Plasma Pyridoxal Research Articles

Adult hypophosphatasia presenting with recurrent acute joint pain.

Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5'-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms. A diagnosis of adult HPP without bone-related symptoms can be challenging. A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia. Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.

Associations of Dietary Intake of Vitamin B6 and Plasma Pyridoxal 5'-Phosphate Level With Depression in US Adults: Findings From NHANES 2005-2010.

Evidence regarding the associations of pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk is scarce. Accordingly, we investigated the aforementioned associations in US adults. This is a cross-sectional study that included data from two independent samples of 12,716 and 11,967 individuals (aged ≥20years) participating in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The associations of the pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk were examined through multivariable logistic regression. In addition, we determined dose-response associations by fitting restricted cubic splines to the data. In the multivariable model, the highest quarter of dietary intake of vitamin B6 was associated with a significantly lower risk of depression compared to the lowest quarter (OR=0.63, 95% CI: 0.50, 0.79, p< 0.001). Similarly, the highest quartile of plasma PLP levels was linked to a reduced risk of depression compared to the lowest quartile (OR=0.76, 95% CI: 0.62, 0.93, p<0.01). With increasing quartiles of dietary intake of vitamin B6 and plasma PLP levels, the risk of depression also decreased accordingly (all p for trend < 0.01). Furthermore, the correlation analysis revealed that for every 1-SD increase in the level of plasma lutein+zeaxanthin and dietary intake of vitamin B6, the risk of depression showed a decreasing trend (all p<0.01). The interaction test results indicated that the dietary consumption of vitamin B6 did not significantly interact with any of the stratification factors (all p for interaction >0.05). Moreover, no significant interaction was found between the amount of plasma PLP and any hierarchical factors (all p for interaction >0.05), except for gender-based subgroup analysis (p for interaction >0.05). The dose-response relationship results showed a linear decrease trend in the relationship between dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate with the risk of depression. Plasma PLP levels and dietary vitamin B6 intake in the highest quartiles are associated with a lower risk of depression. These findings support the promotion of a balanced diet rich in vitamin B6. However, future randomized controlled trials are necessary to confirm the effects of vitamin B6 supplementation on depression risk. We should aim for a healthy and balanced diet in terms of nutritional supplementation.

Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

Vitamin B-6 Status Indices Are Lower in Pregnant than in Nonpregnant Women but Urinary Excretion of 4-Pyridoxic Acid Does Not Differ1–4

The cause of reduced plasma pyridoxal-5'-phosphate (PLP) concentration and the validity of plasma PLP concentration as a vitamin B-6 status indicator during pregnancy are not well understood. In this study, pregnant and nonpregnant women consumed a controlled diet for 5 d to exclude dietary intake as a factor in altered vitamin B-6 metabolic utilization. Plasma PLP and pyridoxal (PL) concentrations were significantly lower and higher, respectively, and plasma PL+PLP concentration was significantly lower during pregnancy. When plasma PLP and PL concentrations were normalized based on plasma albumin concentration, the differences were less marked but were still significant. The erythrocyte aspartate aminotransferase activity coefficient was significantly greater in pregnant women which is a further indication of reduced vitamin B-6 concentrations in the blood. No difference was observed in the urinary excretion of 4-pyridoxic acid between the pregnant and nonpregnant women. Results of this study demonstrate that vitamin B-6 status indices are lower during pregnancy without differences in the urinary excretion of 4-pyridoxic acid.

Impact of lifestyle factors on dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate level in UK adults: National Diet and Nutrition Survey Rolling Programme (NDNS) (2008-2017).

Reduction in dietary vitamin B6 intake is associated with an increased relative risk of diseases such as cancer, atherosclerosis and cognitive dysfunction. The current research has assessed vitamin B6 intakes 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 were analysed using IBM SPSS®. Results are expressed as medians (25th-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 reference nutrient intake and median plasma PLP concentrations were above the cut-off of vitamin B6 deficiency; however, we found an 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 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 for smokers and in the elderly population using multiple medications (polypharmacy).

