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Vitamin B6 status, deficiency and its consequences - An overview
Abstract
Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly.
This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions.
The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters.
In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.
... Он обладает нейропротекторным действием, которое, по-видимому, связано в основном с его способностью регулировать глутаматергическую систему и, следовательно, уровни гамма-аминомасляной кислоты и глутамата [4]. Из-за важной функции кофермента в путях, ответственных за синтез нейротрансмиттеров и миелина, дефицит витамина B 6 может серьезно ухудшать работу ЦНС и ПНС [3,6,28]. ...
... Неврологические симптомы дефицита витамина В 6 включают нарушения когнитивной функции, судорожные припадки, депрессию, а также синдром запястного канала и полинейропатии с такими симптомами, как парестезия, жгучие и болезненные дизестезии [3,6,[27][28][29]. Так, в клиническом исследовании пациентов с синдромом запястного канала (компрессионное пов реж дение) лечение витамином B 6 увеличивало скорость проведения по сенсорным волокнам и таким образом уменьшало клинические симптомы [30]. ...
... Использование витаминов группы В, особенно витаминов В 1 (тиамин), В 6 (пиридоксин) и В 12 (кобаламин), для лечения полинейропатии хорошо известно во всем мире [7,11,16,28,32,36,48] и обычно считается безопасным даже при высоких дозах и в долгосрочной перспективе [11]. В редких случаях введение витамина В 12 может быть связано с кожными побочными эффектами [49], в доступной литературе описано развитие угревых высыпаний, вызванных витамином B 12 [50][51][52]. ...
B-group vitamins are a collection of 8 water-soluble vitamins. They are cofactors for many enzymes, as well as axonal transport, synthesis of neurotransmitters and other metabolic processes. Their function can be divided into catabolic metabolism, leading to energy production, and anabolic metabolism. Some B vitamins are considered neurotrophic and play a particularly important role in both the central and peripheral nervous systems. Neurotropic B-group vitamins (B 1 – thiamine, B 6 – pyridoxine and B 12 – cyanocobalamin) play the role of modulators for the treatment of inflammation and pain, they are essential for the proper functioning of the nervous system. B vitamin deficiencies have been considered as etiological factors in the development of various neurological disorders and a broad spectrum of pathological states. The work examines in detail vitamins B 1 , B 6 and B 12 and their effect on the course of neuropathies, movement disorders, nociceptive and neuropathic pain. The issues of the synergistic action of these vitamins are highlighted. Evidence of neurotropic B vitamin treatment effectiveness of neuropathy symptoms in different groups of patients is presented. The possibility to use vitamin B 1 and B 6 complex in clinical practice under the condition of individual intolerance of vitamin B 12 is discussed. Information about Cytipigam® compositum as a drug containing B 1 and B 6 is provided. A clinical case report on the effective use of this drug in clinical practice is described.
... The functional category includes evaluating PLP-dependent transaminase activities in red blood cells. Red blood cells are rich in the PLP-dependent glutamate-oxaloacetate transaminase (GOT) 43 , whose activity responds to changes in vitamin B6 status and in-vitro-supplied PLP 44,45 . The speci c test includes assessing GOT's activity and that induced by the in vitro addition of saturating concentrations of PLP. ...
... Thus, a higher PAR re ects a lower vitamin B6 status. Advantages of evaluating this ratio include overcoming differences related to various methods and subject variability 45,47 , in addition to serving as a long-term indicator of vitamin B6 status about the life span of the erythrocytes 35 and vitamin B6 intake 48 . Most importantly, the GOT activity test is not associated with albumin, alkaline phosphatase activity 49,50 , some immune indices 51 and kidney function. ...
... Changes in vitamin B6 status have been linked to numerous human diseases and conditions. For instance, GOT apoenzyme contents increase in diseases related to necrotic processes, while decreases had been reported following alcohol intake 45,47 . Low plasma PLP in older adults is not explained by low dietary vitamin B6 or low protein intake 24,68 , de cit in absorption, impaired synthesis or retention of PLP in erythrocytes or liver 69 . ...
Limited studies are available on the vitamin B6 status in domestic cats. To this end, we evaluated glutamate-oxaloacetate transaminase activity in hemolysates with and without pyridoxal 5’-phosphate supplementation in two feline populations: a cohort of 60 domestic (sexually intact and specific pathogen-free) cats maintained under strictly controlled conditions with optimal diets (Feline Nutrition and Pet Care Center) and a cohort of 57 cats randomly selected between December 2022 to January 2023 that visited the Veterinary Medicine Teaching Hospital to seek care under different circumstances. We analyzed the data based on the animal's age, sex, body condition score, and diagnosis to elucidate the main factors driving vitamin B6 deficiencies in domestic cats. Based on the age and body condition scores, most cats with vitamin B6 deficiency had a low body condition score (41.7%), suggesting low food intake and/or malassimilation, as most were of advanced age (≥7 y old; 66.7%). This result is consistent with the increased energy requirements and compromised digestibility in older cats linked to a higher proportion of underweight elderly cats. When the data of vitamin B6-deficient cats were analyzed in terms of medical diagnosis, most (58.4%) had a condition associated with an increased inflammatory response, whether through an infection (feline coronavirus; 25%) or via diseases associated directly or indirectly with an inflammatory response (33.4%). Thus, our study supports that vitamin B6 supplementation may be indicated in older animals, especially those undergoing an active inflammation process.
... Three derivatives of the pyridoxine ring-pyridoxine, pyridoxal, and pyridoxamine forms vitamin B6 (pyridoxine). Phosphorylation in the 5 position is a vital component of pyridoxine activity, in which pyridoxal-50-phosphate (PLP) and pyridoxamine-50-phosphate are its active coenzyme forms [78][79][80]. Pyridoxine source is mainly located within plant-based foods, such as avocado, banana, lentils, potatoes, soybean (in cooked form), walnuts, and wheat bran whilst in contrast, pyridoxal and pyridoxamine are mainly sourced from animal food products such as chicken breast (raw), ground beef, and tuna [80,81]. Pyridoxine, pyridoxal, and pyridoxamine are absorbed in the jejunum through a non-saturable, passive process and phosphorylated in the liver by pyridoxine kinase, in which this process requires zinc and ATP [78][79][80]. ...
... Pyridoxine source is mainly located within plant-based foods, such as avocado, banana, lentils, potatoes, soybean (in cooked form), walnuts, and wheat bran whilst in contrast, pyridoxal and pyridoxamine are mainly sourced from animal food products such as chicken breast (raw), ground beef, and tuna [80,81]. Pyridoxine, pyridoxal, and pyridoxamine are absorbed in the jejunum through a non-saturable, passive process and phosphorylated in the liver by pyridoxine kinase, in which this process requires zinc and ATP [78][79][80]. Also occurring within the liver following phosphorylation-alkaline phosphatase dephosphorylates pyridoxine (those in phosphorylated forms), which leads to pyridoxal and then by the irreversible action of a FAD-dependent aldehyde oxidase, to 4-pyridoxic acid (4-PA) [78][79][80]. The biochemical actions of flavin mononucleotide oxidase allows PLP to be generated from the other two vitamers, and PLP Is transported in plasma bound to albumin and in red cells bound to hemoglobin [78][79][80]. ...
... Pyridoxine, pyridoxal, and pyridoxamine are absorbed in the jejunum through a non-saturable, passive process and phosphorylated in the liver by pyridoxine kinase, in which this process requires zinc and ATP [78][79][80]. Also occurring within the liver following phosphorylation-alkaline phosphatase dephosphorylates pyridoxine (those in phosphorylated forms), which leads to pyridoxal and then by the irreversible action of a FAD-dependent aldehyde oxidase, to 4-pyridoxic acid (4-PA) [78][79][80]. The biochemical actions of flavin mononucleotide oxidase allows PLP to be generated from the other two vitamers, and PLP Is transported in plasma bound to albumin and in red cells bound to hemoglobin [78][79][80]. ...
The number of people living with chronic kidney disease (CKD) is growing as our global population continues to expand. With aging, diabetes, and cardiovascular disease being major harbingers of kidney disease, the number of people diagnosed with diabetic kidney disease (DKD) has grown concurrently. Poor clinical outcomes in DKD could be influenced by an array of factors—inadequate glycemic control, obesity, metabolic acidosis, anemia, cellular senescence, infection and inflammation, cognitive impairment, reduced physical exercise threshold, and, importantly, malnutrition contributing to protein-energy wasting, sarcopenia, and frailty. Amongst the various causes of malnutrition in DKD, the metabolic mechanisms of vitamin B (B1 (Thiamine), B2 (Riboflavin), B3 (Niacin/Nicotinamide), B5 (Pantothenic Acid), B6 (Pyridoxine), B8 (Biotin), B9 (Folate), and B12 (Cobalamin)) deficiency and its clinical impact has garnered greater scientific interest over the past decade. There remains extensive debate on the biochemical intricacies of vitamin B metabolic pathways and how their deficiencies may affect the development of CKD, diabetes, and subsequently DKD, and vice-versa. Our article provides a review of updated evidence on the biochemical and physiological properties of the vitamin B sub-forms in normal states, and how vitamin B deficiency and defects in their metabolic pathways may influence CKD/DKD pathophysiology, and in reverse how CKD/DKD progression may affect vitamin B metabolism. We hope our article increases awareness of vitamin B deficiency in DKD and the complex physiological associations that exist between vitamin B deficiency, diabetes, and CKD. Further research efforts are needed going forward to address the knowledge gaps on this topic.
... The study of the time-dependence of the vitamins administration was performed on the female rats only. A significant part (about 70%) of both vitamins is known to be excreted from the body 24 h after the injection [37,38]. However, the injections significantly increase the internal pool of vitamins [39] that can be stored in the liver, where concentrations of thiamine diphosphate and B6 vitamers are higher than in other tissues [14,40]. ...
... However, high doses of vitamin B6 are neurotoxic [38,43]. For instance, 2-6 g of vitamin B6 per day, resulted in acute sensory neuropathies [38,44]. ...
... However, high doses of vitamin B6 are neurotoxic [38,43]. For instance, 2-6 g of vitamin B6 per day, resulted in acute sensory neuropathies [38,44]. At the same time, such effects were not reported in patients with various B6-dependent syndromes who received 0.5-1.5 g of vitamin B6 per day [38]. ...
Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.
... A major part (about 70%) of both vitamins is known to be excreted from the body 24 h after the injection [74,75]. However, the injections significantly increase the internal pool of vitamins [76] stored in the liver, where concentrations of thiamine diphosphate and B6 vitamers are higher than in other tissues [14,77]. ...
... No toxic or side effects in humans are known for vitamin B1 at a daily dose of 0.5 g for a month [78]; clinically used injections of vitamin B1 may be up to 0.5 g three times a day [79]. However, high doses of vitamin B6 are neurotoxic in humans [75,80], with 2-6 g of vitamin B6 per day resulting in acute sensory neuropathies [75,81]. Intracerebroventricular administration of pyridoxal-5 -phosphate and its synthetic analogs led to seizures in rats [51]. ...
... No toxic or side effects in humans are known for vitamin B1 at a daily dose of 0.5 g for a month [78]; clinically used injections of vitamin B1 may be up to 0.5 g three times a day [79]. However, high doses of vitamin B6 are neurotoxic in humans [75,80], with 2-6 g of vitamin B6 per day resulting in acute sensory neuropathies [75,81]. Intracerebroventricular administration of pyridoxal-5 -phosphate and its synthetic analogs led to seizures in rats [51]. ...
The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.
... Subsequently, it is the preferred form to be used in pharmacological supplementation. Apart from the general implications of vitamins and their vital role in global cell operation and metabolic processes, B6 is particularly linked with amino acid and homocysteine metabolism, neurotransmitter production and deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis (Spinneker et al., 2007), whereas B12 is especially known for its role in the treatment and prevention of pernicious anaemia (Rizzo and Laganà, 2020). Although clinically identifiable vitamin B6 deficiency is not a common disorder, as far as the general population is concerned, it is associated with symptoms such as impaired cognitive function, cardiovascular disease and even cancer, especially in the elderly (Spinneker et al., 2007). ...
... Apart from the general implications of vitamins and their vital role in global cell operation and metabolic processes, B6 is particularly linked with amino acid and homocysteine metabolism, neurotransmitter production and deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis (Spinneker et al., 2007), whereas B12 is especially known for its role in the treatment and prevention of pernicious anaemia (Rizzo and Laganà, 2020). Although clinically identifiable vitamin B6 deficiency is not a common disorder, as far as the general population is concerned, it is associated with symptoms such as impaired cognitive function, cardiovascular disease and even cancer, especially in the elderly (Spinneker et al., 2007). In the case of B12, however, the scenario is different. ...
