The effect of aloe vera syrup on the components of metabolic syndrome in patients with bipolar disorder type 1

doi:10.21203/rs.3.rs-1839857/v1

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The effect of aloe vera syrup on the components of metabolic syndrome in patients with bipolar disorder type 1

https://doi.org/10.21203/rs.3.rs-1839857/v1

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Objective

The aim of this study was to determine the effect of aloe vera syrup on the indicators of metabolic syndrome, anthropometric indices and lipid profile in patients with bipolar disorder type 1.

Methods

This randomized controlled trial was performed on 68 bipolar patients with metabolic syndrome. Patients received aloe vera or placebo syrups for 12 weeks. Assessment of blood pressure, biochemical and anthropometric indices, and physical activity were performed before and after the intervention. Dietary intakes were assessed three times.

Results

There was no significant difference between groups in most of the baseline characteristics (P > 0.05). Results showed that aloe vera syrup only decreased aspartate aminotransferase significantly (P = 0.02) and had no significant effect on the indicators of metabolic syndrome (P > 0.05), but placebo syrup increased weight and body mass index and decrease diastolic blood pressure significantly (P = 0.006, P = 0.004, P = 0.04 respectively). Aloe vera syrup did not show significant effects on indices compared with placebo (P > 0.05).

Conclusion

This clinical trial showed that aloe vera syrup had no significant effect on indicators of metabolic syndrome, anthropometric indices, and lipid profile.

Clinical trial registration in Iranian Registry of Clinical Trials

IRCT registration number: IRCT20200429047235N1 (First registration date: 2020-06-06).

Aloe

Bipolar disorder

Body weight

Lipid metabolism disorders

Metabolic syndrome

Bipolar disorder (BD) is a severe mental disease, defined as prominent mood fluctuation and deficits in emotion regulation ¹. Severity and duration of the altered mood cause the different types of bipolar disorder. One of the main types is bipolar disorder type 1 (BID), in which the patient experiences at least one manic episode or more major depressive episodes ². BD influence 2.4 percent of the population worldwide ³. In Iran, the prevalence of BID is 3.3 percent ⁴.

The usual treatment for these patients is the use of mood stabilizers. Other types of psychiatric medications may also be prescribed, depending on the severity of the disease ⁵. A long-term use of antipsychotics and mood stabilizers is associated with metabolic side effects such as metabolic syndrome (MetS) ⁶. MetS is a main global public health problem that consists of several abnormalities, such as central obesity, insulin resistance, hypertension, and dyslipidemia ⁷. In addition to drugs, mechanism of bipolar disorder and stress, smoking, substance abuse, alcohol consumption, incorrect eating habits, and sedentary lifestyle play a role in the development of MetS ⁸. MetS significantly increase the risk of type 2 diabetes mellitus, cardiovascular diseases, stroke, and other related somatic disease ⁷. Somatic diseases, especially cardiovascular diseases are one of the main causes of death in these patients and may worsen the patient's adherence to treatment. MetS can increase the severity of symptoms of bipolar phases ⁸. Therefore, interventions that reduce the risk of MetS are essential in these patients.

The use of herbs may be effective in reducing the indicators of MetS ⁹. Aloe barbadensis Miller (aloe vera) is a plant that has several metabolic properties such as lipid-lowering, antihypertensive, antidiabetic, anti-obesity, and cardio-protective effects .It is from the Liliaceae family and grows in hot and dry climates ¹⁰. Some studies have shown that aloe vera extract can reduce the risk of MetS in patients with diabetes, hyperlipidemia and pre-diabetes ^11–13. Based on our researches, the effect of aloe vera syrup in reducing MetS in bipolar patients had not been performed. Therefore, the aim of this study was to evaluate the effect of aloe vera syrup on indicators of MetS in BID patients.

