Enhanced External Counterpulsation Improves Cognitive Function of Persons with Long COVID.

OBJECTIVE: To determine the effects of Enhanced External Counterpulsation (EECP) in patients with long COVID and objectively assessed cognitive impairment. DESIGN: A retrospective evaluation of long COVID patients referred for EECP, with cognitive sequela, and having completed an objective digital assessment before and after therapy. Patients had either cognitive impairment (CI) or no cognitive impairment (NCI) at baseline. We assessed changes in composite score using multi-factor ANOVA. Multiple linear and logistic regression analyses were conducted to evaluate several independent variables. RESULTS: 80 long COVID patients (38 CI vs 42 NCI) were included for analyses. All baseline characteristics were well matched. There was significant improvement in composite score post-EECP in those with objective cognitive impairment at baseline. There were no notable documented safety concerns. CONCLUSION: This is the first study showing that EECP led to significant improvement in cognitive functioning of long COVID patients with objectively defined cognitive impairment. Although a lack of a negative control group is a limitation of this study, EECP appears to be highly safe and effective with the potential for widespread application.

Enhanced External Counterpulsation for the Treatment of Angina With Nonobstructive Coronary Artery Disease.

Angina and nonobstructive coronary artery disease (ANOCA) is associated with poor outcomes and limited treatment options. Enhanced external counterpulsation (EECP) is a noninvasive treatment that involves applying external inflatable cuffs to the lower extremities to increase blood flow during diastole, followed by deflation during systole. Although EECP is approved for treatment in patients with refractory angina due to obstructive coronary artery disease, its effectiveness in treating patients with ANOCA with refractory angina is limited to small studies. We assessed the efficacy of EECP treatment in patients with ANOCA (defined as ≤50% stenosis in any major epicardial vessels) with refractory anginaby measuring changes in Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test, Duke Activity Status Index (DASI), Seattle Angina Questionnaire 7 (SAQ7), and weekly anginal episodes pre-EECP and post-EECP treatment. A total of 101 patients with ANOCA with CCS class III/IV angina completed a full course of EECP treatment at 2 large EECP centers. In 101 patients with ANOCA the mean age (SD) of 60.6 (11.3) years and 62.4% of the cohort were women. We found significant improvements post-EECP treatment in CCS angina class (mean (SD) 3.4 (0.5) to 2.4 (2.9), p <0.001), 6-minute walk test (median 1200 (IQR 972 to 1411) to 1358 (1170 to 1600), p <0.001), DASI (mean (SD) 15.2 (11.6) to 31.5 (16.3), p <0.001), SAQ7 (mean (DS) 36.2 (24.7) to 31.5 (16.3), p <0.001), and weekly anginal episodes (mean (SD) 5.3 (3.5) to 2.4 (2.9), p <0.001). After EECP treatment, 71 patients (70.3%) had an improvement of ≥1 CCS angina class, including 33 (32.7%) patients improving by ≥2 CCS classes. In conclusion, in patients with ANOCA, EECP therapy reduces CCS angina class and improves exercise tolerance and capacity; and should be considered a part of optimal medical therapy.

Management of Long-COVID Postural Orthostatic Tachycardia Syndrome With Enhanced External Counterpulsation.

A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. A 57-year-old female was diagnosed with COVID-19 in December 2020. As a result of her acute illness, she was hospitalized for COVID pneumonia and respiratory failure, followed by stays at an acute care facility and home rehabilitation center. After the acute phase, the patient was diagnosed with long-COVID-19-associated POTS with symptoms such as fatigue, "brain fog," and dyspnea. The patient was referred to an enhanced external counterpulsation (EECP) treatment center and underwent 15, one-hour sessions over three weeks. Upon completion of therapy, the patient reported improvements with "brain fog" and the ability to perform activities of daily living. Her Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue score was reduced by three points, six-minute walk distance increased by 85 feet, and Duke Activity Status Index (DASI) improved by over 15 points. EECP therapy was chosen due to the overlap in underlying pathology driving POTS and the mechanisms of action of EECP. This report is the first case of using EECP for the successful management of COVID-19-associated POTS and warrants further trials.

