Aloe Vera ja diabeet

Alternative Therapies

Alternative Therapies Oral aloe vera for treatment of diabetes mellitus and dyslipidemia

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he National Health Interview Survey herpes, psoriasis vulgaris, and seborrheic revealed that 4 out of 10 adults in the dermatitis.11 Monographs from Health United States age 18 and older used a Canada, the German Commission E, and form of complementary and alternative the World Health Organization recognize medicine (CAM) in 2007.1 Aloe vera the use of oral aloe vera as a laxative11-13; use has been reported in 8.5–13.8% of however, limited or conflicting evidence predominantly Hispanic populations in exists for other uses, including diabethe southern United States.2,3 Aloe vera is tes mellitus, dyslipidemia, sore throat, used just as frequently outside the United hypertension, osteoarthritis, inflammaStates—by 10.8%, 10.3%, and 7.6% of tory bowel disease, fever, itching, asthma, adults in Australia, Italy, and Jamaica, epilepsy, depression, glaucoma, multiple sclerosis, and vision problems.3,8,11 respectively, according to surveys.4-6 7 Aloe is a succulent plant belonging Patients with uncontrolled medical to the Liliaceal family, of which there conditions are often drawn to using natare more than 360 species.8 Aloe vera is a common name for Aloe barbadensis, the most widely used species of aloe (figure).9 It is often used in ointments, creams, and lotions intended for wound healing or skin protection. The International Aloe Science Council (IASC) describes three components of the plant that are used: leaf juice (whole leaf as the starting point), innerleaf juice (from the inner gel fillet), and aloe latex (yellow-brown sap between the inner paren- Aloe vera (Aloe barbadensis). chymous tissues). 10 Good scientific evidence exists for beneficial ural products, although fewer than 50% effects of topical aloe vera in genital of herb and supplement users report their use to physicians.14 Type 2 diabetes mellitus affects an estimated 23.6 million Americans, and fewer than half of these The Alternative Therapies column features short reviews of herbals and other “nutraceuticals” for patients have their condition adequately which there is some scientific evidence of effeccontrolled.15 It is estimated that patients tiveness. Readers are invited to send ideas for the with diabetes mellitus are 1.6 times more column to AJHP at ajhp@ashp.org. likely to use CAM (i.e., acupuncture,

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homeopathic therapy, spiritual healing, hypnosis, and herbal remedies) than patients without diabetes.16 In an evaluation of children with diabetes mellitus (type 1) from Turkey and Germany, aloe vera was one of the most commonly consumed herbal medicines, used by 12.9% and 7.3% of the patients, respectively.17,18 Hypercholesterolemia is another chronic condition, affecting 16% of U.S. adults age 20 years and older.19,20 CAM use was reported by 1.8 million patients with dyslipidemia in 2007.1 In a 2007 review article, Ulbricht et al.11 concluded that the evidence regarding oral aloe vera efficacy in patients with diabetes mellitus was conflicting. Since that publication, additional studies investigating aloe vera for lowering fasting blood glucose and glycosylated hemoglobin (HbA1c) concentrations have been reported.

Further, to our knowledge, no clinical review of aloe vera use in dyslipidemia has been performed. With the emergence of new data and a lack of consensus on the glycemic and lipid effects of aloe vera in humans, a thorough review was warranted. This article reviews the available literature on the efficacy of oral aloe vera in diabetes mellitus and dyslipidemia in humans.

Clinical trials. Electronic searches for articles containing the keyword “aloe” were performed in the following databases: MedLine, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Excerpta Medica Database, HerbMed, and InternationContinued on page 1806

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al Pharmaceutical Abstracts. Manual searches were conducted of relevant references. All articles examining oral use of aloe vera and measuring either blood or serum glucose, HbA1c, or any lipid parameter were extracted for review and analysis. Nonhuman studies and those using an aloe species other than A. barbadensis were excluded. One study was available only in Spanish and was translated to English by an independent Spanish-speaking clinician. A metaanalysis of the extracted studies was not possible because of inadequate reporting of data.

Eight trials were found, including a total of 5285 patients, that assessed oral aloe vera use in humans.21-28 Seven of the studies evaluated diabetes endpoints and six evaluated effects on lipids. Five of these studies evaluated endpoints for both conditions. Of the eight studies investigating aloe vera treatment for diabetes mellitus or lipid endpoints in humans, three were randomized, placebo-controlled trials available only as abstracts.23,26,27 The remaining reports included two placebo-controlled trials that used similar methods and produced similar results24,25 and three noncontrolled clinical studies.21,22,28 Agarwal. The first and largest (observational) study that was reviewed was performed by Agarwal21 in 5000 patients age 35–65 years with hyperlipidemia and evidence of ischemic heart disease.