Vitamins are a vast group of fundamental organic compounds, which are not produced by the human body but are essential for the living organisms' good health. Vitamins B6 and B12 belong to the same group of hydrophilic vitamins. Structurally unrelated, they share the same purpose as essential components for normal cellular operation, growth and development. Vitamin B6 is an enzymatic co-factor that is vital for countless biochemical reactions, and is also important in sugar and fatty acid metabolization. It encompasses three natural and inter-convertible pyridine-derivatives: pyridoxine, pyridoxal and pyridoxamine. Vitamin B12 is a cobalt organometallic complex also indispensable in numerous human physiological functions. It has four bioactive forms: cyanocobalamin, methylcobalamin, hydroxocobalamin and 5'-deoxyadenosylcobalamin, and only a few prokaryotes have the ability to biosynthesize cobalamin. This work reviews the significant aspects of vitamins B6 and B12: their vital roles, consequences of deficit; food sources; and methods of determination and respective matrices, with heavy emphasis on chromatographic techniques developed within the last two decades.
... Vitamin B6 deficiency is very uncommon in the general population [17]. It mostly occurs as a part of mixed vitamin B hypovitaminosis with alcoholism as the main cause [17]. ...
... Vitamin B6 deficiency is very uncommon in the general population [17]. It mostly occurs as a part of mixed vitamin B hypovitaminosis with alcoholism as the main cause [17]. Supplementation with a daily dose of 100 mg is recommended when levels of plasma PLP are below < 20 nmol/l with hypovitaminosis symptoms [18]. ...
High alcohol intake leads to an inadequate diet and impaired absorption, transport, and utilization of nutrients in the body, which results in malnutrition. Micronutrient supplementation, such as vitamins A, E, group B vitamins, folic acid zinc, and selenium may have a positive effect on those patients. In this article, the actual supplementation recommendations for vitamins and microelements in ethanol-induced liver disease patients are presented.
... reactions [40]. In the cognitive domain, it has been observed that higher concentrations of serum vitamin B6 are associated with better memory performance in older adults. ...
... In the cognitive domain, it has been observed that higher concentrations of serum vitamin B6 are associated with better memory performance in older adults. Conversely, vitamin B6 deficiency is associated with poor cognitive performance and dementia [40], likely due to increased plasma homocysteine levels. ...
Objective:
To identify the nutrients that influence the performance of working memory, which is greatly affected as age progresses.
Method:
A total of 1646 healthy adults between 21 and 80 years old participated in the study. The daily consumption of 64 nutrients was examined using a food frequency questionnaire that assessed food intake during the previous year. Working memory was measured in the verbal and spatial domains using a computerized task. We examined which nutrients influence working memory across the entire adult lifespan and whether the influence of any of these nutrients on working memory is moderated by individuals' ages.
Results:
Working memory, across the entire adult lifespan, benefits from the intake of cholesterol, alcohol, gamma- and delta-tocopherol, vitamin B6, and palmitoleic, oleic, alpha linoleic and linoleic acids. Moderator analyses revealed that fats, energy, lactose and sodium negatively influenced working memory in middle-aged and older adults, whereas vitamin D and vitamin C had positive effects on memory beyond 70 years of age.
Conclusion:
Nutrients have the ability to positively or negatively affect working memory, which varies as a function of age.
... Vitamin B1 and vitamin B6 are absorbed in the proximal parts of the small intestine. Vitamin B1 is absorbed in the duodenum and proximal jejunum, [13] while vitamin B6 is absorbed mainly in the upper jejunum, as well as in the ileum, [14] leading us to believe a RYGB procedure would have a greater impact in the absorption of these vitamins since it excludes duodenum and part of the proximal jejunum [15]. ...
... Deficiency is rarely associated with insufficient dietary intake, since this vitamin is present in various foods and it is normally accompanied with deficiency of other B-complex vitamins. B6 deficiency may also cause microcytic anemia [14]. ...
Bariatric surgery, although an effective method, still has complications, like nutritional deficiencies. Our aim was to summarize the evidence on the frequency of complex B vitamin deficiencies in studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). We included 25 studies for qualitative synthesis and 21 studies for quantitative synthesis. Relevant data was extracted, including proportion of patients with deficiency and mean serum vitamin values in 3 different timeframes. B12 and folate were the most prevalent deficiencies. B12 deficiency was more common after RYGB and folate serum mean levels were higher after RYGB. SG causes less nutrient deficiency and is therefore a better technique from this point of view. More studies are needed on B2, B3, and B6 vitamins to draw better conclusions.
Graphical abstract
... Vitamin B6 may also improve cognitive symptoms (Malouf & Evans, 2003;Selhub, 2002). In bipolar disorder, we see an increase in dopamine levels in the manic episode (Spinneker et al., 2007;Tang & Wei, 2004). Also, the regulation of serotonin is impaired (Qureshi & Al-Bedah, 2013) and inflammatory factors such as C-reactive protein (CRP) rise (Chistyakov et al., 2018). ...
... Vitamin B6, regardless of the level of serum, by acting on the blood levels of inflammatory factors and dopamine can reduce these factors and regulate serotonin levels (Spinneker et al., 2007;Ueland et al., 2017). ...
Objective
Vitamin B6 has been linked to a variety of probable roles, including anti‐inflammatory, homocysteine‐lowering, serotonin‐regulating, and dopamine‐lowering. In this study, we investigated the possible effect of vitamin B6 on bipolar disorder in manic episode with psychotic feature in a placebo‐controlled double‐blind clinical trial in a psychiatric hospital.
Methods
This study was performed on 50 patients who were equally divided into two groups (each group included 25 patients) using 80 mg of vitamin B6 daily or placebo. At the beginning and end of the study, they were evaluated for lab tests, inflammatory biomarkers and level of blood homocysteine. Also, at the baseline and in weeks 2, 4, and 8, they were evaluated based on the anthropometric measurements, score obtained from the Young Mania Questionnaire, Mini‐Mental State Examination (MMSE), and the Pittsburgh Sleep Questionnaire.
Results
Accordingly, based on Yang Mania scoring scale, no significant difference was observed between the two groups receiving vitamin B6 and placebo (22.68 ± 5.39 vs. 21.80 ± 5.39 [p‐value = .51]). Based on MMSE, significant improvement in cognitive status was obtained in group placebo compared to vitamin B6 group (25.24 ± 1.96 vs. 24.40 ± 3.25, respectively [p‐value = .01]). At the Pittsburg scale (total, there was no statistically significant difference between the two groups receiving vitamin B6 and placebo (1.04 ± 0.20 vs. 0.48 ± 0.50 [p‐value = .23]). Additionally, no significant difference was observed between the two groups regarding the anthropometric status.
Conclusions
According to this study, the daily dose of 80 mg of vitamin B6 for 8 weeks in patients with bipolar disorder in the manic episode with psychotic feature treated daily with lithium, was not associated with a significant improvement in mood status compared to the control–placebo group. It is recommended to perform similar studies in a multi‐center manner with a larger sample size and longer duration.
... Riboflavin also protects against excitotoxicity in multiple ways. First, riboflavin is required for the production of the active form of vitamin B6, pyridoxal phosphate (PLP; Adelekan et al., 1987), which is necessary for the formation of many neurotransmitters in the nervous system (Spinneker et al., 2007). One of the neurotransmitter pathways where PLP is active, is as a cofactor for glutamate decarboxylase, which converts glutamate into gamma aminobutyric acid (GABA). ...
... GABA is the major inhibitory neurotransmitter in the nervous system and ideally needs to be in balance with glutamate for optimal neuronal functioning (Petroff, 2002). A deficiency in riboflavin can lead to reduced production of PLP [essentially a vitamin B6 deficiency (Madigan et al., 1998)], preventing it from serving as a cofactor in the production of GABA (Spinneker et al., 2007); meaning that riboflavin deficiency can cause increased glutamate and deceased GABA levels, thereby contributing to excitotoxicity. Riboflavin and PLP are also essential cofactors in the kynurenine pathway (Marashly and Bohlega, 2017), where adequate intake of these vitamins has been associated with production of kynurenic acid (Theofylaktopoulou et al., 2014), rather than quinolinic acid, which acts as an agonist to the NMDA receptor, thereby potentiating excitotoxicity (Zinger et al., 2011;Curto et al., 2015). ...
Excitotoxicity has been implicated in many neurological disorders and is a leading cause of oxidative stress and neuroinflammation in the nervous system. Most of the research to date has focused on each of these conditions individually; however, excitotoxicity, oxidative stress, and neuroinflammation have the ability to influence one another in a self-sustaining manner, thus functioning as a “neurotoxic triad.” This perspective article re-introduces the concept of the neurotoxic triad and reviews how specific dietary micronutrients have been shown to protect against not only oxidative stress, but also excitotoxicity and neuroinflammation. Future dietary interventions for neurological disorders could focus on the effects on all three aspects of the neurotoxic triad.
... Although its role goes far beyond, it is particularly well known for its important function in the synthesis of neurotransmitters like dopamine from L-3,4-dihydroxyphenylalanine, serotonin from Cardiology in the Young 5 5-hydroxytryptophan, and gamma-aminobutyric acid from glutamate. 38,39 According to its function for the previously mentioned neurotransmitters, pyridoxine affects the adrenergic, the serotonergic, and the glutamatergic system. Some authors hypotheses that enhanced serotonin responsiveness with clomipramine leading to a presumed greater sympatholytic effect supports a mechanistic role for serotonin in the central pathways leading to vasovagal syncope initiation. ...
... Since gamma-aminobutyric acid serves as the major inhibitory neurotransmitter, it seems obvious that gamma-aminobutyric acid deficiency can lead to serious consequences, such as syncope and seizures. 8,39 It should be emphasised that there was no significant difference in folate level and its deficiency between children with vasovagal syncope and healthy individuals in our study. However, decreased levels of folic acid were closely associated with longer duration of syncope (r = −0.42, ...
Background
Recent studies confirm the role of B vitamins deficiency and hyperhomocysteinaemia in the development of dysautonomia that has been considered to be the main factor in vasovagal syncope development. The aim of the study was to investigate serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope and to analyse the correlation between them and main clinical parameters of syncope.
Methods
We studied 40 children, ages 8–17 years with a history of vasovagal syncope and 24 healthy volunteers. The serum pyridoxine, folate, cobalamin, and homocysteine levels were measured by a quantitative sandwich enzyme immunoassay technique using a commercial kit (Monobind, USA). Twenty-four-hour Holter monitoring and 24-hour ambulatory blood pressure monitoring were conducted for all participated patients.
Results
Serum pyridoxine (9.42 ± 4.87, 16.11 ± 5.53 µg/L) and cobalamin (307.48 ± 95.50, 447.28 ± 108.85 ng/L) levels were reasonably low (p < 0.05) in patients with vasovagal syncope. Although there was no significant change in folate levels between syncope and healthy children (4.00 ± 1.34, 4.71 ± 1.73 µg/L; p = 0.20), we detected low folate-level association with longer duration of syncope (r = −0.42) and post syncope (r = −0.43) symptoms (p < 0.05). Finally, there was increased serum homocysteine level (13.55 ± 5.03, 7.81 ± 1.71 µmol/L; p < 0.05) in patients with vasovagal syncope. It was positively correlated with the average PQ interval (r = 0.35, p < 0.05) and average QTc interval (r = 0.49, p < 0.05).
Conclusions
The results suggested that pyridoxine, folate, cobalamin, and homocysteine may be involved in the pathogenesis of vasovagal syncope. This might provide a new approach for effective treatment of paediatric vasovagal syncope, requiring further study.
... Vitamin B6 is a most versatile coenzyme that participates in many biochemical reactions such as the amino acid metabolism, carbohydrate metabolism, and lipid metabolism. It is also effective in situations such as the cognitive development of the neurotransmitter synthesis, the immune function with interleukin-2 production, the haemoglobin formation, and gene expression (67,68). ...
... The human body cannot store B6, so external intake is essential. It is found in high quantities in meat, and pyridoxine, while plants contain less (67). The daily recommended dose of RDA for B6 in adults is 1 to 1.7mg. ...
