The Effect of Aloe Vera Juice on Liver Enzymes and Hepatic Structure in a Healthy Population

Abstract

Background

There have been isolated reports of Aloe vera hepatotoxicity, usually manifested by transient liver function test abnormalities. While the European Food Safety Authority has recommended that whole leaf products containing the rind of the Aloe vera plant should not be used for human oral consumption, those Aloe vera gels made of the treated plant pulp alone are considered safe for daily consumption, provided recommended quantities are not exceeded. We aimed to assess hepatic function in healthy volunteers consuming the purified plant pulp Aloe vera gel over a 60 day period.

Methods

35 healthy volunteers consumed the maximum recommended daily dose of 2 oz (57 mL) of Aloe vera gel twice daily for a total of 60 days. The participants attended an initial baseline visit where biochemical measurements of hepatic synthetic function were obtained, and each volunteer underwent hepatic ultrasound with elastography, superb microvascular imaging and image quantification. Further visits were undertaken at days 30 and 60 to undergo the same biochemical and imaging measurements of liver function to monitor if there were any changes in the parameters measured.

Results

Seven volunteers failed to complete the study, citing unspecified gastrointestinal upset and/or an inability to tolerate the taste of the Aloe vera gel. None of these individuals had disturbance of biochemical or imaging parameters of hepatic function. Of the remaining 27 healthy volunteers, none had a change in either biochemical indices of liver function, or of ultrasound markers of hepatic blood flow or liver tissue elasticity after 60 days of Aloe vera gel consumption. However, there was a non-significant reduction in serum homocysteine levels as the only detectable change in the cohort.

Conclusions

Despite reports of potential hepatotoxicity with some Aloe vera products, in this healthy cohort, extended consumption of purified plant-pulp Aloe vera gel did not have any detectable effects on hepatic function, blood flow or tissue elasticity.

Aloe vera gel is a juice product created from the inner pulp of Aloe vera leaves.¹ It has been promoted widely around the world as a health product with suggested health benefits, such as alleviation of skin rashes, menstrual problems, arthralgia, acid reflux and nausea.^1-3 Other suggested effects, although with limited evidence, include lowering blood glucose and serum cholesterol, aiding wound healing and analgesic properties.^4-9 For these reasons, it has been promoted widely and consumed by many millions of people on a daily basis.

There have been research studies to suggest that Aloe vera has a hepatoprotective and an antifibrotic effect in animal models.^10-13 However, there has been some publicity recently which has linked Aloe vera products to potential liver damage with reports of hepatic liver inflammation and increased liver enzymes, measured on blood tests.¹⁴ While scientific studies have suggested that components of Aloe vera products (anthroquinones) may indeed be toxic,^10,15-17 these have generally been linked to consumption of whole leaf products,^14,18 rather than the refined, decolourised Aloe vera gel.

The European Food Safety Authority (EFSA) has deemed that Aloe vera gel, created from the inner pulp of the skinned Aloe vera plant, is not harmful to drink if individual consumers do not exceed the recommended dosage, but have not recommended whole leaf products for human oral consumption.¹⁹

However, given the uncertainty raised by these reports of adverse hepatic side effects, we conducted this study to examine whether daily refined Aloe vera gel consumption, within recommended doses, over a period of 60 days, causes elevation in the measured serum liver enzymes in healthy volunteers. We also aimed to assess biophysical properties of the liver and its blood flow, measured through parallel ultrasound imaging with standard ultrasound, ultrasound tissue elastography, microvascular imaging and image quantification.

Methods

The effect of Aloe Vera Juice on liver enzymes and structure in a healthy population study was conducted in adherence to the principles laid out in Helsinki Declaration 1975 following institutional and regulatory review (REC reference 18/WM/0065). A total of 37 volunteers were recruited into the from internal institutional advertisement. Two individuals from this cohort were not able to participate in the study as they did not meet eligibility criteria. These two participants failed initial screening due to abnormal blood tests, one due to a raised aspartate aminotransferase (ALT) and another due to the presence of hepatic steatosis on preliminary baseline ultrasound screening.

Inclusion criteria were being aged between 18–75 years old at start of study. Exclusion criteria were abnormal liver function test results at baseline, any known concurrent health issues and alcohol consumption at levels that could potentially cause liver damage (consumption in excess of 14 units/week without two days a week abstinence). All participants provided written, informed consent and the study received prior ethics committee (LREC) approval (18/WM/0065).

