Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

Serum 25-hydroxyvitamin D, vitamin D supplement and asthma control: The HUNT study.

Few studies have investigated the association between serum 25-hydroxyvitamin D (25[OH]D), vitamin D supplement and asthma control among adults. We aimed to examine whether low levels of serum 25(OH)D or not taking vitamin D supplement were associated with an increased risk of poorly controlled asthma among Norwegian adults with asthma. We used a definition of asthma control adapted from the Global Initiative for Asthma. We first examined cross-sectional associations between serum 25(OH)D (n = 806) or vitamin D supplement (n = 1179) and poorly controlled asthma. Next, among those with well controlled asthma at baseline, we examined prospective associations between serum 25(OH)D (n = 147) or vitamin D supplement (n = 208) and poorly controlled asthma at follow-up, approximately 11 years later. We estimated risk ratios (RR) and 95% confidence intervals (CI) with Poisson regression. The adjusted RR for poorly controlled asthma was 1.00 (95% CI, 0.89-1.13) for adults with serum 25(OH)D < 50 nmol/L in cross-sectional and 1.50 (95% CI, 0.46-4.95) in prospective analyses. The adjusted RR for poorly controlled asthma was 1.17 (95% CI 1.00-1.37) for non-users of vitamin D supplement in cross-sectional and 1.66 (95% CI 0.49-5.67) in prospective analyses. Our study did not show strong evidence that among adults with asthma, having a low serum 25(OH)D or being a non-user of vitamin D supplement was associated with an increased risk of poorly controlled asthma. Some point estimates indicated an increased risk, however our estimates were generally imprecise and further evidence is needed.

Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies.

Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival.Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI).Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500-600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800-1,200 mg/d); HR (95% CI) was 1.07 (1.01-1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04-1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model.Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients.Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060-70. ©2017 AACR.

Factors associated with vitamin D deficiency in a Norwegian population: the HUNT Study.

Vitamin D deficiency occurs worldwide. Winter season and high Body Mass Index (BMI) are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D). We estimated the prevalence of vitamin D deficiency in a Norwegian adult population and examined factors associated with vitamin D deficiency. A cohort of 25, 616 adults (19-55 years) who participated in both the second and third Nord-Trøndelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)) was established in a previous study. A 10% random sample of the cohort population was recruited for serum 25(OH)D measurements (n=2584), which was used for the current cross-sectional study. Vitamin D deficiency was defined as serum 25(OH)D level <50 nmol/L. The overall prevalence of vitamin D deficiency was 40%, but varied by season (winter: 64%; summer: 20%). Winter season (adjusted prevalence ratio (PR): 3.16, 95% CI 2.42 to 4.12) and obesity (BMI ≥30.0 kg/m2) (PR: 1.74, 95% CI 1.45 to 2.10) were strongly associated with prevalent vitamin D deficiency. Current smoking also demonstrated an increased PR (1.41, 95% CI 1.21 to 1.65). Daily intake of cod liver oil (PR: 0.60, 95% CI 0.41 to 0.77), increased physical activity (PR: 0.80, 95% CI 0.68 to 0.95) and more frequent alcohol consumption (PR: 0.76, 95% CI 0.60 to 0.95) were associated with a reduced PR. The prevalence of vitamin D deficiency was high in Norwegian adults. Winter season, high BMI and current smoking were positively associated, and intake of cod liver oil, increased physical activity and more frequent alcohol consumption were inversely associated with vitamin D deficiency.

Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway.

OBJECTIVE: To prospectively study the relation between TSH and risk of hip and forearm fractures. DESIGN: A population-based cohort study. METHODS: In a substudy of the second survey of the Nord Trøndelag Health Study, Norway (HUNT2, 1995-97), linked with a hospital-based fracture registry, we investigated the relation between baseline TSH and risk of hip and/or forearm fractures. POPULATION: A total of 16 610 women and 8595 men aged 40 years or more, without previous self-reported thyroid disease and hip or forearm fractures. RESULTS: During 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or forearm fractures. Overall, there was no relation between baseline TSH and fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5 mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95% CI 0.97-1.94 and HR 1.19, 95% CI 0.93-1.52) compared with the reference group with TSH of 1.5-2.4 mU/l. Supplementary analyses showed higher hip fracture risk in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb) compared with the reference group (HR 1.75, 95% CI 1.24-2.46). CONCLUSION: We found no statistically significant relation between baseline TSH and subsequent fracture risk, but the data suggest a weak positive association with hip fracture risk among women with both low and high TSH. The latter association was confined to women with negative TPOAb status.

Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study.

BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.

Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri- and postmenopausal women: the Nord-Trondelag Health Study.

Use of cod liver oil, which is rich in vitamins A and D, is traditionally recommended during the fall and winter months as a protective measure against vitamin D deficiency in several countries. It is not known whether childhood cod liver oil intake is related to variations in bone mineral density (BMD) or fractures in adult life. In 2001, a total of 3,052 Norway women aged 50-70 years had forearm BMD measured in a substudy of the population-based Nord-Trøndelag Health Study. Women reporting no childhood cod liver oil intake had statistically significantly higher BMD than those with any ingestion of cod liver oil. The odds ratio for low BMD (>1 standard deviation below age-specific mean) in women reporting cod liver oil intake throughout the year as compared with women with no intake was 2.3 (95% confidence interval: 1.4, 3.9), adjusted for body mass index, smoking, menopausal status, estrogen use, and current milk consumption. There were indications of a negative dose-response effect of childhood cod liver oil intake on bone. Although the vitamin A content of commercial cod liver oil was recently reduced by 75% in Norway, the past high concentration remains a possible explanation for the observed negative association between childhood cod liver oil intake and forearm BMD.

Correlates of forearm bone mineral density in young Norwegian women: the Nord-Trøndelag Health Study.

Maximizing attainment of optimal peak bone mineral density (BMD) is a potential osteoporosis prevention strategy. The main objective of this study was to identify correlates of forearm BMD in young adult women. Population-based data derived from standardized questionnaires administered to healthy women aged 19-35 years in Nord-Trøndelag, Norway (n = 963), were collected in 1995-1997. Forearm BMD was assessed by single x-ray absorptiometry. Multiple linear and logistic regression analyses were used to determine correlates of BMD (g/cm(2)) and lowest quintile of BMD, respectively, at the ultradistal and distal sites. The mean age and weight of the cohort were 29.7 years (standard deviation 4.7) and 68.6 kg (standard deviation 12.5), respectively. Age and weight were positively associated with BMD at both forearm sites. When data were controlled for age and weight, later age at menarche and lack of milk consumption were associated with lower BMD values. In both linear models and logistic models, none of the factors vitamin D intake, physical activity, smoking, alcohol consumption, amenorrhea, oral contraceptive use, number of pregnancies, history of breastfeeding, and family history of osteoporosis were found to be significantly associated with BMD. Prior studies have suggested that calcium supplementation in children is useful for optimizing peak BMD. Further studies exploring the relation between lifestyle factors and BMD are warranted to search for ways to maximize attainment of peak BMD.