Energy Drink-Associated Electrophysiological and Ischemic Abnormalities: A Narrative Review.

An increasing number of cardiovascular adverse effects, emergency room visits, and deaths have been linked to energy drinks. In this review, we summarized available published literature assessing electrophysiological and ischemic adverse effects associated with energy drink consumption. Overall, 32 case reports and 19 clinical trials are included in this review. Ventricular arrhythmia, supraventricular arrhythmia, and myocardial ischemia were amongst the most commonly reported in case reports with 3 having a fatal outcome. Although serious ischemic changes, arrhythmias, or death were not observed in clinical trials, significant electrophysiological changes, such as PR/PQ interval shortening/prolongation, QT/QTc shortening/prolongation, and ST-T changes, were noted. QT/QTc interval prolongation appears to be the most significant finding in clinical trials, and there appears to be a dose-response relationship between energy drink consumption and QTc prolongation. The exact mechanisms and the particular combination of ingredients behind energy drink-induced cardiac abnormalities require further evaluation. Until more information is available, energy drink use should be considered as part of the differential diagnosis in appropriate patients presenting with electrocardiographic changes. Further, certain patient populations should exercise caution and limit their energy drink consumption.

Effects of the hangover secret on mitigating hangover symptoms: A pilot study.

BACKGROUND: Due to the popularity of excessive alcohol consumption, there is an increasing need for hangover symptom remedies. Most commercially available hangover treatment products have not been tested for efficacy through clinical study. AIMS: The purpose of this pilot study was to characterize the activity of a commercially available hangover product, The Hangover Secret (THS). METHODS: This was a randomized, double-blinded, placebo-controlled, crossover pilot study. Healthy volunteers of 21- to 40-years-old were eligible for participation, and received either THS or placebo on two different occasions. Participants were given 43 mL of whiskey every twenty minutes for up to 3 hours to achieve a blood alcohol concentration (BrAC) ≥ 0.12%. Hangover severity was assessed using the Acute Hangover Scale (AHS) and Acute Hangover Severity Scale (AHSS) validated tools. RESULTS: Nine participants completed the study. AHS scores increased from baseline to 7 am by 4.11 ± 3.17 and 1.26 ± 2.29 for the placebo and active arms respectively (P = .16). AHS headache scores increased from baseline to 7 am by 2.44 ± 1.67 and 1.11 ± 1.17 for the placebo and active arms respectively (P = .06). AHSS scores increased from baseline to 7 am by 1.0 ± 1.05 and 0.41 ± 1.08, for the placebo and active arms respectively (P = .30). There was no significant difference between average BrAC at 7 am between the placebo and active arms. CONCLUSION: THS showed positive signals in the prevention of alcohol-induced hangover, especially headaches. The improvements with THS surpassed the minimum clinically important difference in overall AHS score and three individual AHS symptoms scores (hangover, headache, and thirsty). THS's reduction in AHS or AHSS scores did not reach statistical significance likely due to the small sample size. Larger studies with appropriate sample sizes are needed in light of these promising findings.

Enhanced External Counterpulsation as a Novel Treatment for Post-acute COVID-19 Sequelae.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. As patients recover from COVID-19, some continue to report persisting symptoms weeks to months after acute infection. These effects have been referred to as post-acute sequelae of SARS-CoV-2 infection (PASC). We report the case of a 38-year-old woman suffering from PASC symptoms following acute COVID-19 in October 2020. During her acute infection phase, she had a home recovery and reported her predominant symptoms as fatigue, headaches, body pain, and shortness of breath. After most of her symptoms were resolved, she continued to have periodic episodes of fatigue and headaches, along with random shortness of breath while at rest and during activities for months beyond the acute phase of the illness. She also noted the presence of "brain fog," as if lacking the same clarity that she had prior to her illness. These symptoms persisted for three months before the patient underwent enhanced external counterpulsation (EECP) therapy in one-hour sessions, three times per week. This therapy was chosen based on the mechanism of action of EECP benefiting patients with ischemic cardiovascular diseases. After one week, her "brain fog" had improved, with shortness of breath improving after 1.5 weeks. The patient reported returning to pre-COVID health and fitness after approximately five weeks of EECP treatment. To our knowledge, this is the first case of using EECP for post-COVID shortness of breath, fatigue, and "brain fog."