Vitamin B-6 Status of Women with a Constant Intake of Vitamin B-6 Changes with Three Levels of Dietary Protein

To determine the effect of varying levels of dietary protein with a constant intake of vitamin B-6 (B-6) on B-6 status, nine women were fed diets providing daily intakes of 1.25 mg B-6 and 0.5, 1.0 and 2.0 g protein/kg body weight. After an 8-d adjustment period, the women consumed each level of dietary protein for 14 d in a Latin-square design. Several direct and indirect B-6 status indicators were measured in blood and urine. Significant differences among protein levels were found for urinary 4-pyridoxic acid (4-PA) excretion (P < 0.01), plasma pyridoxal 5′-phosphate (PLP) concentration (P < 0.05), and urinary excretion of volatile amines (VA, kynurenine plus acetylkynurenine) after a 2-g L-tryptophan load (P < 0.05). Nitrogen intake was significantly negatively correlated with urinary 4-PA excretion (r = -0.619, P < 0.001) and plasma PLP concentration (r = -0.549, P < 0.01), and positively correlated with erythrocyte alanine aminotransferase percentage stimulation (r = 0.418, P < 0.05) and urinary post-tryptophan load excretion of xanthurenic acid (r = 0.535, P < 0.05), kynurenic acid (r = 0.563, P < 0.05) and VA (r = 0.626, P < 0.01). Compared with men consuming diets with similar B-6 to protein ratios in a previous study, the women excreted a greater percentage of the B-6 intake as 4-PA, had lower plasma PLP concentrations and excreted greater amounts of postload urinary tryptophan metabolites at all three protein levels. If the Recommended Dietary Allowance (RDA) of vitamin B-6 is to be based on the dietary B-6 to protein ratio, gender differences in response to varying protein intakes should be considered. For the levels of protein intake used in this study and a B-6 intake of 1.25 mg/d, a B-6 to protein ratio of greater than 0.020 mg/g is required for adequate vitamin B-6 status in women.

Men with oligozoospermia had lower level of seminal plasma pyridoxine compared to normozoospermic men

The contribution of pyridoxine on various human disorders has been revealed in so many studies; however, this contribution on poor semen quality has yet to be investigated. Here, we intended to measure the level of seminal plasma pyridoxine (SPP) in men with oligozoospermia compared to normozoospermic men. Thirty-three men with oligozoospermia and forty-three normozoospermic men were randomly enrolled in this study. Collected semen were tested for sperm motility, sperm concentration, semen volume, and pyridoxine status. Liquid chromatography with tandem mass spectrometry was used to measure SPP in the collected samples. There was a significant reduction (p < 0.0001) in the concentrations of SPP in men with oligozoospermia (0.79 ± 0.41 μg L−1) compared to normozoospermic men (3.17 ± 0.96 μg L−1). Besides, SPP was not significantly correlated (p > 0.05) with sperm motility, sperm concentration, and semen volume in both tested groups, but, independently, it was found to be positively correlated (p = 0.0154) with male age in oligozoospermic group. Men with oligozoospermia had lower level of SPP compared to normozoospermic men. These results may open a new research gate for the use of pyridoxine in the management of male infertility.

Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults.

