrated from 500 mg daily up to 2000 mg over 4 weeks, continued for an additional 8 weeks and then tapered for 2 weeks, does not improve symptoms of depression or schizophrenia or improve quality of life when compared with placebo (93997). Another small clinical study in patients with schizophrenia with predominantly negative symptoms shows that taking carnosine 400 mg daily for 12 weeks and then titrating up to 800 mg daily until 24 weeks does not improve positive or negative symptoms when compared with placebo. Measures of cognitive function, with the exception of an executive functioning test, were not improved with carnosine over placebo (111264). More evidence is needed to rate carnosine for these uses.

(Read more about CARNOSINE)

EFFECTIVE

• Thiamine deficiency. Oral thiamine prevents and treats thiamine deficiency syndromes. Details: Thiamine deficiency is treated with oral thiamine 5-30 mg daily as a single dose or in divided daily doses for one month. For severe deficiency, thiamine up to 300 mg daily can be used (15).Thiamine deficiency can occur in people with malabsorption conditions such as alcohol use disorder, cirrhosis, and gastrointestinal diseases; in those with inadequate intake due to anorexia, nausea, and vomiting; and in those with increased requirements, including pregnancy, increased carbohydrate intake, increased physical activity, hyperthyroidism, infection, and liver disease. However, deficiency is rare with these conditions (15). The elderly might also be at increased risk for subclinical thiamine deficiency (11076).
• Wernicke-Korsakoff syndrome (WKS). Parenteral thiamine is effective for treating symptoms of WKS. Details: Parenteral administration of thiamine 5-200 mg daily for 2 days decreases the risk of developing WKS and decreases symptoms of WKS in acute alcohol withdrawal. Between 30% and 80% of alcoholics are suspected to have thiamine deficiency (11075). An optimal dose for treating WKS has not been established; however, early research suggests that a 200 mg intramuscular dose may be more effective than lower doses (11075). In contrast, a moderate-sized clinical trial in adults with a history of heavy alcohol use who were asymptomatic or symptomatic for WKS shows that there is no benefit to administering high doses (300 mg 3 times daily) compared with medium (100 mg 3 times daily) or low (100 mg daily) doses of parenteral thiamine on cognitive or neurological functioning (111690). The study may have been inadequately powered to detect a difference between groups.

POSSIBLY EFFECTIVE

• Dysmenorrhea. Oral thiamine might reduce pain in some patients with dysmenorrhea. Details: A clinical study in adolescent Iranian females with dysmenorrhea shows that taking thiamine 100 mg alone or along with fish oil 500 mg daily for 2 months moderately reduces pain intensity and duration when compared with placebo (89341). Another preliminary clinical study in Indian females 12-21 years of age with moderate to severe primary dysmenorrhea shows that taking thiamine 100 mg daily for 90 days eliminates pain in 87% of participants when compared to baseline (77820). The validity of this finding is limited by the lack of a placebo group. Furthermore, available research was conducted in India and Iran, so it is unclear if these findings are generalizable to other geographic locations.

