Proposed Regulatory Framework for Aloe Vera Beverages and Food Supplements

-Kshitij Shrestha, SFRO, DFTQC

Abstract

The safety of Aloe vera (L.) Burm. f. preparations in food and beverages remains scientifically contentious due to hydroxyanthracene derivatives (HADs), including aloin A, aloin B, aloe-emodin, emodin, and chrysophanol. The European Food Safety Authority (EFSA) concluded in 2018 that HADs should be considered genotoxic and carcinogenic unless specific data to the contrary exist, and was unable to establish a tolerable daily intake (Younes et al., 2018). In November 2024, the General Court of the European Union annulled Commission Regulation (EU) 2021/468, which had prohibited Aloe species preparations containing HADs (General Court of the European Union, 2024). Critically, however, the European Commission appealed this judgment in January 2025, and the case remains pending before the Court of Justice (European Commission, 2025). This manuscript provides a comprehensive technical analysis of the chemistry, toxicology, exposure assessment, and risk characterization for both Aloe vera juice products and food supplements. Physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) has yielded predicted BMDL₁₀ values for aloe-emodin, enabling Margin of Exposure (MOE)-based risk characterization (Ren et al., 2024). Cancer risk estimates for non-decolorized whole-leaf extracts range from 7.4×10⁻⁴ (1 mg/kg-day) to 4.7×10⁻² (63.8 mg/kg-day) (Boudreau et al., 2013; National Toxicology Program, 2013). Purified preparations with HAD content below 10 ppm show no genotoxicity in validated test systems, with a NOAEL exceeding 1,845 mg/kg bw/day (Shao et al., 2013). A 2024 LC-MS/MS study of commercial Aloe vera beverages found considerable variability in aloin concentrations, yet the tested products did not show mutagenicity in the reported Ames experiments (Di Minno et al., 2024). We propose a risk-based regulatory framework incorporating product-specific HAD quantification, refined exposure assessment, and a tiered permissible limit system based on consumption patterns, while acknowledging that the European regulatory landscape remains in flux pending the outcome of the pending appeal.

Keywords: Aloe vera, hydroxyanthracene derivatives, genotoxicity, benchmark dose, margin of exposure, physiologically based kinetic modeling, risk assessment, food regulation

1. Introduction

Aloe vera (Aloe barbadensis Miller), a member of the Asphodelaceae family, has been utilized for centuries in traditional medicine systems and has gained considerable popularity in contemporary food supplements and beverages (Jangra et al., 2022). The global market for Aloe products in foods and cosmetics is currently valued at approximately US$ 1.6 billion, which is estimated to double by 2026 (Baldi et al., 2021). The plant is marketed for purported digestive health, immunomodulatory, and antioxidant benefits. However, the safety of oral consumption has been a persistent regulatory concern due to the presence of naturally occurring hydroxyanthracene derivatives (HADs), particularly aloin (a mixture of aloin A and B), aloe-emodin, emodin, and chrysophanol (Younes et al., 2018).

The European Food Safety Authority published a pivotal scientific opinion in 2018, concluding that emodin, aloe-emodin, and the structurally related substance danthron have shown evidence of in vitro genotoxicity; aloe extracts have also been shown to be genotoxic in vitro, possibly due to the presence of HADs in the extract (Younes et al., 2018). Furthermore, aloe-emodin was shown to be genotoxic in vivo, and whole-leaf aloe extract and danthron were shown to be carcinogenic. Epidemiological data suggested an increased risk for colorectal cancer associated with the general use of laxatives, several of which contain HADs (Younes et al., 2018). Critically, the Panel concluded that HADs should be considered genotoxic and carcinogenic unless there are specific data to the contrary, such as for rhein, and was unable to provide advice on a daily intake that does not give rise to concerns about harmful effects to health (Younes et al., 2018).

This hazard-based conclusion prompted the European Commission to adopt Regulation (EU) 2021/468, which added "preparations from the leaf of Aloe species containing hydroxyanthracene derivatives" to Part A of Annex III of Regulation (EC) No 1925/2006, effectively prohibiting their use in food (European Commission, 2021). The regulation also added aloe-emodin, emodin, danthron, and all preparations in which these substances are present to Part A of Annex III (European Commission, 2021).

However, in November 2024, the General Court of the European Union annulled the regulation, determining that the Commission had exceeded its implementing powers (General Court of the European Union, 2024). The Court found that the concept of "preparations" in the contested provisions had a broader scope and meaning than the concepts of "substances" and "ingredients" within the meaning of Article 8 of Regulation (EC) No 1925/2006, and could not be substituted for them (General Court of the European Union, 2024). The Court emphasized that Regulation No 1925/2006 permits the inclusion in Part A of Annex III only of a "substance" or an "ingredient containing [that] substance" (General Court of the European Union, 2024).

Critically, the European Commission appealed the General Court's judgment on 22 January 2025 (Case C-38/25 P), and the appeal remains pending before the Court of Justice of the European Union (European Commission, 2025). The Commission argues that the General Court erred in law by declaring that Regulation (EC) No 1925/2006 establishes two cumulative requirements for prohibiting the addition to foods of certain substances and preparations and, consequently, by applying such a legal standard to assess the validity of Regulation (EU) 2021/468 (European Commission, 2025). The Commission further alleges that the General Court erred in law by failing to fulfill its obligation to state reasons and by exceeding its powers of review in scientific matters regarding whether HADs are harmful to health (European Commission, 2025). This manuscript provides a comprehensive scientific framework for regulating both Aloe vera juice beverages and food supplements, incorporating detailed chemical characterization of HADs, toxicological data, exposure assessment methodologies, and specific permissible limits for different product categories, while acknowledging the ongoing legal uncertainty.