A Survey of Energy Drink Consumption and Associated Adverse Effects in Air Force Personnel.

INTRODUCTION: Energy drinks are an increasingly utilized beverage and are gaining popularity in recent years. The U.S. Air Force (USAF) represents a unique population where energy drink consumption may be higher than the general population. To better understand the safety and health impact of energy drinks, this large-scale comprehensive survey was conducted to study energy drink consumption patterns and its associated adverse effects. MATERIALS AND METHODS: A survey was conducted across 12 USAF installations to assess self-reported energy drink consumption and adverse effects in the military population. This study was approved by the David Grant USAF Medical Center Institutional Review Board. RESULTS: A total of 9,655 participants participated in the survey. Energy drink consumption was reported in 76.7% of the participants, with 12.0% consuming ≥1 energy drink per day. Male gender, younger age, and enlisted military members are more likely to be high consumers; 58.6% of participants reported having at least once tried a premixed beverage that combines alcohol, caffeine, and other stimulants. Among energy drink users, 60.0% reported experiencing ≥1 adverse effect, and 0.92% reported needing to see a physician or going to the emergency department because of adverse effects from energy drinks. Higher energy drink or premixed combination beverage consumption frequency was associated with increased likelihood of physician or emergency department visits (P ≤ 0.002 for both). CONCLUSION: Approximately three in four USAF members reported ever consuming an energy drink. Caution should be exercised on the amount of energy drink consumed to limit the risk of serious adverse effects. Future studies should identify populations at greatest risk for adverse effects and alternative sources of energy maintenance to attain optimal mission readiness.

Differences in glucose level between right arm and left arm using continuous glucose monitors.

BACKGROUND: Continuous glucose monitoring (CGM) measures interstitial glucose levels through a sensor with a thin filament inserted under the skin. It is customary for patients to rotate sensor application sites between arms to minimize skin irritation. However, there is limited data regarding the degree of inter-arm differences with CGM technology. METHODS: Self-proclaimed right-handed (n = 5) and left-handed (n = 5) participants, regardless of concurrent comorbidities, were enrolled for CGM. Participants wore a FreeStyle Libre Pro sensor on each arm for a maximum of 14 days. Muscle mass and body fat analysis was conducted using a multi-frequency segmental body composition analyzer. Glucose levels from both arms were time-matched with the first 12 hours eliminated from analysis. Mean glucose and time in target range were compared between readings from the right and left arm. RESULTS: A total of 9830 paired glucose levels were included for analysis. In all participants (n = 10), mean glucose on the right arm was 89.1 mg/dL (SD, 19.9) and 85.3 mg/dL (SD, 19.3) on the left arm (P < 0.001). Glucose was out of target range (70-180 mg/dL) for 12.7% of the time in the right arm compared to 18.5% in the left arm (P < 0.001). CONCLUSIONS: In a group of 10 nondiabetic and diabetic adults, there was a statistically significant difference in CGM readings between the right and left arms. Time in target range may differ based on arm selection when using a CGM. Arm dominance did not explain the inter-arm glucose level discordance.

EECP improves markers of functional capacity regardless of underlying ranolazine therapy.