We investigated the utility of urine phosphoethanolamine (PEA) as a marker to aid in diagnosing and/or confirming hypophosphatasia (HPP) in adults and for monitoring patients on enzyme replacement therapy (ERT). Data was collected from seventy-eight adults who were referred to the Vanderbilt Program for Metabolic Bone Disease for evaluation of a possible or confirmatory HPP diagnosis between July 2014 through December 2019. Fifty-nine patients were diagnosed with HPP and nineteen were excluded from a diagnosis of HPP. The urine PEA results of those patients with a confirmed diagnosis of HPP and those patients with a diagnosis of HPP excluded were captured and compared to other laboratory and clinical parameters consistent with HPP, including alkaline phosphatase (ALP) activity, plasma pyridoxal 5'-phosphate (PLP), the presence of musculoskeletal abnormalities, and genetic testing for pathogenic mutations in ALPL. Initial urine PEA values in patients in our HPP cohort and not on ERT were significantly higher (median=150.0nmol/mg creatinine, IQR=82.0-202.0) compared patients in our HPP negative group (median 18.0nmol/mg creatinine, IQR=14.0-30.0, p<0.0001) and higher than patients on ERT (median 65.0nmol/mg creatinine, IQR=45.3-79.8). Patients who began ERT had a decline in urine PEA levels after treatment with a mean decrease of 68.1%. Plasma ALP levels were significantly lower in the group of patients with HPP and not on ERT group (median=24.0U/L, IQR=15.0-29.50) compared to the patients without HPP (median=45.50U/L, IQR=34.0-62.0;) and plasma PLP levels were significantly higher in the HPP non-ERT group (median=284.0nmol/L, IQR=141.0-469.4) compared to the patients without HPP (median=97.5nmol/L, IQR=43.7-206.0;). The area under the curve (AUC) of urine PEA, ALP, and PLP to distinguish between HPP and non-HPP patients is 0.968, 0.927 and 0.781, respectively, in our cohort. Urine PEA had 100% specificity (95% CI of 83.2% to 100.0%) for diagnosing HPP at a value >53.50nmol/mg creatinine with a sensitivity of 88.4%; 95%CI 75.5 to 94.9%. ALP had a 100% specificity (95% CI of 82.4% to 100.0%) for diagnosing HPP at a value <30.5U/L with a sensitivity of 77.2%; (95%CI 64.8 to 86.2%). PLP had a 100% specificity (95% CI of 81.6% to 100.0%) for diagnosing HPP at a value >436nmol/L with a sensitivity of 26.9%; (95%CI 16.8 to 40.3%). The most common pathogenic or likely pathogenic mutations in our cohort were c.1250A>G (p.Asn417Ser), c.1133A>T (p.Asp378Val), c.881A>C (p.Asp294Ala), c.1171C>T (p.Arg391Cys), and c.571G>A, (p.Glu191Lys). Urine PEA is a promising diagnostic and confirmatory marker for HPP in patients undergoing investigation for HPP. Urine PEA also has potential use as a marker to monitor ERT compliance. Future studies are necessary to evaluate the association between PEA levels and clinical outcomes.

Associations of Vitamin B6 Intake and Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids in US Older Adults: Findings from NHANES 2003-2004.

Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA biosynthesis. Perturbation of PUFA compositions during B6 deficiency could be linked to age-related health outcomes. However, little is known about the interrelationships between vitamin B6, PUFA, and gender in the older population. Therefore, we investigated whether gender-specific associations of B6 intake and plasma pyridoxal 5’-phosphate (PLP) concentration, respectively, with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA) existed in older adults. We further examined the relationships of adequate B6 status (PLP ≥ 20 nmol/L) with high (above median) plasma PUFA relative to deficient B6 status. This cross-sectional study analyzed 461 participants aged ≥60 years from NHANES 2003–2004. Nutrient intakes were assessed using two 24-h recalls and supplement questionnaires. PLP and PUFA concentrations were measured. Multivariate linear regression assessed the association of B6 intake and PLP with PUFA; multivariate logistic regression evaluated the relationship of adequate B6 status with high plasma PUFA, adjusting for demographic, socioeconomic, and dietary factors; physical activity; smoking; alcohol; medication; and BMI. There were interactions between gender and B6 intake on EPA (P-interaction = 0.008) and AA (P-interaction = 0.004) only, whereas no interaction existed between gender and PLP on PUFA. PLP was directly associated with EPA (β = 0.181, P = 0.002), DHA (β = 0.109, P = 0.005), EPA + DHA (β = 0.14, P = 0.002), EPA/AA (β = 0.186, P = 0.004), and (EPA + DHA)/AA (β = 0.13, P = 0.026). The odds of having high plasma EPA (adjusted (a) OR: 2.03, P = 0.049) and EPA/AA (aOR: 3.83, P < 0.0001) were greater in those with adequate B6 status compared to those with deficient B6 status. In conclusion, in US older adults, a higher PLP level was associated with a greater level of EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA. Adequate B6 status was associated with high EPA and EPA/AA status. These findings suggest that sufficient vitamin B6 status may positively influence PUFA metabolism in older adults.