2. Chemistry of Hydroxyanthracene Derivatives in Aloe Vera

2.1. Chemical Classification and Structure

Hydroxyanthracene derivatives belong to the class of organic compounds known as anthracenes, which contain a system of three linearly fused benzene rings (Jangra et al., 2022). Aloe vera comprises more than 75 unique compounds, which include vitamins, enzymes, minerals, sugars, anthraquinones (such as aloin and emodin), fatty acids (such as lupeol and campesterol), and hormones (auxins and gibberellins), along with other substances including salicylic acid, lignin, and saponins (Khan et al., 2025). These compounds are characterized by the presence of hydroxyl (-OH) groups and, in many cases, glycosidic moieties. The anthracene core structure (C₁₄H₁₀) serves as the fundamental backbone, with various substituents determining the specific biological and toxicological properties of individual HADs.

The primary HADs of toxicological concern in Aloe vera include:

Aloin A and Aloin B (Barbaloin and Isobarbaloin): These are C-glycosyl anthrones with the molecular formula C₂₁H₂₂O₉. The compounds consist of an anthrone aglycone linked to a glucose moiety via a carbon-carbon bond (C-glycosidic linkage). The anthrone core features hydroxyl groups at positions 1 and 8, with a hydroxymethyl group at position 3. The difference between aloin A and B lies in the stereochemistry at the C-10 position of the anthrone ring (Jangra et al., 2022). The molecular weight is approximately 418.4 g/mol, with a topological polar surface area of 188.0 Ų and 8 hydrogen bond donors (Ren et al., 2024).

Aloe-emodin: This aglycone (without the sugar moiety) has the molecular formula C₁₅H₁₀O₅ and is formed through the metabolic conversion of aloin by human gut microflora (Ren et al., 2024). The structure features an anthraquinone core with hydroxyl groups at positions 1 and 8, and a hydroxymethyl group at position 3. Aloe-emodin is a key metabolite responsible for many of the toxicological effects attributed to Aloe vera consumption (Ren et al., 2024). Physicochemical evaluations of aloe-emodin have demonstrated favorable drug-like characteristics, such as low molecular weight, well-balanced hydrogen bonding, moderate solubility, and reasonable permeability (logKp of −6.66), which position it as a compound with significant biological activity (Khan et al., 2025).

Emodin (1,3,8-trihydroxy-6-methylanthraquinone): This compound shares the anthraquinone core with aloe-emodin but features a methyl group at position 6 instead of a hydroxymethyl group. Emodin has been shown to be genotoxic in vitro and is a known hepatotoxic agent (Younes et al., 2018). Research has demonstrated that fermentation can significantly increase emodin content; for example, fermented Aloe arborescens leaf extract showed emodin content approximately 13 times higher than that of the raw material (Kim et al., 2023).

Chrysophanol (1,8-dihydroxy-3-methylanthraquinone): This HAD is also present in Aloe vera and is known to affect various metabolic pathways, including cytochrome P450 enzyme activity and the expression of transporters such as ABCB11 and ABCC2 (Jangra et al., 2022). Studies on anthraquinone glucuronidation have shown that substitution on the anthraquinone ring is crucial to the activity and regioselectivity of glucuronidation, with activity generally decreased greatly with a β-COOH (rhein) while enhanced dramatically with a β-OH (emodin) (Wu et al., 2014).

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid): Notably, EFSA identified rhein as a HAD for which specific data may indicate a different toxicological profile. Rhein is used as a reference substance for standardization of rhubarb preparations in the EU Pharmacopoeia (Younes et al., 2018). The glucuronidation of rhein shows unique characteristics, with UGT1A9 being the most prominent isoform in most cases (Wu et al., 2014).

2.2. Metabolic Activation and Biotransformation

The metabolic fate of HADs is central to understanding their toxicological profile. Aloin is metabolized by human gut microflora through deglycosylation and oxidation reactions, resulting in the formation of aloe-emodin anthraquinone (Ren et al., 2024). This metabolite has been associated with several harmful effects, including carcinogenicity, genotoxicity, nephrotoxicity, and purgative activity (Jangra et al., 2022).

Physiologically based kinetic modeling studies have revealed that aloe-emodin undergoes further metabolism to rhein, with hepatic clearance playing a critical role in determining systemic exposure (Ren et al., 2024). The conversion of aloe-emodin to rhein is mediated by cytochrome P450 enzymes, with CYP3A4 identified as a key enzyme in this pathway. The variability in Vmax and Km for this conversion significantly influences the toxicokinetic profile (Ren et al., 2024).

Glucuronidation represents a major metabolic pathway for anthraquinones in vivo. Studies examining the glucuronidation of five rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, rhein) in liver and intestinal microsomes from rats and humans have demonstrated that all anthraquinones form mono-glucuronides, with substitution on the anthraquinone ring being crucial to the activity and regioselectivity of glucuronidation (Wu et al., 2014). The high glucuronidation activity of UGT1A9 towards anthraquinones highlights potential drug interactions (Wu et al., 2014).