Sixty-three percent of the patients had diabetes mellitus. The study patients prepared aloe vera as a bread by mixing 100 g of fresh flesh gelatin from the aloe vera plant, 20 g of husk of isabgol (psyllium husk), and wheat flour. The bread was to be consumed twice daily. At the end of the study, more than 93% of the patients had returned to normal ranges (although not to values now considered normal) for both diabetes and lipid markers.

However, compliance, formulation, and laboratory measurements were not adequately controlled or reported, so it is difficult to interpret and determine the clinical applicability of the study results.

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Ghannam et al. Ghannam et al. 22 studied five otherwise healthy, noninsulin-dependent patients with diabetes mellitus who admitted to once using aloe vera latex. After a run-in period with no treatment of 2–24 weeks, patients received a half-teaspoonful of aloe latex, in the form of dried resin, daily for 4–14 weeks. Mean ± S.D. fasting serum glucose concentrations decreased in all patients from a baseline 273 ± 56 mg/dL to 151 ± 51 mg/dL after treatment (p < 0.001).

Body weight and insulin levels remained unchanged. Three patients were screened for HbA1c, and a reduction from a mean of 10.6% to a mean of 8.2% was observed. Although these results appear favorable, they should be interpreted with caution because of the very small number of patients included in the study and the variability in administration and duration of treatment.

Nasiff et al. In a study evaluating lipid variables, Nasiff et al.23 examined the effect of oral aloe vera extract on lipid metabolism in patients with hyperlipidemia uncontrolled by dietary interventions.

Sixty patients between the ages of 40 and 60 years with hypercholesterolemia and hypertriglyceridemia were randomized into three groups of 20 and received either 10 or 20 mL of aloe vera or placebo daily. Lipid profiles were measured at baseline and at 4, 8, and 12 weeks.

From baseline, the 10-mL group showed reductions in cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations of 15.4%, 18.9%, and 25.2%, respectively. The 20-mL group showed reductions from baseline of 15.5% in cholesterol, 18.2% in LDL cholesterol, and 31.9% in triglycerides.

In addition, patients in the 20-mL group had a 16.9% reduction in apolipoprotein B, another marker for atherosclerosis. In the placebo group, no significant changes in lipid parameters from baseline were noted. No statistical analyses or adverse effects were reported. Contrary to an expected dose-related response, the 10and 20-mL doses appeared to lower lipid markers by similar degrees.

Yongchaiyudha et al. In a placebocontrolled, single-blind study, Yongchai-

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yudha et al.24 evaluated the effects of oral aloe vera juice in 72 patients age 35–60 years who had high fasting blood glucose and had not been previously treated with hypoglycemic drugs. Patients were equally divided into intervention and control groups. The study group received 1 tablespoonful of investigator-prepared aloe juice twice daily for 42 days, while the control group received a carminative (placebo) mixture. The a priori level of significance was 0.01.

Mean ± S.D. blood glucose concentrations decreased to 141.9 ± 4.1 mg/ dL (from 250.4 ± 7.7 mg/dL at baseline) in the intervention group but remained similar at 257.1 ± 7.8 mg/dL (compared with 251.1 ± 8.0 mg/dL at baseline) in the control group (p < 0.01) by day 42.

Triglyceride concentrations were lower in the intervention group, at 122.7 ± 5.5 mg/dL (220.3 ± 11.4 mg/dL at baseline) compared with 232.4 ± 9.6 mg/dL in the control group (214.3 ± 10.8 mg/dL at baseline) (p < 0.01). No differences in blood cholesterol levels occurred (p > 0.01).

Bunyapraphatsara et al. Bunyapraphatsara et al.25 studied 72 men and women 35–70 years old with diabetes mellitus. The methods, intervention, and treatment duration were identical to those in the study by Yongchaiyudha et al., but all of these patients were being treated with glyburide 5 mg orally twice daily. Mean ± S.D. fasting blood glucose concentrations in the intervention group decreased from 288.1 ± 8.5 mg/dL at baseline to 148.0 ± 4.6 mg/dL by day 42.

