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Fulltext SARS CoV-2 aggravates cellular metabolism mediated complications in COVID-19 infection

Singh Y, Gupta G, Kazmi I, Al-Abbasi FA, Negi P, Chellappan DK, et al.

Dermatol Ther, 2020 11;33(6):e13871.
PMID: 32558055 DOI: 10.1111/dth.13871

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.

Matched MeSH terms: Vitamin B 6/administration & dosage
Fulltext Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk

Zuo H, Ueland PM, Midttun Ø, Vollset SE, Tell GS, Theofylaktopoulou D, et al.

Cancer Res, 2018 Jan 01;78(1):302-308.
PMID: 29070616 DOI: 10.1158/0008-5472.CAN-17-1923

Circulating pyridoxal-5'-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose-response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27-1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.Significance: This large cohort study firmly establishes an association between an index of vitamin B6 levels with lung cancer risk. Cancer Res; 78(1); 302-8. ©2017 AACR.

Matched MeSH terms: Vitamin B 6/blood; Vitamin B 6/metabolism*
Do folate, vitamins B₆ and B₁₂ play a role in the pathogenesis of migraine? The role of pharmacoepigenomics

Shaik MM, Tan HL, Kamal MA, Gan SH

CNS Neurol Disord Drug Targets, 2014;13(5):828-35.
PMID: 24040787

Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine. Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the occurrence of migraine.

Matched MeSH terms: Vitamin B 6/metabolism*
Fulltext Rapid resolution liquid chromatography method development and validation for simultaneous determination of homocysteine, vitamins B(6), B(9), and B(12) in human serum

Shaik MM, Gan SH

Indian J Pharmacol, 2013 Mar-Apr;45(2):159-67.
PMID: 23716893 DOI: 10.4103/0253-7613.108303

Hyperhomocysteinemia and vitamins B(6), B(9), and B(12) deficiencies usually result in various neurological, vascular, ocular, renal, and pulmonary abnormalities. However, to date, there are no simultaneous detection methods available for determining homocysteine, vitamins B(6), B(9), and B(12) levels in various biological fluids. In this study, we aim to develop a new validated simultaneous detection method for all four compounds to save both cost and time of analysis.

Matched MeSH terms: Vitamin B 6/analysis*
A placebo-controlled trial of oral pyridoxine in hyperemesis gravidarum

Tan PC, Yow CM, Omar SZ

Gynecol. Obstet. Invest., 2009;67(3):151-7.
PMID: 19077388 DOI: 10.1159/000181182

To evaluate oral pyridoxine in conjunction with standard therapy in women hospitalized for hyperemesis gravidarum (HG).

Matched MeSH terms: Vitamin B 6/administration & dosage*
Fulltext Relationships between dietary nutrients intake and lipid levels with functional MRI dorsolateral prefrontal cortex activation

Lau H, Shahar S, Mohamad M, Rajab NF, Yahya HM, Din NC, et al.

Clin Interv Aging, 2019;14:43-51.
PMID: 30613138 DOI: 10.2147/CIA.S183425

Background: Dorsolateral prefrontal cortex (DLPFC) is a key node in the cognitive control network that supports working memory. DLPFC dysfunction is related to cognitive impairment. It has been suggested that dietary components and high-density lipoprotein cholesterol (HDL-C) play a vital role in brain health and cognitive function.
Purpose: This study aimed to investigate the relationships between dietary nutrient intake and lipid levels with functional MRI (fMRI) brain activation in DLPFC among older adults with mild cognitive impairment.
Participants and methods: A total of 15 community-dwelling older adults with mild cognitive impairment, aged ≥60 years, participated in this cross-sectional study at selected senior citizen clubs in Klang Valley, Malaysia. The 7-day recall Diet History Questionnaire was used to assess participants' dietary nutrient intake. Fasting blood samples were also collected for lipid profile assessment. All participants performed N-back (0- and 1-back) working memory tasks during fMRI scanning. DLPFC (Brodmann's areas 9 and 46, and inferior, middle, and superior frontal gyrus) was identified as a region of interest for analysis.
Results: Positive associations were observed between dietary intake of energy, protein, cholesterol, vitamins B6 and B12, potassium, iron, phosphorus, magnesium, and HDL-C with DLPFC activation (P<0.05). Multivariate analysis showed that vitamin B6 intake, β=0.505, t (14)=3.29, P=0.023, and Digit Symbol score, β=0.413, t (14)=2.89, P=0.045; R2=0.748, were positively related to DLPFC activation.
Conclusion: Increased vitamin B6 intake and cognitive processing speed were related to greater activation in the DLPFC region, which was responsible for working memory, executive function, attention, planning, and decision making. Further studies are needed to elucidate the mechanisms underlying the association.