The molecular weight thresholds for biliary excretion differ between species: in rats, the threshold ranges from 200 to 325 g/mol, while in humans it ranges from 500 to 600 g/mol (Ren et al., 2024). Aloe-emodin glucuronides (446 g/mol) and rhein glucuronide (460 g/mol) are below the human threshold, indicating that enterohepatic circulation would not occur in humans as it does in rats (Ren et al., 2024). This species difference is critical for toxicological extrapolation and risk assessment.

The endoplasmic reticulum stress response has been identified as involved in apoptosis induced by aloe-emodin in HK-2 cells, suggesting a mechanism for nephrotoxicity (Zhu et al., 2012). This finding adds to the understanding of the mode of action for aloe-emodin toxicity at the cellular level.

3. Hazard Characterization

3.1. Genotoxicity

In Vitro Evidence

The EFSA ANS Panel's 2018 opinion concluded that emodin, aloe-emodin, and danthron have shown evidence of in vitro genotoxicity (Younes et al., 2018). Aloe extracts have also been shown to be genotoxic in vitro, possibly due to the presence of HADs in the extract (Younes et al., 2018). The evidence base includes positive results in bacterial reverse mutation assays (Ames test) and mammalian cell tests for these compounds (Younes et al., 2018).

The mode of action underlying aloe-emodin genotoxicity appears to involve the induction of reactive oxygen species (ROS) formation, rather than direct DNA interaction (Ren et al., 2024). Recent PBK modeling studies have demonstrated that hepatotoxicity is a more sensitive endpoint than nephrotoxicity, with ROS generation and Nrf2 activation in the liver predicted to occur at comparable dose levels as induction of hepatotoxicity (Ren et al., 2024).

However, a critical distinction must be made between unpurified (non-decolorized) extracts containing high HAD concentrations and purified (decolorized) preparations with HADs reduced to trace levels. A 2024 study evaluating five commercial Aloe vera gel beverages demonstrated no signs of mutagenicity in experiments with samples increasing in concentration (0.0016–5 μL/mL), using different strains of bacteria (Di Minno et al., 2024). Notably, even the sample with the highest concentrations of aloin A and B did not show any in vitro genotoxicity, suggesting the importance of standardizing operating procedures to obtain Aloe vera gel to minimize the content of HADs in commercial formulations (Di Minno et al., 2024).

A study on purified Aloe vera whole leaf dry juice containing 0.3 ppm of total aloins and non-detectable aloe-emodin (LOD = 0.01 ppm) evaluated genotoxic potential in the L5178Y mouse lymphoma assay (OECD 490) and in vivo comet assay (OECD 489) (Hu et al., 2021). No marked increases in mutant frequency at the tk locus were observed in the MLA at concentrations up to 5000 µg/mL for 3 h and 24 h (-S9), and up to a precipitating concentration of 3000 µg/mL for 3 h (+S9) compared to concurrent vehicle control (Hu et al., 2021). In the comet assay, no statistically significant increases in DNA strand breaks were detected in the colon or kidney following oral gavage of 500, 1000, or 2000 mg/kg/day in male F344 rats for 2 days compared to concurrent vehicle control (Hu et al., 2021). Overall, these findings demonstrated that the test article containing minimal HAD is not genotoxic under the described experimental conditions (Hu et al., 2021).

In Vivo Evidence

Aloe-emodin was shown to be genotoxic in vivo, and whole-leaf aloe extract was shown to be carcinogenic in animal models (Younes et al., 2018). The National Toxicology Program studies (NTP TR 577, 2013; Boudreau et al., 2013) remain the "gold-standard" animal studies demonstrating relevant carcinogenic effects for oral consumption of non-decolorized Aloe vera extracts (National Toxicology Program, 2013; Boudreau et al., 2013).

Purified decolorized whole-leaf Aloe vera juice with total anthraquinones <0.1 ppm demonstrated no toxicologically significant findings in a 90-day drinking water toxicity study in F344 rats, with a NOAEL established as >2% w/v (>1,845 mg/kg bw/day for males) (Shao et al., 2013).

In a technical assessment conducted in 2022, EFSA evaluated two new in vivo comet assays on aloe-emodin and dried whole Aloe ferox juice (European Food Safety Authority, 2022). The results of the aloe-emodin study were considered inconclusive for the induction of DNA strand breaks with the standard comet assay protocol. However, results obtained with a modified protocol using the lesion-specific enzyme hOGG1 suggested that aloe-emodin can induce oxidative DNA damage in colon cells in vivo (European Food Safety Authority, 2022). The lack of DNA damage observed in the Aloe ferox juice study was considered of low relevance due to the low concentrations of HADs and the potential counteracting effect of other components present in the juice (e.g., antioxidants). Based on the available evidence, EFSA concluded that the new information presented does not justify a revision of the 2018 opinion (European Food Safety Authority, 2022).

3.2. Carcinogenicity

Non-Decolorized Extracts

The NTP studies demonstrated a significant increase in the incidence of adenomas and carcinomas of the large intestine in male and female F344/N rats administered non-decolorized whole-leaf Aloe vera extracts in drinking water for 104 weeks at aloin concentrations of 60 ppm (National Toxicology Program, 2013; Boudreau et al., 2013). No significant tumor increases were observed in B6C3F1 mice (National Toxicology Program, 2013). These findings are consistent with other studies involving non-decolorized, high-anthraquinone aloe preparations (Yokohira et al., 2009).