Mean ± S.D. blood glucose concentrations in the control group remained unchanged, measuring 289.2 ± 7.1 mg/ dL at baseline and 289.7 ± 8.1 mg/dL at the end of the study. Triglyceride concentrations at baseline were 264.7 ± 15.2 mg/dL in the intervention group and 223.3 ± 12.2 mg/dL in the control group (p = 0.037). On day 42, mean ± S.D. triglyceride concentrations were 128.3 ± 5.5 and 233.1 ± 13.7 mg/dL for the intervention and control groups, respectively (p < 0.01). No differences in blood cholesterol concentrations Continued on page 1808

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were observed (p > 0.01). Although the baseline values for triglycerides were different between the groups, the degree and direction of benefit suggest that the change was clinically significant.

Chalaprawat. Chalaprawat 26 conducted a crossover, double-blind, randomized, controlled trial comparing aloe vera juice against placebo juice in 16 asymptomatic, normotensive Thai patients newly diagnosed with non-insulindependent diabetes mellitus who were not concurrently taking hypoglycemic agents. Participants were divided into two groups (n = 8 in each) receiving aloe vera juice prepared from aloe vera extract or placebo juice, to be administered as 15 mL twice daily (the treatment duration was not reported). In the group that received placebo first, mean plasma glucose concentrations were 252 mg/dL before crossover and 256 mg/dL after crossover.

Similarly, mean plasma glucose concentrations were 229 mg/dL (aloe) and 239 mg/dL (placebo) in the group that received the aloe juice first. The changes were not statistically significant (p values not reported). Since only an abstract is available, it is difficult to discern whether the lack of significant change was due to differences in aloe vera preparation or study duration or was a true effect.

Devaraj et al. Devaraj et al.27 conducted a randomized, double-blind, placebo-controlled trial of 45 patients with prediabetes to examine the hypoglycemic effects and safety of two aloe products: UP780, a chromone-enriched aloe vera gel fillet powder, and AC952, an aloe vera gel fillet powder standardized to 10% polysaccharide without chromone. Patients received 500-mg tablets of UP780, AC952, or placebo twice daily for eight weeks. Fasting blood glucose and urine glucose concentrations were obtained at baseline and at eight weeks.

Significant reductions (p < 0.05) were seen in HbA1c, fructosamine, insulin, and urinary F2-isoprostanes (a marker of oxidative stress) in the UP780 group, while treatment with AC952 was associated with significantly decreased levels

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of glucose, fructosamine, and total and LDL cholesterol (actual data not reported). This study is available only in abstract form and did not provide detailed endpoint data. Hence, despite the reported significant decreases in blood glucose and lipid levels, it is difficult to discern the clinical significance of these changes.

Yagi et al. Yagi et al.28 reported on 15 patients age 42–55 years whose type 2 diabetes mellitus was uncontrolled on metformin and glyburide. Participants received 2 tablespoonfuls (0.05 g) of aloe vera gel high-molecular-weight fractions (AHM) three times daily for 12 weeks.

AHM was prepared from water-washed gel of aloe vera leaves. The end product had <10 ppm of barbaloin, a compound found in aloe exudates with strong stimulant laxative properties.10 By the end of the study, fasting blood glucose concentrations had decreased 32% from baseline (baseline concentration of 235 mg/dL estimated from a graph) and HbA 1c had decreased 20% from baseline (baseline of 7.6% estimated from a graph) (p < 0.001 for both endpoints). Triglyceride levels decreased 35% (baseline concentration of 236 mg/dL estimated from a graph) by study end (p < 0.001), although there was no change in total cholesterol levels. The authors described their study methods well, but the lack of a control group and the small sample size are inherent limitations.

Discussion. Five out of the seven studies that evaluated diabetes endpoints in humans showed significant reductions in fasting blood glucose after treatment with oral aloe vera in patients with diabetes or prediabetes21,22,24,25,28; the remaining two studies reported a trend toward decreased blood or plasma glucose concentrations in the aloe-treated groups.26,27 Significant reductions in HbA1c—up to 22.6% of baseline—were seen in all three studies that evaluated this measure.22,27,28 One of these studies reported improvements in fructosamine levels,27 suggesting an improvement in average blood glucose levels over time.

