|Year : 2022 | Volume
| Issue : 1 | Page : 13-17
Cardiac autonomic reactivity to acute ingestion of glucose and fructose in healthy subjects
Savitri Sidddanagoudra1, Shantala Herlekar2, Ashwini Doyizode3, Pooja Hittalamani4
1 Department of Physiology, KAHER's JGMM Medical College, Hubballi, Karnataka, India
2 Department of Physiology, JNMC Belgavi, Belgavi, Karnataka, India
3 Department of Physiology, SDM College of Medical Sciences & Hospital, A constituent College of Shri Dharmasthala Manjunatheshwar University, Dharwad, Karnataka, India
4 MBBS, Intern, SDM College of Medical Sciences & Hospital, A Constituent College of Shri Dharmasthala Manjunatheshwar University, Dharwad, Karnataka, India
|Date of Submission||30-Sep-2021|
|Date of Acceptance||16-Mar-2022|
|Date of Web Publication||02-Sep-2022|
Dr. Savitri Sidddanagoudra
Department of Physiology, KAHER's JGMM Medical College Hubballi, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Excess intake of fructose in the form of soft drinks and corn syrup is increasing and considered as an interest of community health. The effects on the cardiovascular system due to acute intake of these sugars have not well-studied in humans. Animal studies show a clear relation between ingestion of simple sugar and pathogenesis of hypertension and metabolic disorders. Ingestion of glucose increases cardiac output (CO) without change in blood pressure (BP) and reduces total peripheral resistance (TPR). Fructose increases heart rate (HR), BP, and CO without reduction in TPR. Aims: This study aimed to evaluate the cardiac autonomic reactivity by HR variability (HRV) of basal and after ingestion of water, glucose, and fructose. Settings and Design: Randomized crossover study. Subjects and Methods: The study included 30 healthy both-gender subjects of age 18–24 years. In three separate sessions, HRV responses to one of the three test drinks were measured. (1) plain water, (2) 60 g glucose, and (3) 60 g fructose. Each drink is made up of 500 ml solution by addition of water. Statistical Analysis Used: Analysis was performed by two-way ANOVA. Results: Fructose ingestion showed decreased RR interval (RRI) (696.8 ± 102.7), increased Low frequency power (LF)/High frequency power (HF) (0.94 ± 0.2) compared to glucose (RRI: 747.0 ± 75.1, LF/HF: 0.89 ± 0.3) and water (RRI: 877.1 ± 107.0, LF/HF: 0.84 ± 0.1). Conclusions: Acute consumption of these simple sugars may result in different cardiac autonomic responses, fructose stimulating decreased vagal response.
Keywords: Heart rate variability, simple sugars, sympathovagal response
|How to cite this article:|
Sidddanagoudra S, Herlekar S, Doyizode A, Hittalamani P. Cardiac autonomic reactivity to acute ingestion of glucose and fructose in healthy subjects. Muller J Med Sci Res 2022;13:13-7
|How to cite this URL:|
Sidddanagoudra S, Herlekar S, Doyizode A, Hittalamani P. Cardiac autonomic reactivity to acute ingestion of glucose and fructose in healthy subjects. Muller J Med Sci Res [serial online] 2022 [cited 2022 Dec 5];13:13-7. Available from: https://www.mjmsr.net/text.asp?2022/13/1/13/355297
| Introduction|| |
Over the past four decades, the prevalence of hypertension, obesity, metabolic syndrome, diabetes, and kidney disease, has drastically increased. In parallel to the dramatic rise in the prevalence of these diseases, a similar increase in the consumption of fructose has occurred. Overconsumption of fructose, particularly in the form of soft drinks, is increasingly recognized as a public health concern, while fructose is a simple sugar that exists naturally in fruits and vegetables. The majority of dietary fructose comes from two sweeteners, sucrose and high-fructose corn syrup, which are commonly used in manufactured foods and beverages. Animal studies have shown a clear relationship between sugar intake and the development of increased heart rate (HR) and hypertension, elevated plasma triglycerides, insulin resistance, hyperinsulinemia, development of cardiac hypertrophy, and reduced baroreceptor sensitivity.,, Ingestion of glucose increases cardiac output (CO) without change in blood pressure (BP) and reduces total peripheral resistance (TPR), and fructose ingestion increases HR, BP, and CO but without compensatory reduction in TPR, which leads to cardiovascular diseases such as hypertension, cardiomyopathy, and cardiac failure.