Vitamins are an indispensable food source and important due to the enzyme cofactor and catalytic roles they play in the body. Fat-soluble vitamins, A, D, E, K, and B12 are stored in the body and cause problems with their excessive accumulation. Other vitamins rarely accumulate in the body, as they dissolve in water and are excreted through the kidneys. Alcoholism, strict diets, insufficient parental nutrition, and gastrointestinal absorption problems may be included in the causes of vitamin deficiencies. Although clinical findings due to vitamin deficiencies display different characteristics depending on the vitamins, the signs that generally occur are cutaneous pigmentation, pigmentation on mucous membranes, palmoplantar keratoderma characterized by fissures, palmar streaking, yellow streaking on the nails, nail layering, and intra-nail hemorrhage.
... December 2020 / 5 camels (Faye and Bengoumi, 2018). The results of vitamin B6 in the serum of healthy camels in the present study were higher than those reported in people (Spinneker et al, 2007). On the other hand Bisp et al, (2002); Jungert et al (2020) reported lower results for Vitamin B6 in plasma than those reported in the present study. ...
... The variation in our results among previous studies in human may be due to the different nature of nutrition between ruminants and humans, as the camel eats plant-based foods while their digestive system synthesises this vitamin (Wernery et al, 2009), while humans depend on their animal-based foods with has a higher bioavailability to absorb vitamin B6 (Reynolds, 1988). On the other hand, the method of analysing this compound in the blood, as there are many associated forms of it (Spinneker et al, 2007), could affect the variation of its levels among studies (Zhang et al, 2018). There is a relationship between B6 levels in serum and CSF (Albersen et al, 2015). ...
... ation/Guidances/ucm078932.pdf (accessed on 5 May 2023), the doses of vitamins B1 and B6 used in this study on rats (100 mg/kg each of the vitamins per day) correspond to a dose of 16 mg/kg, or 1 g for an average weight of 60 kg, in humans. These doses are within the interval of the doses used in the vitamin therapy [46,48,[97][98][99]. ...
Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal is to reveal the molecular mechanisms of the changes upon repeated challenges of this balance, suggesting knowledge-based neuroprotection. To address this goal, a set of metabolic indicators in the post-seizure rat brain cortex is compared before and after pharmacological kindling with pentylenetetrazole (PTZ). Vitamins B1 and B6 supporting energy and neurotransmitter metabolism are studied as neuroprotectors. PTZ kindling increases the seizure severity (1.3 fold, p < 0.01), elevating post-seizure rearings (1.5 fold, p = 0.03) and steps out of the walls (2 fold, p = 0.01). In the kindled vs. non-kindled rats, the post-seizure p53 level is increased 1.3 fold (p = 0.03), reciprocating a 1.4-fold (p = 0.02) decrease in the activity of 2-oxoglutarate dehydrogenase complex (OGDHC) controlling the glutamate degradation. Further, decreased expression of deacylases SIRT3 (1.4 fold, p = 0.01) and SIRT5 (1.5 fold, p = 0.01) reciprocates increased acetylation of 15 kDa proteins 1.5 fold (p < 0.01). Finally, the kindling abrogates the stress response to multiple saline injections in the control animals, manifested in the increased activities of the pyruvate dehydrogenase complex, malic enzyme, glutamine synthetase and decreased malate dehydrogenase activity. Post-seizure animals demonstrate correlations of p53 expression to the levels of glutamate (r = 0.79, p = 0.05). The correlations of the seizure severity and duration to the levels of GABA (r = 0.59, p = 0.05) and glutamate dehydrogenase activity (r = 0.58, p = 0.02), respectively, are substituted by the correlation of the seizure latency with the OGDHC activity (r = 0.69, p < 0.01) after the vitamins administration, testifying to the vitamins-dependent impact of the kindling on glutamate/GABA metabolism. The vitamins also abrogate the correlations of behavioral parameters with seizure duration (r 0.53–0.59, p < 0.03). Thus, increased seizures and modified post-seizure behavior in rats after PTZ kindling are associated with multiple changes in the vitamin-dependent brain metabolism of amino acids, linked to key metabolic regulators: p53, OGDHC, SIRT3 and SIRT5.
... We also found that the concentration of PLP in plasma decreased with the severity of asthma. As an active form of vitamin B6, PLP is also the main form existing in plasma [52]. Lys27-linkages have been related to mitochondrial biology [48]. ...
Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.
... Taurine is endogenously synthesized in mammalian tissues, especially in the brain, heart, retina, and liver cells as part of the L-cysteine and L-methionine metabolic pathway (Huxtable, 1992). This process requires vitamin B6 as an enzyme cofactor; therefore, its dietary deficiency can lead to taurine depletion (Park and Linkswiler, 1970;Spinneker et al., 2007). Even though there are endogenous mechanisms for taurine production, an exogenous supply of taurine is required to meet physiological needs, especially in infants, in which taurine is a conditionally essential amino acid (Papet et al., 2019;Wu, 2020). ...
... Despite its widespread use, serum PLP level is an unreliable parameter as it is affected by inflammation, smoking, alcohol consumption and oral contraceptive use. Therefore, it is difficult to interpret the daily adequate dietary intake level for vitamin B6 [9,10]. Due to physiological variability, the daily requirement of vitamin B6 may differ among individuals. ...
... [ [68][69][70] [ [71][72][73] The main outcome of the methionine cycle is the formation of SAM that powers methylation reactions such as DNA methylation and histone methylation. SAM donates the methyl group to the epigenetic machinery such as DNA methyltransferases (DNMTs) that methylate the DNA or to histone methyltransferases (HMTS/KMTs) that methylate histones [6,38,53] (Figure 2). ...
Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 and B12 are critical players in the one-carbon metabolism and have neuroprotective functions. The one-carbon metabolism comprises a series of interconnected chemical pathways that are important for normal cellular functions. Among these pathways are those of the methionine and folate cycles, which contribute to the formation of S-adenosylmethionine (SAM). SAM is the universal methyl donor of methylation reactions such as histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and play roles in human health and disease. Epigenetic mechanisms have been considered a bridge between the effects of environmental factors, such as nutrition, and phenotype. Studies in human and animal models have indicated the importance of the optimal levels of methyl donors on brain health and behavior across the lifespan. Imbalances in the levels of these micronutrients during critical periods of brain development have been linked to epigenetic alterations in the expression of genes that regulate normal brain function. We present studies that support the link between imbalances in the levels of methyl donors, epigenetic alterations, and stress-related disorders. Appropriate levels of these micronutrients should then be monitored at all stages of development for a healthier brain.
... Vitamin B 6 is probably the most important cofactor in metabolism because it involves >100 coenzyme reactions related to 1-carbon metabolism, neurotransmitter synthesis, immune function, hemoglobin function, protein, fat, and carbohydrate metabolism processes such as gluconeogenesis and glycogenolysis. 96 There is evidence that circulating vitamin B 6 levels are associated with a modest decrease in lung cancer risk. 97 However, 2 large, randomized, double-blind, placebo-controlled trials reported that vitamin B 6 treatment (40 mg/d) was not associated with significant effects on cancer outcomes such as cancer incidence, mortality, or all-cause mortality. ...
Gene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.
... The concentration of vitamin B 6 in cultivar Daniel and Davidson is 55.00 ± 1.06 and 31.5 ± 2.60 mAU, respectively. Vitamin B 6 (pyridoxine) is the most functional coenzyme that helps in the cognitive development of neurotransmitter synthesis, immune function, gene expression, and hemoglobin formation (37,38). The concentration of vitamin B 9 found in Daniel and Davidson is 229.53 ± 3.72 and 130.01 ± 80.20 mAU, respectively. ...
This paper aims to quantify the micronutrients in black walnut and address its human health benefits. The metabolic profiling of 11 black walnut cultivars was accomplished using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight high-resolution mass spectrometer. Results revealed that the highest concentration of vitamin B9 was present in cultivar “Daniel” (avg. relative signal intensity 229.53 × 104 mAU). “Surprise” and “Daniel” cultivars had the highest amount of vitamin B5. However, vitamin A, D3, E, and K showed no significant difference among the cultivars. The vitamin content levels among the cultivars were compared by applying one way ANOVA method with (P < 0.05) significance level. Mineral analysis for the black walnut kernel, Persian walnut, and black walnut protein powder was done using Inductively Coupled Plasma Optical Emission spectroscopy. The experimental data for black walnut kernel is 0.04 mg/g for Fe and 0.03 mg/g for Zn, and for black walnut, protein powder is 0.07 mg/g for Fe and 0.07 mg/g for Zn. The amino acid analysis and comparison with black walnut kernel show that black walnut flour and protein powder have a higher amount of essential and non-essential amino acids. Therefore, researchers, food process engineers, and food product developers should consider the health benefits of black walnuts and explore the commercial potential of this native agroforestry crop.
... The current RDA (Recommended Dietary Allowance) for vitamin B 6 from foods or supplements is the dose of 1.3 mg/day for adult males and females through age of fifty. The RDA is 1.7 mg and 1.5 mg for male and females over the age of fifty years, respectively [2,27,28]. ...
This work aims to introduce a simple high-performance sensitive electrochemical sensor of reformed carbon paste (CP) with iron oxide nanoparticles (IONs). It was developed to determine one of the most important drugs called vitamin B 6 in a medium of phosphate buffer (PBS) over pH ranging from 5.0 to 8.0. The electrochemical and surface characterization was achieved by different techniques comprising electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and scanning electron microscopy (SEM). The studied effects were, pH, buffer, interference, scan rate, accumulation time, and calibration plot. The sensitive electrode produced a linear calibration curve in a concentration range from 8.88 up to 1000.0 µM, with limits of detection and qualification estimated at 9.06 and 30.2 µM, respectively Also, this method was established in human urine real samples and pharmaceutical drugs which have been shown a good result for vitamin B 6 detection.
... Taurine is endogenously synthesized in mammalian tissues, especially in the brain, heart, retina, and liver cells as part of the L-cysteine and L-methionine metabolic pathway (Huxtable, 1992). This process requires vitamin B6 as an enzyme cofactor; therefore, its dietary deficiency can lead to taurine depletion (Park and Linkswiler, 1970;Spinneker et al., 2007). Even though there are endogenous mechanisms for taurine production, an exogenous supply of taurine is required to meet physiological needs, especially in infants, in which taurine is a conditionally essential amino acid (Papet et al., 2019;Wu, 2020). ...
Taurine is considered the most abundant free amino acid in the brain. Even though there are endogenous mechanisms for taurine production in neural cells, an exogenous supply of taurine is required to meet physiological needs. Taurine is required for optimal postnatal brain development; however, its brain concentration decreases with age. Synthesis of taurine in the central nervous system (CNS) occurs predominantly in astrocytes. A metabolic coupling between astrocytes and neurons has been reported, in which astrocytes provide neurons with hypotaurine as a substrate for taurine production. Taurine has antioxidative, osmoregulatory, and anti-inflammatory functions, among other cytoprotective properties. Astrocytes release taurine as a gliotransmitter, promoting both extracellular and intracellular effects in neurons. The extracellular effects include binding to neuronal GABAA and glycine receptors, with subsequent cellular hyperpolarization, and attenuation of N-methyl-D-aspartic acid (NMDA)-mediated glutamate excitotoxicity. Taurine intracellular effects are directed toward calcium homeostatic pathway, reducing calcium overload and thus preventing excitotoxicity, mitochondrial stress, and apoptosis. However, several physiological aspects of taurine remain unclear, such as the existence or not of a specific taurine receptor. Therefore, further research is needed not only in astrocytes and neurons, but also in other glial cells in order to fully comprehend taurine metabolism and function in the brain. Nonetheless, astrocyte’s role in taurine-induced neuroprotective functions should be considered as a promising therapeutic target of several neuroinflammatory, neurodegenerative and psychiatric diseases in the near future. This review provides an overview of the significant relationship between taurine and astrocytes, as well as its homeostatic and neuroprotective role in the nervous system.
... Sendo está de fundamental importância para saúde do indivíduo, devido à participação em diversas reações bioquímicas (Spinneker et al., 2007) Algumas intervenções têm sido utilizadas para atingir a neofobia alimentar, dentre essas a educação sensorial tem sido citada por envolver o uso de todos os cinco sentidos para ensinar as crianças. Para isso, ocorre a exposição através da apresentação repetida de um novo alimento e o envolvimento de pessoas de confiança interagindo e consumindo o mesmo alimento. ...
