DISCUSSION: ADVANCED B COMPLEX was designed to provide the most advanced forms of B vitamins in the most scientifically discerning ratios available. These nutrients help metabolize carbohydrates, proteins and fats for energy and support tissue and red blood cell formation.
|NPN (what's this?)||Product Code||Size||Per Capsule||Vegetarian|
|80025646||AOR04167||90 Vegi-Caps||602 mg||Vegetarian|
|80025646||AOR04206||180 Vegi-Caps||602 mg||Vegetarian|
|Serving Size: 3 Vegi-Caps|
|B1 (Benfotiamine)||100 mg|
|B2 (Riboflavin-5-phosphate sodium)||7.5 mg|
|B3 (Niacin – from 388 Inositol Hexanicotinate)||353 mg|
|B5 (Pantethine, Calcium d-Pantothenate)||300 mg|
|B6 (Pyridoxal-5-phosphate)||100 mg|
|B12 (Methylcobalamin)||1000 mcg|
|Folic Acid (calcium L-5-MTHF)||1000 mcg|
|Choline bitartrate (provides 240 mg of choline)||600 mg|
|Inositol (from Inositol Hexanicotinate, Inositol)||393 mg†|
|†85 mg from Inositol Hexanicotinate, 308 mg from Inositol. Non-medicinal ingredients: microcrystalline cellulose, dicalcium phosphate, silicon dioxide, sodium stearyl fumarate. Capsule: hypromellose, chlorophyll.|
AOR Guarantees: that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, peanuts, sesame seeds, sulphites, mustard, dairy, soy, eggs, fish, shellfish or any animal byproduct.
Adult Dosage: Take 1 capsule one to three times daily with food, or as directed by a qualified health care practitioner.
Cautions: Consult a health care practitioner for use beyond 8 weeks. People with thiamine hypersensitivity should not take this product.
Pregnancy/Nursing: Consult a health care practitioner
The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide or replace medical advice to individuals from a qualified health care professional. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes.
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The B-complex is an officially recognized grouping of eight essential vitamins. Some sources dispute that number, claiming that there are in fact nine or ten (or more) vitamins within the B-complex, yet within most official, academic, and scientific circles, the number is generally accepted as eight, and these are:
• Vitamin B1 (thiamin)
• Vitamin B2 (riboflavin)
• Vitamin B3 (niacin)
• Vitamin B5 (pantothenic acid)
• Vitamin B6 (pyridoxine)
•Vitamin B7 (biotin)
• Vitamin B9 (folic acid or folate)
• Vitamin B12 (cobalamin)
There is a great deal of biological activity for which this group of vitamins is responsible, and there is also a great deal of overlap between the respective functions of each vitamin in the B-complex family. However, most of the overlap is centered around the metabolism of the three macronutrients (protein, carbohydrates and fat). Other tasks more specific to certain members of the B-complex group of vitamins include support for the brain and central nervous system, the growth and development of red blood cells, the maintenance of healthy skin and muscle tone, immune function and hormone activity. Metaphorically speaking, the B-complex family of vitamins can be described as the ‘transmission fluid’ of the complex automobile that is the human body.
Vitamin B1 (a.k.a. thiamin): Thiamin is required to convert glucose and amino acids into energy as well as to develop red blood cells and maintain muscle tissue. Thiamin is converted by the body into its active coenzyme form thiamin pyrophosphate (TPP). TPP is a catalyst for pyruvate dehydrogenase (PDH), a key enzyme responsible for the conversion of pyruvate into the all-important acetyl-CoA, which is central to the Kreb’s Cycle that in turn generates cellular respiration. In ‘underdeveloped’ countries, B1 deficiencies are usually found where foods made from white flour are staples. In the ‘developed’ world, where such foods are often fortified with thiamin, the main reasons for deficiencies are alcohol consumption (which impairs thiamin absorption) and poor dietary choices. The most serious deficiencies can lead to degenerative nerve disorders such as beriberi and Wernicke-Korsakoff syndrome, diseases also common among chronic alcoholism.
Thiamin deficiency has also been linked to Type II Diabetes, particularly in the formation of advanced glycation end products (AGEs), which occur at an abnormally high rate among diabetics. Simply put, AGEs are cellular proteins that are damaged as a result of being exposed to glucose without the mediating action of a co-enzyme. Increased AGE occurrence is also commensurate with the aging process. Benfotiamine is a lipid-soluble form of thiamin that has been shown in studies to be 5 times more bioavailable than regular thiamin. In fact, clinical trials have demonstrated that benfotiamine can improve nerve function by 30% and decrease nerve pain by 50% among diabetics.