Study design and participants

This study is a triple-blind randomized controlled trial performed on 68 BID patients with MetS in Yazd, Iran, from December 2019 to December 2021 in two stages. Inclusion criteria were: 1.volunteer BID patients, 2.aged 19-65 years old, 3. having MetS, 4.no smoking or smoking less than 15 cigarettes a day, 5.no alcohol or substance abuse in 6 months before entering the project, 6. no pregnancy and lactation, 7. no comorbid psychiatric illness or mental retardation, 8.not having certain diseases such as cancer, renal and hepatic problems , 9. no hormonal problems, 10.patients with stable mood , 11.not having a special diet, 12.no sensitivity to aloe vera,13.not taking omega-3 or vitamin E supplements in the past 3 mounts. Exclusion criteria were: 1. less than 80% adherence to the intervention, 2.no desire to continue cooperation, 3.failure to complete the food records.

Criteria for diagnosing BID and MetS

Diagnosis and confirmation of BID was done by a psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria¹⁴. To recognize MetS, we used International Diabetes Federation (IDF) criteria¹⁵ that consist of :1.central obesity (waist circumference ≥90 cm in males and ≥80 cm in females (Asian Origin)¹⁶, and 2.at least two of the following: a. systolic blood pressure ≥130 mmHg and/or diastolic blood pressure (DBP) ≥85 mmHg (or on treatment for hypertension),b. triglyceride (TG) levels ≥150 mg/dl (or on specific treatment for this abnormality),c. high-density lipoprotein (HDL) cholesterol levels <40 mg/dl for males and <50 mg/dl for females (or on specific treatment for this abnormality),d. fasting blood glucose (FBG) ≥100 mg/dl (or on specific treatment for diabetes mellitus)

Study Design

This study was performed in two stages. In the first stage, the diagnosis of BID in 1000 patients was confirmed by a psychiatrist. Then the researcher evaluated the patients based on age, alcohol consumption, smoking, substance abuse, pregnancy & lactation, hormonal problems, specific disease, specific diet, and allergy to aloe vera. At this stage, 800 patients were excluded due to lack of inclusion criteria (mostly due to alcohol consumption and substance abuse, hormonal problems, especially hypothyroidism and age out of range). 200 patients were invited to the laboratory for evaluation of MetS. 139 patients underwent Mets assessments. Of these, 59 patients were excluded (54 due to lack of MetS, 2 due to vitamin E and omega 3 supplementation intake, and 3 due to mental retardation). Finally, 80 eligible patients were selected to participate in the clinical trial. In the second stage, the goals and methods of research were explained to the participants and written consent was obtained from all patients. Also, patients were assured that they could leave the study whenever they want. Then the patients were allocated into intervention and placebo groups (40 patients in each group). Intervention and placebo groups received 10 ml of aloe vera syrup or 10 ml of placebo syrup, respectively (twice a day, 5 ml each time (after breakfast (or lunch) and after dinner) for 12 weeks. Patients were asked not to change their diet, physical activity level and type of medication during the intervention, and not taking any new supplements. For following, syrup consumption was reminded, weekly. Also, at each visit, the patient was given the required amount of syrup for 6 weeks and empty bottle were delivered.

Randomization and Blinding

Participants were randomly assigned to two groups by permutation block method with blocks that the size was four. To do this research in a triple-blind manner, before starting the study, the relevant syrups coded in A and B by third person. Until the end of the study, the researchers and participants were masked to the coding. Also, statistics specialist was blinded to the coding.

Aloe vera and placebo syrups

Aloe vera syrup (sucralose + aloe vera gel extract) and placebo syrup (sucralose + xanthan gum) were prepared by Barij Essence Pharmaceutical Company (Mashhad-Ardehal, Iran). Placebo syrup was similar to aloe vera syrup in color, viscosity and almost in smell and taste. Each 5 ml of aloe vera syrup contains at least 2.5 mg of glucomannan (Table 1). Dosage of aloe vera was determined based on previous studies using the syrup form ^17,18 as well as the recommendation of manufacture.