Cancer risk estimates derived from these studies indicate that individuals consuming 1 mg/kg-day of non-decolorized whole-leaf extract exhibit an increased cancer risk of 7.4×10⁻⁴ (approximately 7 persons per 10,000 exposed developing cancer over their lifetime) (Boudreau et al., 2013). Individuals consuming 63.8 mg/kg-day exhibit a 4.7×10⁻² increase in cancer risk (approximately 5 persons per 100 exposed) (Boudreau et al., 2013).

Purified (Decolorized) Extracts

In contrast, purified decolorized whole-leaf Aloe vera juice with total anthraquinones <0.1 ppm demonstrated no toxicologically significant findings in a 90-day drinking water toxicity study, with a NOAEL established as >1,845 mg/kg bw/day for males and >2,920 mg/kg bw/day for females (Shao et al., 2013). This critical finding supports the assertion that HADs are the responsible mediators of the adverse effects observed on the colon.

There is extensive evidence in the literature implicating anthraquinones as having carcinogenic effects (Boudreau & Beland, 2006; National Toxicology Program, 2005; Gorkom & Vries, 1999; Siegers et al., 1992, cited in Shao et al., 2013). The U.S. FDA has banned the use of cathartic anthraquinone-containing over-the-counter drugs (U.S. Food and Drug Administration, 1999, cited in Shao et al., 2013).

3.3. Epidemiological Evidence

Epidemiological data have suggested an increased risk for colorectal cancer associated with the general use of laxatives, several of which contain HADs (Younes et al., 2018). However, the Panel noted that uncertainty persists in these associations, and confounding factors cannot be excluded (Younes et al., 2018).

3.4. Regulatory Considerations in Health Foods

In China, between 1997 and 2022, more than 270 health food products containing Aloe vera components were approved (Cao et al., 2025). Among these, only 17% were single-ingredient products containing Aloe vera alone; 74.7% were compound formulations containing Aloe vera without other anthraquinone-containing ingredients; among them, 25.3% included Aloe vera combined with other anthraquinone-containing ingredients such as cassia seed, rhubarb, senna leaf, or polygonum multiflorum (Cao et al., 2025). The safety of consuming health foods containing anthraquinone components remains a matter of concern and warrants continued attention (Cao et al., 2025).

4. Physiologically Based Kinetic Modeling and Benchmark Dose Estimation

4.1. PBK Modeling-Facilitated QIVIVE Approach

Recent advances in toxicological risk assessment have employed PBK modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) to predict the effects of aloe-emodin in rats and humans (Ren et al., 2024). This methodology integrates in vitro data from diverse cell models quantifying different endpoints, including hepatotoxicity, nephrotoxicity, ROS generation, and Nrf2 activation, to establish dose-response relationships at the whole-organism level (Ren et al., 2024).

The PBK model for aloe-emodin incorporates:

· Absorption: Oral bioavailability and first-pass metabolism

· Distribution: Tissue partitioning based on physicochemical properties

· Metabolism: CYP450-mediated conversion to rhein, with Vmax and Km derived from in vitro incubations

· Excretion: Renal and biliary clearance mechanisms

The sensitivity analysis reveals that variability in Vmax and Km for the conversion of aloe-emodin to rhein significantly influences the model predictions (Ren et al., 2024). Model predictions for Cmax of rhein fit well with available data in rats, validating the model's adequacy for extrapolation purposes (Ren et al., 2024).

4.2. Predicted BMDL₁₀ Values

The PBK modeling-facilitated QIVIVE approach provides predicted BMDL₁₀ values for aloe-emodin based on in vitro concentration-response data (Ren et al., 2024). The key findings include:

Hepatotoxicity: Hepatotoxicity is predicted to be a more sensitive endpoint than nephrotoxicity for aloe-emodin (Ren et al., 2024). ROS generation and Nrf2 activation in the liver are predicted to occur at comparable dose levels as induction of hepatotoxicity (Ren et al., 2024).

ROS Generation: The predicted BMDL₁₀ values for ROS generation are lower than those for Nrf2 activation, consistent with the mechanism that aloe-emodin induces Nrf2 activation through ROS formation (Ren et al., 2024).

Cell Model Sensitivity: HepG2 cells show lower CYP3A4 activity than other hepatic cell models like HepaRG cells (Ren et al., 2024). This explains the lower predicted in vivo hepatotoxicity based on in vitro data from HepG2 cells compared to metabolically competent cells, as the conversion of aloe-emodin to its more active metabolite, rhein, is less efficient in HepG2 cells (Ren et al., 2024).

The specific BMDL₁₀ values derived from the predicted in vivo dose-response curves demonstrate that estimated dose levels of aloe-emodin resulting from food supplements or beverages are unlikely to result in induction of hepatotoxicity, nephrotoxicity, ROS generation, or Nrf2 activation in liver and kidney (Ren et al., 2024).

