Efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. METHODS: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. RESULTS: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. CONCLUSION: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KPW5E.

Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient.

Background Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient's vitamin B12, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90-300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.

Are the Recommended Dietary Allowances for Vitamins Appropriate for Elderly People?

BACKGROUND: An adequate vitamin intake is essential for a good nutritional status, especially in older women, who are more sensitive to nutritional deficiencies. The American, European and Italian Recommended Dietary Allowances (RDAs) derive mainly from studies on adults, and it is not clear whether they also apply to elderly people. Comparing the RDAs with the actual vitamin intake of a group of healthy older women could help to clarify the real needs of elderly people. OBJECTIVE: Our aim was to compare the American, European, and Italian RDAs with the actual vitamin intake of a group of healthy older women. DESIGN: This was a cross-sectional study. PARTICIPANTS: The study included 286 healthy women aged older than 65 years. MAIN OUTCOME MEASURES: For each micronutrient, the 50th percentile of the distribution of its intake was considered as the average requirement, and the corresponding calculated RDA for our sample was the average requirement×1.2, as recommended by the US Food and Nutrition Board. This calculated RDA was then compared with the American, European, and Italian RDAs. STATISTICAL ANALYSES PERFORMED: Student's t test or the Mann-Whitney test (after checking the normal distribution of the micronutrient) for continuous variables; the χ(2) test for categorical variables. RESULTS: The calculated RDA were 2,230 µg retinol equivalents for vitamin A, 2.8 µg for vitamin B-12, 0.9 mg for thiamin, 1.4 mg for riboflavin, 3.6 mg for pantothenic acid, 1.4 mg for vitamin B-6, 320 µg for folic acid, and 115 mg for vitamin C. CONCLUSIONS: Our findings suggest that the current RDAs are adequate for older women's intake of riboflavin, vitamin B-6, and folic acid, but should be raised for vitamin B-12 and for vitamin C.

Systematic review on daily vitamin B12 losses and bioavailability for deriving recommendations on vitamin B12 intake with the factorial approach.

AIMS: To systematically review the literature on daily losses and bioavailability of vitamin B12. These estimates could be used for deriving recommendations on vitamin B12 intake for adults and elderly. METHODS: We identified publications on daily vitamin B12 losses (July 2011) and publications on the bioavailability of vitamin B12 from foods or diets (June 2010) in MEDLINE, EMBASE and the Cochrane Library. RESULTS: A pooled analysis of five studies (52 subjects) showed that 0.13 ± 0.03% of the total body store is lost per day. Absorption of vitamin B12 ranged from 4.5 (dose of 38 µg from consumption of liver) to 83% (dose of 3.0 µg from consumption of mutton meat). Data from eight studies including 83 subjects suggested that the amount of vitamin B12 absorbed from food (Ai) increased with increasing doses of vitamin B12 (Di) as described by the equation: ln(Ai) = 0.7694 * ln(Di) - 0.9614. CONCLUSION: Daily vitamin B12 losses in apparently healthy adults and elderly probably range from 1.4 to 5.1 µg. Vitamin B12 intakes needed to compensate for these losses seem to range from 3.8 to 20.7 µg. More evidence is needed on the relationships between biochemical markers of vitamin B12 status, vitamin B12 body store and long-term health outcomes to evaluate whether current recommendations on vitamin B12 intake (1.4-3 µg) need to be changed.

The development and role of international biological reference materials in the diagnosis of anaemia.

Anaemia is a major global health problem. Although the main cause is iron deficiency, anaemia also results from other nutritional deficiencies (folate and vitamin B12), haemolytic disorders including haemoglobinopathies, and bone marrow disorders. Accurate diagnosis of anaemia is dependent on reliable diagnostic tests and reference ranges, which in turn are dependent on effective standardisation. Standardisation is achieved through the availability of reference materials and reference measurement procedures. International biological reference materials have therefore been developed to standardise and control diagnostic tests for anaemia for a diverse range of analytes including total haemoglobin and haemoglobin types, ferritin, the serum transferrin receptor, serum vitamin B12 and folate, whole blood folate, and alloantibodies which mediate immune haemolytic anaemia.

Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs).

Diet as a key factor in determining genomic stability is more important than previously imagined because we now know that it impacts on all relevant pathways, namely exposure to dietary carcinogens, activation/detoxification of carcinogens, DNA repair, DNA synthesis and apoptosis. Current recommended dietary allowances for vitamins and minerals are based largely on the prevention of diseases of deficiency such as scurvy in the case of vitamin C. Because diseases of development, degenerative disease and aging itself are partly caused by damage to DNA it seems logical that we should focus better our attention on defining optimal requirements of key minerals and vitamins for preventing damage to both nuclear and mitochondrial DNA. To date, our knowledge on optimal micronutrient levels for genomic stability is scanty and disorganised. However, there is already sufficient evidence to suggest that marginal deficiencies in folate, vitamin B12, niacin and zinc impact significantly on spontaneous chromosome damage rate. The recent data for folate and vitamin B12 in humans with respect to micronucleus formation in blood and epithelial cells provide compelling evidence of the important role of these micronutrients in maintenance of genome integrity and the need to revise current RDAs for these micronutrients based on minimisation of DNA damage. Appropriately designed in vitro studies and in vivo placebo controlled trials with dose responses using a complementary array of DNA damage biomarkers are required to define recommended dietary allowances for genomic stability. Furthermore these studies would have to be targeted to individuals with common genetic polymorphisms that alter the bioavailability of specific micronutrients and the affinity of specific key enzymes involved in DNA metabolism for their micronutrient co-factor. That there is a need for an international collaborative effort to establish RDAs for genomic stability is self-evident.

