Functional Vitamin B12 Deficiency Research Articles

Laughing with serious consequences- a case report of recreational laughing gas use with functional vitamin B12 deficiency

Laughing with serious consequences- a case report of recreational laughing gas use with functional vitamin B12 deficiency

Poūmės kombinuotos nugaros smegenų degeneracijos, sukeltos diazoto monoksido („linksminančių dujų”) vartojimo, klinikinio atvejo aprašymas

Although nitrous oxide (N2O) has long been used as an anesthetic, it’s use as a recreational drug has recently increased. As N2O abuse is associated with a number of adverse health effects, it has become a significant public health issue. Chronic abuse can lead to a number of neurological complications, most commonly related to functional vitamin B12 deficiency. One of the most encountered forms of N2O neurotoxicity is a subacute combined degeneration, which can cause permanent neurological damage. The medical community should therefore be aware of the increasing scale of recreational N2O exposure and the possible complications of this drug abuse. Early recognition and treatment of N2O toxicity are crucial. We present the case of an 18-year-old male who was diagnosed with subacute combined spinal cord degeneration related to N2O abuse.

Neuropsychiatric disorders associated with recreational nitrous oxide use

Background Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. Purpose This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians’ awareness of this public health problem. Methods We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. Results There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted “V” sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. Conclusion Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

Functional vitamin B12 deficiency is a consistent feature in hospital admissions for neurological disorders due to the use of nitrous oxide

Introduction: Misuse of inhaled nitrous oxide is a growing concern in France. It is known to alter concentrations of vitamin B12, which is required as a cofactor for methionine synthase and methylmalonyl-CoA mutase activity. Hence, measurement of the concentrations of cobalamin metabolism biomarkers, including vitamin B12, homocysteine, and methylmalonic acid, could assist in the management of patients with a complex clinical presentation or in those who deny the consumption of nitrous oxide. Methods: We retrospectively collected clinical and biological data in patients hospitalized for nitrous oxide use in a university hospital in southern France between January 2020 and October 2022. Results: Thirty-one patients were identified during 34 months; 79% were men with a median age of 23.7 years. Most (97%) presented with peripheral polyneuropathy and/or myelopathy. The median vitamin B12 concentration was 134.6 pmol/L, with 17 of 31 patients having values less than 145 pmol/L (the lower limit of the normal range). The median plasma folate concentration was 20.1 nmol/L, which is within the normal range. The median plasma homocysteine concentration was 87.7 µmol/L (normal range >15 µmol/L), and the median plasma methylmalonic acid concentration was 3.8 µmol/L (normal range >0.5 µmol/L). Conclusion: Nitrous oxide use is an emerging public health problem in France, as shown by the number of patients admitted to our hospital. The presence of a functional vitamin B12 deficiency was a consistent feature that could be helpful in diagnosis in complex cases.

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report

BackgroundNitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature.Case reportA 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected.ConclusionThis case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.

Lachgas: om te lachen?

Nitrous oxide: no laughing matter In this case study, the authors discuss the dangers and medical relevance of the increasing recreational use of nitrous oxide. Nitrous oxide is a legal and readily available gas that has been gaining popularity as a drug in recent years, especially among young people. Unlike medicinal use where the nitrous oxide is mixed with oxygen, this is not the case when it comes to nitrous oxide used as a drug. For this reason, acute intoxication can cause temporary hypoxia resulting in coordination disorders, a slight loss of consciousness and a headache. Chronic intoxication causes myelo- and neuropathy due to a functional vitamin B12 deficiency. Clinically, motor weakness, gait ataxia and sensory abnormalities are mainly observed, in which the lower limbs are classically more affected than the upper limbs. The diagnosis is based on a combination of anamnestic and clinical findings, as well as typical findings on an MRI and electromyographic examination. The administration of vitamin B12 can be considered as part of the treatment. However, cessation of the nitrous oxide abuse itself is paramount for symptoms to disappear. In the event of a suspicious clinical presentation, care providers should therefore actively inquire about possible nitrous oxide use so that timely action can be taken.