Demographic and Anthropometric assessments

Demographic information (including age, sex, marital status, smoking, medical and pharmaceutical history, level of education, employment, use of herbal medicines and supplements and duration of the disease) were completed by a general questionnaire. Anthropometric indices including height, weight, waist circumference, hip circumference and neck circumference were measured at the beginning and the end of the intervention. Height was measured using a non-stretchable tape in a standing position, without shoes and a hat. We used WHO protocol for measuring waist and hip circumference. Waist circumference was measured using a non- elastic meter at the midpoint between the top of the iliac crest and the lower margin of the last palpable rib ¹⁹ , in a standing position. The largest circumference at the level of the buttocks in standing position with the legs close together was used for measuring hip circumference. Also, neck circumference was measured using a non-flexible tape, in sitting position, head held erect, at the level of the thyroid cartilage. All of these measurements were done to the nearest 0.1 cm. Weight was measured by a digital scale (HN286, Omron, Japan) to the nearest 0.1 kg, barefoot and in light clothing. Body mass index (BMI) was determined by dividing weight in kg by height in m squared. Blood pressure was measured at the beginning and the end of the study, in a sitting position and in the left arm, three times approximately every 5 minutes, by a digital sphygmomanometer (M6AC, Omron, Japan) after resting for 10 minutes. Then the average of three measurements was reported.

Biochemical assessment

To determine the levels of biochemical factors, blood samples was taken from each patient after 9-12 hours overnight fasting from cubital vein at the beginning and also, the end of the study. Then, the blood sample was kept at room temperature for 20-30 minutes. Then it was centrifuged at 3000rpm for 5 minutes. The obtained serum was used to measure the biochemical factors by Auto Analyzer (Alpha Classic). Fasting blood sugar (FBS), triglycerides (TG) and total cholesterol (TC) were measured by the colorimetric method (Biorexfars kit, Fars, Iran). High density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol were determined by an enzymatic method (Pishtazteb kit, Tehran, Iran). Blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined by an enzymatic method (Biorexfars kit, Fars, Iran). Creatinine (Cr) was measured by jaffe method (Pars Azmoon kit ,Tehran, Iran).

Nutritional and Physical activity assessments

For nutritional assessments each patient completed 3-day food records contain two working days and one weekend day (three times, first week, the sixth week, the twelfth week). To evaluate daily intakes of energy, macronutrients, and micronutrients, the information of these records was calculated by the Nutritionist IV software. Mean of three food records reported for each nutrient. Physical activity of the participants was assessed using the short form of the International Physical Activity Questionnaire (IPAQ) before and after the intervention. This questionnaire has been validated in Iran by Vasheghani-Farahani et al. ²⁰.

Sample size

The sample size was calculated based a previous study conducted by Choi et al. ¹² considering the type one error (α) of 0.05 and type two error (β) of 0.2 (statistical power=80%) and considering 20% extra sample to cover possible attrition resulted in 40 patients in each group.

Statistical analysis

We used Statistical Package for Social Science version 25 (SPSS Inc., Chicago, IL, USA) to do statistical analyses. The P value of < 0.05 was considered statistically significant. Data analysis was performed in two areas of descriptive and analytical. Continuous and categorical variables were reported as mean ± SD or mean ± SE, and frequency (percentage). For continuous variables, the Kolmogorov- Smirnov test and Q-Q plot were used to assess the normality. For within group comparisons, we used paired sample t test (normal distribution) or Wilcoxon signed rank test (non-normal distribution). For between groups comparison, two independent samples t test (normal distribution) or Mann–Whitney U test (non-normal distribution) was used. Multivariate analysis of covariance (MANCOVA) also was used for between groups comparisons for comparing continuous main study outcomes at the end of follow up by adjusting their baseline values. .Categorical variables were compared by chi-square test. To compare changes in qualitative variables, before and after the intervention, McNemar's test was used.

Ethics approval

This study was approved by the Regional Bioethics Committee of Isfahan University of Medical Sciences (Project numbers: IR.MUI.RESEARCH.REC.1398.747). Informed consent was taken from all participants involved in the study. We make sure that our study has been performed in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving human subjects.