Vitamin B2 (a.k.a. Riboflavin): While playing a role in the energy metabolism of carbohydrates, fats, and proteins, B2 is particularly active in skin and vision health. B2 has long been used as an adjunct in the treatment of neonatal jaundice and has recently been added to anti-migraine protocols as well. Ariboflavinosis is the specific condition caused by riboflavin deficiency and its symptoms include sores around the mouth and swelling of the throat, cheilosis (cracks on the lips), and glossitis (inflammation of the tongue).
Vitamin B3 (a.k.a. Niacin): The derivatives of B3 form the basis of the oxidized and reduced forms of Nicotinamide Adenine Dinucleotide (NAD+ and NADH). The interaction between these coenzymes forms part of the basis (along with the aforementioned acetyl-CoA) of the Kreb’s cycle, generating cellular respiration and energy in the form of ATP. B3 also plays an essential role in DNA repair, removing toxic chemicals from the body, and assisting in hormone production. Niacin is also effective at inhibiting the release of low-density lipoproteins (or LDL [bad] cholesterol) into the blood from the liver, making it a treatment of choice for hyperlipidemia.
Deficiency in B3 (combined with a deficiency in the essential amino acid tryptophan) can lead to a disease known as pellagra, characterized by deramatitis, insomnia, diarrhea, weakness and progressive dementia. Most niacin supplements are in nicotinic acid form, which has been associated with a ‘flushing’ effect, an unpleasant warming and itching of the skin when taken at significant doses. Inositol hexanicotinate is a form of niacin that is free of this effect.
Vitamin B5 (a.k.a. Pantothenic acid): B5 is needed to form coenzyme A (later becoming acetyl-CoA), which is central to cellular respiration and energy production. Vitamin B5 has also been shown to have a positive effect on cholesterol levels, including lowered total and LDL (bad) cholesterol levels.
Vitamin B6 (a.k.a. Pyridoxine): Vitamin B6 is most commonly known as pyridoxine, but in fact B6 is comprised of three organic forms, namely pyridoxal, pyridoxine, and pyridoxamine. Each represents a different stage in the body’s metabolism of this important vitamin. Pyridoxal-5′-phosphate, or P5P, represents the advanced stage of this metabolism, the stage at which B6 has been converted into a coenzyme, a catalyst for at least 113 known essential enzymatic reactions in the body. These include the metabolism of all endogenous amino acids, including such particularly crucial ones as tyrosine, glutamine, cysteine and glycine. P5P is also important for the proper metabolism of essential fatty acids as well as the formation of red blood cells and neurotransmitters, making P5P a factor in optimal cognitive function as well. Notable features of the latter include the fact that P5P is required to convert tryptophan into serotonin as well as to release glucose from glycogen.
Indeed, a deficiency in vitamin B6 can lead to anemia, depression, dermatitis, hypertension, elevated levels of homocysteine and water retention, insomnia, premenstrual tension, irritability, muscle twitching, convulsions, and kidney stones. B6 has been successfully studied for its ability to enhance the immune system and alleviate the symptoms of autism, carpal tunnel syndrome (CTS), anemia, premenstrual syndrome (PMS), hyperhomocysteinemia and other conditions. While the aforementioned studies used conventional B6 supplementation (mainly pyridoxine hydrochloride), it must be remembered that only the P5P converted from pyridoxine can be used for nitrogen and protein metabolism and heme synthesis. This underlines the potential for P5P in supplement form, especially in cases where the body’s ability to synthesize it from its organic B6 forms is compromised in any way. In fact, it was found that in patients with impaired liver function, only 33% responded to pyridoxine hydrochloride supplementation with an increase in plasma P5P, where as all of the patients receiving P5P supplementation experienced an increase.
Vitamin B12 (a.k.a. cobalamin): Vitamin B12 has distinguished itself among the B-vitamins with the volumes of research attributable to its specific effects on neurological health. B12 is also very important to the methylation cycle. The successful studies with B12′s neuroprotective and neurogenerative benefits were conducted with the methylcobalamin (the active coenzyme) form of B12.