OBJECTIVE: Enhanced external counterpulsation (EECP) and ranolazine are approved treatments for patients with chronic stable angina by the United States Food and Drug Administration (FDA). Whether EECP offers clinical benefits regardless of underlying ranolazine therapy needs further investigation. METHODS: This was a retrospective evaluation of patients referred to a specialized EECP center. Patients having data on 6-Minute Walk Distance (6MWD) or Duke Activity Status Index (DASI) were categorized into two groups (EECP with ranolazine or EECP only). The primary endpoints were change in 6MWD and DASI before and after a full course of EECP within each of the two groups. Inter-group differences were also assessed. The Wilcoxon test was utilized to compare the change from baseline within each group and the Mann-Whitney U test to compare difference between groups. RESULTS: A total of 2836 patient records (age 66.9 ± 10 years) were identified (1193 in EECP and ranolazine group and 1643 in EECP only group). EECP added to baseline ranolazine resulted in a statistically significant improvement in 6MWD and DASI (+126 feet (IQR: 230 feet), and +13.35 (IQR: 17.11), respectively, P<0.001 for both). Similarly, the EECP only group showed a statistically significant improvement in 6MWD and DASI (+140 feet (IQR: 225 feet) and +13.49 (IQR: 18.02), respectively, P<0.001 for both). There was no statistically significant difference between the two groups when comparing the change from baseline in 6MWD and DASI score (P=0.256 and P=0.056 respectively). CONCLUSION: EECP improves markers of functional capacity regardless of baseline ranolazine therapy. EECP's unique safety profile advocates for its early consideration in the treatment algorithm.

Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial.

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central blood pressures were measured at baseline, and every 30 minutes for 240 minutes. A repeated-measures 2-way analysis of variance was performed with the main effects of intervention, time, and an interaction of intervention and time. Thirty-four participants were included (age 22.1±3.0 years). The interaction term of intervention and time was statistically significant for Bazett's corrected QT interval, Fridericia's corrected QT interval, QT , PR , QRS duration, heart rate, systolic blood pressure, diastolic blood pressure, central systolic blood pressure, and central diastolic blood pressure (all P<0.001). The maximum change from baseline in Bazett's corrected QT interval for drinks A, B, and placebo were +17.9±13.9, +19.6±15.8, and +11.9±11.1 ms, respectively ( P=0.005 for ANOVA ) ( P=0.04 and <0.01, respectively compared with placebo). Peripheral and central systolic and diastolic blood pressure were statistically significantly different compared with placebo (all P<0.001). Conclusion Energy drinks significantly prolong the QT c interval and raise blood pressure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT03196908.

Dipeptidyl Peptidase-4 Inhibitors and Inflammatory Bowel Disease Risk: A Meta-analysis.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) inhibitors are a popular second-line treatment for type 2 diabetes mellitus. Several studies have reported on the association between DPP-4 inhibitors and the risk of developing inflammatory bowel disease (IBD), with conflicting results. OBJECTIVE: This meta-analysis aims to elucidate the risk for IBD with DPP-4 inhibitor therapy. METHODS: A comprehensive search of PubMed/MEDLINE, CINAHL, the Cochrane Database, ClinicalTrials.gov, and the European Clinical Trials Database was performed (December 2018). All controlled clinical trials and observational studies of DPP-4 inhibitors that reported events of IBD, Crohn's disease (CD), ulcerative colitis (UC) or colitis and had a duration ≥52 weeks were included. The DerSimonian and Laird random-effects model was utilized to assess the relative risk (RR) for IBD post DPP-4 inhibitor exposure. RESULTS: A total of 16 individual studies evaluating a total of 198 404 patients were included for analysis. Studies ranged from 52 weeks through 5 years. In the primary random-effects analysis, DPP-4 inhibitor exposure resulted in a nonsignificant increase in the risk of IBD (RR = 1.52; 95% CI = 0.72 to 3.24; I2 = 54.2%). Sensitivity analysis using a fixed-effects model demonstrated significantly increased risk (RR = 3.01; 95% CI = 2.30-3.93). DPP-4 inhibitor use significantly increased the risk of CD (RR = 2.47; 95% CI = 1.36 to 4.48). All findings were driven by the inclusion of 1 large study. Conclusion and Relevance: Based on a conservative random-effects analysis, DPP-4 inhibitors do not appear to increase the risk of developing inflammatory bowel disease. However, long-term postmarketing surveillance is warranted.

Effect of water-soluble cinnamon extract on electrocardiographic parameters: An analysis of the CiNNaMON trial.