Matched MeSH terms: Vitamin B 6/administration & dosage*
Fulltext High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus

Lai JS, Pang WW, Cai S, Lee YS, Chan JKY, Shek LPC, et al.

Clin Nutr, 2018 06;37(3):940-947.
PMID: 28381340 DOI: 10.1016/j.clnu.2017.03.022

BACKGROUND & AIMS: B-vitamins and homocysteine may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the cross-sectional associations of plasma folate, vitamins B6, B12, and homocysteine concentrations with GDM and glycemia in a sample of multi-ethnic Asian pregnant women.
METHODS: Plasma concentrations of folate, vitamins B6, B12, homocysteine and glucose were measured at 26-weeks' gestation in 913 pregnant women. GDM was diagnosed using the 1999 World Health Organization criteria. Associations were examined with linear or logistic regression, adjusted for confounders and stratified by ethnicity.
RESULTS: Higher plasma folate was associated with higher 2-h glucose and higher odds of GDM [0.15 (0.02, 0.23) per 1-SD increment in folate, OR 1.29 (1.00, 1.60)], mainly among Indian mothers. Higher plasma vitamin B12 and homocysteine were associated with lower fasting and 2-h glucose, and lower odds of GDM [-0.04 (-0.07, -0.01) per 1-SD increment in B12 and -0.09 (-0.18, -0.003) respectively, OR: 0.81 (0.68, 0.97); -0.05 (-0.08, -0.02) per 1-SD increment in homocysteine and -0.12 (-0.21, -0.02) respectively, OR: 0.76 (0.62, 0.92)]. The highest odds of GDM were observed among women with combined vitamin B12 insufficiency and high folate concentration [OR: 1.97 (1.05, 3.68)]. An association between higher vitamin B6 and higher 2-h glucose shifted towards null adjusting for other B-vitamins.
CONCLUSIONS: Higher maternal folate coupled with vitamin B12 insufficiency was associated with higher GDM risk. This finding has potential implications for antenatal supplement recommendations but will require confirmation in future studies.

Matched MeSH terms: Vitamin B 6/blood
Fulltext Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine

Shaik MM, Gan SH

Biomed Res Int, 2015;2015:469529.
PMID: 25815319 DOI: 10.1155/2015/469529

Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention. For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG. Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine.

Matched MeSH terms: Vitamin B 6/administration & dosage
Fulltext One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition

Vrieling A, Bueno-De-Mesquita HB, Ros MM, Kampman E, Aben KK, Büchner FL, et al.

Int J Cancer, 2019 Nov 01;145(9):2349-2359.
PMID: 30694528 DOI: 10.1002/ijc.32165

Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.

Matched MeSH terms: Vitamin B 6/blood
Epigenetic Changes and Its Intervention in Age-Related Neurodegenerative Diseases