The demonstrated hypoglycemic effect of aloe vera in humans is consistent

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with results of animal studies, which have suggested that orally administered aloe vera gel is associated with an increase in plasma insulin.29 Aloe vera’s effects on lipid markers may be explained by its ability to suppress adipogenic gene expression. 30 It has also been hypothesized that normalization of plasma lipid status by aloe vera may be mediated by the control of lipid metabolism, specifically increased clearance and decreased production of the major transporters of endogenously synthesized cholesterol and triglycerides.29 Lipid markers were evaluated in six human studies,21,23-25,27,28 and the five that reported triglyceride concentrations showed a reduction in this variable in patients treated with oral aloe vera.21,23-25,28 The evidence for total cholesterol is conflicting, as three studies showed reductions in total cholesterol levels in aloe-treated patients21,23,27 and another three showed no change.24,25,28 A significant decrease in LDL cholesterol levels was seen in two studies,23,27 and Agarwal21 reported an increase in high-density lipoproteins (HDL) cholesterol levels to the normal range for 93% of his patients.

However, none of these studies reported actual values for HDL cholesterol, so it is unclear whether the change (or lack thereof) in total cholesterol was driven by reductions in triglycerides or by changes in LDL cholesterol, HDL cholesterol, or both.

Although data on oral aloe vera for treating elevated blood glucose and normalizing lipid parameters in humans appear favorable, there are numerous and noteworthy limitations in the studies that hinder the clinical application of these results. Only two studies used the same formulation and dose of aloe vera.24,25 Therefore, differences in study results may be due to variations in aloe preparations and the part of the plant used.31 Importantly, 95% of the 5285 patients evaluated (in all studies) came from the study conducted by Agarwal,21 whose methods were poor. That study incorporated the husk of isabgol, a psylContinued on page 1810

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lium fiber, into the aloe bread mixture, which could have confounded the results.

The effects of diet and exercise were not accounted or controlled for in any of the studies. The duration of treatment and the use or nonuse of concomitant oral hypoglycemics were also inconsistent among the studies.

Compliance was not adequately accounted for, and many of the studies did not provide a thorough description of baseline patient characteristics. One of the studies was not available in English,23 but we feel confident in the translation since another published report provides a similar summary of the data.32 We do not favor or promote any particular product. We encourage patients who elect to use oral aloe vera to exercise caution in selecting a product.

Certification by IASC would ensure the quality and purity of a product. The only product currently on the market that is described by its vendor as having â&#x20AC;&#x153;generally recognized as safeâ&#x20AC;? status is Qmatrix (Aloecorp, Lacey, WA) in amounts up to 1200 mg daily.33 Since the studies we reviewed did not include a thorough safety evaluation, possible adverse effects should be considered. Aloe vera has known laxative properties, and its use may induce electrolyte imbalance that theoretically could present a risk for arrhythmia. In addition, abdominal pain and cramping, muscle weakness, and hypoglycemia are potential adverse effects.7 Although no changes in alanine transaminase or aspartate transaminase were reported in the three of the studies we included,25,27,28 two cases of acute hepatitis and one case of thyroid dysfunction after oral aloe use have been reported elsewhere.34-36 All but one of the studies in this review were 14 weeks or less in duration. The long-term safety and efficacy of oral aloe vera ingestion remain unknown.

Conclusion. The preponderance of evidence suggests a trend toward benefit from oral aloe vera use in reducing fasting blood glucose concentration and HbA1c. Triglyceride levels also seem to

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Alternative Therapies

be reduced, although evidence regarding changes in LDL, HDL, and total cholesterol levels is conflicting. The weaknesses in study methods and inconsistency in data do not currently warrant recommendation of oral aloe vera for the management of diabetes mellitus or dyslipidemia.

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Abstract.

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35. Rabe C, Musch A, Schirmacher P et al.

Acute hepatitis induced by an aloe vera preparation: a case report. World J Gastroenterol. 2005; 11:303-4.

36. Pigatto PD, Guzzi G. Aloe linked to thyroid dysfunction. Arch Med Res. 2005; 36:608. Letter.

Minh Q. Ngo, Pharm.D., Staff Pharmacist CVS Pharmacy Davis, CA Nancy N. Nguyen, Pharm.D., Associate Professor of Pharmacy Practice Sachin A. Shah, Pharm.D., Assistant Professor of Pharmacy Practice sshah@pacific.edu Thomas J. Long School of Pharmacy and Health Sciences University of the Pacific 3601 Pacific Avenue Stockton, CA 95211 The authors have declared no potential conflicts of interest.

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