Finally, among 80 enrolled eligible patients; 12 patients, 7 in the intervention group and 5 in the placebo group were excluded from the study and analysis was performed on 68 patients (Figure1). Baseline characteristics of the study participants show in Table 2. There are no differences in age, marital status, sex, education, employment, socioeconomic status, history of psychiatric disorder, taking supplements and medical plants, and smoking status between intervention and placebo groups (P > 0.05). Also, we compared the seasons that intervention took place and did not show a significant difference between groups (season not reported in the table due to multiple grouping). Table 3 shows that there was a significant difference between the two groups in recent period of regular use of psychiatric drugs (P = 0.04 )and the dose of mood-stabilizing drugs(P = 0.048 ) but the period of BID, dosage of other psychiatric drugs, and medical conditions associated with metabolic syndrome were not different between groups. Table 4 shows that the intervention and placebo groups did not differ at baseline and at 12 weeks in physical activity level and also in dietary intakes.

Blood pressure, biochemical and anthropometric indices

Table 5 shows that in the intervention group, blood pressure, FBS, and lipid profile had no significant difference after 12-week consumption of aloe vera syrup (P > 0.05). In the placebo group, there was only a significant decrease in diastolic blood pressure (P = 0.04) and other parameters did not differ significantly after intervention (P > 0.05). Also, a comparison of the changes between the two groups demonstrated that aloe vera syrup compared with placebo syrup did not significantly affect any of the indices (P > 0.05). We measured ALT, AST, ALP, BUN, and Cr before and after the study for all of the participants to monitor the toxicity of aloe vera and placebo syrup on liver and kidney function (Table 6). The result showed that ALT, AST, ALP, and BUN decreased in the intervention group after 12 weeks but except for AST that had a significant decrease (P = 0.02), the reduction of other factors was not significant (P > 0.05). Also, in the placebo group, these biomarkers decreased but were not significant (P > 0.05). Cr was constant after intervention in two groups (P > 0.05). Also, comparisons between groups did not show any significant difference (P > 0.05). Therefore, none of the syrups had a toxic effect on liver and kidney function. Table 7 shows that in the intervention group, there was no significant difference between the means of any anthropometric indices before and after the intervention (P > 0.05). In the placebo group, there was a significant increase in weight and BMI after 12 weeks (P = 0.006, P = 0.004 respectively), but there was no significant difference between other anthropometric indices. Between groups comparison, did not show any significant difference in anthropometric indices.

BID is a severe mental illness characterized by periods of mania and depression. Taking psychiatric medications to control this disease, increases the risk of MetS and abnormal lipid profile. The present study was performed to investigate the effect of 10 ml/day aloe vera syrup for 12 weeks on the indicators of MetS, anthropometric indices and lipid profile in BID patients. Our results showed that aloe vera syrup in comparison with placebo had no significant effect on FBS and lipid profile that were consistent with previous study conducted by Zarrintan et al. ²¹. In this study, daily administration of 1000 mg aloe vera capsules for 8 weeks could not significantly reduce FBS and blood lipid levels. Also, Fallah Huseini et al. conducted a study on advanced type 2 diabetes mellitus patients needing insulin therapy ²². In this study, daily intake of 600 mg of aloe vera capsules for 8 weeks only was able to reduce FBS significantly but had no effect on blood lipid profile. In the other study performed by Huseini et al., they did not observe a significant change on HDL and TG levels but there was a significant decrease in FBS, TC and LDL ¹³. Another study was conducted by Alinejad-Mofrad et al. ¹¹. In this study, the effect of two dosages of aloe vera capsules (300 and 500 mg, twice a day) was investigated over a period of 4 and 8 weeks and a significant decrease in FBS was observed in both dosages and both time period. Also this study showed that higher dose of aloe vera capsule and the longer period of intervention, had better effects on lipid profile.

Another interesting finding in our study was that aloe vera syrups had not significant effect on anthropometric indices compared with placebo, although a significant increase was observed in weight and BMI in placebo group. In contrast to our results, Choi et al. observed that aloe vera gel complex can reduce weight significantly after 8 weeks but did not decrease FBS significantly ¹². Also Zareian et al. showed that daily consumption of 1000 mg Aloe vera powder reduced weight, BMI, waist circumference, FBS, TG and systolic blood pressure but did not change HDL, LDL, TC and diastolic blood pressure ²³. In our study aloe vera syrup had not significant effect on blood pressure but Choudhary et al. showed that Aloe vera L. gel powder significantly reduced blood pressure, blood glucose and lipid profile ²⁴. However, in previous studies the effect of aloe vera on blood pressure was contradictory ^23,25.