Vitamin B9 (a.k.a. folic acid or folate): Folic acid is needed for the synthesis of new red blood cells (which carry oxygen throughout the body) and DNA. Folic acid is often prescribed during pregnancy, as it reduces the risk of neural tube defects such as spina bifida in the fetus. A deficiency can also lead to megaloblastic anemia, a specific form of anemia caused by the inhibition of DNA synthesis in red blood cell production, as well as elevated levels of homocysteine.
Vitamin B7 (a.k.a. biotin): Biotin is another B vitamin that is involved in the metabolism of protein, carbohydrates and fats, and finally, although not strictly a vitamin, choline is an essential nutrient that is often grouped with the B-complex.
Choline & Inositol
Choline, a nitrogen-based organic compound that is found in the lipids of cell membranes, is a member of the B-vitamin family without a numeric designation. It plays an important role in the structural integrity of cells as well as in the movement of essential lipids across cell membranes, in important metabolic processes and in the synthesis of the key neurotransmitter acetylcholine. Inositol was also once considered a member of the b-vitamin family but now is not since the body can produce it. It is an important component of structural lipids and signaling molecules.
In summation, the B-complex family of vitamins is essential to processing and disseminating the fuel required to keep the evolutionist miracle known as the human body in constant operation. Maintaining the proper intake of this group of vitamins is indeed essential for keeping that operation as optimal as possible for as long as possible.
A study that investigated the role that B vitamins play in mitigating the effects of occupational stress on the body found that after individual differences in personality and work demands were statistically controlled, the vitamin B complex treatment groups reported significantly lower personal strain and a reduction in confusion and depressed/dejected mood after 12 weeks.
The study examined for the first time the efficacy of 3 months administration of two forms of high dose vitamin B complex on mood and psychological strain associated with chronic work stress. The results of the study are consistent with two previous studies examining multivitamin supplementation and personal (non-work) feelings of strain and suggestive of significant decreases in the experience of workplace stress after 90 day supplementation of a B multivitamin. Sixty participants completed the 3-month, double-blind, randomised, placebo-controlled trial in which personality, work demands, mood, anxiety and strain were assessed. Given the direct and indirect costs of workplace stress, these findings point to the utility of a cost-effective treatment for the mood and psychological strain effects of occupational stress.
The B complex is a popular supplement that people use to increase their level of energy and overall metabolic function.
The coenzyme form of B vitamins makes them readily available to the body and is an advantage for those that are not able to convert regular B vitamins into their more active forms. Many people can benefit from the use of B vitamins; however certain groups such as the elderly, those with a liver disorder, who have poor nutrition or who have certain illnesses may experience significant benefit. This form of vitamin also works longer in the body and provides a lasting metabolic energy source.
AOR offers the most potent B complex available on the market. One of the significant differences between AOR’s Advanced B Complex and other formulas is that the B vitamins are in the optimal dosages in order for them to have a potent effect in the body. Each of the B vitamins is in its co-enzyme form making it accessible for the body to use immediately.
Bertolini S, Donati C, Elicio N, et al. “Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.” Int J Clin Pharmacol Ther Toxicol. 1986 Nov; 24(11): 630-7.
Kira J, Tobimatsu S, Goto I. Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med. 1994 Feb; 33(2): 82-6.
Stough C et al. The effect of 90 day administration of a high dose vitamin B-complex on work stress. Hum Psychopharmacol. 2011 Oct;26(7):470-6.
Vitamin B6 (pyridoxine and pyridoxal 5′-phosphate) – monograph. Altern Med Rev. 2001 Feb;6(1):87-92.
Winkler G, Pal B, Nagybeganyi E, Ory I, Porochnavec M, Kempler P. “Effectiveness of different Benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.” Arzneimittelforschung. 1999 Mar; 49(3): 220-4.
Q: Does AOR use L-5-MTHF or D-5-MTHF? Or both?
A: D-5-MTHF is a more highly absorbed, ineffective and potentially harmful version of the activated folate 5-MTHF that is actually banned in Europe. Some products exist on the market that are a 50/50 mix of the L- and D-forms, which have questionable efficacy, and may be harmful. In accordance with AOR’s philosophy and quality control standards, all of AOR’s 5-MTHF products contain only the highest purity L-5-MTHF on the market, which is guaranteed to be greater than 99% L-5-MTHF. Look for the labels of all of AOR’s products containing 5-MTHF to be updated in the near future with this information.
Q: Is this the best form of folic acid for pregnant women and those trying to conceive?
