1. Introduction
Mental stress, increasingly a feature of modern fast-paced lifestyles, is recognized as contributing to the risk of developing cardiovascular disease [
1,
2]. Mental stressors stimulate cardiovascular responses which can be indirectly assessed via heart rate variability (HRV), a measure of fluctuation in the length of interbeat interval (IBI), modulated by the dynamic regulation of autonomic nervous system (ANS). The ANS consists of two branches that control variations in heart rate (HR), the sympathetic nervous system (SNS) which is activated by conditions of stress and increases HR, and the parasympathetic nervous system (PNS), specifically the vagus nerve, which counteracts the SNS and is dominant under conditions of rest, decreasing HR. Mental stress also attenuates baroreflex sensitivity [
3] and increases endothelial dysfunction [
4], which may be followed by slower recovery of HRV leading to the development of CVD risk [
5,
6]. Evidence from neuroimaging studies shows that HRV is associated with parts of the brain that regulate emotional responses [
7], and greater cardiovascular reactivity in response to mental stress and slower recovery from stress are longitudinally linked to impaired cardiovascular risk status, including higher BP, hypertension and greater carotid intima-media thickness (subclinical atherosclerosis) [
8].
HRV can be reported using the analysis of time- and frequency-domain parameters [
9], as well as non-linear parameters, which are able to assess complexity of patterns and randomness in the HRV signal. Low HRV indicates a dominance of sympathetic activity and suppressed parasympathetic control; prolonged low HRV indicates impaired regulation of HR in response to dynamic demands and is associated with increased risk of cardiovascular morbidity and mortality in both the general healthy population [
10,
11] and patients with coronary heart disease (CHD) [
12,
13,
14,
15]. Conversely, high HRV suggests resilience of the cardiac ANS in adapting to stress and is inversely associated with cardiovascular disease (CVD) [
16].
Lifestyle factors, such as diet and levels of physical activity, may influence HRV [
17]. Scientific understanding of the impact and mechanism of dietary modifications on HRV is still very limited [
17], and mainly relates to the effects of omega-3 supplementation [
18,
19]. During times of stress, people are more inclined to seek reward in the shape of snack foods with a less favorable nutrient profile, for example, higher in saturated fats, refined starch, free sugars, and sodium [
20,
21]. Substituting typical snacks with healthier snacks may ameliorate the reduction in HRV following a stress stimulus by both these pathways. Improvements in diet quality may enhance HRV both by improving neurological function and by directly influencing the responsivity of the target organ (e.g., the heart) to parasympathetic efferent input. Diet may also indirectly enhance HRV through improving mental health and reducing psychological stress, thereby reducing excess sympathetic activity [
17].
In this study, almonds are utilized as a model healthy snack, since they have previously been shown to have cardioprotective effects using intermediary risk factors. Almonds, the most consumed tree nut globally [
22], mostly as a snack food, are rich in unsaturated fats, dietary fiber, potassium, magnesium and vitamin E, and low in saturated fatty acids, sugar and sodium [
23]. Almond consumption can improve intermediary cardiovascular risk factors [
24,
25,
26], such as low-density lipoprotein (LDL), apolipoprotein B (apo-B), blood pressure and adiposity [
27]. Using a randomized, controlled, parallel 6-week arm study design [
28], we aimed to investigate the impact of replacing usual snacks with whole almonds on the HRV response to stress in a healthy, free-living adult population sample who were at above average risk of cardiovascular disease. It was hypothesized that snacking on almonds, relative to control snacks, would result in higher HRV during a laboratory mental stress test.
4. Discussion
Mental stress can lower HRV, which is associated with increased risk of developing CVD [
7,
8]. Improvements in diet quality have the potential to increase HRV, but evidence for a direct causal relationship is limited. We report the novel finding that snacking on whole almonds for six weeks, compared with isocaloric snacks with a more typical nutrient profile (high in saturated fats, starch and free sugars and low in dietary fiber), increased HRV parameters of parasympathetic activity during acute mental stress. This could be due to lower levels of background daily stress in the almond group, improvements in neurological autonomic function, or an increase in cardiac tissue responsivity to ANS neurotransmission and/or hormonal modulation. Although the underlying mechanism of effect is unclear, the results of the study suggest that a simple dietary modification resulting in increased intake of micronutrients, dietary fiber and unsaturated fatty acids and reduced intake of free sugars and sodium improved vagal tone during mental stress.
