Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study.

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = -0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.

A safe strategy for addition of vitamins and minerals to foods.

Addition of vitamins and minerals to foods must be done without health risk to any consumer group. International expert groups have aimed at establishing tolerable upper intake levels (ULs) for vitamins and minerals although lack of solid data on their safety is a major obstacle to this work. In this paper, we summarize the existing ULs and suggest the use of guidance levels (GLs) set by others and temporary guidance levels (TGLs) proposed here, whenever no consensus UL has been established for adults. We suggest the use of body surface area ratios to establish similar levels for younger age groups. The levels are applied in a model for calculation of safe fortification levels for all ages. We have estimated the upper 95(th) percentile intake of vitamins and minerals from food in various Danish age and gender groups and suggest that a daily multivitamin-mineral pill is included in the calculation of total dietary intake levels of all vitamins and minerals. By subtracting this dietary intake level from the UL, GL or TGL, we calculate the amount that can be safely used for fortification. Since safety must be assured for all age groups, the smallest difference relative to energy intake calculated for any age group is proposed as the maximal allowance (MA) for fortification with each nutrient. We suggest that the MA should be expressed in weight units per energy unit in order to distribute it equally between potentially fortifiable food groups according to their usual contribution to total energy intakes.