Mohd Murshid N, Aminullah Lubis F, Makpol S

Cell Mol Neurobiol, 2020 Oct 19.
PMID: 33074454 DOI: 10.1007/s10571-020-00979-z

Epigenetic mechanisms involving the modulation of gene activity without modifying the DNA bases are reported to have lifelong effects on mature neurons in addition to their impact on synaptic plasticity and cognition. Histone methylation and acetylation are involved in synchronizing gene expression and protein function in neuronal cells. Studies have demonstrated in experimental models of neurodegenerative disorders that manipulations of these two mechanisms influence the susceptibility of neurons to degeneration and apoptosis. In Alzheimer's disease (AD), the expression of presenilin 1 (PSEN1) is markedly increased due to decreased methylation at CpG sites, thus promoting the accumulation of toxic amyloid-β (Aβ) peptide. In Parkinson's disease (PD), dysregulation of α-synuclein (SNCA) expression is presumed to occur via aberrant methylation at CpG sites, which controls the activation or suppression of protein expression. Mutant Huntingtin (mtHTT) alters the activity of histone acetyltransferases (HATs), causing the dysregulation of transcription observed in most Huntington's disease (HD) cases. Folate, vitamin B6, vitamin B12, and S-adenosylmethionine (SAM) are vital cofactors involved in DNA methylation modification; 5-azacytidine (AZA) is the most widely studied DNA methyltransferase (DNMT) inhibitor, and dietary polyphenols are DNMT inhibitors in vitro. Drug intervention is believed to reverse the epigenetic mechanisms to serve as a regulator in neuronal diseases. Nevertheless, the biochemical effect of the drugs on brain function and the underlying mechanisms are not well understood. This review focuses on further discussion of therapeutic targets, emphasizing the potential role of epigenetic factors including histone and DNA modifications in the diseases.

Matched MeSH terms: Vitamin B 6
Fulltext Development of a Healthy Dietary Habits Index for New Zealand Adults

Wong JE, Haszard JJ, Howe AS, Parnell WR, Skidmore PML

Nutrients, 2017 May 03;9(5).
PMID: 28467392 DOI: 10.3390/nu9050454

Healthful dietary habits are individually associated with better nutrient intake and positive health outcomes; however, this information is rarely examined together to validate an indicator of diet quality. This study developed a 15-item Healthy Dietary Habits Index (HDHI) based on self-reported dietary habits information collected in the 2008/09 New Zealand Adult Nutrition Survey. The validity of HDHI as a diet quality index was examined in relation to sociodemographic factors, 24-diet recall derived nutrient intakes, and nutritional biomarkers in a representative sample of adults aged 19 years and above. Linear regression models were employed to determine associations between HDHI quintiles and energy-adjusted nutrient data and nutritional biomarkers. Significantly higher HDHI scores were found among women, older age groups, Non-Māori or Pacific ethnic groups, and less socioeconomically-deprived groups (all p < 0.001). Increasing quintiles of HDHI were associated with higher intakes of dietary fibre and seven micronutrients including calcium, iron, and vitamin C, and lower intakes of energy, macronutrients, sodium, zinc, vitamins B6 and B12. Associations in the expected directions were also found for urinary sodium, whole blood folate, serum and red blood cell folate, and plasma selenium (all p < 0.001). The present findings suggest that the HDHI is a valid measure of diet quality as it is capable of discerning quality of diets of subgroups and ranking nutrient intakes among NZ adults.

Matched MeSH terms: Vitamin B 6
Fulltext Association between dietary folate intake and blood status of folate and homocysteine in Malaysian adults

Chew SC, Khor GL, Loh SP

J Nutr Sci Vitaminol (Tokyo), 2011;57(2):150-5.
PMID: 21697634 DOI: 10.3177/jnsv.57.150

Folate is of prime interest among investigators in nutrition due to its multiple roles in maintaining health, especially in preventing neural tube defects and reducing the risk of cardiovascular diseases. We investigated the effect of dietary folate intake on blood folate, vitamin B(12), vitamin B(6), and homocysteine status. One hundred subjects consisting of Chinese and Malay subjects volunteered to participate in this cross-sectional study. Dietary folate intake was assessed by 24-h dietary recall and a food-frequency questionnaire (FFQ). Serum and red blood cell folate were analyzed using a microbiological assay, while serum vitamin B(12) was determined by electrochemiluminescence immunoassay (ECLIA), and high-performance liquid chromatography (HPLC) was used for the determination of serum vitamin B(6) and homocysteine. The mean folate intake, serum folate, RBC folate, serum vitamin B(12), and B(6), were higher in female subjects, with the exception of serum homocysteine. The Chinese tended to have higher folate intake, serum folate, RBC folate, and vitamin B(12). A positive association was found between folate intake and serum folate while a negative association was found between folate intake and serum homocysteine. Stepwise linear regression of serum folate showed a significant positive coefficient for folate intake whilst a significant negative coefficient was found for serum homocysteine when controlling for age, gender, and ethnicity. In conclusion, high dietary folate intake helps to increase serum folate and to lower the homocysteine levels.

Matched MeSH terms: Vitamin B 6/blood*

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