Variability in beat-to-beat intervals, assessed by HF power in the frequency domain, is associated with respiration, known as respiratory sinus arrhythmia (RSA). RSA is mediated by the parasympathetic nervous system modulated by vagal motor neurons linked with the lung inflation reflex [
38,
39,
40]. Only a very limited amount of research has been done previously on the effects of tree nuts on HRV. In agreement with our findings, higher HF power was previously observed by Sauder et al. during two acute stress tests, i.e., mental arithmetic and hand cold pressor, following 4-week pistachio nut consumption at 20% of energy intake, as well as increased rMSSD and LF power [
41]. In our study, there were no treatment effects observed for rMSSD and LF, possibly due to variability across studies in baseline stress levels and methodological differences such as type of mental stressor and measurements being made in the seated position in contrast to our study where measurements were made in the supine position. In the current study, the ratio of LF to HF power was shown to be decreased in almond group, which could suggest that replacing typical snacks with almonds might tip the balance of sympathetic to parasympathetic nervous system activity to a more favorable one. However, the interpretation of LF/HF ratio is controversial; the original belief that LF power is related to sympathetic modulation has been widely discounted as results of experiments inducing pharmacological sympathetic blockade and other manipulations of sympathetic activity [
42]. Thus, the difference between treatments in LF/HF ratio is likely to be largely attributable to increased vagal tone rather than any reduction in sympathetic outflow [
43,
44].
Although weight loss is known to increase parasympathetic activity [
45], there were no differences between groups in the change from baseline in body weight and adiposity, nor energy intake [
28]. The established effects of almond consumption in lowering plasma low-density lipoprotein (LDL) cholesterol concentrations may have some bearing on HRV responses, as the literature reports that plasma TC and LDL are inversely associated with HR and HRV [
46,
47]. Statin treatment was associated with improved HRV in 40 hypercholesterolemic patients with or without CAD [
48] and healthy individuals with 48 h sleep deprivation [
49]. Hypercholesterolemia elevates reactive oxygen species (ROS) and oxidative stress in vessel walls and induces inflammation, causing dysfunctional nitric oxide synthase (eNOS) activity, an enzyme catalyzing nitric oxide (NO) production and greater degradation of NO [
50], resulting in dysregulation of vascular tone [
51]. Baroreceptors sense systemic arterial pressures via stretching, and impaired vascular tone is likely to disrupt baroreceptor sensitivity, resulting in reduced baroreflex control of HR, potentially attenuating HRV [
52]. Therefore, reductions in LDL cholesterol concentrations following almond intervention may have indirectly contributed to enhancement of baroreceptor sensitivity and maintenance of vagal tone. This proposed cardiovascular mechanism is strengthened by our finding reported previously that NO-mediated vasodilation was increased following the almond intervention in the same study [
28].
Lower dietary glycemic load as a result of displacing typical snack nutrient intakes with almonds may be an important factor in the improved HRV observed under mental stress, as previous studies have observed increased LF/HF and reductions in total power from spectral analysis following oral glucose loads [
53,
54,
55,
56]. Insulin secretion is implicated in this effect, since hyperinsulinemia can reduce the functioning of the sinoatrial node and alter ANS activity [
53,
54]. Furthermore, the literature also demonstrated that glucose intake and hyperinsulinemia are dose-dependently associated with the level of circulating NE, a sympathetic-induced neurotransmitter [
57]. Sodium and potassium levels may also play a part. Potassium is inversely associated with aldosterone, a hormone regulating sodium reabsorption which is involved in the renin-angiotensin-aldosterone system (RAAS). Lower sodium leads to reduced water retention in the kidney, smaller blood volume and lower blood pressure [
58]. Blood pressure maintenance could promote baroreflex sensitivity and influence sympathetic activity [
52].
Almonds are a good source of magnesium and in this study, the almond group had higher magnesium intakes relative to the control group. Animal experiments demonstrated that magnesium has anti-arrhythmic effects involving improvement in sinus rhythm [
59], but human data are inconsistent in treatment of arrhythmia [
60,
61,
62] and in associations with HRV [
63,
64,
65]. Almonds are rich in vitamin E, and 4-month supplementation in a double-blind RCT improved HRV by increasing RR interval, TP and HF and reducing LF and LF:HF in T2D patients, possibly due to a reduction in oxidative stress [
66]. Although it is not possible to pinpoint the components of almonds that may be responsible for the greater cardiac resilience to mental stress observed in the current study, it is possible that the relative augmentation in vagal tone during the Stroop test by almond consumption was a combined result of all or many of the mechanisms discussed.
The main strength of our study was the randomized, controlled, single-blinded study design involving control test snacks that represented typical snacks consumed in the adult population. Almond consumption did not affect either body weight, central adiposity (waist circumference) or overall adiposity (body fat percentage), and therefore, fat mass loss was not a confounding factor [
67,
68,
69,
70]. Although we recruited healthy adults at risk of developing CVD, recording of self-reported mental and mood conditions before the mental stress task and HRV measurements were not included and may be a limitation. The Stroop test was conducted following 10 min recovery after blood-pressure cuff inflation applied within a flow-mediated dilation (FMD) measurement that could cause physical stress, which might affect baroreceptor-derived autonomic outflow, and therefore, influence the resting measurements. Furthermore, it would be of interest to determine the response in recovery HRV after the Stroop test. Recruiting patients with obesity or type-2 diabetes, determinants of impaired sympathovagal balance, should be a priority in future research to understand more the effects of whole almonds on HRV in at risk populations.