Objetivo: Identificar os padrões e comportamentos alimentares das crianças com Transtorno do Espectro Autista. Metodologia: Revisão integrativa realizada a partir da busca eletrônica de artigos com texto completo, publicados entre os anos de 2012 e 2022, nas bases de dados Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Health Sciences Literature e Google Acadêmico, nos idiomas inglês e português. Resultados: Pôde-se observar que houve predominância dos comportamentos de seletividade alimentar e baixa variedade nas escolhas alimentares das crianças com TEA. Além disso, houve baixa ingestão de alimentos saudáveis (frutas, hortaliças, legumes e leguminosas) e inadequação de vitaminas, principalmente as do complexo B. Conclusão: Foi possível perceber que crianças com TEA apresentam comportamentos desafiadores na hora das refeições e seletividade alimentar. Este cenário favorece o consumo de alimentos não saudáveis, que incluem doces; guloseimas; salgadinhos e baixa ingestão de frutas; hortaliças; legumes e leguminosas, gerando uma problemática relacionada ao excesso de peso e deficiências nutricionais.
... For example, glutamate is the precursor compound for the production of the inhibitory neurotransmitter GABA (110). Glutamate decarboxylase is the enzyme which converts glutamate to GABA, and it necessitates vitamin B6 [in the form of pyridoxal phosphate (PLP)] as a cofactor for it to function (94,110). Riboflavin is needed for conversion of dietary vitamin B6 into its active PLP form, and also has its own neuroprotective properties against excitotoxicity, as well as antioxidant functions (92). ...
The objective of this pilot study was to examine the effects of the low glutamate diet on anxiety, post-traumatic stress disorder (PTSD), and depression in veterans with Gulf War Illness (GWI). The low glutamate diet removes dietary excitotoxins and increases consumption of micronutrients which are protective against glutamatergic excitotoxicity. This study was registered at ClinicalTrials.gov (NCT#03342482). Forty veterans with GWI completed psychiatric questionnaires at baseline and after 1-month following the low glutamate diet. Participants were then randomized into a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG; a dietary excitotoxin) vs. placebo over three consecutive days per week, with assessments on day three. Data were analyzed across the full sample and with participants categorized by baseline symptom severity. Pre-post-dietary intervention change scores were analyzed with Wilcoxon signed-rank tests and paired sample t-tests across the full sample, and changes across symptom severity categories were analyzed using ANOVA. Crossover challenge results were analyzed with linear mixed modeling accounting for challenge material (MSG v. placebo), sequence (MSG/placebo v. placebo/MSG), period (challenge week 1 v. week 2), pre-diet baseline symptom severity category (minimal/mild, moderate, or severe), and the challenge material*symptom severity category interaction. A random effect of ID (sequence) was also included. All three measures showed significant improvement after 1 month on the diet, with significant differences between baseline severity categories. Individuals with severe psychological symptoms at baseline showed the most improvement after 1 month on the diet, while those with minimal/mild symptoms showed little to no change. Modeling results from the challenge period demonstrated a significant worsening of anxiety from MSG in only the most severe group, with no significant effects of MSG challenge on depression nor PTSD symptoms. These results suggest that the low glutamate diet may be an effective treatment for depression, anxiety, and PTSD, but that either (a) glutamate is only a direct cause of symptoms in anxiety, or (b) underlying nutrient intake may prevent negative psychiatric effects from glutamate exposure. Future, larger scale clinical trials are needed to confirm these findings and to further explore the potential influence of increased micronutrient intake on the improvements observed across anxiety, PTSD, and depression.
... They also play vital roles in immune functions, neurotransmitter synthesis, one-carbon metabolism, cell signalling, and even nucleic acid biosynthesis [3][4][5]. For instance, coenzyme A, an active form of vitamin B5, is a ubiquitous molecule in the cells and acts as a cofactor or direct precursor for numerous cellular intermediates [6,7]. ...
B vitamins act as coenzymes in a myriad of cellular reactions. These include energy production, methyl donor generation, neurotransmitter synthesis, and immune functions. Due to the ubiquitous roles of these vitamins, their deficiencies significantly affect the host's metabolism. Recently, novel roles of B vitamins in the homeostasis of gut microbial ecology and intestinal health continue to be unravelled. This review focuses on the functional roles and biosynthesis of B vitamins and how these vitamins influence the growth and proliferation of the gut microbiota. We have identified the gut bacteria that can produce vitamins, and their biosynthetic mechanisms are presented. The effects of B vitamin deficiencies on intestinal morphology, inflammation, and its effects on intestinal disorders are also discussed.
... Moreover, malnutrition is currently considered as one of the main modifiable prognostic factors for worsening outcomes and mortality in elderly patients [64,65]. Lastly, a nutritional deficiency of micronutrients (vitamin D [66,67], vitamin C [66], vitamin B12 and folate [67,68], vitamins A and E [69], vitamin B6 [70], selenium, zinc, magnesium [71], and copper [72]) has been reported to have a potential role in the immune regulation in the elderly. In this scenario, malnutrition is considered as a risk factor for osteoporosis, sarcopenia, and frailty [73,74]. ...
Frailty is a highly prevalent condition in the elderly that has been increasingly considered as a crucial public health issue, due to the strict correlation with a higher risk of fragility fractures, hospitalization, and mortality. Among the age-related diseases, sarcopenia and dysphagia are two common pathological conditions in frail older people and could coexist leading to dehydration and malnutrition in these subjects. “Sarcopenic dysphagia” is a complex condition characterized by deglutition impairment due to the loss of mass and strength of swallowing muscles and might be also related to poor oral health status. Moreover, the aging process is strictly related to poor oral health status due to direct impairment of the immune system and wound healing and physical and cognitive impairment might indirectly influence older people’s ability to carry out adequate oral hygiene. Therefore, poor oral health might affect nutrient intake, leading to malnutrition and, consequently, to frailty. In this scenario, sarcopenia, dysphagia, and oral health are closely linked sharing common pathophysiological pathways, disabling sequelae, and frailty. Thus, the aim of the present comprehensive review is to describe the correlation among sarcopenic dysphagia, malnutrition, and oral frailty, characterizing their phenotypically overlapping features, to propose a comprehensive and effective management of elderly frail subjects.
... B2 and B6 are the psychomotor vitamins responsible for proper neural activity. The deficiency of these vitamins results in impaired cognitive function, cardiovascular diseases, increased risk of cancer and many more similar complications [2], [3]. B12 acts as a cofactor for metabolic enzymes in the cytoplasm as well as mitochondria and affects key metabolic functions of other enzymes [4], [5]. ...
... It needs to be stressed that vitamin B1, B6 and B12 most likely hold synergistic biochemical roles in the nervous system that is neither of these can replace one of the others. Because of the potential for side effects and interactions with medications, people should take dietary supplements only under the supervision of a knowledgeable health care provider [76]. ...
Vitamins B denote to some diverse kinds of vitamins which collectively, are recognized as B-complex vitamin. At hand are eight types of vitamins in vitamin B complex; thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9) also known as folic acid and cobalamin (B12). B vitamins have a direct impact on body energy levels, brain function and cell metabolism. There is a roundup of four top causes of vitamin B deficiency; a non-balanced diet, excessive alcohol consumption, various medications and gut malabsorption conditions. Deficiencies in these B vitamins can lead to a number of different symptoms like paresthesias, peripheral neuropathy, psychosis and heart attack and stroke over time if the deficiency is not reversed. Vitamins are found in highest abundance in meat, eggs and dairy or milk products such as butter, yogurt and cheese produced from milk of mammals usually buffaloes, cattle, goats, sheep and camels. Most people can get many nutrients they need, including B vitamins, by eating a varied diet of lean meats, grains, fruits and vegetables. This chapter provides an affluent of the most common types of vitamins B, including why body needs these, their deficiency symptoms and which foods contain them.
... A longitudinal study that followed up 3,717 individuals for 5.5 years who were initially healthy showed that dietary niacin intake was associated with a lower incidence of cognitive decline and Alzheimer's disease (Morris et al., 2004). Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine and their phosphorylated forms) participates in the synthesis of several neurotransmitters, such as serotonin and dopamine, and in the metabolism of amino acids, fatty acids and homocysteine (Spinneker et al., 2007). Indeed, dietary vitamin B6 insufficiency or impaired metabolism of vitamin B6 due to inflammation increases plasma homocysteine levels, a condition associated with poor cognition and dementia (Seshadri et al., 2002). ...
The aim of the study was to identify nutrients that have the ability to impact brain functioning and, as a consequence, influence episodic memory. In particular, we examined recollection, the ability to recall details of previous experiences, which is the episodic memory process most affected as age advances. A sample of 1,550 healthy participants between 21 and 80 years old participated in the study. Nutritional intake was examined through a food frequency questionnaire and software developed to determine the daily consumption of 64 nutrients based on food intake during the last year. Recollection was measured through a computerized source memory paradigm. First, we identified which nutrients influence recollection across the entire adult life span. Then, moderator analyses were conducted by dividing the sample into young (21–40 years old), middle-aged (41–60 years old) and older (61–80 years old) adults to establish in which life stage nutrients influence episodic memory. Across the adult life span, recollection accuracy was shown to benefit from the intake of sodium, heme, vitamin E, niacin, vitamin B6, cholesterol, alcohol, fat, protein, and palmitic, stearic, palmitoleic, oleic, gadoleic, alpha-linoleic and linoleic acid. The effects of energy, maltose, lactose, calcium and several saturated fatty acids on recollection were modulated by age; in older adults, the consumption of these nutrients negatively influenced episodic memory performance, and in middle-aged adults, only lactose had negative effects. Several brain mechanisms that support episodic memory were influenced by specific nutrients, demonstrating the ability of food to enhance or deteriorate episodic memory.
... Vitamin B6 is one of the water-soluble vitamins. There are three forms of vitamin B6: pyridoxamine (PM), pyridoxal, and pyridoxine [5]. The deficiency of this vitamin is rare because it is abundant in food sources, such as meat, whole grains, vegetables, and nuts. ...
Obesity has reached epidemic proportions globally. Among several methods for treating obesity, the use of dietary supplements is common recently. One supplement that can help in this regard might be vitamin B6 in high doses. The objective of this study was to evaluate the effect of pyridoxine hydrochloride supplementation on anthropometric indices, body composition, visceral adiposity index (VAI), and metabolic status in obese and overweight women. In this randomized controlled clinical trial, 44 obese and overweight women aged 18-50 years were selected and divided randomly into 2 groups: an intervention group (receiving 80 mg pyridoxine hydrochloride supplement for 8 weeks) and a control group (receiving placebo for 8 weeks). In the pyridoxine hydrochloride group, weight (p = 0.03), body mass index (p = 0.023), fat mass (p = 0.003), waist circumference (p = 0.005), VAI (p = 0.001), fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance; HOMA-IR), total cholesterol, low-density lipoprotein, triglycerides (TG) and leptin (p < 0.001) decreased whereas adiponectin (p < 0.001) increased in comparison to the baseline values. There was a significant difference in fat mass, VAI, fasting insulin, HOMA-IR, and TG between pyridoxine hydrochloride and control groups following intervention in adjusted models (p < 0.05). The findings suggest that vitamin B6 supplementation may be effective in reducing BMI and improving body composition and biochemical factors associated with obesity.
Trial registration:
Iranian Registry of Clinical Trials Identifier: IRCT20181002041206N1.
... The most common symptoms in humans include anemia, seborrheic dermatitis, glossitis, electroencephalographic abnormalities, depression and confusion, neutropenia, and weakened immune function. In experimental animal models, a vitamin B-6 deficiency induced similar changes, including a lowered growth rate, seborrheic dermatitis, acrodynia, convulsions, neurodegeneration in the brain, weakened immune function, anemia, atherosclerosis, weakness, lethargy, paralysis, alterations in tryptophan and alanine metabolism, and elevations in urinary creatinine and xanthurenic acid (39,98). These effects have been observed in monkeys, rabbits, chickens, dogs, rats, and pigs (99)(100)(101)(102)(103). ...
