BRCA1 mutation carriers face a high lifetime risk of developing breast cancer. Physical activity induces broad transcriptional changes and multiple studies have documented its beneficial effects across cancers. Since haploinsufficiency predisposes to breast cancer in these women, factors that increase BRCA1 levels may mitigate the effect of the mutation. Whether physical activity modulates BRCA1 expression, and whether lifestyle factors could benefit women with a mutation remains unclear. The objective of this study was to systematically evaluate whether physical activity or sedentary behavior affect BRCA1 mRNA expression. Activity levels were assessed in 50 female participants (14 BRCA1 mutation carriers and 36 non-carriers) using the GT3X Actigraph accelerometer, and BRCA1 mRNA expression was quantified from peripheral blood lymphocytes using the Nanostring nCounter Analysis System. There was a significant negative correlation between the longest sedentary bout and BRCA1 mRNA expression (ρ = ─ 0.32; P = 0.02). Women below the median for the longest sedentary bout had significantly higher BRCA1 mRNA levels compared to women above the median (161 vs. 132 counts; P = 0.04; one-sided Mann-Whitney U test). There was no significant relationship between mean Metabolic Equivalents of Task (MET) rate or mean sedentary time and BRCA1 mRNA expression (Spearman correlation P ≥ 0.75; P ≥ 0.14; Mann-Whitney U test). These findings suggest that prolonged periods of sedentary behavior are associated with significantly lower BRCA1 mRNA expression. Whether this translates into a potentially more harmful effect in BRCA1 mutation carriers warrants further investigation.

BACKGROUND:Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies.

OBJECTIVE:We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin) and risk on HNC and HNC subtypes in a large prospective study.

DESIGN:The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) vs. lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model.

RESULTS:A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend<0.001), OCC (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend<0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 vs. quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend<0.01). No statistically significant results were shown for vitamin E,α-carotene, β-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers.

CONCLUSIONS:With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.

This study was designed to determine the effects of vitamin C deficiency on the immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for survival. Five-wk-old male and female gulo-/- mice were provided water or water containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza A/Bangkok/1/79. There were no differences in lung influenza virus titers between vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C-deficient mice was greater at 1 and 3 d after infection but less at d 7 compared with vitamin C-adequate mice. Male vitamin C-deficient mice had higher expression of mRNA for regulated upon activation normal T expressed and secreted (RANTES), IL-1beta, and TNF-alpha in the lungs at d 1 after infection compared with male controls. However, at d 3 after infection, male vitamin C-deficient mice had less expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12 compared with male controls. None of these differences were observed in female mice. Vitamin C-deficient male mice also had greater nuclear factor-kappaB activation as early as 1 d after infection compared with male controls. These data suggest that vitamin C is required for an adequate immune response in limiting lung pathology after influenza virus infection.

The human aging process is often accompanied by significant increases in degenerative spine disease. The pathophysiology of intervertebral disc degeneration has been extensively studied, but the etiology of this aging-related problem remains poorly understood. The elderly often have lower daily vitamin C intakes and circulating ascorbic acid values than younger people because of problems with poor dentition or mobility, and also are more likely to have underlying sub-clinical diseases that can reduce plasma ascorbate concentrations. Ascorbate is essential for collagen production, and vitamin C deficiency will result in defective connective tissue, including reductions in collagen synthesis and structural stability. It is hypothesised that vitamin C deficiencies may be a key contributing factor in the development of degenerative disk disease (DDD) in the elderly. Once degenerative disc disease has begun, the tissue inflammation that accompanies DDD may further increase vitamin C requirements in the affected patient, thereby creating a cascade of positive feedbacks that potentially accelerates and contributes to further disc degeneration and low-back pain. Aggressive monitoring of patient ascorbate status, as well as more finely-calibrated RDAs for vitamin C that explicitly take into account the patient's age, may be required if aging-related degenerative disk disease is to be minimised.

BACKGROUND:There is no epidemiological study on the association between dietary nitrate (NO3) and nitrite (NO2) and intakes and the risk of type 2 diabetes (T2D).

OBJECTIVE:The aim of this study was therefore to examine the potential effect of dietary NO3 and NO2 on the occurrence of T2D.

DESIGN:This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 2139 T2D-free adults, aged 20-70 years, followed for a median of 5.8 y. Dietary intakes of NO3 and NO2 were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Multivariate Hazard Ratios (HR) and 95% confidence intervals (CI), adjusted for diabetes risk score (DRS), and dietary intakes of fat, fiber and vitamin C,were calculated for residual energy-adjusted NO3 and NO2 intakes. Since significant interaction (P = 0.024) was found between NO2 and vitamin C intakes in the multivariable model, stratified analyses were done for < and ≥ median vitamin C intakes.

RESULTS:Median (inter quartile range; IQR) daily intake of NO3 and NO2 were 410 mg/d (343-499) and 8.77 mg/d (7.53-10.2). An increased risk of T2D was observed among participants who had higher intake of total and animal-based NO2 in participants who had low vitamin C intake (HR = 2.43, 95% CI = 1.45-4.05, HR = 1.88, 95% CI = 1.12-3.15, respectively). We found no significant association between NO3 in overall, and plant- and animal sources as well, with the risk of T2D. Plant-derived NO2 was also unrelated to incidence of T2D.

CONCLUSION:Our findings indicated that higher intakes of total and animal-based NO2 may be an independent dietary risk factor for development of T2D in subjects with lower vitamin C intakes.

Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo-/- mice treated with ascorbate were different from untreated Gulo-/- and normal wild type mice. The cytokine profiles of Gulo-/-mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo-/- mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo-/- mice.

There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.