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LE Magazine December 2000

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Methylcobalamin treatment of Bell's palsy

Sixty patients with Bell's palsy were included in an open randomized trial. Patients were assigned into three treatment groups: steroid (group 1), methylcobalamin (group 2) and methylcobalamin + steroid (group 3). Comparison between the three groups was based on the number of days needed to attain full recovery, facial nerve scores, and improvement of concomitant symptoms. The time required for complete recovery of facial nerve function was significantly shorter ( p < 0.001) in the methylcobalamin (mean of 1.95 +/- 0.51 weeks) and methylcobalamin plus steroid groups (mean of 2.05 +/- 1.23 weeks) than in the steroid group (mean of 9.60 +/- 7.79 weeks). The facial nerve score after 1-3 weeks of treatment was significantly more severe (p < 0.001) in the steroid group compared to the methylcobalamin and methylcobalamin plus steroid groups. The improvement of concomitant symptoms was better in the methylcobalamin treated groups than the group treated with steroid alone.

Methods Find Exp Clin Pharmacol 1995 Oct;17(8):539-44

Enteral vitamin B12 supplements reverse postgastrectomy B12 deficiency

OBJECTIVE: To examine the development of chemical and clinical vitamin B12 deficiency after total gastrectomy, and to evaluate the efficacy of supplemental oral B12 administration. SUMMARY BACKGROUND DATA: Postgastrectomy anemia is due to deficiencies of iron and vitamin B12, and parenteral B12 administration is the only appropriate treatment. However, no guidelines exist for the prophylactic use of B12 in patients who undergo total gastrectomy, the clinical presentation of B12 deficiency in this context has not been defined, and the question of whether oral B12 administration can be used to prevent and treat B12 deficiency has not been examined. METHODS: Serum B12 concentrations were measured in 31 patients who had undergone total gastrectomy. Symptoms related to B12 deficiency were surveyed in detail. Serum B12 concentrations were measured every 6 months after total gastrectomy in 10 patients. Thirty one patients received supplemental B12: 18 patients orally and 13 by intramuscular injection. RESULTS: The B12 concentration dropped below the lower limit of normal (200 pg/mL) for the first time in two patients at 1 year, in four patients at 2 years, in three patients at 3 years, and in one patient at 4 years. Seventy-eight percent of patients reported some symptoms related to B12 deficiency. The serum B12 concentration in patients who received supplemental B12 orally increased rapidly and all symptoms resolved with oral therapy alone. CONCLUSIONS: B12 deficiency can develop as early as 1 year after total gastrectomy and causes symptoms. Because enteral B12 treatment increases the serum B12 concentration and leads to rapid resolution of symptoms, it should be prescribed routinely to patients.

Ann Surg 2000 Aug;232(2):199-201

Vitamin B12 deficiency in the elderly

Vitamin B12 deficiency is estimated to affect 10%-15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels. Although elderly people with low vitamin B12 status frequently lack the classical signs and symptoms of vitamin B12 deficiency, e.g. megaloblastic anemia, precise evaluation and treatment in this population is important. Absorption of crystalline vitamin B12 does not decline with advancing age. However, compared with the younger population, absorption of protein-bound vitamin B12 is decreased in the elderly, owing to a high prevalence of atrophic gastritis in this age group. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, which in turn results in a reduced release of free vitamin B12 from food proteins. Furthermore, hypochlorhydria in atrophic gastritis results in bacterial overgrowth of the stomach and small intestine, and these bacteria may bind vitamin B12 for their own use. The ability to absorb crystalline vitamin B12 remains intact in older people with atrophic gastritis. The 1998 recommended daily allowance for vitamin B12 is 2.4 micrograms, but elderly people should try to obtain their vitamin B12 from either supplements or fortified foods (e.g. fortified ready-to-eat breakfast cereals) to ensure adequate absorption from the gastrointestinal tract. Because the American food supply is now being fortified with folic acid, concern is increasing about neurologic exacerbation in individuals with marginal vitamin B12 status and high-dose folate intake.

Annu Rev Nutr 1999;19:357-77

Effects of vitamin B12 on performance and circadian rhythm in normal subjects

This preliminary study investigates effects of methyl- and cyanocobalamin on circadian rhythms, well-being, alertness, and concentration in healthy subjects. Six women (mean age 35 years) and 14 men (mean age 37 years) were randomly assigned to treatment for 14 days with 3 mg cyano-(CB12) or methylcobalamin (MB12) after 9 days of pre-treatment observation. Levels in the CB12 group increased rapidly in the first, then slowly in the second treatment week, whereas increase in the MB12 group was linear. Urinary aMT6s excretion was reduced by both forms of vitamin B12 over 24 hours with a significant decrease between 0700-1100 hours, whereas urinary excretion of potassium was significantly increased between 0700-1100 hours. Activity from 2300-0700 hours increased significantly under both forms of vitamin B12. Sleep time was significantly reduced under MB12 intake. In this group the change in the visual analogue scales items "sleep quality," "concentration," and "feeling refreshed" between pretreatment and the first week of treatment showed significant correlations with vitamin B12 plasma levels. Cortisol excretion and temperature were not affected by either medication. We conclude that vitamin B12 exerts a direct influence on melatonin. Only MB12 has a positive psychotropic alerting effect with a distribution of the sleep-wake cycle toward sleep reduction.

