Natural sweetener stevia contains steviol glycosides, which are known to be much sweeter than sucrose. Although some data suggests it could have negative impacts, it is regarded to have a number of advantageous qualities. This study looked at the effects of stevia consumption on blood pressure, stress hormone levels, and anthropometrical markers in healthy volunteers in order to determine whether it might have either positive or negative impacts. an experiment using 16 individuals who were randomly randomised to take in either Stevia or sugar for one week. Each subject was given a 3-day introductory period before baseline and in-between interventions, and the measures were taken three times.
Stevia consumption’s impact on healthy people’s blood pressure, stress hormone levels, and anthropometric measurements.
Introduction
Stevia is a natural herb and sweetener from South America that is related to the Asteraceae family. It is much sweeter than sucrose (cane sugar) and has historically been used in traditional medicine. Currently, it is utilised by overweight, obese, and diabetic people in various nations as a sugar alternative.
Isosteviol, stevioside, rebaudiosides A to F, steviolbioside, and dulcoside are among the active stevioside glycoside metabolites that have been discovered in stevia leaves, but stevioside and rebaudioside A are the focal metabolites that are the sweetest, most heat- and pH-stable, and non-fermentable compounds. According to various research, stevia consumption has a range of health advantages. Stevia leaves are also regarded to have helpful medicinal characteristics. The leaves of S. Rebaudiana have been discovered to have therapeutic qualities, including diuretic, antiviral, antifungal, antibacterial, hypertensive, anti-hyperglycaemic, anti-inflammatory, and antitumor activities.
Additionally, toxicological studies have demonstrated that the secondary metabolites in stevia did not have teratogenic, mutagenic, or carcinogenic effects. Stevia has not been associated with any adverse responses when used as a sweetener. Overconsumption of foods and beverages with high levels of refined sugars and calories has been linked to an increase in the incidence of obesity in recent years, which has become a global problem (Bryant et al., 2014). Since it was discovered that stevia has no calories or carbohydrates (Ahmed et al., 2011), it attracted some public notice and has grown in popularity as a sweetener. Therefore, some experts have proposed that using stevia, a natural herb, in place of sugar in the diet may be an effective way to reduce weight gain.
Additionally, it has been hypothesised that stevia may have an anti-hyperglycaemic effect, and a recent study found that rats’ blood glucose levels significantly decreased after consuming stevioside. Additionally, it has been demonstrated that stevioside and steviol have a direct impact on the beta cells of the pancreas, stimulating insulin secretion and enhancing glucose tolerance, which may help to avoid type 2 diabetes mellitus. Ferri et al. (2006) and previous researchers reported that stevia had no appreciable impact on glucose homoestasis. When the systolic and diastolic blood pressure in the arteries rise for an extended period of time at or above 140 mmHg and 90 mmHg, it is referred to as hypertension. Numerous studies have demonstrated that stevia can lower systolic and diastolic blood pressure (BP). According to a recent systematic review and meta-analysis of randomised clinical trials, the reduction in systolic blood pressure was, however, very small and not significant, but there was a significant reduction in diastolic blood pressure and fasting blood sugar.
A different systematic review, however, concluded that the evidence was conflicting and inconclusive regarding whether stevia increased or decreased blood pressure depending on the length of the study and the subjects who participated (Ulbricht et al., 2010). The review also discovered that stevia raised blood pressure in tests conducted for a duration of 1 to 3 months. Therefore, it is clear that this topic is still debatable and needs more research. An intriguing study presented a case study of a middle-aged woman who experienced prehypertension, hypocalcemia, and oedema due to the inhibition of the enzyme HSD2 (11-hydroxysteroid dehydrogenase 2) brought on by consuming stevia over an extended period of time. It was discovered that using stevia as a sweetener on a regular basis could raise blood pressure by lowering the amount of cortisol that was converted into cortisone by inhibiting 11-HSD2 and consequently raising the activity of cortisol in the kidney nephrons to reabsorb sodium and water (Esmail and Kabadi, 2012).