Based on this, few human studies have shown that fructose may cause a variety of metabolic effects, such as lactic acidosis, lipogenesis, hypertriglyceridemia, liver injury, high BP, insulin resistance, and increased weight gain.
Water drinking activates the autonomic nervous system (ANS) and induces acute hemodynamic changes such as an increase in HR and TPR. Water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiacvagal tone.
The last two decades have witnessed the recognition of a significant relationship between the ANS and cardiovascular mortality, including sudden cardiac death. Furthermore, experimental evidence showed an association between propensity for lethal arrhythmias and signs of either increased sympathetic or reduced vagal activity had spurred efforts for the development of quantitative markers of autonomic activity. These cardiac autonomic changes are not well studied in humans using HR variability (HRV) after acute ingestion of these two simple sugars. HRV represents one of the most promising markers being noninvasive, can detect early disturbances in cardiac ANS. By this study, its simple to detect risk factors and further prevent many cardiovascular diseases. Thus, the present study aims to determine the cardiovascular autonomic responses to oral ingestion of water, glucose, and fructose in a randomized crossover study.
| Subjects and Methods|| |
The study was conducted in the department of physiology, from July to September 2015. This randomized crossover study included a total of 30 healthy subjects of both genders, between the age group of 18 and 24 years, from the same institution.
Subjects with any systemic illness, history of taking any medication affecting autonomic regulation, smoking, and alcohol intake.
Institutional ethical clearance is obtained from the same institution, and written informed consent from each subject was obtained. The participants were requested to avoid alcohol or caffeine for 24 h and were studied in the morning after an overnight (12 h) fast. Subjects were also asked to empty their bladders immediately before the experiment. All measurements are performed in a temperature-controlled quiet laboratory. Every subject attends three separate experimental sessions randomly (each session was separated by at least 3 days) according to a randomized crossover design. Following anthropometric parameters were recorded on 1st day.
- Height (in centimeters)
- Weight (in kilograms)
- Body mass index (BMI) (kilogram/meter square).
At each experimental session, the responses to one of three test drinks were measured.
The drinks tested were:
- water (normal temperature)
- Water containing 60 g glucose and
- Water containing 60 g fructose.
Each drink contained 10 ml lemon juice (to provide a more uniform taste) and is made up to a total of 500 ml by the addition of distilled water. The subjects were not told the order of the drinks. Each subject was studied while sitting in a comfortable armchair. Instruments for cardiovascular monitoring INCO IV Channel Data Acquisition system were attached. After the rest period (supine rest for 5 min), 5 min of basal HRV recording was taken. The subject was given a test drink to consume for 4 to 5 min. Then, postdrink recordings of HRV parameters for 5 min, were recorded immediately, after the first 30 min, and then the end of 2 h. Every subject ingested each drink without any problems such as nausea or any unpleasant sensations.
Parameters of HRV: Included were
- Time domain – mean RR interval: (mRRI)
- Frequency domain – Low-frequency power (LF)/High-frequency power (HF): LF/HF ratio.
A sampling rate of 500 Hz was used. The fiducial point of the R wave was identified by an algorithm of parabolic interpolation and a derivative plus threshold algorithm to locate a stable and noise-independent reference point. The last 512 stationary RR interval (RRI) were obtained for HRV analysis. If the percentage of deletion was more than 5%, then the subject was excluded from the study. The power spectrum of 512 RRIs was obtained by means of fast Fourier transformation.
Significance of each parameter:
- Increased mRRI indicates low HR, used as the index of cardiac vagal modulation
- The low-/high-frequency power ratio (LHR = LF/HF) as the index of sympathovagal balance.
| Results|| |
Collected data were analyzed using SPSS software window version 20 (IBM SPSS window version 20 statistics software, Bangalore, Karnataka, India). The basic anthropometric parameters (age, body height, body weight, and BMI), cardiac ANS responses, BP, and HRV parameters (mean RRI and LF/HF) were presented as Mean ± standard deviation (M ± SD).
Statistical analysis was performed by two-way ANOVA test for repeated measures with time (postdrink period) and treatment (drink type) as intrasubject factors. When significant differences were found, the effects of each drink over time were analyzed by comparing values at each time point over the post-drink period with the basal values recorded using Dunnett's test for multiple comparisons. Responses to each type of drink within-subjects were calculated by one-way repeated measures ANOVA followed by paired t-test. P < 0.05 was considered statistically significant.
