Search Results (28)

Despite the development of a wide plethora of different anticancer agents, most of them are not used for patient treatment due to adverse effects caused by untargeted cytotoxicity. To prevent this unwanted toxicity, it is necessary to develop therapies discriminating between healthy and cancerous cells. One possible method is to target proteins overexpressed in cancer but not in normal cells. CD320 is a receptor responsible for the uptake of the transcobalamin-bound fraction of vitamin B12 (cobalamin), which is necessary for DNA synthesis, and thus, cell proliferation. CD320 was shown to be overexpressed in many cancers and its potential role as an early cancer biomarker was confirmed in several studies. Consequently, CD320 may represent a promising anti-cancer therapy target. This review summarizes the current advances and perspectives of anti-cancer CD320 targeting therapy, including therapeutic conjugates of vitamin B12, CD320-specific antibodies and nanobodies, nanoparticles loaded with cytotoxic drugs, porphyrin, and the potential of targeted CD320 therapy in attenuation of tumor tissues. Given the growing interest in CD320 as a novel target for anti-cancer therapy, further in vivo studies are required for the investigation of CD320 targeting effects on systemic cytotoxicity. Full article

Food cobalamin malabsorption (FCM) represents a prevalent, often underdiagnosed, etiology of vitamin B12 deficiency, particularly within an aging population. Unlike pernicious anemia, an autoimmune disorder targeting intrinsic factor, FCM stems from the impaired release of cobalamin from food proteins, primarily due to age-related gastric changes, medication-induced gastric hypochlorhydria, metformin, or non-immune atrophic gastritis. The clinical presentation of FCM mirrors that of general cobalamin deficiency, encompassing a spectrum of neurological (peripheral neuropathy, cognitive decline), hematological (megaloblastic anemia), and gastrointestinal (glossitis, anorexia) manifestations. Given the potential for irreversible neurological sequelae, early detection and intervention are paramount. High-dose oral cobalamin (125–250 mcg daily) has demonstrated efficacy, offering a convenient and cost-effective alternative to parenteral administration. Full article

Vitamin B12 (cobalamin) plays a crucial role in neurodevelopment, particularly during pregnancy and early childhood. It is essential for DNA synthesis, red blood cell formation, and nervous system function. Maternal B12 levels are particularly important, as they influence fetal brain development. Inadequate maternal intake during pregnancy may lead to altered neurodevelopmental trajectories and increase the risk of ASD. Postnatally, insufficient dietary cobalamin in infants and young children could further contribute to cognitive and behavioral impairments. One potential mechanism linking low B12 levels to ASD involves its role in the gut microbiota balance. Dysbiosis, commonly observed in individuals with ASD, is associated with increased gut permeability, low-grade inflammation, and disruptions in the gut–brain axis, all of which may contribute to ASD symptoms. Additionally, B12 is essential for neurotransmitter metabolism, particularly in the synthesis of serotonin and dopamine, which regulate mood, cognition, and behavior. Cobalamin also plays a key role in neuronal myelination, which ensures efficient signal transmission in the nervous system. Disruptions in these processes could underlie some of the cognitive and behavioral features associated with ASD. Despite growing evidence, the link between B12 and ASD remains inconclusive due to inconsistent findings across studies. Research suggests that B12 levels may serve as a potential biomarker for disease progression and treatment response. However, many studies rely on single-time-point measurements, failing to account for individual variability, genetic predispositions, dietary intake, and environmental factors, all of which can influence B12 levels and ASD risk. Further longitudinal studies are needed to clarify this relationship. Full article