Another objective of this study was to determine how stevia leaf extract Earthomaya.com affected the levels of cortisol and cortisone following stevia consumption. The stress hormone cortisol is a glucocorticoid hormone that the body naturally produces. It has two forms: cortisol, which is active, and cortisone, which is inert. The hormone that is generated in reaction to stress and low blood sugar levels suppresses some immune system inflammatory signs while performing a number of metabolic tasks, including controlling inflammation. The enzyme 11-HSD1 transforms cortisone (the inactive form) into cortisol (the active form) (Fig. 1). While 11-HSD2 prevents cortisol from overstimulating the mineral corticoid receptor, which raises the levels of active steroids in sensitive tissues (Quinkler and Stewart, 2013). Studies have also suggested that stevia raises cortisol levels in the body by inhibiting 11-HSD2 in human subjects (Esmail and Kabadi, 2012), although other studies have claimed that stevia consumption by participants for more than a month had little to no impact on cortisol and cortisone levels (Corcuff and Brossaud, 2014). As a result, there seems to be conflicting information regarding how stevia affects glucocorticoid levels.
Resources and Procedures
Study Participants
With the help of the QMU moderator email and the general public outside the University, a total of 16 volunteers who were qualified for the project and qualified to participate were found among the employees and students at Queen Margaret University. Through a health status questionnaire that comprised male or female respondents with a wide range of BMI, the necessary requirements that had to be met by volunteers for this experiment were assessed. The age range of the volunteers was from 19 to 60. Men and women who appeared to be in good health, were not smokers, did not have diabetes, and were not on blood pressure-lowering drugs all met the inclusion criteria.
The exclusion criteria were anyone having a history of CVD, including hypertension and diabetes mellitus, who were younger than 18 or older than 65. Additionally, participants who smoke were not allowed to participate in the study because smoking may affect changes in blood pressure. An information sheet and consent forms, which were filled out by each volunteer, were sent to the 16 volunteers who agreed to take part in the study. Every volunteer’s samples and data were gathered anonymously by replacing their names with identifying numbers. The research ethics committee of Queen Margaret University approved the study’s methodology and its ethical standards.
Study Plan
Each volunteer in this initiative received a code number for identification and participated in a randomised cross over placebo controlled study. Three measurements were made of each volunteer: once at the beginning and once after receiving either stevia or a placebo. The study’s volunteer participants were split into two groups at random, and in order to prevent a carryover effect, each group began with a 3-day washout period before beginning each intervention. The first group received stevia to take for seven days, and the second group received the placebo (sucrose, or table sugar) to take for seven days. Both groups received strict instructions not to consume any extra or excessive amounts of sugar during this time.
Sample Gathering
Each volunteer was required to submit a baseline measurement of a 24-hour urine collection and three samples of saliva (morning, afternoon, and evening). The information was required to compare stevia to a placebo and do repeated measure statistics. Each participant received either 5g of sugar or 0.2g of stevia to ingest three times per day for a week after the initial 3-day introduction period. Each participant was required to collect a 24-hour urine sample as well as three morning, afternoon, and evening saliva samples on the seventh day of the intervention. When participants switched to the opposing intervention, the procedure was repeated for another week, and samples were once more taken on the seventh day.
Dietary Intervention
The stevia utilised in this study was acquired from Boots Ltd. in the UK and is 100 percent pure natural stevia. Tate Lyle table sugar was utilised as the placebo in this investigation. Three times a day, volunteers were instructed to eat either the stevia or the sugar, preferably in a hot beverage of their choosing. Throughout the course of the trial, volunteers were instructed to abstain from consuming any additional sweets or sugar. The amount of stevia given to our participants was designed to mimic the regular usage of stevia as a sugar substitute in their daily lives while avoiding any unfavourable side effects.
Measurements
Blood pressure, weight, height, and BMI were physiological variables that were examined in this study along with the biomarkers in urine and saliva. Participants were seated comfortably and given time to unwind for 5 to 10 minutes before having their blood pressure taken. This was done to prevent “white coat” hypertension (Franklin et al., 2013). The mean of three blood pressure readings taken at 5-minute intervals was calculated and used. Each volunteer’s BMI was calculated based on their height and weight both before and after each intervention. To avoid errors, each volunteer’s weight was recorded using the same digital scale while their height was determined using a leister-height scale. Each volunteer’s BMI was determined using the formula below: Weight (kg)/Height2 equals BMI (kg/m2) (m). To prevent bacterial or fungal growth, the urine and saliva samples were weighed and stored in tiny sample tubes in the freezer at -20°C. Saliva samples were then used to measure cortisol and cortisone using the Enzyme-Linked Immunosorbent Assay (ELISA) technique using Salimetric kits (USA). Prior to solvent extraction, an internal indirect ELISA approach was applied to urine samples (Al-Dujaili et a l., 2012).