Neuropsychopharmacology 1996 Nov;15(5):456-64

Subnormal serum vitamin B12 and behavioural and psychological symptoms in Alzheimer's disease

The objective of this study was to examine whether patients with Alzheimer's disease (AD) with subnormal vitamin B12 levels show more frequent behavioural and psychological symptoms of dementia (BPSD) than AD patients with normal vitamin B12 levels. The design was a prospective case-control study. The study took place at a memory-clinic of a department of geriatric medicine in a teaching hospital. There were seventy-three consecutive outpatients with probable AD, including 61 patients with normal and 12 patients with subnormal (<200 pg/ml) vitamin B12. BPSD were measured using the subscales disturbed behaviour and mood of the Nurses' Observation Scale for Geriatric Patients (NOSGER), the Cornell Scale for Depression and the four criteria for personality change in dementia from the International Classification of Diseases (ICD-10). Controlling for dementia duration and degree of severity of the cognitive deficits, there were significant inverse associations between vitamin B12 status and ICD-10 irritability (p=0.045) and NOSGER subscale disturbed behaviour (p=0.015). Low vitamin B12 serum levels are associated with BPSD in AD. Vitamin B12 could play a role in the pathogenesis of behavioural changes in AD.

Int J Geriatr Psychiatry 2000 May;15(5):415-8

Vitamin B12 levels are low in hospitalized psychiatric patients

BACKGROUND: Deficiency of vitamin B12, a key component in the catabolism of monoamines, is associated with various neuropsychiatric disorders and may be more frequent in hospitalized patients. METHOD: We reviewed vitamin B12 assays performed in a laboratory of a large Israeli psychiatric hospital over a 23-month period to examine prevalence of low values and compared vitamin B12 deficient patients to those with normal levels on various parameters. In addition, vitamin levels in a random sample of in-patients whose nutritional intake was determined, were examined. RESULTS: 20% of 644 vitamin B12 assays were in the low (200 pg/ml) and 10% in the deficient (< 160 pg/ml) range. 24 selected vitamin B12 deficient patients (70.8% with diagnosis of schizophrenia) did not differ from controls (N = 35) in age, sex ratio, hemoglobin concentration, MCV, diagnostic distribution or number and length of hospitalizations, but had slightly lower (but normal) mean folate levels. Rates of vitamin B12 deficiency in the patient sample, whose nutritional intake was adequate, did not differ significantly from those in the laboratory survey. CONCLUSION: Vitamin B12 deficiency is common in chronically ill psychotic patients with adequate nutrition and is not readily detected by routine hematology tests.

Isr J Psychiatry Relat Sci 2000;37(1):41-5

Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy

Despite intensive searches for therapeutic agents, few substances have been convincingly shown to enhance nerve regeneration in patients with peripheral neuropathies. Recent biochemical evidence suggests that an ultra-high dose of methylcobalamin (methyl-B12) may up-regulate gene transcription and thereby protein synthesis. We examined the effects of ultra-high dose of methyl-B12 on the rate of nerve regeneration in rats with acrylamide neuropathy, using the amplitudes of compound muscle action potentials (CMAPs) after tibial nerve stimulation as an index of the number of regenerating motor fibers. After intoxication with acrylamide, all the rats showed equally decreased CMAP amplitudes. The animals were then divided into 3 groups; rats treated with ultra-high (500 micrograms/kg body weight, intraperitoneally) and low (50 micrograms/kg) doses of methyl-B12, and saline-treated control rats. Those treated with ultra-high dose showed significantly faster CMAP recovery than saline-treated control rats, whereas the low-dose group showed no difference from the control. Morphometric analysis revealed a similar difference in fiber density between these groups. Ultra-high doses of methyl-B12 may be of clinical use for patients with peripheral neuropathies.

J Neurol Sci 1994 Apr;122(2):140-3

Helicobacter pylori-is it a novel causative agent in Vitamin B12 deficiency?

BACKGROUND: Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. OBJECTIVES: To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. PATIENTS AND METHODS: We performed a prospective cohort study involving 138 patients who had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. RESULTS: Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS: Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients.

Arch Intern Med 2000 May 8;160(9):1349-53



Activation of PPARgamma may mediate a portion of the anticancer activity of conjugated linoleic acid

A number of human cancer cell lines express the PPARgamma transcription factor, and agonists for PPARgamma are reported to promote apoptosis in these cell lines and impede their clonal expansion both in vitro and in vivo. Conjugated linoleic acid (CLA) can activate PPARgamma in rat adipocytes, possibly explaining CLA's antidiabetic effects in Zucker fatty rats. It is thus reasonable to suspect that a portion of CLA's broad spectrum anticarcinogenic activity is mediated by PPARgamma activation in susceptible tumors.

