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BMJ (Clinical Research Ed.) Nov 2023
Topics: Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 37984968
DOI: 10.1136/bmj-2022-071725 -
Neurotherapeutics : the Journal of the... Jul 2023Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence... (Review)
Review
Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.
Topics: Humans; Niacin; Amyloid beta-Peptides; Pellagra; Nervous System Diseases; Alzheimer Disease; Neurology
PubMed: 37084148
DOI: 10.1007/s13311-023-01376-2 -
Science Advances Jul 2023Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In... (Review)
Review
Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In 2016, the first clinical trial of nicotinamide riboside was conducted to test the safety and efficacy of human supplementation. Many trials have since been conducted aiming to delineate benefits to metabolic health and severe diseases in humans. This review endeavors to summarize and critically assess the 25 currently published research articles on human nicotinamide riboside supplementation to identify any poorly founded claims and assist the field in elucidating the actual future potential for nicotinamide riboside. Collectively, oral nicotinamide riboside supplementation has displayed few clinically relevant effects, and there is an unfortunate tendency in the literature to exaggerate the importance and robustness of reported effects. Even so, nicotinamide riboside may play a role in the reduction of inflammatory states and has shown some potential in the treatment of diverse severe diseases.
Topics: Humans; Niacinamide; NAD; Pyridinium Compounds; Dietary Supplements
PubMed: 37478182
DOI: 10.1126/sciadv.adi4862 -
Nutrients Jun 2023Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine,... (Review)
Review
INTRODUCTION
Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine, pyridoxal, and pyridoxamine. Both vitamin B6 deficiency and high B6 intake have been described as risk factors for developing peripheral neuropathy (PN). The aim of this systematic review is to characterize and comprehensively describe B6-related PN.
METHOD
A systematic, computer-based search was conducted using the PubMed database. Twenty articles were included in this review.
RESULTS
Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type. After pyridoxine discontinuation, such patients subjectively report improved symptoms. However, although low vitamin B6 levels can be seen in patients suffering from peripheral neuropathy of various etiologies, there is no firm evidence that low B6 levels have a direct causal relationship with PN. Many studies suggest subjective improvement of neuropathy symptoms in patients suffering from PN of various etiologies after receiving B6 supplementation; however, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. Therefore, the potential therapeutic role of B6 cannot be confirmed to date. Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from PN.
CONCLUSION
Current scientific evidence supports a neurotoxic role of B6 at high levels. Although some studies suggest that low B6 is also a potential risk factor, further studies in this area are needed.
Topics: Humans; Pyridoxine; Vitamin B 6; Pyridoxal; Pyridoxamine; Vitamins; Peripheral Nervous System Diseases
PubMed: 37447150
DOI: 10.3390/nu15132823 -
Nature Communications Oct 2023Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease...
Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.
Topics: Mice; Animals; Humans; Vitamin B Complex; Niacin; Cachexia; Proteomics; Pyridoxine; Vitamin B 6; Stomach Neoplasms; Liver; Glycine
PubMed: 37803016
DOI: 10.1038/s41467-023-41952-w -
Bioscience Reports Oct 2023Thiamine (thiamin, B1) is a vitamin necessary for proper cell function. It exists in a free form as a thiamine, or as a mono-, di- or triphosphate. Thiamine plays a...
Thiamine (thiamin, B1) is a vitamin necessary for proper cell function. It exists in a free form as a thiamine, or as a mono-, di- or triphosphate. Thiamine plays a special role in the body as a coenzyme necessary for the metabolism of carbohydrates, fats and proteins. In addition, it participates in the cellular respiration and oxidation of fatty acids: in malnourished people, high doses of glucose result in acute thiamine deficiency. It also participates in energy production in the mitochondria and protein synthesis. In addition, it is also needed to ensure the proper functioning of the central and peripheral nervous system, where it is involved in neurotransmitter synthesis. Its deficiency leads to mitochondrial dysfunction, lactate and pyruvate accumulation, and consequently to focal thalamic degeneration, manifested as Wernicke's encephalopathy or Wernicke-Korsakoff syndrome. It can also lead to severe or even fatal neurologic and cardiovascular complications, including heart failure, neuropathy leading to ataxia and paralysis, confusion, or delirium. The most common risk factor for thiamine deficiency is alcohol abuse. This paper presents current knowledge of the biological functions of thiamine, its antioxidant properties, and the effects of its deficiency in the body.