POSSIBLY INEFFECTIVE

• Coronary artery bypass graft (CABG) surgery. Intravenous thiamine does not seem to improve outcomes after CABG surgery. Details: A small clinical study in adults undergoing CABG surgery with cardiopulmonary bypass shows that giving intravenous thiamine 200 mg immediately prior to surgery and immediately after surgery does not improve clinical outcomes or lactate levels when compared with placebo (97010). Larger doses of thiamine also don't seem to be beneficial. Another small clinical study in patients receiving CABG with cardiopulmonary bypass shows that giving thiamine 600 mg intravenously on the day of surgery, and 400 mg daily for three postoperative days, does not improve postoperative outcomes when compared with placebo (103000).
• Heart failure. Most research suggests that oral or intravenous thiamine does not improve outcomes in patients with heart failure. Details: Observational research suggests that having heart failure is associated with 2.5-fold increased odds of having thiamine deficiency, possibly because of diuretic use, intestinal malabsorption, and metabolism changes. However, it is unclear if thiamine supplementation is beneficial. A meta-analysis of 2 small clinical trials in adults with systolic heart failure and unclear thiamine status shows that thiamine 200-300 mg given orally or by IV for 7-28 days improves left ventricular ejection fraction (LVEF) by 3% when compared with control (97012). However, other meta-analyses and clinical studies in adults with heart failure with or without thiamine deficiency show that taking intravenous, intramuscular, or oral thiamine 100-500 mg daily does not improve LVEF fraction, left ventricular end-diastolic volume, dyspnea, mortality, hospitalization, or exercise tolerance when compared with placebo or control (103002,111682,111686,111688).
• Mosquito repellent. Oral thiamine does not seem to repel mosquitos. Details: Clinical research in healthy volunteers shows that taking thiamine does not improve mosquito repellency when compared with taking vitamin C as a control (18016).
• Sepsis. Intravenous or oral thiamine, alone or in combination with vitamin C and hydrocortisone, does not seem to reduce mortality or prevent organ failure in sepsis or septic shock. Details: Multiple meta-analyses of small clinical studies in patients with septic shock show that intravenous or oral thiamine 100-500 mg 2-3 times daily for 3-7 days is no better than placebo for improving mortality, end-organ damage, number of ventilator-free days, and duration of intensive care unit (ICU) stay (105443,107717,107727,111689). One meta-analysis suggests that administration of thiamine alone increases the risk of mortality in these patients (111689). Subgroup analyses including only higher quality studies also fail to show a benefit of thiamine (107717). Another recent small clinical trial in patients with septic shock shows that receiving the same dose of intravenous thiamine does not increase vasopressor-free days when compared with placebo (105441). Intravenous thiamine 200 mg every 12 hours has also been evaluated in combination with intravenous vitamin C 1.5-2 grams and hydrocortisone 50-200 mg every 6-12 hours for 4-10 days (HAT therapy). While some retrospective research found HAT therapy to be beneficial (100315,102980,111689), high-quality, prospective clinical research has shown no benefit (105447,109956,111689). Meta-analyses in patients with sepsis and septic shock shows that receiving HAT therapy does not improve mortality, kidney injury, number of ventilator-free days, or ICU length of stay when compared with control (102129,104027,104028,104032,102998,105447,109956,111642,111689). Additionally, the meta-analyses suggest that HAT therapy does not reverse shock or improve sequential organ failure assessment (SOFA) scores (109556,111642). However, one meta-analysis found that HAT therapy shortened the duration of vasopressor use when compared with placebo (111642). Long-term follow up from a study in patients with sepsis-induced respiratory and/or cardiovascular dysfunction shows that receiving HAT therapy does not improve cognitive, psychological, or functional status after 6 months and, for immediate memory scores and development of posttraumatic stress disorder, HAT therapy was less beneficial when compared with placebo (111299).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute kidney injury (AKI). It is unclear if oral or intravenous thiamine is beneficial for treating or preventing AKI. Details: Observational research in adults admitted to the intensive care unit (ICU) with AKI has found that treatment with thiamine (dose unspecified) within the first 48 hours of admission is associated with 39% lower odds of in-hospital mortality and 28% higher odds of kidney function recovery when compared with patients that did not receive thiamine. Receiving thiamine was also associated with a 0.5-day reduction in ICU length of stay (107719).