In this study, we observed significant decrease on AST in the intervention group, but aloe vera syrup had no significant effect on liver and kidney biomarkers in comparison with placebo. This result was confirmed by previous studies ^13,22,26.

Dosage and formulation of aloe vera products and duration of the study may affect on the results. In comparison with some studies ^11,13,23 that had significant effects on indices, the lack of significant changes in our study may have been due to the different dose and form of aloe vera. Moreover, in our study, although medicines had not significant differences in two groups but medicines related to MetS were considered qualitatively no quantitatively.

This study has some strengths. According to our research, it is the first study that evaluated the metabolic effects of aloe vera syrup in BID patients. Second, the duration of study was longer than most of previous studies. Third, we used aloe vera in syrup form because some drying methods may reduce properties of aloe vera ²⁷. Also, it is a triple blinded study. Additionally, in our study, physical, biochemical and microbial analysis of aloe vera syrup was presented.

However, our study had several limitations. First, reports about nutritional intake and physical activity were taken by a questionnaire and might not be precise. Second, we selected MetS patients according to IDF criteria. So, some patients were taking treatments to control blood sugar, blood pressure, and blood lipids. Although the effect of these drugs was controlled as confounders, because we did not have accurate information about the dosage of these drugs, it may have affected the results.

The results of the present study showed that the use of 10 ml/day aloe vera syrup for 12 weeks had not significant effect on biochemical and anthropometric indices in BID patients with metabolic syndrome. It seems that the type and dosage of aloe vera products, type and dosage of medications that patients used, underlying diseases of patients and duration of intervention affect the results. Thus, we suggest further clinical trials with larger sample size and considering patients with similar conditions to achieve more comprehensive and reliable results.

Acknowledgment: We thank all the participants, their families and those who helped us in doing this project at Imam Ali Clinic and Yazd Comprehensive Psychiatric Center. Also We thank the staff of daily care centers for chronic mental patients in Yazd (Omid , Mehr , Shad Afarid , Salamate Sabz , Beh Ravan) and respected psychiatrists (Amir Reza Chamani, Mahdi Chamani, Atena Fallah , Afshin Ataeian and others) for introducing our project to their patients.

Author Contributions: FM: data collection, data analyses and interpretation, manuscript writing, analysis of food records /AF: statistical analysis /RB: identification and confirmation of BID in patients / MK: study designing, study management and supervising final manuscript. All authors read, revised and approved the final version of manuscript.

Funding: Our study was financially supported by Isfahan University of Medical Sciences (grant number: 398798).

Data Availability Statement: We confirm that the data of our article are available by contacting the corresponding author.

Competing interests: All of authors declare that there are no financial/commercial conflicts of interest.

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Table 1. Physical, biochemical and microbial analysis of aloe vera syrup.

#	Test		Specifications	Result	Method of Analysis
Physical
1	Description & Appearance		A yellow to greenish solution, Cloudy solution	Conform	Visually & organoleptic
2	Taste & Odor		Slightly taste and odor of Aloe vera extract	Conform	Visually & organoleptic
3	Specific Gravity (g/ml)		1.06 - 1.10	1.077	USP41<841>
4	Refractive Index (nD)		1.355 - 1.375	1.3648	ISIRI2274-6
5	PH		4.0 - 5.0	4.11	ISIRI22083
6	Dry residue (%w/w)		18 - 22	20.6	BP 2019
Identification and Assay
7	Assey	Glucomannan (mg/5ml)	At least 2.5	7.10	In House (UV-Vis)
Microbial Analysis
8	Total aerobic microbial count (CFU/g)		N≤10²	N=10²	USP41
9	Salmonella test (10 g)		Negative	Negative	USP41
10	Escherichia coli test		Negative	Negative	USP41
11	Total molds and yeasts Enumeration (CFU/g)		N≤10	N<10	USP41
BP ,Boiling point ;ISIRI ,Institute of Standards and Industrial Research of Iran ; PH, Potential of Hydrogen; USP41, United States Pharmacopeia 41; UV-Vis, Ultraviolet–visible spectroscopy.