Hypophosphatasia: Vitamin B6 status of affected children and adults.

Hypophosphatasia (HPP) is the heritable dento-osseous disease caused by loss-of-function mutation(s) of the gene ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a cell-surface homodimeric phosphomonoester phosphohydrolase expressed in healthy people especially in the skeleton, liver, kidneys, and developing teeth. In HPP, diminished TNSALP activity leads to extracellular accumulation of its natural substrates including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B6 (B6). Autosomal dominant and autosomal recessive inheritance involving >450 usually missense defects scattered throughout ALPL largely explains the remarkably broad-ranging severity of this inborn-error-of-metabolism. In 1985 when we identified elevated plasma PLP as a biochemical hallmark of HPP, all 14 investigated affected children and adults had markedly increased PLP levels. However, pyridoxal (PL), the dephosphorylated form of PLP that enters cells to cofactor many enzymatic reactions, was not low but often inexplicably elevated. Levels of pyridoxic acid (PA), the B6 degradation product quantified to assess B6 sufficiency, were unremarkable. Canonical signs or symptoms of B6 deficiency or toxicity were absent. B6-dependent seizures in infants with life-threatening HPP were later explained by their profound deficiency of TNSALP activity blocking PLP dephosphorylation to PL and diminishing gamma-aminobutyric acid synthesis in the brain. Now, there is speculation that altered B6 metabolism causes further clinical complications in HPP. Herein, we assessed the plasma PL and PA levels accompanying previously reported elevated plasma PLP concentrations in 150 children and adolescents with HPP. Their mean (SD) plasma PL level was nearly double the mean for our healthy pediatric controls: 66.7 (59.0) nM versus 37.1 (22.2) nM (P<0.0001), respectively. Their PA levels were broader than our pediatric control range, but their mean value was normal; 40.2 (25.1) nM versus 39.3 (9.9) nM (P=0.7793), respectively. In contrast, adults with HPP often had plasma PL and PA levels suggestive of dietary B6 insufficiency. We discuss why the B6 levels of our pediatric patients with HPP would not cause B6 toxicity or deficiency, whereas in affected adults dietary B6 insufficiency can develop.

Association of Plasma Vitamin B6 With Coronary Heart Disease in Patients Undergoing Diagnostic Coronary Angiography: New Insight on Sex Differences

Aim: To date, findings on the overall and sex-specific effects of plasma pyridoxal 5′-phosphate (PLP, active coenzyme form of vitamin B6) on the risk of coronary heart disease (CHD) have been inconsistent. This study sought to advance our understanding on the association of plasma PLP with risk of CHD, with particular attention paid to sex differences and effect modifiers.Methods: We conducted a hospital-based, case-control study on suspected CHD patients undergoing diagnostic coronary angiography. A total of 429 CHD cases and 429 controls matched by age, sex, and operation time were included in the final analysis. Plasma PLP was assessed using LC-MS. Logistic regression analyses were performed to evaluate the association between plasma PLP and a first CHD event.Results: The mean (SD) plasma PLP levels were 8.4 (6.3) in male cases and 9.0 (11.0) in female cases, and 9.5 (8.5) in male controls and 12.5 (12.9) in female controls. Each 1 ng/mL increment in log2PLP was associated with a 28% lower risk of CHD in overall population. When stratified by sex, plasma PLP was significantly and independently associated with CHD in women (OR = 0.63, 95% CI: 0.50–0.80), but not in men (OR = 0.86, 95% CI: 0.67–1.09). The association of plasma PLP with CHD risk was modified by sex (adjusted Pinteraction = 0.022).Conclusions: We found a significant, inverse linear association between plasma PLP and CHD in Chinese women, but not in men. Our findings warrant additional investigation.

Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial

BackgroundOlder adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status.MethodsA double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels.ResultsA total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis.ConclusionsThe results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults.Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine

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. 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 200mg PM or a three daily dose of 67mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24h urine and fasted second void urine samples were collected. After a single oral dose of 200mg PM, plasma PM increased in the first 3h to a maximum of 2324±266nmol/L. While plasma PM levels returned to baseline after ~10h of PM intake, PLP increased to a maximum of 2787±329nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5±2.1nmol/L; it was nearly undetectable after ~12h. With a three daily dose of 67mg 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. 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. The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.

Associations Between Vitamin B6 Status and Plasma Polyunsaturated Fatty Acids Among US Older Adults: NHANES 2003–2004

ObjectivesPrevious evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP < 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. MethodsA cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. ResultsPlasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8–2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0–4.33, P = 0.049, respectively]. ConclusionsIn US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding SourcesNo funding sources.

Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Modification of vitamin B6 on the associations of blood lead levels and cardiovascular diseases in the US adults

BackgroundCardiovascular disease (CVD) is a leading cause of death in the US population. Lead exposure is an important risk factor of CVDs, as is associated with elevated homocysteine level and...

Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.

Background: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. Methods: we measured plasma pyridoxal 5’-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1–57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8–8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47–0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51–1.01) and 0.74 (95% confidence interval, 0.53–1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27–0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65–1.51). Conclusions: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.

Vitamin B6 Supplementation Reduces Depression in College Women Taking Oral Contraceptives: A Randomized, Double-Blind Cross-Over Trial

Abstract Objectives Oral contraception (OC) use has been linked to an increased risk of depression in college women and to poor micronutrient status. Of note, when compared to non-OC users, OC users have a heightened risk of low plasma concentrations of vitamin B6, a cofactor in the tryptophan-serotonin pathway critical to mood regulation. The purpose of this crossover study was to determine whether vitamin B6 supplementation impacted mood states and depression in college women using OC. Methods Participants were healthy and between 18–25 y, did not smoke or use dietary supplements, and used OC (estrogen with progestin) consistently for at least one year prior to the start of the study. The 12-week, randomized, double-blind crossover trial (4-week treatment periods [B6: 100 mg/d or control: placebo pill/d] separated by a 4-week washout [no pills taken]) was approved by the university Institutional Review Board, and participants provided written consent. Anthropometric measures, blood sampling, and diet and mood assessments were completed at the start of the trial and at weeks 4, 8, and 12. Participants (n = 8) maintained normal exercise and eating patterns the duration of the study and recorded pill consumption daily. The Profile of Mood States (POMS) and Beck Depression Inventory were used to assess affect. Plasma pyridoxal 5′ phosphate (PLP) concentrations were quantified by enzymatic assay. Repeated measures ANOVA was used to assess treatment effects. Results Plasma PLP concentrations averaged 66 ± 32 nmol/L at the start of the trial; one participant presented with marginal vitamin B6 status (20–30 nmol/L). Average vitamin B6 intakes did not vary during the trial (1.2–1.4 mg/d); whereas, vitamin B6 status rose significantly following the B6 supplementation period compared to the other three timepoints. POMS scores were not impacted by treatment; however, Beck Depression Inventory scores were reduced 30% by B6 supplementation in comparison to the control treatment (P = 0.047). Conclusions These preliminary data support a growing literature suggesting the benefits of B6 supplementation for reducing depression in young women using OC. Funding Sources This study was supported in part by the Graduate and Professional Students Association and the Office of the Vice Provost for Research.