• Anxiety. Although there is interest in using oral thiamine for anxiety, there is insufficient reliable information about the clinical effects of thiamine for this purpose.
• Cardiac arrest. It is unclear if intravenous thiamine reduces the risk of death after resuscitation from cardiac arrest. Details: A small clinical study in adults resuscitated from cardiac arrest shows that receiving intravenous thiamine 100 mg every 8 hours for 7 days does not reduce 28-day mortality when compare with a normal saline placebo (105442).
• Cardiovascular disease (CVD). It is unclear if oral thiamine is beneficial for treating or preventing CVD. Details: Population research in Korea has found that insufficient dietary thiamine intake (daily intake of less than 1.22 mg in males or 1.03 mg in females) is associated with a 16% increased odds of developing angina or myocardial infarction when compared with sufficient dietary thiamine. However, the effects of thiamine supplementation on CVD have not been studied (107725).
• Cataracts. Small studies suggest that increased dietary thiamine might help prevent cataracts. Details: Observational research has found that a high dietary intake of thiamine 10 mg daily is associated with 40% lower odds of nuclear cataracts (6378). Other population research has found that higher dietary intake of thiamine is associated with a modestly reduced risk of age-related lens opacification (14301).
• Cervical cancer. It is unclear if oral thiamine reduces the risk of developing cervical cancer. Details: Epidemiological research has found that increasing intake of thiamine from dietary and supplemental sources, along with folic acid, riboflavin, and vitamin B12, is associated with a lower odds of precancerous cervical lesions (11074).
• Child development. It is unclear if supplementing breastfeeding females with oral thiamine improves infant neurocognitive development. Details: Preliminary clinical research shows that supplementing breastfeeding females with oral thiamine, 1.2-10 mg daily for 22 weeks, starting at 2 weeks postpartum, does not improve most cognitive or neurodevelopmental scores in the child when compared with placebo. However, one subgroup analysis suggests that thiamine supplementation may improve language scores (107726).
• Cognitive function. Oral thiamine has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in healthy, middle-aged adults shows that taking a combination product containing thiamine hydrochloride 50 mg, other group B vitamins, bacopa, and ginkgo daily for 12 weeks does not improve measures of memory, attention, cognition, mood, or stress reactivity when compared with placebo. Subgroup analysis shows a possible benefit of the combination supplementation on measures of attention in those with an optimal diet at baseline (111334). It is unclear if these findings are due to thiamine, other ingredients, or the combination.
• Coronavirus disease 2019 (COVID-19). It is unclear if intravenous or oral thiamine improves clinical outcomes in patients hospitalized with COVID-19. Details: A small observational study of adults admitted to the intensive care unit with COVID-19 has found that treatment with intravenous or oral thiamine 100 mg daily for an average of 7 days is associated with a 63% reduction in the odds of death within 30 days when compared with control. However, there was no associated reduction in duration of hospitalization or mechanical ventilation (107721). In addition, a small observational study of adults with encephalopathy that were mechanically ventilated secondary to COVID-19 has found that taking thiamine 500 mg three times daily orally for 5 days improves neurological manifestations, including ophthalmoparesis and ataxia, when compared with baseline. The validity of this study is limited by the lack of a comparator group (107722).
• Critical illness (trauma). It is unclear if oral or intravenous thiamine is beneficial in patients with critical illness. Details: A meta-analysis of critically ill patients shows that treatment with oral or intravenous thiamine 100-600 mg daily for up to 7 days does not affect the need for mechanical ventilation, duration of hospital stay, or mortality when compared with control (107727).