Table 2. Socio-demographic conditions of the participants.

Variables	Placebo (N = 35)	Intervention (N =33)	p-value
Age (year)	45.48 ± 8.50	40.97 ± 10.80	0.06
Marital status(married)	26 (74.3)	23 (69.7)	0.67
Sex(male)	17 (48.6)	15 (45.5)	0.80
Education(year)	9.83 ± 5.18	10.24 ± 3.66	0.71
Employment (working)	10 (28.6)	7 (21.2)	0.48
Socio-economic status			0.71
Low	6 (17.1)	6 (18.2)
Moderate	25 (71.4)	21 (63.6)
High	4 (11.4)	6 (18.2)
Smoking	1 (2.9)	2 (6.1)	0.61
Calcium supplements	2 (5.7)	1 (3.0)	> 0.99
Vitamin D supplement	9 (25.7)	7 (21.2)	0.66
Antioxidants supplement	1 (2.9)	1 (3.0)	> 0.99
Medical plants	19 (54.3)	12 (36.4)	0.14
Data are expressed as mean ± SD or Number (%). Comparison of quantitative and categorical variables performed by independent samples t-test or Mann-Whitney U-test and Chi-square test or Fisher’s exact test. P < 0.05 was considered statistically significant.

Table 3. Medical conditions of the participants.

Variables	Placebo (N = 35)	Intervention (N =33)	p-value
The period of BID (mount)	202.23 ± 115.77	188.67 ± 102.49	0.61
recent period of regular use of psychiatric drugs (mount)	52.31 ± 54.13	92.53 ± 99.95	0.04
Antianxiety drugs(mg/day)	6.76 ± 12.66	3.80 ± 9.70	0.29
Antipsychotic drugs(mg/day)	25.79 ± 49.25	38.66 ± 68.65	0.38
Mood stabilizing drugs(mg/day)	479.77 ± 522.29	786.72 ± 716.17	0.048
Antidepressants (mg/day)	23.37 ± 53.06	44.30 ± 71.50	0.18
Anticonvulsants (mg/day)	10.71 ± 29.26	10.47 ± 28.24	0.97
Fluphenazine decanoate injection	1(2.9)	1(3.1)	> 0.99
Diabetes	11(4.8)	9(20.3)	0.71
Metformin user	5 (14.3)	6 (18.2)	0.66
Insulin user	1 (2.9)	2 (6.9)	0.61
Other antihyperglysemic drugs user	2 (5.7)	5 (15.2)	0.25
Hypertension	8 (22.9)	4 (12.1)	0.25
Antihypertensive drug user	7(20.0)	4 (12.1)	0.38
Hyperlipidemia	8 (22.9)	9 (27.3)	0.67
Antihyperlipidemic drug user	3 (8.6)	6 (18.2)	0.30
Data are expressed as mean ± SD or Number (%). Comparison of quantitative and categorical variables performed by independent samples t-test or Mann-Whitney U-test and Chi-square test or Fisher’s exact test. P < 0.05 was considered statistically significant.

Table 4. Comparison of physical activity and dietary intake between groups.

variables			Placebo (N=35)	Intervention (N=33)	P-Value
Physical activity	before	low	22(62.9)	26(78.8)	0.11
		moderate	7(20.0)	5(15.2)
		high	6(17.1)	2(6.1)
	after	low	21(60.0)	22(66.7)	0.61
		moderate	9(25.7)	7(21.2)
		high	5(14.3)	4(12.1)