4.3. Margin of Exposure Framework

The Margin of Exposure approach represents the most scientifically defensible framework for risk characterization of genotoxic compounds where a threshold cannot be definitively established (European Food Safety Authority, 2005):

MOE = BMDL₁₀ / Estimated Daily Intake

A critical methodological consideration is that the endpoint underlying the BMDL must match the risk question. A BMDL derived from hepatotoxicity, ROS generation, or Nrf2 activation cannot automatically be treated as a cancer/genotoxicity point of departure for assessing carcinogenic risk. For cancer risk characterization, the BMDL should ideally be derived from the carcinogenicity endpoint itself or from a mechanistically relevant genotoxicity endpoint. For purified low-HAD preparations where the primary concern is not carcinogenicity but potential non-genotoxic effects, a BMDL derived from hepatotoxicity or other relevant endpoints may be appropriate.

The European Food Safety Authority considers MOE values greater than 10,000 to be of low concern for public health when derived from animal studies, although this threshold may be adjusted based on the specific toxicological endpoint and uncertainties (European Food Safety Authority, 2005).

5. Exposure Assessment

5.1. Concentration Data in Commercial Products

Substantial variability exists in HAD concentrations among commercial Aloe vera products. LC-MS/MS-based quantification studies have reported the following concentrations in commercial beverages:

Di Minno et al. (2024) quantified aloin A concentrations ranging from 6.05 to 337.98 ng/mL and aloin B concentrations ranging from 8.84 to 346.89 ng/mL in five commercial samples. Aloe-emodin was detected in three samples at concentrations ranging from 80.30 to 109.40 ng/mL (Di Minno et al., 2024). Four commercial samples contained aloin A and B in concentrations higher than 1 ppm, while one sample contained less than 1 ppm (Di Minno et al., 2024).

The International Aloe Science Council (IASC) recommends a maximum allowable aloin concentration of <10 ppm for orally ingested products (International Aloe Science Council, 2023). The European regulatory framework under Regulation (EU) 2021/468 did not establish a universal 1-ppm maximum for Aloe HADs; rather, it placed "preparations from the leaf of Aloe species containing hydroxyanthracene derivatives" in Part A of Annex III, effectively prohibiting their use (European Commission, 2021). Purified (decolorized) products typically contain total anthraquinones <0.1 ppm (Shao et al., 2013).

A review of Aloe gel-base food products noted that pure Aloe gel shows no toxic effects, but that further toxicological studies remain necessary to establish the maximum permissible limit of HAD contaminants in Aloe gel, considering daily doses and maximum duration of treatments (Baldi et al., 2021).

5.2. Estimated Daily Intake

Exposure assessment must account for the distinct consumption patterns of different product types:

Food Supplements (capsules, tablets, concentrates): Typically consumed at recommended daily doses specified by manufacturers. Estimated daily intakes from food supplements have been compared against predicted BMDL₁₀ values using PBK modeling approaches, with the geometric mean and 95th percentile EDIs generally falling below toxicological reference points (Ren et al., 2024).

Beverages (juices, drinks): Consumption patterns vary from occasional use to regular daily consumption. For non-decolorized preparations, exposure scenarios range from single-day consumption (approximately 1-1.2 mg/kg-day) to repeated monthly consumption (53.2-63.8 mg/kg-day) (Boudreau et al., 2013).

Exposure at Different Aloin Limits:

The estimated daily exposure to aloin at different concentration limits, based on consumption of 540 mg dry gel per day, is presented in Table 1.

Table 1: Estimated Exposure at Different Aloin Limits

Aloin Limit (ppm)	Daily Exposure (mg/day)	Monthly Exposure (mg/month)	Annual Exposure (mg/year)
10	0.36	10.8	131
20	0.72	21.6	263
50	1.80	54.0	657

Note. Based on consumption of 540 mg dry gel per day (Boudreau et al., 2013).

6. Risk Characterization and Proposed Permissible Limits

6.1. Cancer Risk Estimates

Cancer risk estimates for non-decolorized whole-leaf extracts, based on NTP studies, are presented in Table 2.

Table 2: Cancer Risk Estimates for Non-Decolorized Whole-Leaf Aloe Vera Extract

Exposure Scenario	Exposure Level (mg/kg-day)	Cancer Risk Increase	Interpretation
Single-day consumption	1.0 - 1.2	7.4×10⁻⁴	~7 per 10,000 exposed develop cancer
Repeated monthly consumption	53.2 - 63.8	4.7×10⁻²	~5 per 100 exposed develop cancer

Note. Data from National Toxicology Program (2013) and Boudreau et al. (2013); cancer potency = 0.00074 (mg/kg/day)⁻¹ (Boudreau et al., 2013).

6.2. Proposed Permissible Limits

Based on the available toxicological data, PBK modeling results, and exposure scenarios, the following permissible limits are proposed for different product categories in Table 3. These limits should be considered as provisional quality-control and risk-management targets rather than universally valid health-based permissible limits, recognizing that the current evidence does not establish these exact numbers as definitive health-based thresholds.

Table 3: Proposed Permissible Limits for Aloe Vera Products

Product Category	Maximum Total HADs (ppm)	Maximum Aloin A+B (ppm)	Maximum Aloe-Emodin (ppm)	Rationale
Purified decolorized beverages (daily consumption)	<0.1	<0.1	<0.01	NOAEL >1,845 mg/kg bw/day (Shao et al., 2013); no genotoxicity (Di Minno et al., 2024; Hu et al., 2021)
Purified decolorized beverages (occasional consumption)	<1.0	<1.0	<0.1	Conservative quality-control target; recognizes product variability
Food supplements (capsules/tablets)	<1.0	<1.0	<0.1	Quality-control target; requires safety dossier
Food supplements (liquid concentrates)	<1.0	<1.0	<0.1	Stricter serving size control required
Non-decolorized preparations	Not permitted	Not permitted	Not permitted	Clear evidence of carcinogenicity (National Toxicology Program, 2013; Boudreau et al., 2013)

Note. These limits are proposed as provisional quality-control and risk-management targets rather than universally valid health-based permissible limits. The current evidence does not establish these exact numbers as definitive health-based thresholds.