• Delirium. It is unclear if oral or intravenous thiamine helps to prevent or treat delirium. Details: In critically ill patients, a meta-analysis of clinical research shows that treatment with oral or intravenous thiamine 100-600 mg daily for up to 7 days reduces the odds of developing delirium by 42% when compared with control (107727). However, some observational research in adults with septic shock has found that receiving intravenous thiamine 400 mg daily with vitamin C 6 grams daily, both in divided doses, is not associated with reduced delirium when compared with control (103001). In non-critically ill, hospitalized adults with altered mental status, retrospective, observational research has also found that administration of oral or intravenous thiamine is not associated with improved cognitive function or reduced in-hospital mortality when compared with control (107723). Preliminary clinical research in adults undergoing an allogeneic hematopoietic stem cell transplant also shows that administering thiamine 200 mg three times a day intravenously for 7 days does not prevent delirium or shorten duration of delirium when compared with placebo (107718).
• Dementia. It is unclear if oral thiamine is beneficial for the prevention of dementia. Details: Observational research in patients with alcohol use disorder has found that taking thiamine is associated with a 24% to 46% lower risk of developing dementia when compared with not taking thiamine (102999).
• Depression. It is unclear if oral thiamine is beneficial in patients with depression. Details: Meta-analyses of population research in adults has found that high dietary consumption of thiamine is associated with a 10% to 31% lower risk of having depression when compared with low dietary consumption of thiamine. However, this research did not evaluate the effects of thiamine supplementation on depression (107133,107725). One small clinical study in adults with major depressive disorder shows that taking thiamine 300 mg daily in conjunction with fluoxetine 20 mg daily leads to greater improvements in depressive symptoms at 6 weeks when compared to fluoxetine with placebo. This benefit was no longer present at 12 weeks. This suggests that thiamine may accelerate improvement in symptoms during initiation of fluoxetine therapy (97013).
• Diabetes. It is unclear if oral thiamine is beneficial for type 2 diabetes or gestational diabetes. Details: A meta-analysis of 6 clinical studies in adults with type 2 diabetes shows that taking thiamine 100-300 mg or its derivative benfotiamine 120-900 mg daily for 1-3 months does not reduce glycated hemoglobin (HbA1c), fasting blood glucose, or postprandial blood glucose when compared with placebo (111681). A large, prospective cohort study in adults without type 2 diabetes suggests that the risk of new-onset diabetes is minimized in adults consuming thiamine 0.75-1.10 mg daily from the diet, while lower and higher thiamine intake levels are associated with an increased risk of new-onset diabetes (111685). Thiamine has also been studied for preventing gestational diabetes. A large, prospective cohort study in pregnant adults suggests that higher supplementation with thiamine during the first and second trimesters is associated with a lower risk of gestational diabetes when compared with lower levels of total thiamine intake. However, this effect was not found for dietary intake of thiamine, only supplementation. Additionally, the participants were mostly Han Chinese adults, limiting the generalizability of the findings to other populations (111680).
• Diabetic nephropathy. It is unclear if oral thiamine is beneficial for diabetic nephropathy. Details: A small clinical study in patients with early-stage diabetic nephropathy and microalbuminuria shows that taking thiamine 100 mg three times daily for 3 months decreases urinary albumin excretion, but does not affect glomerular filtration rate (GFR), when compared with placebo (16556).
• Diabetic neuropathy. Although there is interest in using oral thiamine for diabetic neuropathy, there is insufficient reliable information about the clinical effects of thiamine for this condition.
• Dry eye. Oral thiamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with dry eye suggests that adding unspecified doses of thiamine and mecobalamin to treatment with daily artificial tears and corticosteroid drops might slightly improve overall symptoms when compared with only artificial tears and corticosteroid drops for 1 month. There were no differences between groups at 2 months (105444). This finding is limited due to incomplete reporting and a lack of adjustment for multiple hypothesis testing.
• Dyslipidemia. It is unclear if oral thiamine is beneficial for treating or preventing dyslipidemia. Details: A meta-analysis of 3 clinical studies in adults with type 2 diabetes shows that taking thiamine 100-300 mg or its derivative benfotiamine 120-900 mg daily for 1-3 months does not improve low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides when compared with placebo (111681). Observational research in Korea suggests that insufficient dietary thiamine intake (daily intake of less than 1.22 mg in males or 1.03 mg in females) is associated with 10% higher odds of developing dyslipidemia when compared with sufficient dietary thiamine intake. However, the effects of thiamine supplementation on dyslipidemia have not been studied (107725).