Dietary intake	Means of three food records	Energy (Kcal)	1785.38 ± 576.5	1875.40 ± 687.92	0.56
		Protein (g)	61.14 ± 19.16	63.84 ± 25.93	0.63
		Carbohydrate (g)	263.51 ± 90.99	280.90 ± 105.41	0.47
		Fat (g)	56.25 ± 21.85	57.56 ± 23.46	0.81
		Cholesterol (mg)	214.98 ± 102.28	240.77 ± 149.30	0.41
		Saturated fatty acid (g)	15.77 ± 8.88	16.27 ± 11.48	0.84
		Mono unsaturated fatty acids (g)	15.05 ± 7.08	14.48 ± 5.89	0.72
		Poly unsaturated fatty acid (g)	16.15 ± 6.40	16.82 ± 6.76	0.68
		Sodium (mg)	1021.99 ± 463.70	1017.40 ± 850.13	0.98
		Potassium (mg)	1921.27 ± 826.82	1927.39 ± 772.35	0.97
		Calcium (mg)	541.42 ± 244.24	641.1 ± 447.38	0.25
		Magnesium (mg)	157.81 ± 72.11	164.13 ± 62.95	0.70
		Phosphorus (mg)	671.65 ± 273.40	739.23 ± 356.42	0.38
		Vitamin E (mg)	2.74 ± 2.36	2.90 ± 1.96	0.76
		Vitamin B1(mg)	1.58 ± 0.53	1.78 ± 0.73	0.19
		Vitamin B6 (mg)	1.03 ± 0.54	1.15 ± 0.57	0.37
		Vitamin D (Ug)	0.47 ± 0.85	0.57 ± 0.72	0.61
		Total dietary fiber (g)	12.24 ± 4.43	12.35 ± 3.75	0.92
		Sugar (g)	55.79 ± 33.36	54.41 ± 33.21	0.86
		Caffeine (mg)	118.69 ± 108.43	105.61 ± 93.10	0.60
Data are expressed as mean ± SD or Number (%). Comparison of quantitative and categorical variables performed by independent samples t-test or Mann-Whitney U-test and Chi-square test or Fisher’s exact test. P < 0.05 was considered statistically significant.

Table 5. Comparison of blood pressure, fasting blood sugar and lipid profile in study groups.

	Placebo (N=35)				Intervention (N=33)
Indices	Week0	Week12	Change from baseline	P* value	Week0	Week12	Change from baseline	P* value	P ** value
SBP (mm Hg)	125.79 ± 18.03	122.83 ± 18.71	-2.96 ± 1.94	0.14	118.99± 14.22	119.61 ± 13.32	0.62 ± 1.42	0.66	0.34
DBP (mm Hg)	88.39 ± 12.55	85.79 ± 11.32	-2.60 ± 1.23	0.04	85.05 ± 9.05	84.15 ± 9.39	-0.89 ± 1.08	0.41	0.56
FBS (mg/dL)	104.91 ± 32.84	113.03 ± 45.57	8.11 ± 5.44	0.14	105.39± 36.77	105.57 ± 31.40	0.18 ± 3.87	0.96	0.24
TC (mg/dL)	191.37 ± 34.74	188.28 ± 33.14	-3.08 ± 6.67	0.65	185.30 ± 46.37	186.09 ± 56.72	0.79 ± 6.56	0.90	0.82
TG (mg/dL)	195.23 ± 82.64	185.11 ± 77.27	-10.11 ± 10.80	0.36	195.12± 121.46	190.33 ± 176.03	-4.79 ± 20.13	0.81	0.81
HDL-C (mg/dL)	43.23 ± 10.47	43.66 ± 8.80	0.43 ± 1.88	0.82	43.73 ± 12.43	45.03 ± 14.52	1.30 ± 2.01	0.52	0.66
LDL-C (mg/dL)	111.11 ± 34.48	112.17 ± 30.23	1.06 ± 6.77	0.88	107.97 ± 37.35	105.73 ± 31.70	-2.24 ± 5.10	0.66	0.44
Data are expressed as mean ± SD or mean ± SE (for changes). SBP, systolic blood pressure; DBP, diastolic blood pressure; FBS, fasting blood sugar; TC, total cholesterol; TG, triglycerides; HDL-C, high density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. : Comparison of differences before and after the intervention in each groups analyzed by paired samples t-test or Wilcoxon signed rank test. *: Resulted from MANCOVA , adjustment was made for baseline values when comparing the mean values of variable at the end of intervention. P < 0.05 was considered statistically significant.