Statistical Evaluation
After determining that all variables had a normal distribution, a parametric test was run. One-way ANOVA was used to compare the variation between the three therapies, basal, stevia, and placebo. Bonferroni’s technique post hock comparisons were used to determine whether groups had statistically significant differences (Pallant, 2001). A student 2-tailpaired t-test was also run to assess differences between the baseline and the two interventions—stevia and a placebo—as the ANOVA reading could be skewed because not all parameters were normally distributed. Microsoft Word Excel 2010 and SPSS Statistics (version 17.0) were used to conduct this method. Every result is reported as the mean, SD, or SEM, with a p value of 0.05 denoting significance (Bland, 2015; Field, 2005).
Results
Subject Specifications
In this study, 16 healthy volunteers—eight men and eight women—participated. Their ages ranged from 18 to 60, and their mean SD was 27.75 13.75 years. The participants’ BMIs ranged from 20.6-36.4 kg/m2, with a mean of 26.33 5.26 kg/m2. The features and demographics of the study participants are shown in Table 1. Ten participants were not regular drinkers of coffee and tea, compared to six who averaged 2-4 cups per day. Three participants consumed protein shakes, and none of the female participants were on any kind of contraceptive medication. Every participant regularly exercised, averaging at least 30 minutes per day of walking.
Blood Pressure Impact
After the initial three days of the introduction phase, participants’ baseline blood pressure measures were taken, and the mean SD values were as follows: systolic blood pressure was 114.5 12.7 mmHg and diastolic blood pressure was 70.8 9.4 mmHg. Following the stevia intervention, the systolic blood pressure raised to 119.912.9mmHg (p0.001), and it marginally increased once more after the placebo sugar intervention to 115.313.6mmHg. However, it was determined that this rise was statistically insignificant (p = 0.685). The mean and standard deviation for each parameter measured were displayed. After stevia intervention, diastolic blood pressure significantly increased from basal 70.89.4 to 75.79.6mmHg (p0.01), however there was no significant difference after placebo intervention. Additionally, there was a statistically significant difference between the BP after stevia consumption and the control group.
Influence on anthropometric variables
The participant’s mean weight and BMI at baseline measurements were 74.8216.5 kg and 26.335.2 kg/m2, respectively. After the stevia intervention, there was a minor drop in both measures (mean of 74.216.1kg and 26.15.1 kg/m2, respectively), although there was no discernible decrease in weight or BMI (p = 0.246 and p = 0.249, respectively). With p = 0.787 for weight and p = 0.796 for BMI, no significant changes were observed after the placebo intervention, however the mean values did reveal a very modest rise at 75.116.6 kg for weight and 26.45.3 kg/m2 for BMI. With p = 0.242 for weight and p = 0.227 for BMI, no significant improvements were discovered when comparing the two therapies equally.
Effect on the levels of cortisol and cortisone in the urine and saliva
According to Fig. 3B, the mean basal levels of free cortisol and free cortisone discharged in urine were 91.849.1 nmole per day and 57.3 nmole per day, respectively. After the stevia intervention, cortisol daily excretion increased in the urine to 125.760.5 nmole/day and to 109.142.6 nmole/day after the placebo intervention, which was not statistically significant. Additionally, there was no statistically significant difference in the cortisol concentration following the stevia and placebo interventions (p = 0.243). Urinary free cortisone was also somewhat lower following stevia intervention, to 49.520.6 nmole/day (p = 0.02), and after placebo intervention, to 55.6 nmole/day (p = 0.703), although these differences were not statistically significant. Most significantly, the ratio of free cortisol to cortisone discharged in urine increased statistically from 1.73 to 0.78 at baseline to 2.65 to 1.03 following stevia or placebo administration to 2.08 to 0.71, which was simply not significant.
Salivary cortisol and cortisone had a consistent diurnal pattern, as seen in Figs. 3C and 3D, which illustrate the daily rhythm for cortisol and cortisone at baseline and after a week of stevia or placebo consumption. At all three time intervals, salivary levels of cortisol increased, but only in the morning did the increase become statistically significant (p0.01) following stevia. Consuming a placebo had no discernible effect on salivary cortisol levels. Stevia has no discernible impact on the circadian cycle of cortisone. However, consumption of the placebo was shown to significantly elevate noon saliva cortisone (p = 0.01).