Subjects mean age 20.32 ± 0.81 years and BMI was 20.94 ± 1.23 kg/m2.
Participants cardiovascular autonomic nervous system responses to the water and simple sugar drinks
All the values are presented in mean ± SD. * P < 0.05.
One-way repeated measures ANOVA revealed no statistical significant difference between water and glucose with time of ingestion for mRRI parameter. F = df (1.070, 31.041) = 4.314, P = 0.06 and F = df (2.043, 59.23) = 1.942, P = 0.152, respectively.
Two-way repeated measures ANOVA showed a statistically significant difference between the type of drink and time of ingestion for mRRI parameter. F = df (2.519, 73.04) = 5.34, P = 0.004. Post hoc Bonferroni test indicated that on fructose ingestion, mRRI was reduced immediately, after 30 min and 2 h post-drink period compared to glucose and water for respective times.
All the values are in mean ± SD. * P < 0.05.
Two-way repeated measure ANOVA revealed a statistically significant difference between the type of drink and time of ingestion for low- to high-frequency ratio (LHR) parameter. F = df (1.00, 29.001) = 2.086, P = 0.01. Post hoc Bonferroni test indicated that on fructose ingestion, LHR was increased immediately, after 30 min and 2 h post-drink period compared to glucose and water for respective times.
All the values are in mean ± SD.
One-way repeated measures ANOVA revealed a statistically significant difference between water ingestion and time of ingestion for the LHR parameter. F = df (1.081, 31.20) =13.20, P = 0.001. Post hoc test indicated that on water ingestion, LHR was decreased immediately (P = 0.02) and after 30 min (P = 0.001) compared to basal reading. And was increased significantly (P = 0.003) after 2 h of postdrink.
All the values are in mean ± SD.
One-way repeated measures ANOVA revealed a statistically significant difference between glucose ingestion and time of ingestion for the LHR parameter. F = df (1.549, 44.918) =24.34, P = 0.000. Post hoc test indicated that on glucose ingestion, LHR was increased immediately, after 30 min and decreased significantly after 2 h (P = 0.00) compared to basal reading.
All the values are in mean ± SD.
One-way repeated measures ANOVA revealed a statistically significant difference between fructose ingestion and time of ingestion for mRRI parameter. F = df (1.473, 42.42) = 66.63, P = 0.00.
mRRI was decreased consistently from basal level to immediate, after 30 min and 2 h of post drink. The mean difference was from basal to end of 2 h was 174 ms.
All the values are in mean ± SD.
One-way repeated measures ANOVA revealed a statistically significant difference between fructose ingestion and time of ingestion for the LHR parameter. F = df (1.574, 45.66) = 31.78, P = 0.000. Post hoc test indicated that on fructose ingestion, LHR was increased immediately, after 30 min and 2 h compared to basal reading.
[Figure 1] and [Figure 2] represents Mean RR interval (in ms) and Low-to high-frequency ratio (in nu) of subjects for all time and drink types respectively. [Figure 3] and [Figure 4] depicts Low-to high-frequency ratio (in nu) of subjects for water and glucose drink respectively.
|Figure 1: Mean RR interval (in ms) of subjects for all time and drink types|
Click here to view
|Figure 2: Low- to high-frequency ratio (in nu) of subjects for all time and drink types|
Click here to view
|Figure 3: Low- to high-frequency ratio (in nu) of subjects for water drink type and all time|
Click here to view
|Figure 4: Low- to high-frequency ratio (in nu) of subjects for glucose drink type and all time|
Click here to view
[Figure 5] and [Figure 6] shows Mean RR interval (in ms) and Low-to high-frequency ratio (in nu) of subjects for fructose drink type and all time.