• Emergence delirium. It is unclear if intravenous thiamine helps to prevent emergence delirium in patients after surgery. Details: One clinical study in adults in the intensive care unit (ICU) after gastrointestinal surgery shows that receiving intravenous thiamine 200 mg daily for 3 days is associated with up to 84% lower odds of emergence delirium on the first two days, but not on the third day, when compared with a normal saline control (105440).
• Fatigue. It is unclear if oral thiamine is beneficial in patients with fatigue. Details: A small clinical crossover study in patients with chronic fatigue and inflammatory bowel disease (IBD) shows that taking thiamine 600-1800 mg daily for 20 days reduces fatigue scores when compared with placebo (105438). Taking oral thiamine 300 mg daily for an additional 12 weeks did not seem to affect fatigue scores when compared with placebo. However, an observational follow-up study found that those who self-continued thiamine for an additional 24 weeks after the study ended reported lower fatigue scores when compared with those who did not self-continue thiamine (107720).
• Glaucoma. Although there is interest in using oral thiamine for glaucoma, there is insufficient reliable information about the clinical effects of thiamine for this condition.
• Herpes zoster (shingles). It is unclear if subcutaneous thiamine is beneficial in patients with shingles. Details: A small clinical trial shows that receiving subcutaneous thiamine 100 mg injections six times weekly for 4 weeks reduces itching by at least 30% in 67% of patients with herpes zoster. However, thiamine does not appear to significantly reduce pain in most patients (90396).
• Hypertension. It is unclear if oral thiamine is beneficial in treating or preventing hypertension. Details: Population research in Korea has found that insufficient dietary thiamine intake (daily intake of less than 1.22 mg in males or 1.03 mg in females) is associated with a 5% increased odds of developing hypertension when compared with sufficient dietary thiamine. However, the effects of thiamine supplementation on hypertension have not been studied (107725).
• Impaired glucose tolerance (prediabetes). It is unclear if oral thiamine is beneficial in patients with prediabetes. Details: A very small clinical trial in patients with prediabetes shows that taking thiamine 100 mg by mouth three times daily for 6 weeks modestly decreases 2-hour postprandial plasma glucose levels when compared to baseline and decreases fasting blood glucose levels when compared with placebo (91168).
• Kidney failure. Oral thiamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary, low-quality, clinical research in adults with kidney failure undergoing regular hemodialysis shows that taking oral thiamine 90 mg daily with folic acid 30 mg daily for 96 weeks reduces overall mortality by 67% and improves cognitive scores by 31% when compared with no intervention (107724). It is unclear if this effect is due to thiamine, folic acid, or the combination.
• Migraine headache. It is unclear if dietary thiamine is beneficial for the prevention or treatment of migraine headache. Details: A large, retrospective, cross-sectional study suggests that higher dietary intake of thiamine is associated with lower odds of severe headache or migraine, especially in females (111684). The validity of these effects is limited by the subjective outcome measures and retrospective study design.
• Pneumonia. It is unclear if thiamine is beneficial for patients with pneumonia. Details: A large retrospective cohort study in adults hospitalized with pneumonia and active alcohol use disorder suggests that parenteral administration of thiamine is associated with reduced 14-day mortality and more frequent discharges home, but not a shorter length of stay or fewer ICU transfers, when compared with no thiamine use. Furthermore, parenteral thiamine doses above 200 mg do not appear to improve mortality but may be associated with longer length of stay and less frequent discharges home when compared with low oral doses of thiamine or parenteral thiamine at doses under 200 mg (111679). The validity of these effects is limited by the retrospective study design.
• Ventilator-associated pneumonia (VAP). It is unclear if oral or parenteral thiamine is beneficial for patients with VAP. Details: A retrospective study in adults with VAP in the intensive care unit (ICU) suggests that supplementation with intravenous or oral thiamine may be associated with reduced ICU and in-hospital mortality (111683). The validity of these effects is limited by the retrospective study design. More evidence is needed to rate thiamine for these uses.