6.3. MOE-Based Decision Framework

A product-specific MOE-based decision framework is recommended for regulatory evaluation, as presented in Table 4.

Table 4: MOE-Based Decision Framework

MOE Range	Regulatory Action	Rationale
> 10,000	Low concern; routine monitoring	BMDL₁₀/EDI indicates low public health concern (European Food Safety Authority, 2005)
1,000 - 10,000	Closer monitoring required	Margin insufficient for full reassurance
< 1,000	Regulatory action warranted	Margin inadequate; risk management required

For purified preparations (HAD <0.1 ppm), MOE calculations based on available BMDL₁₀ values (Ren et al., 2024) and estimated daily intakes would be expected to exceed 10,000, indicating low concern. However, for cancer risk characterization, the BMDL should be derived from the carcinogenicity endpoint itself, not from hepatotoxicity or ROS generation.

7. Regulatory Framework Recommendations

7.1. Analytical Requirements

The following analytical requirements are recommended for food control authorities:

Mandatory HAD quantification: All Aloe vera food products must undergo LC-MS/MS or HPLC analysis for quantification of aloin A, aloin B, aloe-emodin, emodin, and chrysophanol, with LOQ at least 0.1 ppm as established in validated methods (Di Minno et al., 2024). Official validated analytical methods for determination of HADs are required as tools for use by companies and competent authorities to ensure the absence of HAD contamination in raw materials or in finished products (Baldi et al., 2021).

Product-specific testing: Finished products, not just raw materials, must be tested to account for processing effects on HAD content (Di Minno et al., 2024; Shao et al., 2013). The optimization of the Aloe gel extraction process to avoid HAD contamination is essential (Baldi et al., 2021).

Batch-to-batch consistency: Regular monitoring of HAD content across production batches is essential for ensuring consistent consumer exposure.

Standardized methodology: Adoption of validated LC-MS/MS methods with accreditation to international standards (Di Minno et al., 2024).

7.2. Labeling and Consumer Information

The following labeling requirements are recommended:

Clear HAD content declaration: Labels must indicate total HAD content, aloin A+B content, and aloe-emodin content. Recommendations have been proposed to improve labeling for Aloe vera ingredients in health food instructions, particularly for products combining Aloe vera with other anthraquinone-containing substances (Cao et al., 2025).

Serving size specifications: Recommended serving sizes must be clearly indicated with maximum daily intake guidance.

Warnings for sensitive populations: Products must carry warnings for pregnant women, nursing mothers, and individuals with gastrointestinal conditions (Younes et al., 2018).

Distinction between product types: Labels must clearly distinguish between decolorized (purified) and non-decolorized preparations.

7.3. Regulatory Actions

The following regulatory actions are recommended:

Risk-based classification: Products should be categorized based on HAD content rather than the presence of Aloe vera material per se. Products with HAD content below 0.1 ppm should be considered low-risk; those above 1 ppm require strict regulation or prohibition.

Exposure monitoring: Regular market surveillance to monitor HAD concentrations in commercial products (Di Minno et al., 2024). Market surveillance of botanical food products is essential, and a more rigorous approach is needed (Baldi et al., 2021).

Intake surveys: Conduct consumption surveys specific to Aloe vera beverages and supplements to refine exposure estimates.

Dynamic regulation: Regulatory frameworks must be adaptable to accommodate new scientific evidence and the outcome of the pending appeal before the Court of Justice (European Commission, 2025). Products should be placed under monitoring (Annex III, Part C of Regulation 1925/2006) if data are insufficient for definitive prohibition.

Compound formulation considerations: For health foods combining Aloe vera with other anthraquinone-containing ingredients such as cassia seed, rhubarb, senna leaf, or polygonum multiflorum, specific attention must be paid to cumulative HAD exposure (Cao et al., 2025).

8. Discussion

8.1. Hazard vs. Risk: The Regulatory Distinction

The 2024 annulment of the EU ban on Aloe vera preparations by the General Court serves as a powerful precedent for the principle that hazard identification alone is insufficient to justify regulatory action in the absence of demonstrated risk under actual exposure conditions (General Court of the European Union, 2024). The Court explicitly found that the European Commission exceeded its implementing powers by prohibiting preparations rather than substances, and by failing to demonstrate that EFSA had established a "potential risk" under normal conditions of consumption (General Court of the European Union, 2024).

However, it is critical to note that the General Court did not conclude that Aloe HADs are safe, nor did it overturn EFSA's toxicological assessment (General Court of the European Union, 2024). The judgment was based on a legal interpretation of Regulation (EC) No 1925/2006, specifically finding that the Commission could not prohibit "preparations" containing HADs when the regulation only permits the prohibition of "substances" or "ingredients containing substances" (General Court of the European Union, 2024).