A: Methyltetrahydrofolate (5-MTHF, which is the form of folic acid in this product) is the most biologically active form of folic acid, making it the best form for pregnancy and those trying to conceive.
Q: Can Advanced B Complex cause gastric ulcers?
A: Theoretically, some herbs and vitamins can irritate GI tissue. There’s no well-known side effects of vitamin-only supplementation that include actual ulcers, but vitamins (like anything else taken orally) can cause nausea or stomach upset (which a lot of people misinterpret as ulcers), especially when taken on an empty stomach. That can usually be dealt with by just taking with food or a glass of milk. It might also be aggravating an existing condition.
Q: Why isn’t there PABA in Advanced B Complex?
A: PABA is classified as non-essential. Most people get a more than adequate supply form their diet. Also, humans usually lack the enzymes necessary to convert PABA to folate. There are some bacteria that convert PABA to folate and, if an individual has those organisms in their digestive tract, supplemental folate may not be required. Since the presence or absence of these organisms is not easily determined, the safest route is to take supplemental folate: and 5-MeTHF is the best source of folate. In addition, there isn’t much research on it, plus there is a certain percentage of people sensitive (allergic) to PABA.
Q: Can folate cause breast cancer?
A: Research suggests that too low folic acid can be related to certain conditions and cancers while high amounts of folic acid can be related to other types of cancers. Other studies show that high doses of folate can be beneficial in other cases. The evidence is inconclusive. The best suggestion is to use folate in moderation at the recommended dietary intake levels.
Q: What foods contain benfotiamine?
A: Only crushed garlic, onions, leeks and shallots.
Q: Can one overdose on B-vitamins taking a B-complex with another multivitamin?
A: Let’s review these one by one.
B1: it’s a water soluble vitamin, so any excess is usually just excreted. There are studies with benfotiamine that show it used safely at up to 900 mg/day
B2: excess B2 can inhibit its absorption
B5: generally very well tolerated, but higher dose products such as Advanced B Complex and especially Pantethine can occasionally cause heartburn, mild itching, and diarrhea. The most common side effect noted with high doses is diarrhea.
B6: no noted toxicity at moderately higher doses than the max recommended doses, some studies at up to the equivalent of 700 mg/day were done in children showing no toxicity or side effects
B12: methylcobalamin has a very good safety profile (trials up to 15 mg/day). Cyanocobalamin also has a relatively good safety profile, but can be contraindicated in some conditions, such as Leber’s disease.
Folate: there are studies indicating safety at up to 5 mg of folic acid per day
Biotin: there are trials using up to 2 mg/day, so going over the recommended amounts by a small amount should be fine
Choline: exceeding the suggested dose by a large margin has been shown in animals to slightly reduce red blood cell count, due to improved oxygen status of the bone marrow. This effect is mitigated by combination with the B vitamins.
Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial.
Am J Med. 2013 Feb;126(2):141-9.
Fonseca VA, Lavery LA, Thethi TK, Daoud Y, DeSouza C, Ovalle F, Denham DS, Bottiglieri T, Sheehan P, Rosenstock J.
PURPOSE: To determine whether a combination of L-methylfolate, methylcobalamin, and pyridoxal-5′-phosphate (LMF-MC-PLP [Metanx; Pamlab LLC, Covington, La]) improves sensory neuropathy.
RESEARCH DESIGN AND METHODS: This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5′-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B(6) and B(12), methylmalonic acid (MMA), and homocysteine.
RESULTS: There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P=.013 vs placebo) and week 24 (P=.033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7±3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5±2.4 μmol/L with placebo (P=.0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects.
CONCLUSIONS: LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration may have been too short to show an effect on VPT. In addition, further research on the effects in patients with cobalamin deficiency would be useful.
Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.
Am J Clin Nutr. 2012 Mar;95(3):766-72.
Wilson CP, Ward M, McNulty H, Strain JJ, Trouton TG, Horigan G, Purvis J, Scott JM.
BACKGROUND: We recently reported that the elevated blood pressure (BP) observed in patients with cardiovascular disease who are homozygous for the 677C→T polymorphism (TT genotype) in the gene encoding methylenetetrahydrofolate reductase (MTHFR) was responsive to supplementation with riboflavin-the cofactor for MTHFR.