Vitamin B-6 in the form of pyridoxine (PN) is commonly used by the general population. The use of PN-containing supplements has gained lots of attention over the past years as they have been related to the development of peripheral neuropathy. In light of this, the number of reported cases of adverse health effects due to the use of vitamin B-6 have increased. Despite a long history of study, the pathogenic mechanisms associated with PN toxicity remain elusive. Therefore, the present review is focused on investigating the mechanistic link between PN supplementation and sensory peripheral neuropathy. Excessive PN intake induces neuropathy through the preferential injury of sensory neurons. Recent reports on hereditary neuropathy due to pyridoxal kinase (PDXK) mutations may provide some insight into the mechanism, as genetic deficiencies in PDXK lead to the development of axonal sensory neuropathy. High circulating concentrations of PN may lead to a similar condition via the inhibition of PDXK. The mechanism behind PDXK-induced neuropathy is unknown; however, there is reason to believe that it may be related to γ-aminobutyric acid (GABA) neurotransmission. Compounds that inhibit PDXK lead to convulsions and reductions in GABA biosynthesis. The absence of central nervous system-related symptoms in PDXK deficiency could be due to differences in the regulation of PDXK, where PDXK activity is preserved in the brain but not in peripheral tissues. As PN is relatively impermeable to the blood–brain barrier, PDXK inhibition would similarly be confined to the peripheries and, as a result, GABA signaling may be perturbed within peripheral tissues, such as sensory neurons. Perturbed GABA signaling within sensory neurons may lead to excitotoxicity, neurodegeneration, and ultimately, the development of peripheral neuropathy. For several reasons, we conclude that PDXK inhibition and consequently disrupted GABA neurotransmission is the most plausible mechanism of toxicity.
... Deficiency is associated with a range of symptoms including irritability, depression, confusion, inflammation of the tongue and seizures. Deficiency is also associated with anaemias and hyperhomocysteinaemia (Spinneker et al, 2007). ...
A range of nutrients has been studied or proposed for use in preventing respiratory tract infections and reducing their severity. This article gives a narrative review of the existing literature, biological rationales and current state of clinical evaluation for micronutrient therapies. The importance of vitamin A, the B vitamins, vitamin C, vitamin D, eicosapentaenoic acid, vitamin E, selenium, zinc and a range of combination therapies are discussed, looking at their effects on reducing rates of infection, reducing severity of infection and improved recovery from infection. Further discussion regarding the level of evidence required for nutritional interventions is included.
... The biosynthesis of B vitamins (biotin, thiamine, and vitamin B6) was also enriched. Although studies have shown that vitamin B6 deficiency is associated with impaired cognitive function, cardiovascular disease, and different types of cancer [55], a recent Cochrane review concluded that there were no differences in supplements B vitamins comparing with placebo on myocardial infarction, death from any cause or adverse events [56]. Whether the enriched biosynthesis of B vitamins is compensatory to the host's deficiency cannot be ascertained. ...
Androgen deprivation therapy (ADT), either by medical or surgical castration, is the backbone for standard treatment of locally advanced or metastatic prostate cancer, yet it is also associated with various metabolic and cardiovascular complications. Recent evidence have shown that obesity, insulin resistance, or metabolic disturbances can be associated with changes in the gut microbiome, while animal studies also show that castration is associated with changes in the gut microbiome. This study aims to investigate whether the fecal microbiota in prostate cancer patients who had undergone prostatectomy or ADT are different, and explore changes in phylogeny and pathways that may lead to side effects from ADT.
A total of 86 prostate cancer patients (56 patients on ADT and 30 patients with prostatectomy) were recruited. The fecal microbiota was analyzed by the 16S rRNA gene for alpha- and beta-diversities by QIIME2, as well as the predicted metabolic pathways by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2.
The alpha-diversity was significantly lower in the ADT group. The beta-diversity was significantly different between the groups, in which Ruminococcus gnavus and Bacteroides spp were having higher relative abundance in the ADT group, whereas Lachnospira and Roseburia were reduced. The Firmicutes-to-Bacteroidetes ratio is noted to be lower in the ADT group as well. The functional pathway prediction showed that the biosynthesis of lipopolysaccharide (endotoxin) and propanoate was enriched in the ADT as well as the energy cycle pathways. This study is limited by the cross-sectional design and the clinical heterogeneity.
There is a significant difference in gut microbiome between prostate cancer patients on ADT and prostatectomy. We theorize that this difference may contribute to the development of metabolic complications from ADT. Further longitudinal studies are awaited.
Context
Previous research evaluating the effects in B-vitamins on the prevention and treatment of cardiovascular disease (CVD) has substantial limitations and lacks recently published large prospective studies; hence, conducting an updated meta-analysis is needed.
Objective
We investigated the association between vitamin B status and human CVD development in order to provide more specific advice about vitamin B intake for those at risk of CVD.
Data Sources
Relevant articles were identified by JSTOR, PubMed, and ProQuest databases.
Data Extraction
Key words used to identify the studies included the different combinations of B-vitamins, folate, folic acid, vitamin B6, vitamin B12, homocysteine, cardiovascular disease, stroke, coronary disease, myocardial infarction, and cerebrovascular and transient ischemic attack. The database search was supplemented by hand-searching of reference lists of selected articles.
Data Analysis
Pooled estimates were calculated from the mean differences using a random-effects model.
Results
Supplementation with folic acid was reported to have a clinical benefit of significantly reducing carotid intima-media thickness. Higher intakes of folic acid, vitamin B6, and vitamin B12 were generally associated with a lower risk of CVD in the general population, except in those without normal renal function and those with unstable angina or past non–ST-elevation myocardial infarction.
Conclusion
Vitamin B supplementation resulted in the greatest cardiovascular benefit in those with normal renal function and without unstable angina or non–ST-elevation myocardial infarction recently. Factors such as age, gender, and genetic polymorphisms contribute to varying effects.
Reduction in dietary vitamin B6 intakes is associated with increased relative risk of diseases such as cancer, atherosclerosis, and cognitive dysfunction. All forms of dietary vitamin B6 are converted to pyridoxal 5'-phosphate (PLP), that is needed for the proper function of a spectrum of metabolic pathways needed to maintain health. To better understand vitamin B6 homeostasis, it is important to identify lifestyle factors that influence vitamin B6 intake and plasma PLP concentration in the UK population. Therefore, this research has assessed vitamin B6 intake and PLP concentrations as a marker of vitamin B6 status among the UK adult (≥ 19 years) population. This study was carried out using a cross-sectional analysis of the National Diet and Nutrition Survey Rolling Programme (NDNS) (2008 - 2017). The impacts of lifestyle factors including type of diet, smoking, alcohol consumption, and commonly used medications grouped by therapeutic usage, were determined and data analysed using IBM SPSS®. Results are expressed as medians (25th to 75th percentiles), with P values ≤ 0.05 considered statistically significant. Among UK adults, the median intakes of total population of dietary vitamin B6 met the RNI and median plasma PLP concentrations were above the cut-off of vitamin B6 deficiency, however, we found association between reduction in vitamin B6 intake and plasma PLP concentration and age group (P<0.001). Smokers had significantly lower plasma PLP concentrations than the non-smokers (P<0.001). Moreover, regression analysis showed some commonly used medications were associated with plasma PLP levels reduction (P <0.05). Taken together, we report on a tendency for dietary vitamin B6 intake and plasma PLP concentrations to decrease with age, and lifestyle factors such as smoking, and medication usage. This information could have important implications in smokers, and in elderly population using multiple medications (polypharmacy).
Everybody eats, and what we eat – or do not – affects the brain and mind. There is significant general, applied, academic, and industry interest about nutrition and the brain, yet there is much misinformation and no single reliable guide. Diet Impacts on Brain and Mind provides a comprehensive account of this emerging multi-disciplinary science, exploring the acute and chronic impacts of human diet on the brain and mind. It has a primarily human focus and is broad in scope, covering wide-ranging topics like brain development, whole diets, specific nutrients, research methodology, and food as a drug. It is written in an accessible format and is of interest to undergraduate and graduate students studying nutritional neuroscience and related disciplines, healthcare professionals with an applied interest, industry researchers seeking topic overviews, and interested general readers.
To support EFSA in the preparatory work for the assessment of Tolerable Upper Intake Levels (UL) for vitamin B6, a tailored ‘high level’ protocol was developed, based on a template protocol and taking into account the specificities of vitamin B6. This protocol outlined the methods, the relevant endpoints and priority adverse health effects in relation to high intakes of vitamin B6. Systematic reviews (SR) were conducted following a tailored literature search, data extraction, evidence appraisal (i.e. risk of bias (RoB) assessment) and evidence synthesis. Narrative reviews (NR) were conducted to gather contextual evidence relevant to the interpretation of the main body of evidence. In the SR on the dose‐response relationship between vitamin B6 and peripheral neuropathy, 3793 records were identified and reduced to 32 individual records after screening for eligibility. The evidence appraisal revealed an overall moderate to high RoB of the individual studies and an overall rating of the total body of evidence as very low due mainly due to the type of data from case studies/case reports and limited number of other data. The available evidence confirmed a high degree of inter‐individual variability to sensitivity to a high exposure of vitamin B6 in relation to development of peripheral neuropathic outcomes but did not allow to determine a No Observed Adverse Effect Level or Lowest Observed Adverse Effect Level. In the SR on developmental toxicity, 4941 records were identified and reduced to 23 individual records including human and animal studies after screening for eligibility. The available data demonstrated a high degree of heterogeneity with respect to exposure and adverse health outcomes and overall, showed no positive or causal relationship between vitamin B6 intake and adverse developmental effects, including congenital defects. The NRs showed a paucity of data on high intake of vitamin B6 vitamers and their metabolism.
The role of nicotinamide adenine dinucleotide (NAD+) in ageing has emerged as a critical factor in understanding links to a wide range of chronic diseases. Depletion of NAD+, a central redox cofactor and substrate of numerous metabolic enzymes, has been detected in many major age-related diseases. However, the mechanisms behind age-associated NAD+ decline remains poorly understood. Despite limited conclusive evidence, supplements aimed at increasing NAD+ levels are becoming increasingly popular. This review provides renewed insights regarding the clinical utility and benefits of NAD+ precursors, namely nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline and phenotypic characterization of age-related disorders, including metabolic, cardiovascular and neurodegenerative diseases. While it is anticipated that NAD+ precursors can play beneficial protective roles in several conditions, they vary in their ability to promote NAD+ anabolism with differing adverse effects. Careful evaluation of the role of NAD+, whether friend or foe in ageing, should be considered.
Vit B6 is a water-soluble vitamin, but the name refers to a group of at least ten chemically similar pyridine derivatives (vitamers), which can be interconverted in biological systems.
consEnso Med Int Méx 2022; 38 (4): 887-902. Uso clínico de las vitaminas B neurotrópicas en enfermedades del sistema nervioso periférico en México y América Central Resumen La neuropatía periférica puede ser provocada por diferentes factores y manifestarse a través de síntomas variados. A menudo, es mal diagnosticada debido a la falta de evaluación de rutina o de tiempo, en particular en la atención primaria. Las vitaminas B neurotrópicas (B 1 , B 6 y B 12) se prescriben ampliamente para mejorar la función ner-viosa. En esta revisión se resume el uso clínico de las vitaminas B neurotrópicas en el tratamiento de la neuropatía periférica y la deficiencia de las vitaminas B en México y América Central, y se insiste en la necesidad de un diagnóstico y tratamiento tem-pranos de la neuropatía periférica. El contenido se basa en una asamblea del Comité Asesor realizada en Ciudad de México en 2019 con el objetivo de comprender mejor el uso regional de las vitaminas B neurotrópicas a dosis terapéuticas y desarrollar una declaración de consenso que ofrezca una guía para los profesionales de cuidados de la salud. Expertos de diferentes especialidades y varios países de América Latina, con experiencia en el tratamiento de pacientes con neuropatía periférica y deficiencia de vitamina B, compartieron sus visiones sobre las prácticas regionales en el tratamiento de la neuropatía periférica. PALABRAS CLAVE: Vitaminas B; neuropatía periférica; neuropatía periférica diabética; vitamina B 1 ; vitamina B 6 , vitamina B 12. Abstract Peripheral neuropathy can be caused by multiple factors and manifest in various symptoms. It is often misdiagnosed if routine or time is lacking, particularly in primary care. Neurotropic B vitamins (B 1 , B 6 and B 12) are widely used to improve nerve function. This review summarizes the clinical use of neurotropic B vitamins in the treatment of peripheral neuropathy and B vitamin deficiency in Mexico and Central America and highlights the need of an early diagnosis and treatment of peripheral neuropathy. The content is based on an Advisory Board meeting in Mexico City in 2019 with the aim of better understanding the regional use of high-dose B vitamin products and developing a consensus statement providing guidance for healthcare professionals. Experts from multiple specialties and several Latin American countries, experienced in treating patients with peripheral neuropathy and B vitamin deficiency, gave insights on established regional practices in the treatment of peripheral neuropathy.