More importantly, the European Commission appealed the General Court's judgment on 22 January 2025 (Case C-38/25 P), and the appeal remains pending before the Court of Justice of the European Union (European Commission, 2025). The Commission argues that the General Court erred in law by declaring that Regulation (EC) No 1925/2006 establishes two cumulative requirements for prohibiting substances and preparations (European Commission, 2025). The Commission also alleges that the General Court erred by failing to fulfill its obligation to state reasons and by exceeding its powers of review in scientific matters regarding whether HADs are harmful to health (European Commission, 2025). Therefore, the regulatory status of Aloe vera preparations in the EU remains uncertain pending the outcome of this appeal.

8.2. The General Court's Reasoning on the "Preparations" Issue

The General Court's reasoning focused on whether the concept of "preparations" in the contested regulation fell within the scope of Article 8 of Regulation (EC) No 1925/2006. The Court found that Regulation No 1925/2006 permits the inclusion in Part A of Annex III only of a "substance" or an "ingredient containing [that] substance" (General Court of the European Union, 2024). The same applies for inclusion in Part C of that annex, which is only permitted for a "substance" (General Court of the European Union, 2024).

The Court emphasized that the concept of "preparations" in the contested provisions has a broader scope and meaning than the concepts of "substances" and "ingredients," within the meaning of Article 8 of Regulation No 1925/2006, and cannot be substituted for them (General Court of the European Union, 2024). The Court noted that Recital 10 of the contested regulation acknowledges that during manufacture, HADs can be removed from the botanical preparations through filtering processes, resulting in products that contain those substances only at trace levels as impurities (European Commission, 2021; General Court of the European Union, 2024). Despite this, the regulation prohibited all preparations regardless of HAD content (General Court of the European Union, 2024).

The Commission appears to have assumed that the insufficiency of data regarding a daily intake that does not give rise to concerns for health authorized it to suppose that no level of safe use of HADs exists, so that it could prohibit them in their totality (General Court of the European Union, 2024). The Court found this approach to exceed the Commission's implementing powers under Regulation (EC) No 1925/2006 (General Court of the European Union, 2024).

8.3. Product-Specific Toxicology

The weight of scientific evidence supports the distinction between non-decolorized and purified preparations in terms of toxicological profile:

Non-decolorized extracts containing high HAD concentrations (aloin >60 ppm) have demonstrated clear carcinogenic potential in animal studies, with increased incidence of colon adenomas and carcinomas (National Toxicology Program, 2013; Boudreau et al., 2013). These findings are consistent with other studies involving non-decolorized, high-anthraquinone aloe preparations (Yokohira et al., 2009).

Purified (decolorized) preparations with total anthraquinones <0.1 ppm have shown no toxicologically significant findings, with a NOAEL >1,845 mg/kg bw/day in a 90-day rat study (Shao et al., 2013). Genotoxicity testing of purified preparations with aloin content <10 ppm has consistently demonstrated negative results in validated test systems (Di Minno et al., 2024; Hu et al., 2021).

The primary issue highlighted in stakeholder feedback on the draft regulation is that the draft prohibits the use of Aloe leaf extracts "containing HADs" in foods and food supplements, but no guidance has been provided on appropriate analytical methodology for quantifying levels of HADs, or indeed a limit of detection or limit of quantification (Baldi et al., 2021). Furthermore, the feedback presented additional criticisms, such as the limited number of toxicological studies available for EFSA's safety assessment, and the use of test samples poorly representative of marketed Aloe products (Baldi et al., 2021).

8.4. Mode of Action and Risk Characterization

The PBK modeling-facilitated QIVIVE approach has elucidated the mode of action underlying aloe-emodin toxicity and provided quantitative BMDL₁₀ values for risk characterization (Ren et al., 2024). The mechanism appears to involve ROS-mediated oxidative stress, with hepatotoxicity predicted to be a more sensitive endpoint than nephrotoxicity (Ren et al., 2024). This understanding supports the threshold-based approach implicit in MOE calculations, as ROS-mediated effects may exhibit a dose-response relationship with a practical threshold.

The endoplasmic reticulum stress response has been identified as involved in apoptosis induced by aloe-emodin in HK-2 cells (Zhu et al., 2012), providing a mechanistic basis for nephrotoxicity. Additionally, fermented Aloe arborescens leaf extract has shown potential therapeutic benefits, including attenuation of ethanol-induced increases in aspartate aminotransferase, alanine aminotransferase, and triglyceride levels, as well as regulation of cytochrome P450 2E1, superoxide dismutase, and glutathione levels (Kim et al., 2023). These findings highlight the complexity of Aloe preparations and the importance of considering both adverse and protective effects.

8.5. The BMDL/MOE Discussion

The MOE equation (MOE = BMDL₁₀ / Estimated Daily Intake) is scientifically valid, but a critical methodological consideration must be emphasized: a BMDL derived from hepatotoxicity, ROS generation, or Nrf2 activation cannot automatically be treated as a cancer/genotoxicity point of departure. The endpoint underlying the BMDL must match the risk question. For cancer risk characterization, the BMDL should ideally be derived from the carcinogenicity endpoint itself (e.g., from the NTP studies) or from a mechanistically relevant genotoxicity endpoint. For purified low-HAD preparations where the primary concern is not carcinogenicity but potential non-genotoxic effects (hepatotoxicity, nephrotoxicity), a BMDL derived from these endpoints may be appropriate.