Recommended dietary allowances (RDAs) for genomic stability.

Diet as a key factor in determining genomic stability is more important than previously imagined because we now know it impacts on all relevant pathways, i.e. exposure to dietary carcinogens, activation/detoxification of carcinogens, DNA repair, DNA synthesis and apoptosis. Current recommended dietary allowances for vitamins and minerals are based largely on the prevention of diseases of deficiency such as scurvy in the case of Vitamin C. Because diseases of development, degenerative disease and ageing itself are partly caused by damage to DNA, it seems logical that we should focus better our attention on defining optimal requirements of key minerals and vitamins for preventing damage to both nuclear and mitochondrial DNA. To date our knowledge on optimal micronutrient levels for genomic stability is scanty and disorganised. Appropriately designed placebo, controlled trials are required to define recommended dietary allowances for genomic stability. Recently, it has been shown that above RDA intakes of folic acid and Vitamin B12 are required to reduce the micronucleus index in humans by 25%. In the future, clinical trials with a defined wider array of complementary DNA damage end-points would be necessary. That there is a need for an international collaborative group to establish RDAs for genomic stability is self-evident and this paper is a call for such a process to begin.

[Cyanocobalamin Reference Standard (Control 951) of the National Institute of Health Sciences].

The raw material of cyanocobalamin was tested for preparation of the "Cyanocobalamin Reference Standard (Control 951)". Analytical data obtained are as follows: loss on drying, 1.8%; infrared spectrum, the same as that of the JP Cyanocobalamin Reference Standard (Control 936); thin-layer chromatography, three impurities were detected; high-performance liquid chromatography (HPLC), eight to nine kinds of impurities were detected and the total amount of impurities was estimated to be 1.6 +/- 0.13% (n = 4); assay, 99.7% by spectrophotometry specified in the JP XII and 100.4% by HPLC, respectively. Based on the above results, the raw material was authorized as the JP Cyanocobalamin Reference Standard (Control 951).

Dietary intake of female collegiate heavyweight rowers.

The purpose of this study was to evaluate the adequacy of dietary intake in 16 female heavyweight rowers during the sprint racing phase of the season. Caloric intake for the rowers was 2,633 kcal/day, lower than expected given the training regimen of these athletes. On average, rowers consumed below-optimal levels of carbohydrate. Protein intake was satisfactory but fat intake was higher than recommended. For the majority of rowers, micronutrient intake met the RDA. However, calcium, zinc, B6, and B12 fell short of meeting two-thirds of the RDA for a significant percentage of rowers. The preevent meal consumed both 15 hr and 2 hr before the event provided less carbohydrate and fluid but more fat than desirable. Female heavyweight rowers would benefit from nutritional counseling that provides strategies for increasing complex carbohydrates, calcium, zinc, B6, and B12 while reducing dietary fat. Adequate fluid intake is also essential.

[The Cyanocobalamin Reference Standard (Control 931) of the National Institute of Health Sciences].

Raw cyanocobalamin material was tested for preparation of the "Cyanocobalamin Reference Standard (Control 931)". Analytical data obtained were as follows: loss on drying, 4.2%; infrared spectrum, the same as that of the JP Cyanocobalamin Reference Standard (Control 901); thin-layer chromatography, four impurities were detected; high-performance liquid chromatography (HPLC), seven to eight kinds of impurities were detected, but the total amount of impurities was only 1.0 +/- 0.52% (n = 5); assay results, 100.6% by spectrophotometry in the JP XII and 99.7% by HPLC. Based on the above findings, the raw material was authorized as the JP Cyanocobalamin Reference Standard (Control 931).

[Cyanocobalamin Reference Standard (Control 891) of National Institute of Hygienic Sciences].

Cyanocobalamin was tested for preparation on the "Cyanocobalamin Reference Standard (Control 891)". Analytical data obtained were as follows: loss on drying, 9.77%; infrared spectrum, same as that of the Cyanocobalamin Reference Standard (Control 871); thin-layer chromatography, five contaminants were detected; high-performance liquid chromatography, nine contaminants were detected; assay, 100.00% by JP XI method and 99.79% by HPLC method in terms of the JP Reference Standard (Control 871), respectively. On the basis of the above results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 891).

[Cyanocobalamin Reference Standard (Control 871) of National Institute of Hygienic Sciences].

Cyanocobalamin was tested for the preparation of "Cyanocobalamin Reference Standard (Control 871)". Analytical data obtained were as follows: loss on drying, 11.6%; infrared spectrum, same as that of Cyanocobalamin Reference Standard (Control 861); thin-layer chromatography, two contaminants were detected; high-performance liquid chromatography, seven contaminants were detected; assay, 99.9% by JP XI method and 100.2% by HPLC method in terms of J.P. Reference Standard (Control 861), respectively. On the basis of those results, this material was authorized as the Japanese Pharmacopoeia Standard (Control 871).

British standard for human serum vitamin B12.

Seven laboratories took part in a collaborative study of an ampouled preparation of normal serum labelled 81/563. Each laboratory calibrated the preparation in terms of pure cyanocobalamin by use of Euglena assay. The inclusion of pernicious anaemia serum in the study and additional tests for safety and stability indicated that 81/563 would be a suitable standard for diagnostic testing. In 1985 the National Biological Standards Board established the preparation as the British Standard for Human Serum Vitamin B12 and, with the agreement of participants in the study, assigned it a potency of 320 picograms per ampoule.