Nutritional dermatoses are traditionally taught in the context of developing countries, famine, population displacement, and limited access to healthcare. In the United States, nutritional dermatoses may be underdiagnosed and lead to increased morbidity and utilization of hospital resources. These findings underscore the need for providers in developed nations to be able to identify these deficiencies. Dermatologists play a critical role in the diagnosis and management of nutritional deficiencies as they often present with cutaneous findings. Part two of this review series will focus on the epidemiology, impact, manifestations, and diagnosis of B-complex vitamins that can present with cutaneous findings, including thiamine, riboflavin, niacin, pyridoxine, and biotin.
Carboxylic acid containing compounds (R-COOH) are involved in a large number of biological processes and they are relevant for several pathological processes such as neurodegeneration or cancer. Comprehensive methodologies for the quantitative determination of R-COOH in biological samples are required. In this study we have developed a LC-MS/MS method for the quantification of 20 endogenous R-COOH belonging to different pathways such as kynurenine metabolism, serotoninergic pathway, glycolysis, tricarboxylic acid cycle, dopaminergic pathway, short chain fatty acids and glycine metabolism. The approach included derivatization with o-benzylhydroxylamine (reaction time 1 h), liquid-liquid extraction with ethyl acetate and LC-MS/MS detection (run time 10 min). The method was optimized and validated in 5 different matrices (urine, plasma, saliva, brain and liver) following two different approaches: (i) using surrogate matrices and (ii) using actual human samples by standard additions. A suitable linearity was obtained in the endogenous range of the analytes. Adequate intra and inter-assay accuracies (80-120%) and intra- and inter-assay precisions (<20%) were achieved for almost all analytes in all studied matrices. The method was applied in several scenarios to confirm (i) human urinary changes produced in glycolysis after exercise, (ii) metabolic changes produced in rat brain and plasma by methamphetamine administration and (iii) metabolic alterations in human plasma caused by vitamin B6 deficiency. Additionally, the application of the method allowed for establishing previously unreported alterations in R-COOH metabolites under these conditions. Due to the comprehensive analyte and matrix coverage and the wide applicability of the developed methodology, it can be considered as a suitable tool for the study of R-COOH status in health and disease by targeted metabolomics.
People with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD) commonly have altered metabolism or actions of many vitamins and abnormal vitamin function. Vitamin intake is frequently reduced at all CKD stages. The following are among the disorders or key findings concerning vitamins commonly encountered found in people with advanced CKD or ESKD. Plasma vitamin A is usually elevated, and even relatively small vitamin A supplements may cause toxicity. The potential benefits of supplemental vitamin E have not been confirmed. Vitamin K may have an important role in preventing vascular calcification, and clinical trials examining this potential benefit are being conducted. There is an increased dietary need for vitamin B6, in the form of pyridoxine hydrochloride, of about 5 mg/d for advanced CKD and chronic peritoneal dialysis patients and 10 mg/d for maintenance hemodialysis patients. Vitamin C intake is often low, and without vitamin C supplements, deficiency is not uncommon because of a low intake with potassium-restricted diets and because it is readily removed during the dialysis procedure. Folate supplements are effective for decreasing plasma homocysteine levels, but several randomized controlled clinical trials did not demonstrate a reduction in adverse cardiovascular events or mortality with large doses of either folic acid or combinations of folic acid, pyridoxine HCl, and vitamin B12. Vitamin B1 status should be assessed in CKD or ESKD patients who present with atypical neurologic symptoms. Niacin, in large doses, appears to effectively inhibit intestinal phosphate absorption but often causes unpleasant symptoms. Except for vitamins A and E, there is an increased risk of deficiency of other vitamins, such as riboflavin, biotin, and pantothenic acid, in both CKD and chronic dialysis patients, especially in those suffering from protein–energy wasting. It is suggested, even in the absence of a strong evidence base, that multivitamin supplements should commonly be used in advanced CKD and ESKD patients to prevent vitamin deficiencies.
Given the rise in worldwide chronic diseases, supplemented by an aging population, the volume of global major surgeries, encompassing cardiac and orthopedic procedures is anticipated to surge significantly. Surgical trauma can be accompanied by numerous postoperative complications and metabolic changes. The present review summarized the results from studies assessing the effects of orthopedic and cardiovascular surgery on vitamin concentrations, in addition to exploring the possible mechanisms associated with changes in concentrations. Studies have revealed a potentially severe depletion in plasma/serum concentrations of numerous vitamins following these surgeries acutely. Vitamins C, D and B1 appear particularly vulnerable to significant depletions, with vitamin C and D depletions consistently transpiring into inadequate and deficient concentrations, respectively. The possible multifactorial mechanisms impacting postoperative vitamin concentrations include changes in hemodilution and vitamin utilization, redistribution, circulatory transport and absorption. For a majority of vitamins, there has been a lack of investigation into the effects of both, cardiac and orthopedic surgery. Additionally, studies were predominantly restricted to short-term postoperative investigations, primarily performed within the first postoperative week of surgery. Overall, results indicated that further examination is necessary to determine the severity and clinical significance of the possible depletions in vitamin concentrations that ensue cardiovascular and orthopedic surgery.
Background and aims
Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5′-phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and age-related diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose.
Materials and methods
We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, twenty-four hour urine and fasted second void urine samples were collected.
Results
After a single oral dose of 200 mg PM, plasma PM increased in the first three hours to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after ∼10 hours of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after ∼12 hours. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time.
Conclusion
In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency.
Clinical Trial Registry
The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.
Micronutrients are class of dietary components which are highly essential for the optimal health, growth, and development. These nutrients can overcome birth defects, maternal impairment, and increased risk of death. According to 2017 statistics, around 2 billion people in the developing countries are affected by micronutrient deficiency. There are around 13 essential vitamins which are found in nature. Vitamin B is more important as it plays a vital role in maintaining good health and well-being. Among several existing forms, the native and active form of vitamin B6 is PLP (pyridoxal 5- phosphate). PLP is a co-factor for several biochemical reactions and plays an imperative role in synthesis of amino acids, carbohydrates and fatty acids. Vitamin B6 supplementation in RDA showed to be highly health promising in controlling several clinical alignments such as cardiovascular disease, diabetes, neurological disease, premenstrual syndrome, stroke, peripheral vascular disease, coronary artery disease, pellagra skin disease, ataxia, hyperacuosis, suppression of colon tumor genesis and hyper irritability. Recently, it has been reported that 43.8% people are suffering from cardiovascular disease followed by stroke (16.8%) and is also expected to reach up to1.1 trillion by the end of 2035. It has been found that vitamin B6 lowers Homocystein in blood, which damages the inner linings of arteries causing blood clots and thereby reducing the symptoms of cardiovascular diseases. In addition to it humans have to depend on dietary sources of vitamin B6 which are produced by plants, fungi and bacteria. The present review currently focuses on the action of Vitamin B6 in the management of cardiovascular diseases.
Folate deficiency causes massive incorporation of uracil into human DNA
(4 million per cell) and chromosome breaks. The likely mechanism is the
deficient methylation of dUMP to dTMP and subsequent incorporation of
uracil into DNA by DNA polymerase. During repair of uracil in DNA,
transient nicks are formed; two opposing nicks could lead to chromosome
breaks. Both high DNA uracil levels and elevated micronucleus frequency
(a measure of chromosome breaks) are reversed by folate administration.
A significant proportion of the U.S. population has low folate levels,
in the range associated with elevated uracil misincorporation and
chromosome breaks. Such breaks could contribute to the increased risk of
cancer and cognitive defects associated with folate deficiency in
humans.
The metabolism of methionine was studied in 10 control and in 14 women using estrogen-containing oral contraceptives during 28 days of vitamin B6 deficiency and then for another 28 days while ingesting the same diet with daily supplements of 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride. Urinary cystathionine excretion after a 3-g load of L-methionine increased promptly in both groups and continued to increase throughout the 28 days of vitamin B6 depletion; there was no significant difference in the amount excreted by controls and oral contraceptive users. Two milligrams of pyridoxine-HCl restored the cystathionine excretion to predepletion levels within three to four weeks for both control and oral contraceptive users. Daily supplements of 0.8 mg of pyridoxine-HCl for as long as four weeks failed to restore cystathionine excretion to normal levels for either controls or contraceptive users; supplements of 2.0 mg met the vitamin B6 requirements for both groups. Urinary methionine, cysteine sulfinic acid, and taurine excretion did not differ significantly between the two groups at any time. The data indicate that oral contraceptive users are not generally different from non-users with respect to vitamin B6 requirements as evidenced by methionine metabolism.
Fifteen women who had used combination type oral contraceptives (estrogen plus progestogen) and 9 control women who had never used these agents were given a diet deficient in vitamin B6. After 1 month, this diet was supplemented daily with 0.8, 2.0 or 20.0 mg of pyridoxine hydrocholride for an additional month. At weekly intervals, measurements were made of urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythocyte alanine and aspartate aminotransterases. No significan differences were observed between oral contraceptive users and controls in any of the above measured indices. The data suggest that if the use of oral contraceptives of the combined estrogen-progestogen type does alter the requirement for vitamin B6, the effect is a mild one and of doubtful clinical significance to the majority of women taking these steroid preparations. The amount of vitamin B6 (as pyridoxine) needed to maintain normal levels of the above indices of vitamin B6 nutrition in these subjects were between 0.8 and 2.0 mg/day.
Oral glucose tolerance, urinary xanthurenic acid excretion, and plasma pyridoxal phosphate concentrations were determined in nine women taking oral contraceptives and in four controls. The tests were repeated after 4 weeks ingestion of a vitamin B6-deficient diet, and again after pyridoxine supplementation. Vitamin B6 deficiency, as judged by an increased xanthurenic acid excretion and reduced plasma pyridoxal phosphate, was associated with a deterioration in the glucose tolerance of the contraceptive steroid-treated group despite normal or elevated plasma insulin levels. This abnormality was reversed by pyridoxine. There was no change in the glucose tolerance of the vitamin B6-deficient controls. The observed pyridoxine-responsive alteration in carbohydrate metabolism may involve the complexing of insulin with xanthurenic acid with a consequent loss of biological activity. In addition, oral contraceptives may enhance gluconeogensis.
This study evaluates the effects of vitamin B-6 supplementation (20 mg pyridoxine HCL daily for 3 months) on mood and performance in 38 self-supporting healthy men, aged between 70-79 years. Effects were compared with 38 controls who received placebo and were matched for age, plasma pyridoxal-5'-phosphate (PLP) concentration and intelligence score. Before and after drug intervention vitamin B-6 status was determined, and mood and performance were measured by means of a computerized testing system. In addition, the phasic pupil response was measured in order to assess mental effort. Positive effects of vitamin B-6 supplementation were only found with respect to memory, especially concerning long-term memory. In view of the finding that mental performance improvement and delta PLP values were most strongly correlated within an intermediate range of delta PLP, it is suggested that cognitive effects are primarily associated with a certain range of vitamin B-6 status increment. The general conclusion is that vitamin B-6 supplementation improves storage of information modestly but significantly.
The dietary intake and biochemical status of vitamin B-6 in 476 apparently healthy Dutch elderly people (aged 65-79 y), who were not using drugs known to affect vitamin B-6 metabolism, were evaluated. Intake of vitamin B-6 per gram protein was related to biochemical data, namely plasma pyridoxal 5'-phosphate (PLP) and cofactor stimulation of aspartate aminotransferase in erythrocytes (AST-AC). Based on a cutoff point of 2.02 for AST-AC, approximately 9% of the elderly people not using vitamin B-6 supplements had a marginal vitamin B-6 status. About 7% were using vitamin B-6 supplements. Dietary intake of vitamin B-6 per gram protein was negatively related to AST-AC. Vitamin B-6 intakes per gram protein higher than 0.020 mg were necessary to ensure an AST-AC value less than 2.02. At high PLP values AST-AC hardly varied. The results seem to indicate a higher requirement of vitamin B-6 in elderly people than in younger adults.
Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.