Vitamin B12 is the common name for a group of cobalamins, which are cobalt corrines. Cobalamins are water-soluble B vitamins. Vitamin B12, as a coenzyme of various enzymes, is an essential component of many key metabolic processes in the body. Vitamin B12 deficiency causes dysfunction of various organs and systems in the body, including the central nervous system. Humans, like other animals, are unable to synthesize cobalamin. This vitamin must be supplied with a balanced diet. The only valuable dietary sources of cobalamin are foods of animal origin, especially offal (e.g., liver). Vegan and vegetarian diets are deficient in vitamin B12. People who follow this nutritional model require systematic cobalamin supplementation, usually in oral form. Other causes of cobalamin deficiency are various pathogenetic processes, in the course of which any of the stages of the complicated process of absorption of this vitamin from the gastrointestinal tract are impaired. Disorders of intestinal absorption of vitamin B12 require systematic supplementation of cobalamin parenterally (usually by intramuscular or subcutaneous injections) for the rest of life. Supplementary therapy with vitamin B12 may cause various adverse reactions, among which hypersensitivity reactions of various spectrums and intensity of symptoms are possible. According to available data, hypersensitivity to cobalamin is more likely after intramuscular or subcutaneous administration than in oral form. It also seems that long-term administration of cobalamin predisposes to allergy to vitamin B12, regardless of its chemical form. Although hypersensitivity to cobalamin is rather rare, it can also be of great clinical importance. This is due to the fact that vitamin B12 deficiency affects a significant part of the population, especially the elderly and those with chronic diseases that impair its absorption. In addition, supplementary therapy with cobalamin is long-term (usually lifelong) and there is no alternative form of treatment. For these reasons, solutions are sought that will allow for the safe continuation of treatment supplementing cobalamin deficiency. Various cyanocobalamin desensitization protocols are proposed, differing in duration, the dynamics of gradual dose increase, or the method of injection (intramuscular or subcutaneous). An analysis of available data in this field suggests that desensitization with cyanocobalamin seems to be an effective way to obtain tolerance to vitamin B12, allowing for long-term supplementation of this vitamin regardless of the chemical form, dose size, frequency, or route of administration. Full article

Chronic enteropathy (CE) or chronic inflammatory enteropathy is a group of diseases with multiple and different etiologies characterized by chronic gastrointestinal signs such as vomiting, diarrhea, anorexia, weight loss for more than 3 weeks, and inflammatory cell infiltration, such as lymphoplasmacytic cells in the intestinal mucosal lamina propria. The diagnosis was histologically confirmed after excluding other diseases such as parasitic infections, tumors, pancreatitis, exocrine pancreatic insufficiency, metabolic diseases, and endocrine diseases, such as hypoadrenocorticism. Nutritional management depends on several important functions, such as digestion and absorption processes, digestive enzymes and nutritional transporters, and barrier functions. Intestinal dysbiosis may have been found to be involved in various functions. Recently, cobalamin (vitamin B₁₂) and vitamin D have been considered negative prognostic factors in dogs with CE. Cobalamin supplementation ameliorates clinical disease severity in dogs with CE, and vitamin D supplementation ameliorates hypocalcemia in dogs with CE and hypoalbuminemia. Therefore, the aim of this review is to provide an overview of CE and present treatment and nutritional management strategies for CE and prognostic vitamins. Full article

The ability to over-proliferate is a hallmark of cancer cells, so inhibiting proliferation is crucial for successful cancer treatment. Vitamin B12 (cobalamin) is among the factors necessary for replication of genetic material and cell division. There is currently no cobalamin antagonist with therapeutic use. Nevertheless, the idea of inhibiting cobalamin-dependent metabolic pathways as a potential anticancer strategy is of interest to many researchers. In this study, we investigated, for the first time, the impact of cobalamin deficiency on melanoma cells’ growth. To achieve a cobalamin-deficient state in cellulo, hydroxycobalamin[c-lactam] was used as an antivitamin B12. Here, we describe a new and efficient method for synthesizing this analog from hydroxycobalamin. Interestingly, no cytostatic effect of cobalamin deficiency was observed on C32 and COLO 829 melanoma cell lines. However, we show the variously enhanced pro-proliferative action of vitamin B12 towards these cells. The presented experimental model can be used for further studies on the effects of the cobalamin status on melanoma cells. Full article

The 2007 Horse NRC reduced cobalt (Co) requirements from 0.1 ppm to 0.05 ppm in dietary dry matter, though preliminary research suggested increasing dietary-Co enhanced fiber digestion in horses. This study aimed to evaluate fiber digestion with varying dietary Co amounts, as well as to compare serum Co concentrations with dietary Co content. Four geldings (mean body weight [BW] 503 ± 37 kg) were studied in a 4 × 4 Latin square design consisting of four 5-week periods, each comprising a 2-week washout phase followed by a 3-week treatment phase. Supplementing 0.0, 5.6, 16.8, or 28.0 mg of Co daily resulted in total Co dietary concentrations of 0.06, 0.7, 2.0, and 3.0 ppm, respectively. Feces and urine were collected to evaluate fiber digestibility and Co balance. Co supplementation did not affect neutral detergent fiber, acid detergent fiber, or lignin digestibility. Co balance was negative for the control diet but positive for the other three treatments (p = 0.04). Serum cobalamin concentrations slightly decreased (6%) with increasing dietary Co intake (p = 0.003), while folate concentrations were unaffected. Serum Co concentration differed (p < 0.01) with a mean of 4.7 μg/mL for the high treatment and 0.8 μg/mL for the control. Results suggest that serum Co concentrations above regulatory limits are likely due not to higher levels of Co in fortified feeds, but rather to parenteral administration of Co solutions. Full article