SAT-375 A 59 Year Old Female with Isolated Vitamin B6 Deficiency and Muscle Spasms

IntroductionVitamins are essential micronutrients required by biological organisms in small quantities for maintaining basic cellular metabolism. Vitamin B6 is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters, and organelle-specific compounds, as well as in detoxifying reactive oxygen species within the cell. (1) Due to the role of Vitamin B6 in intracellular metabolism and synthesis of neurotransmitters, deficiency of the vitamin results in impaired transcellular signaling between neurons, and classically presents with muscular convulsions, hyperirritability, and peripheral neuropathy. (2)Case PresentationHistoryWe present a case of a 59-year old female with Type 2 diabetes who complained of muscle spasms. She experienced muscle spasms in her feet which have spread proximally to involve her legs. She also admitted to experiencing intermittent spasms in her left arm. The spasms occurred intermittently throughout the day and persist throughout the night, making it difficult for her to fall asleep. She had taken cyclobenzaprine twice daily and tried leg stretches, however her spasms persist. She had also tried baclofen in the past without significant alleviation of her symptoms.EvaluationAn extensive investigation was conducted including tests for water-soluble vitamins. Her plasma pyridoxal 5-phosphate was 3 mcg/L (reference range 5-50 mcg/L), confirming vitamin B6 deficiency. She was also tested for Vitamins B1, B3, B12 and folate. None of the respective tests indicated deficiencies. Other test results were within normal limits.TreatmentThe patient received standard-dose intramuscular vitamin B6 injections for three weeks followed by oral supplements for 3 months. She was also given cyclobenzaprine (10 mg tablet) three times a day for muscle spasms in her legs. Although she had reported cyclobenzaprine did not significantly alleviate her spasms per se, it produces a sedative effect which improves her tolerance to the spasms and helps her to fall asleep at night.ConclusionThis case illustrates the rare instance of isolated vitamin B6 deficiency with normal serum levels of other water-soluble vitamins, manifesting as myoclonic spasm involving the legs and arms in the absence of objective polyneuropathy.References i1 Parra, Marcelina, Seth Stahl, and Hanjo Hellmann. “Vitamin B6 and its role in cell metabolism and physiology.” Cells 7.7 (2018): 84. i2 Brown, Mary J., and Kevin Beier. “Vitamin B6 Deficiency (Pyridoxine).” StatPearls [Internet]. StatPearls Publishing, 2018.

Homocysteine is associated with severity of microvasculopathy in sickle cell disease patients.

The pathophysiology of sickle cell disease (SCD) includes vasculopathy as well as anaemia. Elevated plasma homocysteine is a risk factor for vascular disease and may be associated with increased risk of vascular complications in SCD patients. In the present study, microvascular characteristics were assessed in the bulbar conjunctiva of 18 paediatric and 18 adult SCD patients, using the non-invasive technique of computer-assisted intravital microscopy. A vasculopathy severity index (SI) was computed to quantify the degree of microvasculopathy in each patient. Plasma homocysteine and several of its determinants [serum folate and vitamin B12, plasma pyridoxal-5'-phosphate (vitamin B6 status) and creatinine (kidney function)] were measured. Age was strongly correlated with microvasculopathy in the SCD patients, with the SI increasing about 0·1 unit per one-year increase in age (P<0·001). After adjusting for age, gender, B-vitamin status and creatinine, homocysteine concentration was directly correlated with severity index (P<0·05). Age and homocysteine concentration were independent predictors of microvasculopathy in SCD patients. It remains to be determined whether lowering homocysteine concentrations using appropriate B-vitamin supplements (folate and vitamins B12 and B6) - particularly if started early in life - could ameliorate microvasculopathy and its associated complications in SCD patients.