Assessment of vitamin B6 status in never-pregnant, pregnant and postpartum women and their infants

Purpose: Pyridoxal 5´-phosphate (PLP) is the main form of vitamin B6 in humans and functions a coenzyme for more than 160 different enzymatic reactions. The purpose of the study was to find plasma PLP concentrations, which ensure an optimal vitamin B6 status determined by a metabolic marker, in never-pregnant, pregnant and lactating women and their infants. Methods: In an observational, prospective study, plasma PLP and the metabolic marker, HKr (hydroxykynurenine/(kynurenic acid + anthranilic acid + xanthurenic acid + hydroxyanthranilic acid) were assessed in women (n = 114) from pregnancy week 18 to 6 months postpartum and related to infant status. Never-pregnant women 18-40 years (n = 127) were included as controls. Results: Compared to controls, plasma PLP decreased during pregnancy and increased postpartum, while HKr increased from week 18 to 6 weeks postpartum, indicating maternal vitamin B6 insufficiency during this period. In never-pregnant women, HKr increased gradually with plasma PLP < 100 nmol/L, and in pregnancy week 28 a sharp increase in HKr was seen at plasma PLP < 30 nmol/L. Despite correcting for maternal vitamin B6 status, infant median plasma PLP decreased with months of exclusive breastfeeding. Conclusions: Plasma PLP and kynurenine concentrations differ substantially between never-pregnant, pregnant and postpartum women and infants. A plasma PLP concentration in the range of 50-100 nmol/L seems to ensure an optimal vitamin B6 status for never-pregnant women, whereas a plasma PLP > 30 nmol/L in pregnancy week 28 ensures an adequate vitamin B6 status during pregnancy and lactation. Infant vitamin B6 status at age 6 months is inversely correlated to number of months of exclusive breastfeeding.publishedVersio

Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial

Background: Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months. Methods: Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month. Results: Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03). Conclusions: The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency.publishedVersio

Cadmium, lead and mercury in Norwegian obese patients before and 12 months after bariatric surgery

Purpose Previous studies have suggested a role for the toxic elements lead (Pb), mercury (Hg) and cadmium (Cd) in the development of insulin resistance and hypertension. Increased blood Pb levels have been reported after bariatric surgery and weight loss. As about 80% of patients undergoing bariatric surgery are women, most of them of childbearing age, there are concerns regarding fetal exposure to toxic trace elements. We measured whole blood Hg, Pb and Cd concentrations in morbidly obese patients before and 12 months after Roux-en-Y gastric bypass (RYGB). Patients and methods Forty-six patients eligible for bariatric surgery were recruited at Innlandet Hospital Trust, Norway (2012–2014). The majority were women and 54% were of reproductive age. Whole blood samples were collected prior to and 12 months after surgery. Trace element concentrations were measured using mass spectrometry (HR-ICP-MS). Results Median whole blood Pb concentrations increased by 73% during the 12 months study period while Hg and Cd decreased by 31% and 27%, respectively. We found a negative correlation between Pb levels before surgery and BMI (p = 0.02). Before surgery patients with hypertension had significantly higher median whole blood Hg levels compared to patients with normal blood pressure (p < 0.001). Conclusion One year after bariatric surgery, the median whole blood Pb concentration was increased, while Hg and Cd concentrations were decreased. The majority of bariatric surgery patients are women of reproductive age and weight loss is associated with improved fertility. As even low dose Pb exposure during fetal life is associated with negative effects on the central nervous system, the observed increase in whole blood Pb after weight loss causes concern. Further studies are needed to elucidate these observations.submittedVersionpublishedVersio

Essential trace elements in Norwegian obese patients before and 12 months after Roux-en-Y gastric bypass surgery: Copper, manganese, selenium and zinc