OBJECTIVE: The objective was to investigate the effect of riboflavin on BP targeted at patients with the TT genotype 4 y after initial investigation, during which time major changes in the clinical guidelines for antihypertensive therapy were introduced.
DESIGN: A total of 83 patients (representing all 3 genotypes) who participated in a placebo-controlled riboflavin intervention for 16 wk in 2004 agreed to take part. Nested within this follow-up, those with the TT genotype (n = 31) proceeded to intervention with riboflavin (1.6 mg/d for 16 wk) or placebo, conducted in a crossover style whereby the 2004 treatment groups were reversed.
RESULTS: At follow-up in 2008, as in 2004, patients with the TT genotype had higher systolic BP (P < 0.01), with a nonsignificant trend noted for higher diastolic BP (P = 0.051). Despite the marked changes in antihypertensive therapy that had occurred, BP remained unchanged in patients with the TT genotype at the time of follow-up. Riboflavin supplementation (administered in 2004 and 2008) produced an overall decrease in systolic (-9.2 ± 12.8 mm Hg; P = 0.001) and diastolic (-6.0 ± 9.9 mm Hg; P = 0.003) BP.
CONCLUSIONS: Optimizing riboflavin status offers a low-cost targeted strategy for managing elevated BP in this genetically at-risk group. These findings, if confirmed in the general population, could have important implications for the prevention of hypertension.
A nutrient-wide association study on blood pressure.
Circulation. 2012 Nov 20;126(21):2456-64.
Tzoulaki I, Patel CJ, Okamura T, Chan Q, Brown IJ, Miura K, Ueshima H, Zhao L, Van Horn L, Daviglus ML, Stamler J, Butte AJ, Ioannidis JP, Elliott P.
BACKGROUND: A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner.
METHODS AND RESULTS: Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate CONCLUSIONS: We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.
B vitamin intakes and incidence of colorectal cancer: results from the Women’s Health Initiative Observational Study cohort.
Am J Clin Nutr. 2013 Feb;97(2):332-43.
Zschäbitz S, Cheng TY, Neuhouser ML, Zheng Y, Ray RM, Miller JW, Song X, Maneval DR, Beresford SA, Lane D, Shikany JM, Ulrich CM.
BACKGROUND: The role of one-carbon metabolism nutrients in colorectal carcinogenesis is not fully understood. Associations might be modified by mandated folic acid (FA) fortification or alcohol intake.
OBJECTIVE: We investigated associations between intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and colorectal cancer (CRC) in the Women’s Health Initiative Observational Study, stratified by time exposed to FA fortification and alcohol intake.
DESIGN: A total of 88,045 postmenopausal women were recruited during 1993-1998; 1003 incident CRC cases were ascertained as of 2009. Quartiles of dietary intakes were compared; HRs and 95% CIs were estimated by Cox proportional hazards models.
RESULTS: Dietary and total intakes of vitamin B-6 in quartile 4 compared with quartile 1 (HR: 0.80; 95% CI: 0.66, 0.97 and HR: 0.80; 95% CI: 0.66, 0.99, respectively) and total intakes of riboflavin (HR: 0.81; 95% CI: 0.66, 0.99) were associated with reduced risk of CRC overall and of regionally spread disease. In current drinkers who consumed CONCLUSIONS: Vitamin B-6 and riboflavin intakes from diet and supplements were associated with a decreased risk of CRC in postmenopausal women. Associations of B vitamin intake were particularly strong for regional disease and among women drinkers who consumed alcohol infrequently. Our study provides new evidence that the increased folate intake during the early postfortification period may have been associated with a transient increase in CRC risk.
L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials.
Am J Psychiatry. 2012 Dec 1;169(12):1267-74.
Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M.
OBJECTIVE: The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs).
METHOD: In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, in a 2:3:3 ratio, to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the l-methylfolate dosage was 15 mg/day during both 30-day periods.
RESULTS: In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures (response rate and degree of change in depression symptom score) and two secondary outcome measures of symptom severity. The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day. L-Methylfolate was well tolerated, with rates of adverse events no different from those reported with placebo.
CONCLUSIONS: Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs.
Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy.
Exp Clin Endocrinol Diabetes. 2012 Jun;120(6):329-34.
Polizzi FC, Andican G, Çetin E, Civelek S, Yumuk V, Burçak G.
BACKGROUND: It is well known that advanced glycation plays an important role in the progression of diabetic complications. Although several studies have been done on protein glycation, studies related to DNA glycation is limited. The aim of this study is primarily to investigate DNA glycation in diabetes mellitus and secondarily to observe the effects of vitamins B(1) and B(6).
