Fylkesforskjeller i utredning og behandling av vitamin B12-mangel.

BACKGROUND: Severe vitamin B12 (cobalamin) deficiency is rare, but international reports show that up to 26 % of the general population may have subclinical vitamin B12 deficiency. The prevalence of vitamin B12 deficiency has not been investigated in Norway. Since 2017, treatment with vitamin B12 tablets has represented an alternative to traditional treatment with intramuscular injections in Norway. When we studied the transition from injection to tablet treatment, we discovered an unexpected difference in the counties' use of vitamin B12 supplements, which we wished to investigate in more detail. MATERIAL AND METHOD: Data on the dispensing of vitamin B12 supplements from pharmacies in 2020, broken down by the patients' county of residence, were retrieved from the Norwegian Prescription Database. The Norwegian Health Economics Administration (Helfo) provided figures on the number of reimbursed vitamin B12-related laboratory tests in 2020, classified by patients' municipality of residence. RESULTS: In 2020, the sale of vitamin B12 supplements on prescription in Norway amounted to 12 defined daily doses (DDD) per inhabitant and varied from 7 to 15 between the counties. The number of laboratory analyses that were performed varied by county from 26 to 46 per 100 inhabitants for total vitamin B12, and from 21 to 37 for folate. The number of analyses varied correspondingly from 1 to 12 per 100 inhabitants for homocysteine, from 1 to 13 for methylmalonic acid and from 0.01 to 8.13 for active vitamin B12. INTERPRETATION: Our study showed large intercounty differences in the consumption of vitamin B12 supplements. These differences may have a number of explanations. Variations in the number of vitamin B12-related laboratory analyses requisitioned may indicate that doctors' assessment and diagnosis of vitamin B12 deficiency could be a contributory factor.

Review article: Clinical manifestations and outcomes of chronic nitrous oxide misuse: A systematic review.

Recreational nitrous oxide (N2 O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N2 O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose-dependent nature of chronic N2 O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management.

Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain.

BACKGROUND AND AIM: Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered. METHODS: A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed. RESULTS: B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 µmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested. CONCLUSIONS: Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population.

Methylmalonic acid administration induces DNA damage in rat brain and kidney.

Accumulation of methylmalonic acid (MMA) in tissues and biological fluids is the biochemical hallmark of methylmalonic aciduria. Affected patients present renal failure and severe neurological findings. Considering that the underlying pathomechanisms of tissue damage are not yet understood, in the present work we assessed the in vivo e in vitro effects of MMA on DNA damage in brain and kidney, as well as on p53 and caspase 3 levels, in the presence or absence of gentamicin (acute renal failure model). For in vitro studies, tissue prisms were incubated in the presence of different concentrations of MMA and/or gentamicin for one hour. For in vivo studies, animals received a single injection of gentamicin (70 mg/kg) and/or three injections of MMA (1.67 µmol/g; 11 h interval between injections). The animals were killed 1 h after the last MMA injection. Controls received saline in the same volumes. DNA damage was analyzed by the comet assay. We found that MMA and gentamicin alone or combined in vitro increased DNA damage in cerebral cortex and kidney of rats. Furthermore, MMA administration increased DNA damage in both brain and kidney. Gentamicin per se induced DNA damage only in kidney, and the association of MMA plus gentamicin also caused DNA damage in cerebral cortex and kidney. On the other hand, p53 and caspase 3 levels were not altered by the administration of MMA and/or gentamicin. Our findings provide evidence that DNA damage may contribute to the neurological and renal damage found in patients affected by methylmalonic aciduria.

Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy.

This study was designed to determine the prevalence of definite vitamin B(12) deficiency (defined as < or =240 pg/ml) and possible vitamin B(12) deficiency (defined as >240 pg/ml and a methylmalonic acid [MMA] level >243 nmol/L) in patients with polyneuropathy and to determine whether patients in both groups respond to vitamin B(12) repletion. We performed a retrospective cohort study of 581 patients presenting with polyneuropathy over a 2-year period; 4% had definite vitamin B(12) deficiency and 32% had possible deficiency as the sole or contributing cause for their polyneuropathy. For those who received treatment with vitamin B(12), subjective improvement was seen in 87% with definite and in 43% with possible deficiency. Possible vitamin B(12) deficiency, defined as an elevated MMA level, is a common finding in patients with polyneuropathy and treatment of these patients with vitamin B(12) may lead to clinical improvement.

Efficacy and cross-resistance studies on N, N'-bis (3,4 ditrifluoromethylphenyl) methylmalonamide, a novel anticoccidial agent.

N,N'-bis (3,4 ditrifluoromethylphenyl) methylmalonamide (Sch 18545) completely controlled a mild Eimeria necatrix infection at 50, 40 or 30 p.p.m. in the diet, and controlled E. tenella infections at 50 and 40 p.p.m. Slight oocyst passage was observed at each E. tenella treatment level with a marked increase at the 30 p.p.m. treatment level. Fifty p.p.m. were necessary to control E. acervulina infections; levels of 40 p.p.m. reduced E. acervulina oocyst production while 30 p.p.m. were ineffective. Evaluations of Sch 18545 using a mixed infection (Coccivac D) further suggested that activity with this compound was weakest against E. acervulina. Weight gains decreased with increasing concentration of drug in the diet of treated, infected birds and thus the compound showed an insufficient safety margin to be of practical value. Such 18545 administered at 35 p.p.m. in the diet was effective against amprolium, zoalene, aklomide or nicarbazin-resistant strains of E. tenella.