Objectives: The objective of the present study was to assess trace element status in morbidly obese subjects before and one year after Roux-en-Y gastric bypass (RYGB) in order to identify possible deficiencies. Methods: The study population included 46 patients in the age range 27-59 years, the majority (85 %) were women. The enrolled patients attended an eight week course on lifestyle changes before bariatric surgery. After RYGB they were recommended daily micronutrient supplements with a commonly used multivitamin-mineral tablet in addition to intramuscular vitamin B12 injections (1 mg) every third month for 12 months. Whole blood concentrations of Cu, Mn, Se and Zn were determined using high resolution inductively coupled plasma mass spectrometry. Results: During the 12 months follow up after bariatric surgery, the patients had lost mean 32.3 kg and median whole blood concentrations of Cu (-16 %) were reduced, Mn (+14 %) and Zn (+6%) were increased, while the Se values were essentially unchanged. Compared with reference ranges, median postoperative concentrations of all essential trace elements were either below (Zn) or in the lower reference range (Cu, Mn, Se). Conclusion: Essential trace elements were below or in the lower reference range twelve months after RYGB. Our results indicate a need for updated guidelines in Nordic countries for trace metal monitoring and supplements in patients after bariatric surgery, especially when gastric bypass surgery is used. Further studies are required to explore and prevent trace element deficiency related to obesity and bariatric surgery.This research was funded by Innlandet Hospital Trust, Norway. We thank senior engineer Syverin Lierhagen at Department of Chemistry, Norwegian University of Science and Technology, for performing the HR-ICP-MS analyses.publishedVersio

A novel case of impaired C-reactive protein response following open-heart surgery: A case report and review of the literature

Background C-reactive protein (CRP) is expected to increase in response to a range of inflammatory stimuli such as infections or extensive tissue trauma. Case report We present a novel case of severely impaired CRP response following NSTEMI, influenza A infection and open-heart surgery in which serum CRP concentrations remained < 1 mg/L during an observational period of 28 days. Conclusion To our knowledge, no previous publications exists describing patients with a lack of CRP response following cardiothoracic surgery. We believe this to be a novel finding warranting further investigations regarding the etiology and prevalence of this phenomenon.publishedVersio

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Background: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. Objectives: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. Methods: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. Results: We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5–8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). Conclusions: In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.publishedVersio

The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants

Background Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. Aims To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. Methods In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Results Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. Conclusion We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.publishedVersio

Dietary behaviors and attitudes among Norwegian medical students

Abstract Background Dietary patterns and beliefs are influenced by socioeconomic status, cultural influences, as well as medical advice, social media and marketing. Medical doctors are expected to provide correct, updated and non-biased nutritional advice to their patients, but their own dietary behaviors and attitudes may influence nutritional counselling. Methods We have investigated dietary habits and food attitudes among medical students by using an anonymous survey distributed to all students at the Medical Faculty, University of Bergen, Norway. The survey included a 36-item questionnaire covering information about demographics, former and current diet, use of nutritional supplements, tobacco and alcohol, in addition to food attitudes and nutritional knowledge. Descriptive statistics were calculated for each survey item. Results Of the 880 students, 394 responded to the survey. Although 90% of the students were omnivores, the majority had a negative attitude towards meat, and considered fish to be healthier than meat. Significantly more women than men reported use of a special diet and excluded meat from their diet, even if they were omnivores. The most frequently used supplement was cod liver oil or omega 3 fatty acids. Conclusion The medical students’ diet and food attitudes not only reflect current health recommendations, but also popular beliefs and marketing in Norway. Curriculum planners should make the students capable of recognizing the influence of social media, marketing and medicine-food industry interactions, to ensure relevant nutrition knowledge for future doctors

Vitamin B12 – a scoping review for Nordic Nutrition Recommendations 2023

Vitamin B12 (cobalamin) is essential for normal metabolic function, and even moderate deficiency of this vitamin has negative health effects. Vitamin B12 is found in animal foods, and as vegetarian diets are increasingly popular in Western countries, one might expect a higher prevalence of vitamin B12 deficiency in the Nordic population. Setting recommendations for vitamin B12 intake has proven to be difficult, as uptake of vitamin B12 varies substantially, the clinical deficiency symptoms are often diffuse, and there is no clear agreement on the decision limits for vitamin B12 deficiency. Vitamin B12 deficiency is reported to be particularly common among pregnant women and infants, despite the fact that less than 1% of Norwegian pregnant women have a cobalamin intake below the Nordic Nutrition Recommendations 2012-recommended level of 2.0 µg/day. In addition, the assumption that breast milk contains sufficient vitamin B12 for optimal health and neurodevelopment during the first 6 months of life does not comply with the high prevalence of insufficient vitamin B12 status in this age group. Recommended intakes of vitamin B12 vary among age groups and must be based on markers of cobalamin status, indicating an optimal intracellular biochemical status, and not merely absence of clinical signs of vitamin B12 deficiency