Topics: Humans; Thiamine; Thiamine Deficiency; Korsakoff Syndrome; Wernicke Encephalopathy; Vitamin B Complex; Malnutrition
PubMed: 37389565
DOI: 10.1042/BSR20230374 -
International Journal of Medical... 2023B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide... (Randomized Controlled Trial)
Randomized Controlled Trial
A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial.
B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide energy, each B vitamin acts as a cofactor in energy metabolism processes. Based on the evidence presented above, we hypothesized that a 28-day supplementation of vitamin B would enhance physical performance and reduce physical fatigue. The objective of this study was to evaluate the anti-fatigue effect of vitamin B supplementation, specifically vitamin B1, B2, B6, and B12, and its potential to improve exercise performance. We employed a randomized double-blind crossover design with a 28-day supplementation period. Sixteen male and sixteen female subjects, aged 20-30 years, were divided into two groups: the placebo group (n=16, equal gender distribution) and the Ex PLUS group (n=16, equal gender distribution). The participants received either placebo or Ex PLUS (one tablet per day) for 28 consecutive days. Following the intervention, there was a 14-day wash-out period during which the subjects did not receive any further interventions. After supplementation with Ex PLUS, we found a significant increase in the running time by 1.26-fold ( 0.05) to exhaustion compared to that before supplementation and that in the placebo group. In addition, the Ex PLUS supplementation group presented significantly reduced blood lactate and blood ammonia concentrations during exercise and at rest after exercise compared with placebo ( < 0.05). In conclusion, 28 consecutive days of vitamin B complex (Ex PLUS) supplementation significantly improved exercise endurance performance and reduced exercise fatigue biochemical metabolites in not athletes. In addition, it does not cause adverse effects in humans when taken at appropriate doses.
Topics: Humans; Male; Female; Vitamin B Complex; Dietary Supplements; Folic Acid; Health Status; Fatigue; Double-Blind Method
PubMed: 37786445
DOI: 10.7150/ijms.86738 -
Cancer Research Jan 2024The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across... (Review)
Review
The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small-molecule inhibitors to the isozymes MTHFD2 and MTHFD1 that show promise as anticancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers.
Topics: Humans; Neoplasms; Methylenetetrahydrofolate Dehydrogenase (NADP); Antineoplastic Agents; Folic Acid; DNA Repair
PubMed: 37922465
DOI: 10.1158/0008-5472.CAN-23-1290 -
Nutrients Jul 2023Dietary vitamin B3 components, such as nicotinamide and nicotinic acid, are precursors to the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD). NAD... (Review)
Review
Dietary vitamin B3 components, such as nicotinamide and nicotinic acid, are precursors to the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD). NAD levels are thought to decline with age and disease. While the drivers of this decline remain under intense investigation, strategies have emerged seeking to functionally maintain NAD levels through supplementation with NAD biosynthetic intermediates. These include marketed products, such as nicotinamide riboside (NR) and its phosphorylated form (NMN). More recent developments have shown that NRH (the reduced form of NR) and its phosphorylated form NMNH also increases NAD levels upon administration, although they initially generate NADH (the reduced form of NAD). Other means to increase the combined levels of NAD and NADH, NAD(H), include the inhibition of NAD-consuming enzymes or activation of biosynthetic pathways. Multiple studies have shown that supplementation with an NAD(H) precursor changes the profile of NAD(H) catabolism. Yet, the pharmacological significance of NAD(H) catabolites is rarely considered although the distribution and abundance of these catabolites differ depending on the NAD(H) precursor used, the species in which the study is conducted, and the tissues used for the quantification. Significantly, some of these metabolites have emerged as biomarkers in physiological disorders and might not be innocuous. Herein, we review the known and emerging catabolites of the NAD(H) metabolome and highlight their biochemical and physiological function as well as key chemical and biochemical reactions leading to their formation. Furthermore, we emphasize the need for analytical methods that inform on the full NAD(H) metabolome since the relative abundance of NAD(H) catabolites informs how NAD(H) precursors are used, recycled, and eliminated.
Topics: NAD; Niacinamide; Niacin; Metabolome; Oxidation-Reduction; Biomarkers
PubMed: 37447389
DOI: 10.3390/nu15133064 -
Diabetes Research and Clinical Practice Dec 2023Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three... (Review)
Review
Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.
Topics: Humans; Combined Modality Therapy; Diabetes Mellitus; Diabetic Neuropathies; Pain; Thioctic Acid
PubMed: 38245327
DOI: 10.1016/j.diabres.2023.110764