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LIKELY SAFE ...when used orally and appropriately. Benfotiamine has been used safely at doses of 150-600 mg daily for up to 24 weeks (82931,98024,82799,98032,98045,98046). Benfotiamine has also been used safely at doses of 900 mg daily for up to 6 weeks (98031).

PREGNANCY AND LACTATION:
Insufficient reliable information is available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately. In clinical trials, carnosine has been used safely at doses of 200-1500 mg daily, alone or in combination with other ingredients (91886,93996,94000,103289). There is insufficient reliable information available about the safety of carnosine when used topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Carnosine has been used in with apparent safety in children 3-16 years of age at doses of 500-800 mg daily for up to 8 weeks (39926,100483).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately. A tolerable upper intake level (UL) has not been established for thiamine, and doses up to 50 mg daily have been used without adverse effects (15,6243). ...when used intravenously or intramuscularly and appropriately. Injectable thiamine is an FDA-approved prescription product (15,105445).

CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts. A tolerable upper intake level (UL) has not been established for healthy individuals (6243).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 1. 4 mg daily. A tolerable upper intake level (UL) has not been established for healthy individuals (3094,6243).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking carnosine with antidiabetes drugs might increase the risk of hypoglycemia.  Details Some, but not all, preliminary clinical research shows that carnosine might reduce fasting blood glucose levels (98682,103287,106083,111263).

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TRIMETHOPRIM (Proloprim) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Probable •  Level of Evidence = B Trimethoprim might increase blood levels of thiamine.  Details In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations (111678).

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General ...Orally, benfotiamine is generally well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.

Dermatologic ...Orally, allergic skin reactions have been reported in two out of 98 patients taking benfotiamine 300-600 mg daily for 6 weeks in one clinical study (98032). The rate of adverse events was not different between treatment and placebo groups.

Gastrointestinal ...Orally, slight gastrointestinal discomfort has been reported in six out of 98 patients taking benfotiamine 300-600 mg daily for 6 weeks in one clinical study (98032). The rate of adverse events was not different between treatment and placebo groups.

Immunologic ...Orally, allergic skin reactions have been reported in two out of 98 patients taking benfotiamine 300-600 mg daily for 6 weeks in one clinical study (98032). The rate of adverse events was not different between treatment and placebo groups.

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General ...Orally and topically, carnosine is generally well tolerated.

Dermatologic ...Orally, rash and itchiness have been reported with carnosine (93997).

Gastrointestinal ...Orally, decreased appetite, dry mouth, and small weight changes have been reported with carnosine (93997).

Musculoskeletal ...Orally, foot and joint pain have been reported with carnosine (93997).

Neurologic/CNS ...Orally, sporadic hyperactivity has been reported with carnosine. This may be alleviated by decreasing the dose (39926). Other adverse effects reported with oral use include sleepiness, slurred speech, lethargy, and feelings of pins and needles (93997).

Psychiatric ...Orally, vivid dreams have been reported with carnosine (93997).

Pulmonary/Respiratory ...Orally, pneumonia has been reported with carnosine (93997).

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General ...Orally and parenterally, thiamine is generally well tolerated.
Serious Adverse Effects (Rare):
Parenterally: Hypersensitivity reactions including angioedema and anaphylaxis.

Immunologic ...Orally, thiamine might rarely cause dermatitis and other allergic reactions. Parenterally, thiamine can cause anaphylactoid and hypersensitivity reactions, but this is also rare (<0.1%). Reported symptoms and events include feelings of warmth, tingling, pruritus, urticaria, tightness of the throat, cyanosis, respiratory distress, gastrointestinal bleeding, pulmonary edema, angioedema, hypotension, and death (15,35585,105445).
In one case report, a 46-year-old female presented with systemic allergic dermatitis after applying a specific product (Inzitan, containing lidocaine, dexamethasone, cyanocobalamin and thiamine) topically by iontophoresis; the allergic reaction was attributed to thiamine (91170).

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