OBJECTIVE: To ensure that cinnamon extract does not cause electrocardiographic (ECG) effects in patients with prediabetes. DESIGN: A subgroup analysis was carried out on data from 103 prediabetic patients participating in the "Effect of Lifestyle Intervention Plus Water-Soluble Cinnamon Extract on Lowering Blood Glucose in Prediabetics" trial. The trial was a randomized, double-blind, placebo-controlled trial comparing cinnamon extract versus placebo in prediabetic adults who committed to participate in a standard-of-care, aggressive lifestyle therapy program. SETTING: Family Medicine Residency, Mike O'Callaghan Military Medical Center; Family Medicine Residency, David Grant Medical Center, Travis AFB; Wilford Hall Ambulatory Surgical Center, Family Medicine Residency; Eglin AFB, Family Medicine residency; Offutt AFB, Family Medicine Residency. MAIN OUTCOME MEASURES: QTc interval, QT interval, PR interval, QRS duration and heart rate from ECGs at baseline, 3 months, and 6 months. RESULTS: Analysis of the ECGs showed no time-matched intra-group differences in any of the ECG parameters (QTc interval, QT interval, PR interval, QRS duration and heart rate; all p-values >0.05). CONCLUSIONS: Use of cinnamon extract in prediabetic patients does not affect electrocardiographic measures.

Randomized Controlled Trial of High-Volume Energy Drink Versus Caffeine Consumption on ECG and Hemodynamic Parameters.

BACKGROUND: Caffeine in doses <400 mg is typically not considered arrhythmogenic, but little is known about the additional ingredients in energy drinks. We evaluated the ECG and blood pressure (BP) effects of high-volume energy drink consumption compared with caffeine alone. METHODS AND RESULTS: This was a randomized, double-blind, controlled, crossover study in 18 young, healthy volunteers. Participants consumed either 946 mL (32 ounces) of energy drink or caffeinated control drink, both of which contained 320 mg of caffeine, separated by a 6-day washout period. ECG, peripheral BP, and central BP measurements were obtained at baseline and 1, 2, 4, 6, and 24 hours post study drink consumption. The time-matched, baseline-adjusted changes were compared. The change in corrected QT interval from baseline in the energy drink arm was significantly higher than the caffeine arm at 2 hours (0.44±18.4 ms versus -10.4±14.8 ms, respectively; P=0.02). The QTc changes were not different at other time points. While both the energy drink and caffeine arms raised systolic BP in a similar fashion initially, the systolic BP was significantly higher at 6 hours when compared with the caffeine arm (4.72±4.67 mm Hg versus 0.83±6.09 mm Hg, respectively; P=0.01). Heart rate, diastolic BP, central systolic BP, and central diastolic BP showed no evidence of a difference between groups at any time point. Post energy drink, augmentation index was lower at 6 hours. CONCLUSIONS: The corrected QT interval and systolic BP were significantly higher post high-volume energy drink consumption when compared with caffeine alone. Larger clinical trials validating these findings and evaluation of noncaffeine ingredients within energy drinks are warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023723.

Do Studies Evaluating QT/QTc Interval Prolongation with Dietary Supplements Meet FDA Standards: A Systematic Review.

PURPOSE: Dietary supplement use is continuously increasing, but the safety evaluation of these products remains partial. While dietary supplements have no mandate for assessing cardiovascular safety, all new drug entities (NDE) are required to undergo a thorough QT/corrected QT (QTc) assessment to determine their propensity to impact cardiac repolarization. Independent investigators and manufacturers of dietary supplements voluntarily initiate safety studies; however, the quality of these studies is controversial. We sought to compare studies evaluating the QT/QTc effects of dietary supplements based on the International Conference of Harmonization (ICH)-E14 recommendations for NDE. CASE SUMMARY: Twenty-six published dietary supplement studies assessed QT/QTc interval prolongation. Sample sizes ranged from nine subjects to 206 among the 15 crossover studies, six parallel design studies, and five observational studies. A plan to account for electrocardiogram (ECG) morphological abnormalities was included in 10 studies, and two studies reported cardiovascular adverse events. Eight studies found a significant change in QT/QTc intervals. CONCLUSIONS: The majority of studies included in this review contained many of the critical elements recommended by the ICH E14, which includes the U.S. Food and Drug Administration guidance document for QT/QTc interval assessment. Compared with the thorough QT (TQT) standards, studies are typically well performed but can be bolstered by some study design changes. More than 30% of the included studies showed some degree of ECG changes, suggesting the need for continued cardiovascular safety assessment of dietary supplements.