The remaining 35 healthy volunteers were asked to consume 2 oz (57mL) of Aloe vera gel product (Forever Living Products, GmbH, Frankfurt, Germany), twice daily (breakfast and dinner) for a total of 60 days. The juice provided to the participants, originated from four different batches (delivered to Imperial College over a 6-month window). The participants attended an initial baseline visit where liver metrics were obtained, and further visits at days 30 and 60 to undergo the same measurements of liver function to monitor if there were any changes in the parameters measured.

Measurements

• At each visit (0, 30 and 60 days)

  • Abdominal ultrasound, performed by two experienced sonographers using a 6C probe, Aplio 500 system (Canon Medical Systems Europe, Zoetermeer).

  • Fibroscan^™ (EchoSens, Paris France)

  • Blood pressure

  • Height, weight, BMI and waist-hip ratio (WHR)

  • Blood test to include:

    • Serum chemistry panel

    • Full blood count

    • Blood clotting function: INR (International Normalized Ratio)

    • Fasting serum glucose and HbA1c (glycosylated haemoglobin)

    • Standard blood tests for liver function (hepatic transaminases, serum albumin, alkaline phosphatase)

    • Serum lipids

    • Serum homocysteine

• At visit 30 and 60 days

  • Adherence diary check

• Withdrawals

Continued consent was reaffirmed at every visit, and participants were asked for any remarks, comments and problems they may have encountered in relation to the Aloe vera gel consumption.

All patients were starved for the blood collection and for the ultrasound examination for at least 6 hours prior to investigation. Blood for the above parameters was collected and analyzed in a standard clinical, hospital laboratory.

Statistics

As data were normally distributed, parametric ANOVA tests were used to examine difference in specific blood values and imaging parameters between measurement days using SPSS (Mountain View, California, USA).

Results

Demographics

All 35 study participants were normotensive and had normal hepatic synthetic and renal function on entering the study. The baseline BMI in all subjects was normal (median of 22.9).

Alcohol Consumption & BMI

Overall alcohol consumption as assessed through a standardized NHS alcohol assessment form did not increase or decrease significantly over the course of the study. Furthermore, there was no significant increase in BMI during the course of the study. Therefore, we assume that the healthy volunteers maintained a similar lifestyle throughout the study, whereby the Aloe vera gel was the only addition.

Participant Withdrawal

Out of 35 participants who were eligible to participate in the study and started Aloe vera gel consumption, six withdrew from the study and two did not attend further appointments and did not respond to attempts to contact them (lost to follow-up). Reasons for withdrawal are provided in Table 1, some participants giving more than one reason. None of those participants who reported adverse events (nausea and ‘stomach problems’ (n = 2)) had abnormal blood tests, ultrasound or Fibroscan results. Both of these participants declined further follow-up, but one of them indicated that they believed their nausea originated from their strong dislike of the product flavor

Table 1.

Reasons for withdrawal as by participants. Some participants provided more than one reason. Two participants provided no reason and were withdrawn as lost to follow-up.

Reason for withdrawal	n
Unable to tolerate taste	6
Nausea	1
“Stomach problems”	1
Lost to follow-up	2

Markers of Hepatic Synthetic Function and Renal Function

There was no statistically significant difference in liver enzymes: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), serum albumin and serum bilirubin levels at baseline time 0 (visit 1), time 30 (visit 2) and time 60 days (visit 3) in the 27 volunteers completing the study. There was also no statistically significant difference in INR measurements between baseline and 60th day measurements, or between 30th and 60th day measurements.

There was no statistically significant difference in serum glucose, HbA_1c, circulating serum lipids (total cholesterol, triglycerides, serum high density lipoprotein [HDL] and serum low density lipoprotein [LDL]) or HDL/LDL ratio, between baseline and 60th day measurements, nor between 30th and 60th day measurements.

There was no statistically significant difference in measures of renal function (serum urea, glomerular filtration rate, serum creatinine) between baseline and 60th day measurements, or between 30th day and 60th day measurements.

With respect to serum homocysteine levels, a difference between the mean value at baseline and 60th day measurement reached statistical significance (P = .049); however, this was no longer significant when a multiple comparison test [ANOVA] was performed (P = .06).

Imaging Parameters

There was no statistically significant difference in liver stiffness measurements, or continuous attenuation parameter (CAP) between baseline and 60th day measurements, or between 30th and 60th day measurement. Ultrasound examinations were normal at baseline for all participants and remained normal at every subsequent visit. No structural abnormalities, gallstones, or significant size changes were observed in any participant.

