Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women

Psychosocial stress is implicated in the development of non-communicable diseases. Chronic stress can increase systemic vascular resistance (SVR) and blood pressure, potentially leading to vascular damage and altered myocardial perfusion. Furthermore, stress can promote overconsumption of sugary foods, potentially contributing to obesity and related metabolic issues. Sweet foods are often consumed to alleviate stress responses. However, the effects of nutritive and non-nutritive sweeteners (NNS) on hemodynamic stress responses remain largely unknown. Previous research in rodents and humans suggests that sucrose consumption might reduce sympatho-adrenal activation and hemodynamic responses to acute stress. Studies in rats also indicate that sucrose and NNS consumption may downregulate corticotropin-releasing factor (CRF) expression in the brain, possibly through non-metabolic properties like opioid release. However, other findings suggest that the metabolic effects of sucrose also play a role. A human study showed decreased salivary cortisol response to mental stress after a high-sucrose diet but an increased response after an NNS diet. This study aimed to compare the effects of sucrose-containing and NNS-containing drinks, compared to water, on hemodynamic responses to acute stress in healthy women, using both mental stress and cold pressure tests (CPT) to elicit different hemodynamic responses.

The existing literature suggests a complex relationship between stress, sweet food consumption, and cardiovascular health. Studies have shown that chronic stress can increase the risk of various metabolic disorders. This relationship might involve increased consumption of energy-dense foods as a coping mechanism. Additionally, stress-induced glucocorticoid secretion can promote visceral fat deposition, leading to abdominal obesity, insulin resistance, and increased cardiometabolic risk. Acute stress responses, including hemodynamic changes, can contribute to myocardial ischemia. Prior research showed that sucrose consumption can reduce sympatho-adrenal activation and hemodynamic responses to acute stress in both rodents and humans. The non-metabolic properties of sweeteners, possibly through opioid release, were suggested to play a role in downregulating CRF. However, studies also indicated a role for sucrose's metabolic effects. Discrepancies exist across studies, particularly regarding the effects in children versus adults.

This randomized, crossover trial involved 12 Caucasian women aged 18-40 years with a BMI of 18.5-25 kg/m². Participants were excluded based on several criteria including high blood pressure, psychological or cardiovascular disorders, anemia, high caffeine/alcohol/sweetened beverage consumption, color blindness, significant weight fluctuations, excessive physical activity, medical treatment, smoking, or illicit drug use. Each participant underwent three functional evaluations, each separated by 1-3-week washout periods. They consumed either water, a sucrose-sweetened drink, or an NNS-sweetened drink. Before each evaluation, they followed a weight-maintenance diet for two days, avoiding sugar-rich foods, caffeine, and alcohol. On evaluation days, they arrived after an overnight fast. Hemodynamic sensors were placed to enable thoracic electrical bioimpedance measurements for continuous cardiac output monitoring. Mean arterial pressure was recorded using an automatic sphygmomanometer. Each evaluation included a 90-minute resting period, followed by a 30-minute mental stress test (Stroop test and mental arithmetic), a 30-minute recovery period, and a 3-minute cold pressure test (CPT). Participants ingested 25-ml test drinks every 15 minutes starting at 60 minutes, rinsing their mouths with each drink before swallowing. SVR was calculated using the formula: SVR = (mean arterial pressure – central venous pressure) / cardiac output. The primary outcome was changes in SVR across drink conditions. Mixed-model analyses were used to investigate the effects of acute stress, condition, and their interactions. A sample size of 12 was calculated to detect a 6 ± 4% difference in postprandial SVR after sucrose compared to water. Data are presented as mean ± SD.

Participants showed no significant differences in body weight or hemodynamic parameters before drink ingestion across the three conditions. Mental stress significantly increased mean arterial pressure, cardiac output, and heart rate but did not significantly change SVR. CPT significantly increased SVR, mean arterial pressure, and heart rate but did not change cardiac output. No significant differences in hemodynamic responses were observed between water, sucrose, and NNS conditions during either the mental stress or CPT tests, indicating no significant interaction between the type of drink and the hemodynamic response to stress. These findings are consistent with previously reported hemodynamic responses to mental stress and CPT in the literature, which shows increases in heart rate and mean arterial pressure. The absence of significant differences between the drink conditions suggests that neither sucrose nor NNS alters stress-induced increases in heart rate, enhances cardiac muscle contraction strength, or induces significant changes in peripheral vasodilation or vasoconstriction.

This study found no significant effect of sucrose or NNS on hemodynamic responses to acute stress, suggesting that the consumption of these sweeteners does not modulate the sympathetic nervous system activation during stress. This contrasts with some studies showing that sucrose reduces heart rate in newborns before painful procedures, possibly due to taste-related mechanisms. The discrepancies might stem from differences in age or sensitivity to sweet taste receptors. The study's ecological validity was prioritized by having participants swallow drinks after a mouth rinse; however, potential metabolic effects of glucose may have not been fully accounted for, and a Valsalva maneuver during CPT could have also impacted the results. The study's findings, however, do not invalidate other mechanisms through which stress might promote consumption of sweet foods, nor does it challenge the idea that repeated acute stress can contribute to the development of non-communicable diseases via other pathways. The findings are limited to young, healthy women and cannot be extrapolated to other demographics.

This study showed that consuming drinks sweetened with sucrose or NNS does not alter hemodynamic responses to standardized acute stress protocols. Future research should investigate the effects of chronic stress exposure and sweetener consumption, as well as the potential role of other factors such as taste receptors and hormonal responses in stress-induced eating behaviors.

This study focused on acute stress and did not directly assess sympathetic nervous system (SNS) activity or hypothalamic-pituitary-adrenal (HPA) axis activity. The use of mouth rinsing before drink ingestion may have introduced potential confounding factors due to taste receptor stimulation. The study design did not directly assess the role of glucose metabolism or possible Valsalva maneuvers during the CPT. The sample consisted only of young, healthy women, limiting the generalizability of the findings to other populations.