Impact of Acute Energy Drink Consumption on Blood Pressure Parameters: A Meta-analysis.

OBJECTIVE: Hospitalizations associated with energy drinks have increased in the past decade. Whereas energy drinks are suspected to cause hemodynamic effects, the magnitude of risk remains controversial. We evaluated the effects of acute energy drink consumption on systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR). DATA SOURCES: A search in PubMed, Cumulative Index of Nursing and Allied Health Literature, and Cochrane database through December 31, 2015, was performed. STUDY SELECTION AND DATA EXTRACTION: Prospective clinical studies assessing the effects of commercially available energy drinks on BP and HR were included. A weighted mean change from baseline was calculated using the DerSimonian and Laird random-effects model for all end points. DATA SYNTHESIS: In all, 15 studies were included, encompassing a total of 340, 322, and 340 individuals for SBP, DBP, and HR, respectively. SBP and DBP increased significantly by 4.44 mm Hg (95% CI = 2.71 to 6.17; Cochrane Q P = 0.001) and 2.73 mm Hg (95% CI = 1.52 to 3.95; Cochrane Q P = 0.050), respectively. HR changed nonsignificantly by 0.80 beats per minute (95% CI = -1.26 to 2.87; Cochrane Q P < 0.001). The largest change in SBP was seen with drinks administering ≥200 mg of caffeine (6.44 mm Hg, 95% CI = 4.62 to 8.27). CONCLUSIONS: Our results indicate that acute consumption of caffeinated energy drinks significantly raises SBP and DBP. Further investigation of the ingredients in energy drinks and the impact of chronic energy drink consumption is warranted.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

BACKGROUND: Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. METHODS: This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. RESULTS: A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. CONCLUSIONS: Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters.

Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis.

PURPOSE: Diabetes mellitus is a global epidemic and one of the leading causes of morbidity and mortality. Additional medications that are novel, affordable, and efficacious are needed to treat this rampant disease. This meta-analysis was performed to ascertain the effectiveness of oral aloe vera consumption on the reduction of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c). METHODS: PubMed, CINAHL, Natural Medicines Comprehensive Database, and Natural Standard databases were searched. Studies of aloe vera's effect on FBG, HbA1c, homeostasis model assessment-estimated insulin resistance (HOMA-IR), fasting serum insulin, fructosamine, and oral glucose tolerance test (OGTT) in prediabetic and diabetic populations were examined. After data extraction, the parameters of FBG and HbA1c had appropriate data for meta-analyses. Extracted data were verified and then analyzed by StatsDirect Statistical Software. Reductions of FBG and HbA1c were reported as the weighted mean differences from baseline, calculated by a random-effects model with 95% confidence intervals. Subgroup analyses to determine clinical and statistical heterogeneity were also performed. Publication bias was assessed by using the Egger bias statistic. RESULTS: Nine studies were included in the FBG parameter (n = 283); 5 of these studies included HbA1c data (n = 89). Aloe vera decreased FBG by 46.6 mg/dL (p < 0.0001) and HbA1c by 1.05% (p = 0.004). Significant reductions of both endpoints were maintained in all subgroup analyses. Additionally, the data suggest that patients with an FBG ≥200 mg/dL may see a greater benefit. A mean FBG reduction of 109.9 mg/dL was observed in this population (p ≤ 0.0001). The Egger statistic showed publication bias with FBG but not with HbA1c (p = 0.010 and p = 0.602, respectively). CONCLUSION: These results support the use of oral aloe vera for significantly reducing FBG (46.6 mg/dL) and HbA1c (1.05%). Further clinical studies that are more robust and better controlled are warranted to further explore these findings.