Table 6. Comparison of liver and kidney biomarkers in study groups.

	Placebo (N=35)				Intervention (N=33)
Indices	Week0	Week12	Change from baseline	P* value	Week0	Week12	Change from baseline	P* value	P ** value
ALT (IU/L)	40.91 ± 24.37	39.20 ± 18.15	-1.71 ± 2.87	0.55	38.48 ± 12.30	35.54 ± 13.72	-2.94 ± 2.78	0.30	0.44
AST (IU/L)	38.51 ± 13.54	35.40 ± 12.53	-3.11 ± 1.84	0.10	37.70 ± 11.69	32.54 ± 10.09	-5.15 ± 2.06	0.02	0.29
ALP (IU/L)	269.43 ± 150.63	258.03 ± 80.59	-11.40 ± 23.87	0.64	239.36 ± 101.84	221.64 ± 67.76	-17.73 ± 14.58	0.23	0.09
BUN (mg/dL)	27.28 ± 8.65	27.06 ± 10.36	-0.23 ± 1.46	0.88	26.73 ± 10.39	26.06 ± 8.59	-0.67 ± 1.63	0.68	0.72
Cr (mg/dL)	0.79 ± 0.11	0.81 ± 0.11	0.02 ± 0.02	0.39	078 ± 0.10	0.81 ± 0.13	0.03 ± 0.02	0.23	0.92
Data are expressed as mean ± SD or mean ± SE (for changes). ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BUN, blood urea nitrogen; Cr, creatinine. : Comparison of differences before and after the intervention in each groups analyzed by paired samples t-test or Wilcoxon signed rank test. *: Resulted from MANCOVA , adjustment was made for baseline values when comparing the mean values of variable at the end of intervention. P < 0.05 was considered statistically significant.

Table 7. Comparison of anthropometric indices in study groups.

	Placebo (N=35)				Intervention (N=33)
Indices	Week0	Week12	Change from baseline	P* value	Week0	Week12	Change from baseline	P* value	P ** value
Weight(kg)	83.25 ± 18.66	84.25 ± 19.11	1.00 ± 0.34	0.006	85.31 ± 15.77	85.98 ± 16.46	0.67 ± 0.39	0.10	0.46
BMI (kg/m²)	29.95 ± 4.48	30.30 ± 4.57	0.34 ± 0.11	0.004	31.47 ± 3.70	31.71 ± 3.94	0.24 ± 0.14	0.09	0.45
WC(cm)	107.13 ± 11.24	107.02 ± 11.45	- 0.11 ± 0.47	0.82	108.88 ± 9.93	109.43 ± 10.52	0.55 ± 0.58	0.35	0.38
HC(cm)	109.27 ± 9.61	109.63 ± 9.45	0.36 ± 0.36	0.33	109.76 ± 7.81	110.23 ± 8.46	0.47 ± 0.43	0.28	0.83
NC(cm)	38.73 ± 3.66	38.81 ± 3.65	0.08 ± 0.16	0.61	39.85 ± 3.72	39.59 ± 3.69	-0.26 ± 0.23	0.26	0.31
WHR	0.98 ± 0.04	0.97 ± 0.05	- 0.004 ± 0.004	0.28	0.99 ± 0.06	0.99 ± 0.05	0.001 ± 0.005	0.90	0.37
Data are expressed as mean ± SD or mean ± SE (for changes). BMI, body mass index ;WC, Waist circumference ; HC, Hip circumference ; NC, Neck circumference ;WHR, Waist-to- hip ratio. : Comparison of differences before and after the intervention in each groups analyzed by paired samples t-test or Wilcoxon signed rank test. *: Resulted from MANCOVA , adjustment was made for baseline values when comparing the mean values of variable at the end of intervention. P < 0.05 was considered statistically significant.

No competing interests reported.

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The effect of aloe vera syrup on the components of metabolic syndrome in patients with bipolar disorder type 1

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