MATERIALS AND METHODS: Patients with diabetes (n=31) were divided into 2 groups as patients with nephropathy (n=17) and without nephro-pathy (n=14). The control group was recruited from age and sex matched healthy individuals (n=30). In the experimental groups, DNA glycation was measured in DNA isolated from leukocytes. HbA(1c), thiamine pyrophosphate (TPP) and pyridoxal 5-phosphate (PLP) levels were determined in whole blood; glucose and insulin levels in plasma. Patients with nephropathy were further divided into 2 groups and were administered either vitamins B(1) + B(6) (n=6) or B(6) (n=11), for 5 months. All the measurements were performed both before and after the vitamin administration period.
RESULTS: AGE-DNA levels were found significantly higher in diabetic patients (p CONCLUSION: This study shows that the combined administration of vitamins B(1) and B(6) to diabetic nephropathy patients causes a decrease in DNA glycation in leukocytes. Importantly the administration of vitamin B(6) alone did not have such an effect. To our knowledge, these are the first reported findings related to glycation of leukocyte nuclear DNA in diabetic nephropathy.
Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial.
Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600.
de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD.
BACKGROUND: Homocysteine is a risk factor for Alzheimer’s disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study.
METHODS: This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models.
RESULTS: The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01).
CONCLUSION: In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.
Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status.
J Nutr Health Aging. 2012;16(6):569-73.
Kwok T, Chook P, Qiao M, Tam L, Poon YK, Ahuja AT, Woo J, Celermajer DS, Woo KS.
OBJECTIVE: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians.
DESIGN: Double-blind, placebo controlled, randomised crossover study.
SETTING: Community dwelling vegetarians.
PARTICIPANTS: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited.
INTERVENTION: Vitamin B-12 (500 µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41).
MEASUREMENT: Flow-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound.
RESULTS: The mean age of the subjects was 45±9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels CONCLUSIONS: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.
Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis.
Eur J Clin Nutr. 2010 Sep;64(9):1007-13.
Huang SC, Wei JC, Wu DJ, Huang YC.
BACKGROUND/OBJECTIVES: The purpose of this study was to investigate whether vitamin B(6) supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA).
SUBJECTS/METHODS: This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n=15) or vitamin B(6) (5 mg/day folic acid plus 100 mg/day vitamin B(6); n=20) for 12 weeks. Plasma pyridoxal 5′-phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention.
RESULTS: In the group receiving vitamin B(6), plasma IL-6 and TNF-alpha levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B(6) group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (beta=-0.01, P=0.01).
CONCLUSIONS: A large dose of vitamin B(6) supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-alpha) in patients with RA.
Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Sep;378(3):283-91.
Schupp N, Dette EM, Schmid U, Bahner U, Winkler M, Heidland A, Stopper H.
Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.
Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.
Exp Clin Endocrinol Diabetes. 2008 Nov;116(10):600-5.
Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG.
AIM: Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy.
METHODS: 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).
RESULTS: 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.
Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes.
Diabetes Care. 2006 Sep;29(9):2064-71.
Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D.
OBJECTIVE: Diabetes is characterized by marked postprandial endothelial dysfunction induced by hyperglycemia, hypertriglyceridemia, advanced glycation end products (AGEs), and dicarbonyls (e.g., methylglyoxal [MG]). In vitro hyperglycemia-induced MG formation and endothelial dysfunction could be blocked by benfotiamine, but in vivo effects of benfotiamine on postprandial endothelial dysfunction and MG synthesis have not been investigated in humans until now.
RESEARCH DESIGN AND METHODS: Thirteen people with type 2 diabetes were given a heat-processed test meal with a high AGE content (HAGE; 15.100 AGE kU, 580 kcal, 54 g protein, 17 g lipids, and 48 g carbohydrates) before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially.
RESULTS: The HAGE induced a maximum reactive hyperemia decrease of -60.0% after 2 h and a maximum FMD impairment of -35.1% after 4 h, without affecting endothelium-independent vasodilatation. The effects of HAGE on both FMD and reactive hyperemia were completely prevented by benfotiamine. Serum markers of endothelial dysfunction and oxidative stress, as well as AGE, increased after HAGE. These effects were significantly reduced by benfotiamine.
CONCLUSIONS: Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.