Background and Objectives: This study investigated the impact of nutritional status and foods consumed on inflammation and disease activity in patients with rheumatoid arthritis (RA). Materials and Methods: We designed a cross-sectional observational study, involving 110 patients diagnosed with RA. The patients included were between 18 and 75 years old, diagnosed with rheumatoid arthritis two years ago or earlier, with stable treatment for the last 8 weeks. Data on anthropometric parameters, body mass composition, nutritional status, individual food consumption records, inflammation, disease activity, quality of life, clinical, and laboratory parameters were collected for each study participant. The evaluation parameters of the patients were the simple disease activity index (SDAI), clinical disease activity index (CDAI), systemic immune-inflammation index (SII) and individual food consumption records. A bioimpedance device and measuring tape were used to take body composition and anthropometric measurements of the patients. Results: According to the body mass index, waist circumference and waist-to-height ratio, in our study, we found that 60% of the patients were obese, 80% were at a very high health risk, and approximately 91% were in need of nutritional treatment. There was a significant negative correlation between the dietary intake of total energy, total fat, omega 3, calcium, zinc, cobalamin and the disease activity (SDAI, CDAI). There was a significant negative correlation between polyunsaturated fatty acids, omega 3, carotene, vitamin E, selenium and the SII. Additionally, there was a positive correlation between omega 6 and the SII, SDAI, CDAI (p < 0.05). Conclusions: The results of this study show that the foods consumed in the nutrition of RA patients may have effects on their inflammation and disease activity. Full article

The water-soluble vitamin, vitamin B₁₂, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B₁₂ deficiency. A prolonged lack of vitamin B₁₂ may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B₁₂ deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B₁₂ in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B₁₂ deficiency are also highlighted. We also discuss clinical warnings of vitamin B₁₂ deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B₁₂ metabolic pathways. Full article

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable. Full article

Background: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance. Methods: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects (n = 40; four groups, n = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid–base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake. Results: Statistical analyses displayed ten significant main effects (p < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group (p < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping—demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level. Conclusions: Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress. Full article

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T₀), 30 days after the start of treatment (T₁), and at 60 days (T₂). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T₀, 481.4 (±170.21) at T₁, and 513.2 (±174.50) at T₂. In the omeprazole group, the values were 424.62 (±161.57) at T₀, 454.5 (±160.96) at T₁, and 414.87 (±127.90) at T₂. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17–218.75] at T₀, 76.06 [30.67–199.87] at T₁, and 63.02 [35.81–176.06] at T₂. The median gastrin value in the omeprazole group was 67.59 [55.96–101.60] at T₀, 191.77 [75.31–1901.77] at T₁, and 128.16 [43.62–1066.46] at T₂. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment. Full article

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period. Full article

Nitrous oxide abuse may cause functional cobalamin deficiency and subsequent damage to the peripheral nerves, the spinal cord, and the brain, a symptom complex best described by the term cobalamin neuropathy. Here, we report a case of cobalamin neuropathy with uncommon cerebral symptomatology following nitrous oxide intoxication and contextualize the symptomatology. A 22-year-old male with a history of mixed drug dependency presented at the emergency room after inhaling six 615 g cylinders, equal to ~1800 L, of nitrous oxide daily for two weeks. His main complaints were rapidly progressing paresthesias and gait difficulties, but he was also found to suffer from memory impairment and signs of extrapyramidal pathology in the form of dystonic posturing and athetosis. Neuroimaging demonstrated spinal cord hyperintensities consistent with subacute combined degeneration. The patient had low serum cobalamin and high plasma homocysteine, suggesting cobalamin neuropathy. After commencing treatment with parenteral hydroxocobalamin, plasma homocysteine normalized. The extrapyramidal symptoms disappeared during the first days of treatment, whereas the cognitive and peripheral symptoms only partially resolved over the following 20 days. This case highlights how neurological symptoms such as hyperkinetic movements and memory impairment may be associated with chronic nitrous oxide abuse. It is unclear to what extent these and other symptoms of cobalamin neuropathy are reversible, which underscores the public health concern. Full article

Background: Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD. Methods: Data in the PubMed and Embase databases were analyzed. The keywords “chronic kidney disease”, in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients. Results: The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4–5), the inclusion of niacin at a dose of 400–1000 mg, depending on the patient’s tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients. Conclusions: Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition. Full article