We investigated the effect of age on indices of vitamin B-6 metabolism in 36 fasting males aged 25-35, 45-55, and 65-75 y who ingested 17.15 mumol vitamin B-6. There were no significant differences among groups in dietary vitamin B-6 intake, base-line erythrocyte pyridoxal 5'-phosphate (PLP), and total vitamin B-6 concentrations, and 24-h and base-line urinary excretion of total vitamin B-6 and 4-pyridoxic acid (4-PA). Base-line plasma PLP and total vitamin B-6 were higher (p less than 0.05) in the youngest group. Increased serum alkaline phosphatase (AP) and decreased dietary vitamin B-6 intake were correlated with decreased base-line plasma PLP and total vitamin B-6. Changes in plasma and erythrocyte PLP concentrations and excretion of 4-PA and total vitamin B-6 postload were not different among groups. Indices of vitamin B-6 absorption, phosphorylation, and excretion were not affected by age.
The effect of pyridoxine supplementation on lymphocyte responsiveness was investigated in 15 persons aged 65-81 y. Eleven subjects received 50 mg/d pyridoxine HCl (PN). Four subjects received a placebo. Lymphocyte proliferation to T and B cell mitogens, lymphocyte subpopulations with monoclonal antibodies, and plasma pyridoxal 5'-phosphate (PLP) were measured before and after 1 and 2 mo of supplementation. After 1 and 2 mo plasma PLP levels increased by 195 +/- 88 nM and 201 +/- 84 nM, respectively, in subjects receiving PN. With PN supplementation, lymphocyte proliferation increased significantly in response to phytohemagglutinin (p less than 0.01), pokeweed mitogen (p less than 0.01), and Staphylococcus aureus (Cowain I) (p less than 0.05). For PN-treated subjects with low presupplement plasma PLP levels, lymphocyte blastogenesis also increased significantly (p less than 0.01) in response to concanavalin A. Percentages of T3+ and T4+ but not T8+ cells increased significantly (p less than 0.05) in PN-treated subjects. These results suggest that improving vitamin B-6 status is important in stimulating immunocompetence in the elderly.
The role of the pancreaticotrophic hormone cholecystokinin (CCK) in modifying the pancreatic response to carcinogen has been examined in the hamster-nitrosamine pancreatic cancer model. Exogenous CCK, 30 IDU kg-1, stimulated a maximal pancreatic secretory response when given intravenously and caused hypertrophy and hyperplasia of the pancreas when given subcutaneously over a period of 6 weeks (pancreatic wet weight, mg per 100 g body weight, controls 295.6 +/- 61; CCK treated 466.4 +/- 77, P less than 0.001). When the same dose of CCK was given to animals receiving N-nitrosobis (2-oxopropyl)amine (BOP; 5 mg kg-1 weekly) there was a reduction in latency period and increase in induction rate of tumour development (CCK + BOP vs. BOP alone, 12 animals with tumours vs. 2 at 15 weeks; P less than 0.02). These effects are consistent with CCK acting as a co-carcinogen or promoter of pancreatic carcinogenesis in this model.
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Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.
Objective
—To describe the distribution of plasma homocysteine concentrations in an elderly population and to analyze the relationship between homocysteine level and intake of vitamins and serum levels of vitamins that serve as coenzymes in homocysteine metabolism.
Design
—Cross-sectional analysis of homocysteine levels and vitamin blood levels and intake in elderly participants in the Framingham Study.
Setting
—Population-based cohort in Framingham, Mass.
Participants
—A total of 1160 adult survivors, aged 67 to 96 years, from the original Framingham Heart Study cohort.
Main Outcome Measures
—Plasma homocysteine concentration correlated with plasma folate, vitamin B12, pyridoxal-5'-phosphate (PLP), and oral intakes of these vitamins, and the contribution of these vitamins to the prevalence of elevated homocysteine in the population.
Results
—Homocysteine levels were positively correlated with age after controlling for vitamin concentrations. After controlling for age, sex, and levels of other vitamins, homocysteine exhibited a strong inverse association with plasma folate. When subjects were grouped by deciles of plasma folate, mean homocysteine was significantly higher in the lowest two folate deciles (15.6 and 13.7 μmol/L, respectively) than in the highest decile (11.0 μmol/L). Homocysteine demonstrated weaker, inverse associations with plasma vitamin B12 and PLP. Similar inverse associations were demonstrated between homocysteine and intakes of folate and vitamin B6, but not vitamin B12. Prevalence of high homocysteine (>14 μmol/L) was 29.3% in this cohort, and was greatest among subjects with low folate status. Inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine.
Conclusions
—These results indicate a strong association between homocysteine concentration and folate, vitamin B12, and vitamin B6 status, as well as age. It is possible that a substantial majority of the cases of high homocysteine in this older population can be attributed to vitamin status.(JAMA. 1993;270:2693-2698)
Nutritional supplementation with anti-oxidant vitamins such as Vitamin C and E or with B vitamins such as Vitamin B6, can lower blood pressure in persons with essential hypertension. These nutritional supplements may act to prevent one of the underlying causes of essential hypertension, elevated tissue aldehydes. In essential hypertension, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. Abnormalities in carbohydrate metabolism may underlie the etiology of the clinical course of hypertension. Insulin resistance and glucose intolerance is a common feature of hypertension in human and in animal models. Elevated endogenous aldehydes in hypertension may be due to increased production of reactive aldehydes such as methylglyoxal, when the glycolytic pathway of glucose metabolism is impaired. In hypertension there is increased oxidative stress which can lead to a further increase in reactive aldehydes. The thiol compound, N-acetylcysteine, normalizes elevated blood pressure by binding excess endogenous aldehydes and normalizing vascular Ca2+ channels and cytosolic free calcium. Vitamin C, vitamin E, vitamin B6 and lipoic acid are nutrients which can increase endogenous cysteine and glutathione. Dietary supplementation with these nutrients may improve carbohydrate metabolism, lower blood pressure and normalize associated biochemical and histopathological changes.
Increased concentrations of the endogenous tryptophan metabolite 3-hydroxykynurenine (3-HK) were measured in the brains of vitamin B6 deficient neonatal rats. Mean concentrations of 3-HK in B6 deficient cerebellum, corpus striatum, frontal cortex, and pons/medulla ranged from 9.7 to 18.6 and 102 to 142 nmol/g of wet tissue at 14 and 18 days of age, respectively. 3-HK was not significantly increased in control neonatal or adult rat brain, vitamin B6 deficient rat brain at 7 days of age, or in brains from adult rats deprived of vitamin B6 for 58 days. The administration of daily intraperitoneal injections of vitamin B6 from the 14th to the 18th day of age decreased the concentration of 3-HK to control levels. 3-HK has been shown by other investigators to produce seizures when injected into the cerebral ventricles of adult rodents. Thus, our studies show the accumulation in brain of a putative endogenous convulsant as the result of a nutritional deficiency.
Vitamin B6 in the form of pyridoxal-5′-phosphate (PLP) has been previously shown to inhibit in vitro platelet aggregation induced by several different agonists. However, this inhibitory effect took place only at millimolar concentrations of PLP that is too high to have physiological relevance. The aim of this work was to study the anti-aggregatory effect of vitamin B6 in the form of pyridoxine (PN) hydrochloride. Experiments were performed on platelets separated from the human blood. Aggregation was measured photometrically. The values of PN HCl concentration causing 50% inhibition of ADP-induced platelet aggregation (IC50) were obtained from concentration-effect curves. PN HCl inhibited platelet aggregation at low concentrations, IC50 being 1.7 ± 0.5 μM. This indicates that the antiplatelet effect of PN HCl may have physiological relevance.
Because both basal and postmethionine load hyperhomocysteinemia are correlated with vascular disease, there is a need to determine the underlying causes. Although deficiencies of folate, cobalamin, and pyridoxine have all been implicated there are difficulties in distinguishing among them.The objective was to determine the changes in total homocysteine, cystathionine, and other methionine, one carbon- and tryptophan-related metabolites in rats with dietary induced folate or pyridoxine deficiency and cobalamin analogue induced deficiency.Pyridoxine-deficient diet (0 mg/kg) increased basal serum cystathionine levels (14 fold) after 51 days with a smaller increase in basal total homocysteine. Diets with 0 to 1.5 mg/kg pyridoxine also caused graded increases in serum cystathionine. Total homocysteine and cystathionine were markedly increased postmethionine load in the pyridoxine deficient rats as compared to the control, folate-, or cobalamin-deficient rats. Folate- and cobalamin-deficient rats had marked increases in basal total homocysteine and moderate increases in basal cystathionine, but the increments in postmethionine load values were not different than control. Pyridoxine deficiency decreased liver serine transhydroxymethylase activity to 6%. Post-tryptophan load serum xanthurenic acid was equal in cobalamin- and pyridoxine-deficient rats. Serum quinolinic acid was increased only in the cobalamin-deficient rats. Plasma pyridoxal-5′-phosphate levels were not as sensitive as serum cystathionine in pyridoxine deficiency.Basal and postmethionine load serum cystathionine levels are very sensitive in detecting pyridoxine deficiency and will be useful when determining the cause of clinical hyperhomocysteinemia.
Plasma homocysteine concentrations in a group of 80-year-old persons were related to symptoms and signs. Plasma homocysteine concentrations higher than 15 μmol/l were associated with lower total life satisfaction (P<0.01), mood (P<0.05), zest for life (P<0.05), lower scores for reasoning (P<0.05), spatial ability (P<0.05), memory recognition (P<0.05), and subjective health (P<0.01). In an instrument comprising of 30 symptoms, plasma homocysteine concentrations higher than 15 μmol/l were associated with impaired concentration (P<0.05), restlessness (P<0.05), feeling cold (P<0.05), loss of weight (P<0.05), and feeling depressed (P<0.01). The above data indicate that plasma homocysteine values over 15 μmol/l could be relevant markers for clinical intervention.
Context.—
Hyperhomocysteinemia is caused by genetic and lifestyle influences,
including low intakes of folate and vitamin B6. However, prospective
data relating intake of these vitamins to risk of coronary heart disease (CHD)
are not available.Objective.—
To examine intakes of folate and vitamin B6 in relation to
the incidence of nonfatal myocardial infarction (MI) and fatal CHD.Design.—
Prospective cohort study.Setting and Patients.—
In 1980, a total of 80082 women from the Nurses' Health Study with no
previous history of cardiovascular disease, cancer, hypercholesterolemia,
or diabetes completed a detailed food frequency questionnaire from which we
derived usual intake of folate and vitamin B6.Main Outcome Measure.—
Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.Results.—
During 14 years of follow-up, we documented 658 incident cases of nonfatal
MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors,
including smoking and hypertension and intake of alcohol, fiber, vitamin E,
and saturated, polyunsaturated, and trans fat, the
relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence
interval [CI], 0.55-0.87) for folate (median intake, 696 µg/d vs 158
µg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median
intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR
was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate
and vitamin B6 intake compared with the opposite extreme. Risk
of CHD was reduced among women who regularly used multiple vitamins (RR=0.76;
95% CI, 0.65-0.90), the major source of folate and vitamin B6,
and after excluding multiple vitamin users, among those with higher dietary
intakes of folate and vitamin B6. In a subgroup analysis, compared
with nondrinkers, the inverse association between a high-folate diet and CHD
was strongest among women who consumed up to 1 alcoholic beverage per day
(RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI,
0.13-0.58).Conclusion.—
These results suggest that intake of folate and vitamin B6
above the current recommended dietary allowance may be important in the primary
prevention of CHD among women.
Figures in this Article
THREE DECADES AGO, premature vascular occlusive disease was identified
in patients with inborn metabolic disorders associated with homocysteinuria,
leading to the hypothesis that elevated blood homocysteine levels may cause
coronary disease.1- 2 More recently,
evidence linking moderately elevated blood homocysteine levels to increased
risk3 has focused attention on genetic and
lifestyle determinants of homocysteine levels. Folate and vitamin B6 are important cofactors for metabolism. Supplementation of the diet
above the recommended dietary allowance (RDA) with folate alone,4- 5
or in combination with vitamin B6 and vitamin B12, reduces
homocysteine levels.3,6- 9
The current RDA for folic acid for nonpregnant women is 180 µg/d,10 and the average dietary intake in this country among
adult women is approximately 225 µg/d.11
Because of evidence that this level of intake may be insufficient to minimize
risk of neural tube defects, and possibly coronary heart disease (CHD), some
have urged that the RDA be reset to the earlier level of 400 µg/d.12
Although homocysteine may be atherogenic, it also may be only a marker
of folate and vitamin B6 status. Recent epidemiologic evidence
suggests that populations with higher plasma levels of folate and pyridoxal
5‘-phosphate (PLP, the active form of vitamin B6) have lower
risk of carotid artery stenosis13 and CHD.14- 16 In 1 retrospective
study15 of 130 myocardial infarction (MI) cases
and 118 controls, folate intake was inversely associated with CHD risk. To
our knowledge, this relation has not been prospectively studied. Furthermore,
previous studies have not examined the independent effects of folate and vitamin
B6 from food or from supplements on risk of CHD, nor have previous
studies collected sufficient detail to examine subpopulations of individuals
at higher risk of CHD due to factors that may directly or indirectly affect
circulating levels of folate (eg, smoking, parental history of MI, and alcohol).