Discussion

Given that many millions of people take Aloe vera every day around the world with no ill effect, hepatotoxicty appears to be a very rare problem, particularly with the decolorized gel, which is purely made from the plant pulp and does not contain any skin of the leaf.¹⁵ It is worth noting though that the skin of the plant is not digestible and can cause liver toxicity; it has therefore not been recommended for human oral consumption by EFSA.¹⁹ Therefore, Aloe vera should only be consumed from a trusted source, using the fresh inner flesh of the plant, or a decolorised derivative.¹⁹

The previous reports of liver toxicity are, barring one case, suspected rather than proven.^14,18 It is sometimes difficult to assess the effects of herbal and health food compounds as hepatotoxic agents in the populations of the developed world, given that 25-30% of the western European population have increased liver enzymes from multiple causes such as obesity, diabetes, high cholesterol levels, consumption of alcohol to excess and the use of a variety of medications which have known liver effects. As there are usually multiple potential reasons for abnormal liver enzymes on blood testing, picking out a single cause does require expert interpretation and in this increasingly obese world, being overweight is becoming the commonest reason.

The cohort in this study represented a varied group of people with a normal BMI and alcohol consumption within healthy limits, and it is important to note that this differs from the general population. The cohort was primarily recruited through communication channels within Imperial College London and Imperial College Healthcare NHS Trust in London, and thus included students and members of staff (typically aged <65yrs). Furthermore, by the very nature of being a ‘healthy volunteer’, the volunteers varied from the general population. The cohort had a lower BMI and alcohol consumption, compared to the average UK citizen. However, it was important to exclude participants with potential health problems, so as to prevent any impact of disease on measurements, and to ensure that any measured difference would be due to the introduction of Aloe vera gel to their diet rather than progression of any health issues.

Six participants indicated that they were unable to tolerate the taste of the Aloe vera juice product, and although 27 participants completed the study and met the final endpoint, almost all of them indicated that the taste of the juice was unpalatable. Two participants also indicated mild gastrointestinal adverse events; both participants refused further follow-up. No abnormalities were detected in the available ultrasound, liver stiffness, or blood values for these participants. Two further participants were lost to follow-up and did not reply to attempts to contact them.

In general, participant compliance was documented as fairly good with only a few missed doses for some participants. Compliance was measured by examining participant diaries, which relies on self-reporting and participant accuracy.

There was no significant difference in liver function from baseline after 60 days consumption of Aloe vera gel in any of the 27 volunteers completing the study. Furthermore, there was no difference in any other measure of liver health, or other standard blood tests. This suggests that there was no measurable liver toxicity after 60 days of the Aloe vera gel consumption. Furthermore, it might be inferred that the juice provided to the participants, originating from four different batches (delivered over a 6-month window), did not contain traces of the outer rind of the Aloe vera plant to a level which could cause harm. The sample size does not allow the exclusion of a possible allergic reaction to the juice for specific cases, but established literature suggests a reaction is extremely rare.¹⁵

There was a small change in serum homocysteine levels in this population: the mean difference between baseline and 60th day measurement was -2.7 micromol/L. This change reached statistical significance by use of one-way-ANOVA testing, but this was no longer significant under further statistical scrutiny using multiple comparison testing. It should be noted that a reduction in homocysteine levels of 2.7 micromol/L is not of clinical significance in a healthy cohort.²⁰ High homocysteine levels have been associated with increased cardiovascular risk, but established literature is not able to conclude that a reduction in homocysteine levels has an ameliorating effect.²¹ Furthermore, this study is not able to conclude that Aloe vera gel could reduce homocysteine levels, as the measured reduction is likely to be due to chance, and confounding factors were not considered.

Two adverse events were noted: nausea and ‘stomach problems’. Nausea and generalized gastrointestinal upset are relatively common, and without a placebo cohort it is not possible to attribute this to the use of Aloe vera gel per se. In both cases, the participants did not wish to elaborate further, but indicated that their problems were directly linked with consumption of the gel and their dislike of the taste. Aloe vera products are associated with a laxative effect in high doses, which may refer to the stomach problems the participant experienced, but without a more detailed description of symptoms, it is not possible to determine if this was the case. All participants were advised to consume an amount that stayed within the recommended daily dose.

Conclusion

There is no evidence to suggest that regular consumption of the Aloe vera gel product used in this study caused liver damage. The taste of the product was disliked by nearly all participants, which led to participant drop-out, but in none of those failing to complete the study were the liver function or imaging parameters abnormal.

Figure 1.

Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), serum albumin and serum bilirubin levels at time 0 (visit 1), time 30 (visit 2) and time 60 days (visit 3) in the 27 volunteers completing the study.