Functional vitamin B12 deficiency: Improving methylmalonic acid reference intervals in urine

Background-AimMost laboratory requests focus on the detection of possible vitamin B12 deficiency. In this context, methylmalonic acid (MMA) is reported as the best biomarker.The aim of our study was to establish the biological reference interval for MMA in urine, and assess the influence of age, sex, and vitamin B12 status on MMA concentrations. MethodsThis is a prospective observational study considering individuals with normal results for blood count and liver and kidney function. Individuals who presented supplementation, any pathology or treatment that could cause cobalamin metabolism disorders, and pregnant women were excluded. Likewise, individuals whose vitamin B12 result presented antibody-mediated interference were excluded.Individuals were grouped by age-group and sex. Reference intervals were determined by non-parametric calculation (percentiles 1–99). ResultsIt was established a single reference interval [0.52 (CI90%: 0.50–0.54) – 5.75 (CI90%: 5.57–6.17) mmolMMA/mol creatinine], with 100 % of individuals with MMA above the upper limit of reference presenting a total vitamin B12 concentration ≤ 238 pmol/L. ConclusionThe establishment of optimal reference intervals for methylmalonic acid excretion in urine is crucial in individuals with a suspicion of functional vitamin B12 deficiency. However, the possibility of establishing a cut-off value for total vitamin B12 suggesting subclinical deficiency remains a challenge for this magnitude.

Neuromyelitis optica spectrum disorders with an inverted V sign on spinal cord magnetic resonance imaging: antiaquaporin-4 antibody and functional vitamin B12 deficiency

Several studies have reported a possible link between antiaquaporin- 4 antibody and vitamin B12 deficiency in neuromyelitis optica spectrum disorder (NMOSD). Bilaterally symmetric hyperintense signals on magnetic resonance imaging (MRI) of the posterior columns, called the inverted V sign, are a characteristic feature of subacute combined degeneration associated with vitamin B12 deficiency. We report a patient with anti-aquaporin-4 antibodypositive NMOSD and an inverted V sign on MRI of the spinal cord and address the association between anti-aquaporin-4 antibody and functional vitamin B12 deficiency.

Nutritional status in pulmonary arterial hypertension.

Nutritional deficiencies have been described in patients with pulmonary arterial hypertension (PAH), such as in iron and vitamin D. However, an extensive description of vitamin and mineral status is lacking and until now there is no data on dietary intake in PAH patients. We analyzed blood samples and determined nutritional intake using a food frequency questionnaire (HELIUS) in a cohort of prevalent PAH patients at a single center in Amsterdam, the Netherlands. Quality of life (QoL) was assessed by the SF-36 questionnaire. In total, 37 patients were included (6 males, 31 females; 48 ± 16 years). The dietary intake of sugar was above 25 g in 87% of the patients and fluid intake was above 1500 ml in 78% of the patients. Sodium intake was below 1800 mg in the majority (56%) of the patients. Sugar and fluid intake were linear related. We confirm previously observed deficiencies of iron and vitamin D in our study population. In addition, we observed a functional vitamin B12 deficiency in 29% of patients, which coincided with an increased expression of methylmalonic acid. 60% of patients had a low vitamin K1 status (<0.8 nmol/L). Finally, 40% of patients had selenium levels below <100 μg/L and low selenium levels associated with reduced vitality in these patients. Besides the known deficiencies in iron and vitamin D levels, we observed in a subset of patients signs of vitamin B12, vitamin K1 and selenium deficiencies. There is room for improving dietary intake. Future research aims to demonstrate the clinical importance and reveal the effect of nutritional interventions.

Functional Vitamin B12 Deficiency in Sleep Disorders in Children

It has been known for some time that an absolute deficiency in vitamin B12 is often associated with sleep disorders in children. The mechanism for the sleep disorders, though, is not generally stated. We have identified a cohort of children, who suffered from long term sleep disorders, who were characterized by elevated serum vitamin B12 levels. Retrospective Organic Acid Analysis of the urine of the children identified many markers of functional vitamin B12 deficiency, despite the elevated serum B12. As such the children may have paradoxical B12 in which serum levels of vitamin B12 were normal or elevated, however they had elevated markers of functional vitamin B12 deficiency. This functional vitamin B12 deficiency appeared to be the result of functional vitamin B2 deficiency. The mechanism is discussed. Effective treatment required resolution of the functional vitamin B2 deficiency as well as high dose vitamin B12 administration.

Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome

Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) is a complex chronic condition, characterized by periods of extreme fatigue, for which an underlying medical condition has previously not been identified. Many of the symptoms of CFS/ME, are, though, similar to those with vitamin B12 deficiency. In contrast to nutritional vitamin B12 deficiency, the majority of individuals with CFS have been shown to have functional vitamin B12 deficiency as well as functional vitamin B2 deficiency. This functional B12 deficiency occurred despite elevated serum B12 being found, and hence presents as Paradoxical vitamin B12 deficiency. As such, CFS due to functional B2 deficiency presents as Paradoxical B12 deficiency. Maintenance of vitamin B12 functional activity is critically dependent upon functional B2 sufficiency, and hence resolution of CFS there must first be resolution of functional B2 deficiency before treatment with vitamin B12 can be effective.

Health Outcomes of Infants with Vitamin B12 Deficiency Identified by Newborn Screening and Early Treated

To evaluate the clinical outcomes at age 1.5±0.5years of infants with vitamin B12 deficiency identified by newborn screening (NBS). Prospective multicenter observational study on health outcomes of 31 infants with vitamin B12 deficiency identified by NBS. Neurodevelopment was assessed by the Denver Developmental Screening Test. In 285 862 newborns screened between 2016 and 2019, the estimated birth prevalence of vitamin B12 deficiency was 26 in 100 000 newborns, with high seasonal variations (lowest in summer: 8 in 100 000). Infants participating in the outcome study (N=31) were supplemented with vitamin B12 for a median (range) of 5.9 (1.1-16.2) months. All achieved age-appropriate test results in Denver Developmental Screening Test at age 15 (11-23) months and did not present with symptoms characteristic for vitamin B12 deficiency. Most (81%, n=25) mothers of affected newborns had a hitherto undiagnosed (functional) vitamin B12 deficiency, and, subsequently, received specific therapy. Neonatal vitamin B12 deficiency can be screened by NBS, preventing the manifestation of irreversible neurologic symptoms and the recurrence of vitamin B12 deficiency in future pregnancies through adequate treatment of affected newborns and their mothers. The high frequency of mothers with migrant background having a newborn with vitamin B12 deficiency highlights the need for improved prenatal care.

Subacute combined degeneration of the spinal cord in functional vitamin B12 Deficiency states

Vitamin B12 is an essential enzymatic cofactor in multiple cellular metabolic pathways. Deficiency states can arise as a result of both depletion of absolute systemic levels and pathological processes that block its ability to act as an enzymatic cofactor. The latter is also known as functional vitamin B12 deficiency. This can cause a variety of systemic, haematological, and neurological manifestations, some of which may be irreversible if not promptly treated. Neurological syndromes include subacute combined degeneration of the cord (SCDC), peripheral, optic, and autonomic neuropathies, and neuropsychiatric or cognitive deficits. This review presents a case series of vitamin B12 deficiencies leading to SCDC, and we include the clinical features, significant investigations, treatments, and prognoses.

Functional vitamin B12 deficiency in phenylketonuria patients and healthy controls: An evaluation with combined indicator of vitamin B12 status as a biochemical index.

Vitamin B12 deficiency frequently appears in phenylketonuria patients having a diet poor in natural protein. The aims of this study were to evaluate vitamin B12 status in phenylketonuria patients by using combined indicator of vitamin B12 status (cB12) as well as methylmalonic acid and homocysteine, more specific and sensitive markers, in comparison with healthy controls. Fifty-three children and adolescents with phenylketonuria under dietary treatment and 30 healthy controls were assessed cross-sectionally. Serum vitamin B12 and folate concentrations were analysed by chemiluminescence immunoassay. Plasma methylmalonic acid and total homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and liquid chromatography, respectively. cB12 was calculated by using a formula involving blood parameters. Methylmalonic acid and folate concentrations in phenylketonuria group were higher compared with controls. Methylmalonic acid concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 concentrations. Based on cB12, a significant difference within the normal values was detected between the groups. However, although 24.5% of phenylketonuria patients and 13.3% of controls had decreased vitamin B12 status according to cB12, there was no significant difference. Children and adolescents with phenylketonuria having a strict diet can be at risk of functional vitamin B12 deficiency. This deficiency can be accurately determined by measuring methylmalonic acid concentrations. Calculation of cB12 as a biochemical index did not provide additional information compared with the measurement of methylmalonic acid alone, but may be helpful for classification of some patients with increased methylmalonic acid as having adequate vitamin B12 status.

Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation

Nitrous oxide (N2O) is widely used as an anesthetic or an analgesic. N2O prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to N2O. This was an incentive to prospectively investigate functional vitamin B12 deficiency in patients affected by sickle cell disease regularly exposed to N2O. We measured plasma concentrations of vitamin B12, total homocysteine, methionine and methylmalonic acid in 39 patients with sickle cell disease between 2015 and 2016. No patients developed neurological symptoms related to N2O administration but 19 patients (49%) had biochemical abnormalities suggesting mildly disturbed vitamin B12 metabolism e.g. decreased B12 vitamin, hypomethioninemia, or slightly increased methylmalonic acid or homocysteine. The clinical case highlight the potential severe deleterious effects of N2O over exposure on B12 vitamin metabolism in particular in patients affected with sickle cell disease. Conversely, when used without excess even repeatedly, there seem to be no overt clinically relevant abnormalities in vitamin B12 metabolism as observed on the cohort of 39 sickle cell disease affected patients.

Neurobiology of Increase in Violence in Pakistan and the Role of Online Medical Care in its Reduction

Causes of increase in violence in a named society, apart from socio-political and economical reasons, will be examined in this study. One of the most important reasons for increase in levels of hostility in a society is prevalence of psychological depression among population, which can lead to violent behavior and cause physical harm to one or others, increase in suicidal tendencies and destruction of property. Increase and prevalence of internal medical diseases are one of the main causes of increase in depression, among which diabetes, hypothyroidism, vitamin D, calcium, and vitamin B12 deficiency, hypo and dyslipidemia can be mentioned. The main cause for increasing prevalence of depression in Pakistan can be attributed to: -Rapid increase in spread of diabetes (mean prevalence13.14%), which increased 2 times in during 7 years period. Share of other illnesses contributing to depression can be summarized as follows, 20% to spread of diabetes in urban areas. - 6.6% to spread of vitamin B12 deficiency - 84.3% to spread of vitamin D deficiency - 8.29% of subclinical hypothyroidism In order to have more accurate results further measurements of prevalence of functional vitamin B12 deficiency and calcium is recommended. By using on line medical care system in Iran, it was found that 85% of people suffering from depression had at least one of the above mentioned causes, and after treatment symptoms of depression were noticeably reduced. At the end of this article there is an announcement for specialists in Pakistan and other countries to adapt the online medical care system to their own circumstances.

Vitamin B12 deficiency and impaired expression of amnionless during aging.