Only in the morning (from 1.220.65 to 1.750.72, p = 0.05) when stevia was administered, was the cortisol/cortisone ratio elevated in comparison to the basal ratio; it was not significant at midday or at night. Only in the morning after the placebo, there was a substantial drop in the ratio (from 1.220.65 to 1.06048, p 0.01). Following stevia, the overall mean basal cortisol concentration in saliva increased from 5.582.5 to 6.773.1 nmole (p0.01), but no significant change was seen after the placebo. This rise was measured by averaging the levels at dawn, noon, and night. Salivary cortisone levels were not significantly different after taking stevia or a placebo, either.
The average cortisol/cortisone salivary production ratio increased after stevia, which was only statistically significant (p = 0.050), but there was no difference between the ratio at average basal and after placebo.
Physiological and biochemical markers in healthy individuals and the effects of stevia consumption: (a) Systolic and diastolic blood pressure at basal, following stevia or placebo treatment. When compared to baseline values, SBP and DBP increased somewhat but significantly after stevia. After the placebo, (b) urinary free glucocorticoid excretion, no discernible difference was seen. In comparison to baseline levels, the daily excretion of free cortisol has dramatically risen following stevia. Both before and after the placebo, there was no discernible change in the excretion of free cortisone. (c) Circadian rhythm of salivary cortisol (mean sem).
Salivary cortisol levels increased following stevia at all 3 time points, however only during the AM session was the increase substantial. Between placebo and baseline salivary levels, (d) salivary cortisone circadian rhythm (mean sem), there was no discernible difference. Stevia had no discernible impact on the levels of cortisone in the circadian rhythm. In contrast to stevia consumption, however, taking a placebo dramatically raised salivary cortisone levels around lunchtime.
This study’s key finding was that stevia consumption for one week did modestly raise both systolic and diastolic blood pressure, and that rise was statistically significant. However, systolic and diastolic blood pressure were not significantly altered by placebo. Additionally, this study showed that, despite the fact that stevia consumption did not significantly reduce body weight, it did show a tendency toward potential weight loss, especially given the short study time. Salivary and urinary free cortisol levels significantly increased at both the baseline and post-intervention times, according to the results of the analysis of the participant’s urine and saliva samples. However, the levels of cortisol were barely impacted. Following stevia consumption, the ratio of cortisol to cortisone—a telltale indicator of the 11-HSD enzymes’ activity—has dramatically increased. The case study by Esmail and Kabadi (2012), which featured a middle-aged lady with oedema, prehypertension, and hypocalcemia who ingested stevia regularly for 9 months, verified the rise in both systolic and diastolic blood pressure. This increase led to the woman acquiring hypertension. The ratio of plasma cortisol to cortisone increased as a result of the laboratory testing, which seemed to indicate that the 11-HSD2 enzyme was limiting cortisol’s conversion to cortisone at a slower pace.
This was once more looked at in a systematic review, which found that trials lasting 1-3 months found stevia consumption to raise blood pressure, but those lasting 1-2 years found stevia consumption to lower BP in hypertensive patients (Ulbricht et al., 2010). In contrast to our findings, other research have discovered that consuming stevia extract or its separated glycosides has helped to regulate healthy blood pressure by causing vaso-relaxation in a 2-year study utilising a very high dose of 1500mg stevioside daily (Gupta et al., 2013). Ahmed et al. (2011) also noted that stevia has anti-hypertensive properties, and results from a different trial employing a high dose of 750 mg stevia in people with mild hypertension shown a reduction in systolic and diastolic blood pressure (Thomas and Glade, 2010). It appears that the later trials utilised significantly higher doses than those in our study, which could have resulted in some side effects and interfered with other systems that modulate BP. yet, numerous researches have discovered no links between stevia use and blood pressure (Ferri et al., 2006; Barriocanal et al., 2008; Maki et al., 2008).
In this study, it was discovered that stevia consumption significantly raised cortisol levels in both urine and saliva samples. The mean cortisone values, however, did not vary appreciably. However, a different study found that stevia consumption over a month had little to no impact on cortisol and cortisone levels (Corcuff and Brossaud, 2014). Esmail and Kabadi (2012) reported that daily stevia consumption over a period of nine months resulted in an increase in plasma cortisol/cortisone ratio because less cortisol was transformed into cortisone as a result of 11-HSD2 enzyme inhibition, which is consistent with our findings. It is known that the relationship between cortisol and cortisone levels, blood pressure, and hypertension can either be caused by a genetic deficiency in 11-HSD2 or be blocked by long-term licorice use (Stewart et al., 1990; Edwards, 1991). When taken orally, liquorice and stevia appear to have similar effects on blood pressure and glucocorticoid levels (Al-Dujaili et al., 2011). Other researchers have also looked into how rebaudioside A affects the excretion of cortisol metabolites in 23 healthy individuals who consume 4 stevia-sweetened pellets three times a day (Corcuff and Brossaud, 2014).