Copyright 2000 Harcourt Publishers Ltd. Med Hypotheses 2000 Sep;55(3):187-188

Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes

Four sets of experiments were conducted to examine the influence of conjugated linoleic acid (CLA) isomers during proliferation and differentiation of cultures of 3T3-L1 preadipocytes using physiological culturing conditions. Cultures treated with either albumin [bovine serum albumin (BSA) vehicle] or linoleic acid (LA) served as controls. For the proliferation study (Expt.1), cells were cultured in media containing a crude mixture of CLA isomers or pure LA at 0, 10, 50, or 200 microM for 4 d. Preadipocyte proliferation (cell number, 3H-thymidine incorporation into DNA) decreased as the level of CLA increased in the cultures. In contrast, LA had no impact on DNA synthesis. In Experiment 2a, postconfluent cultures were grown in media containing a crude mixture of CLA isomers or LA at 0, 10, 50, or 200 microM for the next 6 d. Postconfluent cultures supplemented with 50-200 microM CLA had less triglyceride (TG) and were smaller in size than cultures supplemented with similar amounts of LA. In Experiment 2b, postconfluent cultures supplemented with 200 microM of a crude mixture of CLA isomers or LA were harvested on days 1, 3, 6, or 9. Differences in TG content of cultures supplemented with 200 microM CLA compared to control and LA-supplemented cultures became apparent after 3 d of culture. Experiments 3a and 3b examined whether the fatty acid vehicle (BSA vs. ethanol) or the vitamin E status (+/-0.2 mM alpha-tocopherol) of the cultures altered CLA's impact on preadipocyte TG content. In Experiment 3a, ethanol-treated cultures had more TG than non-ethanol-treated cultures regardless of the fatty acid treatment. In Experiment 3b, cultures treated with 100 microM of either a crude mixture of CLA or the trans-10,cis-12 CLA isomer without supplemental vitamin E for 6 d had less TG than CLA-treated cultures containing vitamin E. In Experiment 4, postconfluent cultures were grown in media containing 100 microM LA or either a crude mixture of CLA isomers or the trans-10,cis-12 CLA isomer for 24-96 h to assess CLA's influence on the cell cycle and indices of apoptosis. Cultures treated with 100 microM CLA for 24-96 h had more apoptotic cells than BSA- or LA-treated cultures. Furthermore, cultures treated for 48 h with CLA had fewer cells in the S-phase than control cultures. The effects of the trans-10,cis-12 CLA isomer were more pronounced than those of the crude mixture of CLA isomers. These data suggest that CLA may exert its antiobesity effects by inhibiting proliferation, attenuating TG content, and/or inducing apoptosis in (pre)adipocytes.

Lipids 2000 Aug;35(8):899-910

Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.

Diabetes 2000 Sep;49(9):1534-42

The disease burden associated with overweightness and obesity

CONTEXT: Overweight and obesity are increasing dramatically in the United States and most likely contribute substantially to the burden of chronic health conditions. OBJECTIVE: To describe the relationship between weight status and prevalence of health conditions by severity of overweight and obesity in the US population. DESIGN AND SETTING: Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted in 2 phases from 1988 to 1994. PARTICIPANTS: A total of 16884 adults, 25 years and older, classified as overweight and obese (body mass index [BMI] > or =25 kg/m2) based on National Institutes of Health recommended guidelines. MAIN OUTCOME MEASURES: Prevalence of type 2 diabetes mellitus, gallbladder disease, coronary heart disease, high blood cholesterol level, high blood pressure, or osteoarthritis. RESULTS: Sixty-three percent of men and 55% of women had a body mass index of 25 kg/m2 or greater. A graded increase in the prevalence ratio (PR) was observed with increasing severity of overweight and obesity for all of the health outcomes except for coronary heart disease in men and high blood cholesterol level in both men and women. With normal-weight individuals as the reference, for individuals with BMIs of at least 40 kg/m2 and who were younger than 55 years, PRs were highest for type 2 diabetes for men (PR, 18.1; 95% confidence interval [CI], 6.7-46.8) and women (PR, 12.9; 95% CI, 5.7-28.1) and gallbladder disease for men (PR, 21.1; 95% CI, 4.1-84.2) and women (PR, 5.2; 95% CI, 2.9-8.9). Prevalence ratios generally were greater in younger than in older adults. The prevalence of having 2 or more health conditions increased with weight status category across all racial and ethnic subgroups. CONCLUSIONS: Based on these results, more than half of all US adults are considered overweight or obese. The prevalence of obesity-related comorbidities emphasizes the need for concerted efforts to prevent and treat obesity rather than just its associated comorbidities.

JAMA 1999 Oct 27;282(16):1523-9

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