Therefore, we examined the relation of intakes of folate and vitamin B6 to risk of CHD among 80082 women enrolled in the Nurses' Health Study
and followed prospectively for 14 years (1980-1994).
The relation between selected micronutrients and oral and pharyngeal cancer risk was investigated using data from a case-control study conducted between January 1992 and November 1997 in Italy and Switzerland. Cases were 754 incident, histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 subjects with no history of cancer admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were computed after allowance for age, sex, center, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake. Micronutrients were analyzed both as continuous variables and in quintiles. In the former case, the unit was set to 1 SD of the distribution of controls. ORs for the continuous analysis were 0.95 for retinol, 0.61for carotene, 0.91 for lycopene, 0.83 for vitamin D, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87for riboflavin, 0.59 for vitamin B6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc; the 95% confidence interval excluded one for carotene, vitamin C and E, thiamine, vitamin B6, folic acid, niacin, potassium and iron. ORs were similar for the 2 sexes and in strata of age. When the combined intake of vitamins C and E and carotene was considered, the protective effect of each nutrient was more marked or restricted to subjects with low intake of the other 2. The association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco. In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer. Int. J. Cancer 86:122–127, 2000. © 2000 Wiley-Liss, Inc.
The pro-inflammatory cytokines interleukin 1 (IL1) interleukin 6 (IL6) and tumour necrosis factor-α (TNF), and reactive oxygen species (ROS), play a major role in inflammatory aspects of immune function. They are closely linked with pathology in a wide range of diseases and condition which have an inflammatory basis. Alterations in the intake of fats, antioxidant nutrients, protein and specific amino acids change many aspects of inflammation by interacting with cytokine and ROS biology, thereby providing a means of modulating inflammation. Mortality and morbidity, in a diverse range of diseases, have been linked with excessive or untimely oxidant and pro-inflammatory cytokine production. Evidence of oxidative damage has been observed in sepsis, HIV and hepatitis infection, cancer, diabetes mellitus, alcoholic liver disease and cystic fibrosis. ROS produced during the inflammatory response enhances pro-inflammatory cytokine production by activation of nuclear factor kappa B (NFκB). The interaction is an important part of the up-regulation of inflammatory aspects of immune function. The interaction between ROS and cytokines has the potential to damage the host but is held in check by the antioxidant defences. Nutrient intake directly and indirectly influences antioxidant defence. Glutathione is a major endogenous antioxidant and is important for lymphocyte replication. Vitamin B6 and riboflavin participate in the maintenance of glutathione status. Vitamin B6 acts as a cofactor in the synthesis of cysteine (the rate limiting precursor for glutathione biosynthesis) and riboflavin is a cofactor for glutathione reductase. Deficiencies in vitamins E, B6 and riboflavin reduce cell numbers in lymphoid tissues of experimental animals and produce functional abnormalities in the cell mediated immune response. Sulphur amino acid deficient rats exhibit an impaired ability to synthesise glutathione during inflammation and have increased numbers of neutrophils in lung. Ascorbic acid and tocopherols exert anti-inflammatory effects in studies in man and animals. In humans, dietary supplementation with ascorbic acid, tocopherols and vitamin B6 enhances a number of aspects of lymphocyte function, In smokers indices of inflammation inversely relate to the intakes of vitamins C and E. Studies in healthy subjects, patients and experimental animals clearly demonstrate that unsaturated fats modulate pro-inflammatory cytokine biology. In general n-6 polyunsaturated fatty acids enhance, and n-3 PUFAs and monounsaturated fatty acids suppress, cytokine mediated aspects of inflammation. In addition, n-6 PUFAs and cholesterol enhance and n-3 PUFAs suppress cytokine production. Fats rich in n-3 PUFAs are efficacious in a number of inflammatory diseases, however in smokers indices of inflammation are enhanced in subjects consuming greater than 5% of dietary energy in the form of n-6 PUFAs. Fats may modulate cytokine biology by a number of mechanisms closely linked to membrane phospholipid composition. As a consequence of diet induced change, alterations in prostaglandin, leukotriene and diacyl glycerol production, protein kinase C activation and fluidity may occur. Recent studies suggest that changes in bulk membrane fluidity are unlikely to underlie the substantial modulatory effects of fats on cytokine biology. In conclusion nutrients have a major potential for modulating inflammatory aspects of immune function due to interaction with three main areas whereby inflammation is prosecuted and controlled. Firstly by changing provision of substrate for the synthesis of molecules for components for the executive and control systems (protein, sulphur amino acids, glutamine). Secondly by modulating the composition of the membranes of cells involved in the inflammatory process (unsaturated fatty acids and cholesterol) and thirdly by influencing the interaction between ROS and NFκB activation (sulphur amino acids, vitamins C and E, and riboflavin).
In male albino rats (8 weeks of age) exposed to a number of adverse dietary conditions, an approximately linear relationship was found between the amount of body neiqht deficit and the thymus weight deficit. There were 2 exceptions from this apparent rule: (1) in pyridoxin deficiency, the amount of thymus weight deficit was much greater than expected from the obtained body weight deficit; (2) in calcium deficiency an opjmsite effect was observed. Here the thymi of undersized animals were of the same weight as those of younger, normal animals of the same body weight.
A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B 6 , vitamin B 12 ) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B 12 , or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B 6 levels. Compared with men with the lowest vitamin B 6 concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p -trend = 0.02). Adjusting for any of the other serum factors (folate, B 12 , and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B 6 in lung cancer.
This chapter discusses epilepsy and γ-aminobutyric acid (GABA) mediated inhibition. The inhibitory action of short-chain ω-amino acids (such as β-alanine, GABA, and taurine) on central neurons has been established by the microiontophoretic studies. Additional data that have led to the widespread acceptance of the hypothesis that GABA is the inhibitory transmitter at numerous central sites include (1) the demonstration of high GABA content and glutamic acid decarboxylase (GAD) activity in synaptosome preparations, (2) the evidence for the selective local release of GABA when known inhibitory systems are activated in the cerebral cortex or cerebellum, and (3) evidence from intracellular recordings that the changes in membrane potential and in specific ionic conductances produced by physiological inhibitory inputs are similar to those produced by the iontophoretic application of GABA. The principal sites where GABA produces hyperpolarization of the neuronal membrane, which resembles the physiologically induced inhibitory postsynaptic potential (IPSP) in its dependence on an enhanced chloride conductance, and where naturally induced inhibition and the action of applied GABA are blocked by picrotoxin or bicuculline, are the neocortex, the cerebellum, the hippocampus, and the thalamus.
The vitamin B6 status of 196 aged subjects living at home and institutionalised in hospital, residential accommodation and sheltered dwelling was studied. Subjects receiving multivitamins were grouped separately and the effect of regular vitamin supplementation on the vitamin B6 status was assessed. The mean dietary intake of vitamin B6 was less than 2 mg/day in all the groups. The biochemical deficiency, as evaluated by erythrocyte glutamic pyruvic transaminase (EGPT) index, was observed in 42.3 per cent of the total subjects; the highest incidence was in subjects of sheltered dwelling. Twenty per cent of the subjects receiving multivitamin also had deficient biochemical levels. Anaemia was noted in 1.3 per cent of the vitamin B6 deficient subjects. Clinical signs of deficiency were noted in one female subject of sheltered dwelling.
This prospective study assesses the effect of 2.5, 4, and 10 mg of pyridoxine supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal 5'-phosphate (PLP) and on the degree of coenzyme saturation (activation factor) of aspartate aminotransferase and alanine aminotransferase (alphaEGOT and alphaEGPT) in maternal erythrocytes. More than 4 mg of pyridoxine supplementation daily was required for most pregnancies to maintain maternal plasma PLP levels within the range observed during the first trimester and in the nonpregnant state. The plasma PLP concentrations in maternal and cord blood were highly correlated and indicated a dependence of fetal vitamin B6 nutrition on maternal circulating PLP. Measurements of alphaEGOT and alphaEGPT were not as reproducible as plasma PLP assays and were less sensitive and quantitative indicators. In the majority of subjects, the changes in alphaEGOT and alphaEGPT with time correlated poorly with the changes in plasma PLP. However, when the data were analyzed without regard for their dependence on time, they demonstrated a negative, linear correlation between alphaEGOT and log plasma PLP and between alphaEGPT and log plasma PLP for the group on 2.5 mg of pyridoxine and for all the subjects combined. Finally, the dietary records showed that most of the subjects consumed less than 2 mg of vitamin B6 daily from their food. The results indicate that the current Recommended Dietary Allowance for vitamin B6 during pregnancy (2.5 mg) is too low and that supplementation of this vitamin in an amount more than 4 mg daily is recommended.
Pyridoxal phosphate (vitamin B6) concentrations in peripheral and cord blood obtained at the time of delivery were measured in 30 women. The average plasma concentration in nine women with normal pregnancy was 4.3 ng. per milliliter; in 10 women with pre-eclampsia, 3.3 ng. per milliliter; and in nonpregnant women, 17 ng. per milliliter. The average cord blood plasma concentration of normal infants was 28.4 ng. per milliliter, whereas that of infants of pre-eclamptic mothers was 12.2 ng. per milliliter. This twofold difference in the cord plasma concentrations was statistically significant (p smaller than 0.001). Pyridoxal phosphate concentrations in the infants' cord plasma were increased in all pregnancies studied by administration of pyridoxine either orally or intravenously. These findings together with other data, demonstrating (1) that B6 deficiency during pregnancy may lead to abnormal neurologic development in experimental animals and (2) that brain development in infants of toxemic mothers may be retarded, suggest that dietary supplementation with vitamin B6 should be instituted in women at high risk for development of toxemia of pregnancy.
The vitamin B-1, B-2 and B-6 nutritional status of 153 geriatric patients was determined by measurement of the activities of transketolase (TK), glutathione reductase (GR) and glutamic-oxaloacetic transaminase (GOT) from hemolyzed erythrocytes before and after in vitro stimulation with their respective coenzymes. The change in enzyme activity after incubation of the hemolysate with the coenzyme was used to determine the activation coefficient, which was taken as an index for the vitamin B-1, B-2 and B-6 nutritional status. Determination of the normal values in 54 healthy blood donors showed that activation coefficients of TK greater than 1.27 indicated a biochemical vitamin B-1 deficiency. Activation coefficients of GR greater than 1.29 and GOT greater than 1.86 indicated, respectively, deficiencies of vitamins B-2 and B-6. On the basis of these findings 22.9% of the geriatric patients appeared to suffer from vitamin B-1 deficiency, 11.7% from vitamin B-2 deficiency and 19.0% from vitamin B-6 deficiency. Of the total number of patients, 44% showed a deficiency of one or more of these three vitamins. Oral administration of vitamin B-1 (20 mg/day), vitamin B-2 (10 mg/day) and vitamin B-6 (20 mg/day) for twelve days normalized nearly all activation coefficients. Determination of enzyme activities without coenzyme stimulation revealed significantly lower values in the deficient patients as compared with the blood donors. However, the distribution of activities for both groups overlapped to a great extent. Oral administration of vitamins raised the enzyme activities to normal values.
This chapter describes the vitamin plasma concentration data collection, preliminary analysis and results of the Euronut SENECA study. Blood plasma was collected from approximately 2500 elderly subjects born in 1913-1918 living in 17 small towns in 11 European countries, and the plasma levels of carotene, retinol, alpha-tocopherol, vitamin B12, folic acid and pyridoxal 5'-phosphate were determined. There were very large within- and between-centre differences in vitamin levels with no definite geographical pattern emerging. The vitamin status for retinol and folic acid was adequate in all centres. The prevalence of biochemical vitamin B6 deficiency was widespread and reached over 50% in some centres. Vitamin B12 biochemical deficiency was limited to ten centres and its prevalence was 1.6%-10%. Vitamin E biochemical deficiency was found in seven centres and varied from 0.5% to 25%.