They claimed that stevia extract consumption did not significantly alter the ratios of free cortisol/cortisone or their metabolites. However, given that their trial was brief, employed a specific rebaudioside A product, and that stevia extract powder may be a complex mixture of molecules with a wide range of properties, they came to the conclusion that more research was required. To determine the long-term effects of stevia on the cortisone/cortisol ratio and blood pressure, additional research was necessary. Cortisol is an essential hormone that regulates a number of physiological and metabolic processes, especially in type 2 diabetes and metabolic syndrome where enzyme activities may be altered and superimposed rebaudioside effect could act differently in these conditions (Delaney, 2014). Cortisol is known to be produced in response to stress (Pereira et al., 2012).
In addition, elevated cortisol levels may impair insulin sensitivity, which may eventually culminate in Cushing’s syndrome and cardiovascular disease (NHS Choice, 2013). Although statistically insignificant, there was a very slight decrease in body weight and BMI in this trial, which may have been caused by the short study time. According to a study by Curry and Roberts from 2008, mice that were given stevia orally lost weight. Stevia use was also observed to lessen the desire for fatty and sweet meals, which may aid weight loss programmes (Giuffré et al., 2013). Studies have also shown that consuming stevia can help those who are overweight, diabetics, or who have high blood sugar levels by reducing the amount of sugar they consume in their diets (Thomas and Glade, 2010).
Therefore, we can assume that stevia use for a longer period of time—up to 4 weeks or more—might have resulted in a noticeable decrease in body weight and BMI. Recent systematic evaluations that evaluated the effects of stevia and other low-calorie sweeteners with sucrose intake, satiety, and body weight in healthy and obese people found that participants who used stevia consumed fewer calories than those who used sucrose (Ashwell, 2015; Rogers et al., 2016). During the stevia and placebo intervention, our participants were told to cut back on or avoid consuming any extra sucrose in their diet. The effects of stevia on lowering glucose uptake in the small intestine may be responsible for the little decrease in weight and BMI that was observed (O’Brien-Nbors, 2011). All volunteers were also told to continue getting at least 30 minutes of exercise every day and to avoid engaging in strenuous activity because this could affect their mean weight and indicate a potential confounding factor. In comparison to the baseline stevia or placebo intervention, the results might have indicated a substantial difference in weight if a greater dose of stevia (e.g., 1g instead of 0.2 g of stevioside) had been used (Geeraert et al., 2010).
We did not intend to restrict the participants’ habitual diet, so the amount of stevia they ingested was minimal with an ad libitum diet. There were a few problems, though. The first was that it’s possible that not all of the stevia in the sachets was consumed, so there was no reliable way to make sure that everyone was taking the right amount. Despite the fact that stevia has been deemed safe (Puri, 2012; Swithers, 2013), we did not wish to utilise higher doses as the purpose of the study was exploratory and short-term, and the toxicity studies had not yet been fully confirmed. Second, the sugar placebo was crystallised, but the stevia was a fine powder, which may have contributed to participant recognition. Thirdly, while the intervention phase was just one week, the carryover effect, a problem that crossover studies always encounter, could have been avoided by lengthening the washout time (Simpson et al., 2010).
Since the population was so tiny and the participant diversity was so large, it was challenging to draw any firm generalisations. Perhaps if there were more volunteers and stricter admission and exclusion criteria, this problem could be solved. Future studies should investigate the effects of stevia consumption in various forms and preparations in both men and women from a variety of age groups, BMI, and both hypertension and normotensive individuals, as well as a cross-section population for longer and shorter periods of time. In addition, various physiological and biochemical factors such insulin, gastrointestinal and stress hormones, fasting and postprandial blood glucose, and others should be examined. In addition, research on stevia use in diabetic patients might be beneficial to improve our comprehension of glucose metabolism and control that may occur over extended time periods (Sattigeri, 2012).
Conclusion
This tiny study found that stevia use for a brief period increased blood pressure in a minor but substantial way while having no appreciable effects on body weight or BMI. The increase in cortisol levels and regulation of 11-HSD type 1 and 2 enzyme activity may have contributed to the rise in blood pressure. Although more research in this area is required, people who use stevia for longer periods of time as a sweetener or for other purposes should exercise caution.
