Effects of dietary nitrate supplementation on the response to extremity cooling and endothelial function in individuals with cold sensitivity. A double blind, placebo controlled, crossover, randomised control trial

Abstract

Individuals with cold sensitivity have low peripheral skin blood flow and skin temperature possibly due to reduced nitric oxide (NO•) bioavailability. Beetroot has a high concentration of inorganic nitrate and may increase NO-mediated vasodilation. Using a placebo-controlled, double blind, randomised, crossover design, this study tested the hypotheses that acute beetroot supplementation would increase the rate of cutaneous rewarming following a local cold challenge and augment endothelium-dependent vasodilation in cold sensitive individuals. Thirteen cold sensitive participants completed foot and hand cooling (separately, in 15 °C water for 2 min) with spontaneous rewarming in 30 °C air whilst skin temperature and cutaneous vascular conductance (CVC) were measured (Baseline). On two further separate visits, participants consumed 140 ml of either concentrated beetroot juice (nitrate supplementation) or nitrate-depleted beetroot juice (Placebo) 90 min before resting seated blood pressure was measured. Endothelial function was assessed by measuring CVC at the forearm, finger and foot during iontophoresis of 1% w/v acetylcholine followed by foot and hand cooling as for Baseline. Plasma nitrite concentrations significantly increased in nitrate supplementation compared to Placebo and Baseline (502 ± 246 nmol L; 73 ± 45 nmol L; 74 ± 49 nmol L respectively; n = 11; P < 0.001). Resting blood pressure and the response to foot and hand cooling did not differ between conditions (all P > 0.05). Nitrate supplementation did not alter endothelial function in the forearm, finger or foot (all P > 0.05) compared to Placebo. Despite a physiologically meaningful rise in plasma nitrite concentrations, acute nitrate supplementation does not alter extremity rewarming, endothelial function or blood pressure in individuals with cold sensitivity.

Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet

“…The DN4 questionnaire (Bouhassira et al., 2005) was used to identify whether participants had neuropathic pain. Cold exposure was assessed with a cold exposure questionnaire used previously (Appendix 1; Eglin et al., 2017), which asked the participants to recall their previous cold exposure through school, work and leisure activities throughout their life (before 12, 12–18 and after 18 years of age). For each of these phases, the participants were asked where they lived (geographically) and whether they had participated in any sports or activities that took place in cold/wet conditions, giving details including the type of activity, when this occurred (e.g.…”

“…After a 20 min acclimation period to the ambient conditions [23.6 (0.5)°C], ACh was delivered transdermally using iontophoresis to three sites in the following order: the volar aspect of the left forearm, the middle phalanx of the middle finger of the left hand and the dorsal aspect of the left foot, as described previously (Eglin et al., 2017). Acetylcholine (Sigma Chemicals, Aldrich) was diluted with sterile water for injection to achieve a concentration of 1% w/v.…”

“…The camera was positioned 1.0 m away and pointed at the sole of the foot or palm of the hand, and the temperature of the toe/finger pads was recorded using a spot analysis function on the Flir software before immersion and during the rewarming period. A mean toe/finger skin temperature of <32°C before immersion and after 5 min of rewarming was classified as being cold sensitive (Eglin et al., 2017; Hope et al., 2014). Within our laboratory, the coefficient of variation for the CST for finger and toe skin temperature is 2.7 and 8.7%, respectively (Eglin et al., 2017).…”

“…The CST used in the present study has been described in detail elsewhere (Eglin et al, 2013;Maley et al, 2017;Shepherd et al, 2019). laboratory, the coefficient of variation for the CST for finger and toe skin temperature is 2.7 and 8.7%, respectively (Eglin et al, 2017).…”

“…The ‘dose’ (magnitude and duration) of cold exposure required to induce NFCI is not known but is likely to vary between individuals (Burgess & Macfarlane, 2009) and also to be dependent on activity (Kuht et al., 2019). In addition, subclinical forms of NFCI may also exist in individuals frequently exposed to cold conditions for short durations during recreational activities such as windsurfing, surfing and open water swimming (Eglin, 2011; Eglin et al., 2017).…”