BackgroundPhysical frailty and loss of mobility in elderly individuals lead to reduced independence, quality of life, and increased mortality. Vitamin B12 deficiency has been linked to several age‐related chronic diseases, including in the musculo‐skeletal system, where vitamin B12 deficiency is generally believed to be linked to poor nutritional intake. In the present study, we asked whether aging and frailty associate with altered vitamin B12 homeostasis in humans and investigated the underlying molecular mechanisms using preclinical models.MethodsWe analysed a subset of the Singapore Longitudinal Aging Study and stratified 238 participants based on age and Fried frailty criteria. Levels of methyl‐malonic acid (MMA), a marker for vitamin B12 deficiency, and amnionless, the vitamin B12 co‐receptor that anchors the vitamin B12 transport complex to the membrane of epithelial cells, were measured in plasma. In addition, vitamin B12 levels and the molecular mechanisms of vitamin B12 uptake and excretion were analysed in ileum, kidney, liver, and blood using a rat model of natural aging where nutritional intake is fully controlled.ResultsWe demonstrate that aging and frailty are associated with a higher prevalence of functional vitamin B12 deficiency that can be detected by increased levels of MMA in blood (ρ = 0.25; P = 0.00013). The decline in circulating vitamin B12 levels is recapitulated in a rat model of natural aging where food composition and intake are stable. At the molecular level, these perturbations involve altered expression of amnionless in the ileum and kidney. Interestingly, we demonstrate that amnionless can be detected in serum where its levels increase during aging in both rodents and human (P = 3.3e‐07 and 9.2e‐07, respectively). Blood amnionless levels negatively correlate with vitamin B12 in rats (r2 = 0.305; P = 0.0042) and positively correlate with the vitamin B12 deficiency marker MMA in humans (ρ = 0.22; P = 0.00068).ConclusionsOur results demonstrate that aging and frailty cause intrinsic vitamin B12 deficiencies, which can occur independently of nutritional intake. Mechanistically, vitamin B12 deficiency involves the physio‐pathological decline of both the intestinal uptake and the renal reabsorption system for vitamin B12. Finally, amnionless is a novel biomarker which can detect perturbed vitamin B12 bioavailability during aging and physical frailty.

Lower serum B12 vitamin concentrations are not accompanied by hyperhomocysteinaemia in chronic spontaneous urticaria.

Lower serum vitamin B12 concentrations have been observed in patients with chronic spontaneous urticaria (CSU). It is known that vitamin B12 deficiency is closely related to hyperhomocysteinaemia, which is associated with a proinflammatory state. To assess the relationship between vitamin B12 status and concentrations of homocysteine (Hcy) with acute phase response in patients with CSU. Circulating concentrations of vitamin B12, Hcy and C-reactive protein (CRP) were measured in 42 patients with CSU of varying severity, and compared with 19 healthy controls (HCs). Significantly lower concentrations of vitamin B12 and higher concentrations of CRP were observed in the serum of the patients with CSU compared with HCs (P < 0.01 and P < 0.001, respectively). However, there were no significant differences in plasma Hcy concentrations between the investigated groups. In addition, no correlations were found between the concentrations of vitamin B12, Hcy and CRP. Lower values of vitamin B12 concentration in patients with CSU were not associated with higher Hcy concentrations, suggesting that such patients do not have functional vitamin B12 deficiency.

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

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. 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. B12 values were elevated (>900pg/ml) in 30% and low (≤300pg/ml) in 17% of subjects tested. Elevated MMA (>250nmol/l) and homocysteine (>12.1μmol/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 ≥1500pg/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. 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.

Improving Bariatric Patient Aftercare Outcome by Improved Detection of a Functional Vitamin B12 Deficiency.

Vitamin B12 deficiency is common after bariatric surgery. Vitamin B12 is a poor predictor of functional vitamin B12 status, since deficiencies might even occur within the reference limits. Therefore, vitamin B12 deficiencies with serum vitamin B12 levels are between 140 and 200pmol/L remain undetected. Methylmalonic acid (MMA), however, will detect these deficiencies as accumulates due to functional intracellular vitamin B12 deficiencies. MMA is a relative expensive analysis and is therefore not generally available. To lower the costs, we only request MMA when vitamin B12 levels are between these levels. As a result, more biochemical deficiencies are found. However, it was not known whether bariatric patients with vitamin B12 levels between 140 and 200pmol/L would benefit from supplementation. Bariatric patients with vitamin B12 levels between 140 and 200pmol/L with (n = 45) and without (n = 45) intramuscular hydroxocobalamin injections were compared. Treated patients showed a significant increase of vitamin B12 levels (P < 0.001) and a significant decrease in MMA levels (P < 0.001). Biochemical improvement occurs in both patients with and without clinical symptoms. The control group showed a significant increase of MMA levels (P < 0.001). To examine whether biochemical benefits of vitamin B12 supplementation are correlated with clinical improvement, patient records were checked for complaints. Complaints were disappeared after treatment, while no improvement was seen in untreated patients. This study shows that all bariatric patients with vitamin B12 levels between 140 and 200pmol/L benefit clinical and biochemical from vitamin B12 supplementation, regardless the MMA levels.