|Figure 5: Mean RR interval mRRI (in ms) of subjects for fructose drink type and all time|
Click here to view
|Figure 6: Low- to high-frequency ratio (in nu) of subjects for fructose drink type and all time|
Click here to view
| Discussion|| |
The primary endpoint was that on fructose ingestion, mRRI was decreased (increased HR), and LHR was increased persistently from baseline to the end of 2 h compared to glucose. This suggests the withdrawal of cardiovagal tone and elevation in sympathetic tone to the heart. On glucose and water ingestion mRRI remained the same, but LHR was increased for 30 min from baseline suggesting sympathetic dominance, which returned to basal value at the end of 2 h. Our results are consistent with previous studies. Animal studies have shown the cardiovascular effects after fructose ingestion such as hypertension, cardiomyopathy, and metabolic abnormalities such as insulinemia and hypertriglyceridemia.,, A study showed compared to glucose, fructose induced sustained increase in BP and reduction in LHR even at the end of 2 h, probably mediated by an increase in CO without a compensatory increase in TPR indicating cardiovagal withdrawal. Similarly, in impaired glucose tolerance in human and animal studies, sympathetic responses to fructose were demonstrated the fructose-induced sympathetic activation where fructose was given orally, was not administered parentally. Increased LHR was noted in a study after glucose ingestion. Water ingestion had no effect on HRV parameters; in contrast, few studies have shown the opposite results. Water ingestion increased HF and reduced HR without change in BP, indicating a good vagal tone.,
The mechanism of the cardiac sympathetic stimulation following ingestion of glucose and fructose remains to be established. An animal study showed that high-fructose diets upregulate sodium and chloride transporters, resulting in a state of salt overload that increases BP. Excess fructose has also been found to activate vasoconstrictors, inactivate vasodilators, and overstimulate the sympathetic nervous system.
| Conclusions|| |
Acute consumption of simple sugars may result in stimulated cardiac autonomic responses, fructose stimulating decreased vagal response, and increased sympathetic activity compared to glucose in healthy subjects.
Limitations of the study
- Smaller sample size
- No gender, BMI, genetic background differentiation.
Strengths of the study
- Simple and noninvasive test to predict risk factors of cardiovascular diseases such as hypertension
- The intrasubject study, no bias. (crossover design in which every subject was exposed to each of the test drinks.)
- Future scope for effects on chronic ingestion in humans.
The authors thank all the technical staff for their support and participants for their cooperation. We thank ICMR for its funding support.
Financial support and sponsorship
Indian Council of Medical Research, India (Ref no 2015–04006).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Myphuong TL, Frye RF, Rivard CJ, Cheng J, Fann KK, Segal MS, et al
. Effects of high fructose corn syrup and sucrose on acute metabolic and haemodynamic responses in healthy subjects. Metabolism 2012;61:641-51.
Buñag RD, Tomita T, Sasaki S. Chronic sucrose ingestion induces mild hypertension and tachycardia in rats. Hypertension 1983;5:218-25.
Kamide K, Rakugi H, Higaki J, Okamura A, Nagai M, Moriguchi K, et al
. The rennin – Angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose fed-rats. Am J Hypertens 2002;15:66-71.
Martinez FJ, Rizza RA, Romero JC. High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs. Hypertension 1994;23:456-63.
Brown CM, Dulloo AG, Yepuri G, Montani JP. Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol Regul Integr Comp Physiol 2008;294:R730-7.
Steinmann B, Gitzelman R, Berghe GV. Disorders of fructose metabolism. In: Scriver C, Beaudet A, Sly W, editors. The Metabolic and Molecular Bases of Inherited Disease. 8th
ed. New York: McGraw Hill; 2001. p. 1489-520.
Routledge HC, Chowdhary S, Coote JH, Townend JN. Cardiac vagal response to water ingestion in normal human subjects. Clin Sci (Lond) 2002;103:157-62.
Arjunwadekar P, Siddanagoudra SP. Cardioautonomic responses to acute ingestion of ice water and its correlation to body mass index. J Basic Clin Physiol Pharmacol 2018;30:259-64.
Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology, the North American Society of Pacing, electrophysiology. Circulation 1996;93:1043-65.
Young JB, Weiss J, Boufath N. Effects of dietary monosaccharides on sympathetic nervous system activity in adipose tissues of male rats. Diabetes 2004;53:1271-8.
Paolisso G, Manzella D, Ferrara N, Gambardella A, Abete P, Tagliamonte MR, et al.
Glucose ingestion affects cardiac ANS in healthy subjects with different amounts of body fat. Am J Physiol 1997;273:E471-8.
Brown CM, Barberini L, Dulloo AG, Montani JP. Cardiovascular responses to water drinking: Does osmolality play a role? Am J Physiol Regul Integr Comp Physiol 2005;289:R1687-92.
Klein AV, Kiant H. Mechanism underlying fructose induced hypertension. J Hypertens 2015;33:912-20.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]