8.6. Uncertainties and Future Research

Several uncertainties remain in the risk assessment of Aloe vera preparations:

Mixture effects: HADs are present as complex mixtures in botanical products, and potential interactions between aloe-emodin and other hydroxyanthraquinones (rhein, emodin, chrysophanol, physcion) may affect biokinetics and toxicity (Ren et al., 2024). The high glucuronidation activity of UGT1A9 towards anthraquinones highlights potential drug interactions (Wu et al., 2014).

Human relevance: The extrapolation from rodent studies to human risk requires refinement using human-specific PBK models and, where available, human biomonitoring data. The species differences in enterohepatic circulation are particularly relevant (Ren et al., 2024).

Chronic exposure data: While the 90-day NOAEL for purified preparations provides confidence in sub-chronic safety, long-term data on purified preparations would strengthen the risk assessment (Shao et al., 2013).

Product variability: The significant variation in HAD concentrations among commercial products highlights the need for standardized manufacturing processes and quality control (Di Minno et al., 2024). Further toxicological studies remain necessary to establish the maximum permissible limit of HAD contaminants in Aloe gel, considering daily doses and maximum duration of treatments (Baldi et al., 2021).

Regulatory science: The approval status and regulatory recommendations for health foods containing Aloe vera raw materials warrant continued attention, particularly regarding safety assessment data and labeling for Aloe vera ingredients (Cao et al., 2025; Fu et al., 2025).

Pending litigation: The outcome of the European Commission's appeal (Case C-38/25 P) before the Court of Justice will have significant implications for the regulatory status of Aloe vera preparations in the EU (European Commission, 2025). The Court of Justice's ruling on the legal interpretation of Regulation (EC) No 1925/2006 and the scope of the Commission's implementing powers will determine whether the General Court's annulment of Regulation (EU) 2021/468 is upheld or overturned (European Commission, 2025).

9. Conclusions

The scientific evidence supports a differentiated, risk-based regulatory approach for Aloe vera beverages and food supplements, while acknowledging the ongoing legal uncertainty in the EU:

1. Hazard is established for HADs, including genotoxicity and carcinogenicity of non-decolorized extracts (Younes et al., 2018; National Toxicology Program, 2013; Boudreau et al., 2013). However, hazard does not equate to risk under all exposure conditions (General Court of the European Union, 2024). The General Court's judgment annulled Regulation (EU) 2021/468 based on a legal interpretation of the Commission's implementing powers, not on a scientific finding that HADs are safe (General Court of the European Union, 2024).

2. Purified (decolorized) preparations with HAD content <10 ppm have demonstrated no genotoxicity in validated test systems and a NOAEL >1,845 mg/kg bw/day in sub-chronic studies (Shao et al., 2013; Di Minno et al., 2024; Hu et al., 2021). Aloe gel, when properly prepared, is characterized by minimal amounts of HADs, only present as contaminants during extraction (Baldi et al., 2021).

3. PBK modeling-facilitated QIVIVE has provided predicted BMDL₁₀ values for aloe-emodin, enabling MOE-based risk characterization (Ren et al., 2024). However, a BMDL derived from hepatotoxicity, ROS, or Nrf2 activation cannot automatically be treated as a cancer/genotoxicity point of departure; the endpoint underlying the BMDL must match the risk question.

4. Quantitative concentration data from commercial beverages show aloin A and B concentrations ranging from 6.05 to 337.98 ng/mL and 8.84 to 346.89 ng/mL, respectively (Di Minno et al., 2024). A 2024 study found no mutagenicity in the reported Ames experiments for the tested commercial Aloe vera beverages (Di Minno et al., 2024).

5. Exposure assessment indicates that estimated daily intakes from properly purified products are below the predicted BMDL₁₀ values, suggesting favorable MOE values for non-cancer endpoints (Ren et al., 2024).

6. Proposed permissible limits are provided for different product categories based on exposure scenarios, ranging from <0.1 ppm for daily consumption beverages to <1.0 ppm for food supplements (Table 3). These limits are proposed as provisional quality-control and risk-management targets rather than universally valid health-based permissible limits.

The path forward for food control authorities lies in establishing harmonized analytical standards for HAD quantification, refining exposure assessments through consumption surveys, implementing MOE-based risk management that distinguishes between high-HAD and low-HAD preparations, and maintaining dynamic regulatory frameworks that adapt to emerging scientific evidence and legal developments. For health foods combining Aloe vera with other anthraquinone-containing ingredients, cumulative exposure assessment is essential (Cao et al., 2025). The outcome of the European Commission's appeal before the Court of Justice (Case C-38/25 P) will be critical in determining the future regulatory landscape for Aloe vera preparations in the EU (European Commission, 2025). Regulatory action must be proportionate and anchored in demonstrated risk, not merely hazard identification.

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एलोभेरा जुसको सुरक्षाको बारेमा वैज्ञानिक सारांश

परिचय

एलोभेरालाई हामी घ्यूकुमारी भनेर पनि चिन्छौं l यो एक यस्तो बोट हो जसको प्रयोग शताब्दीयौंदेखि औषधिको रूपमा हुँदै आएको छ। आजकल यसलाई पाचन स्वास्थ्य सुधार्न, रोग प्रतिरोधात्मक क्षमता बढाउन र एन्टिअक्सिडेन्टको रूपमा विभिन्न खानेकुरा र पेय पदार्थहरूमा प्रयोग गरिन्छ। तर, यसको सुरक्षालाई लिएर वैज्ञानिकहरू र नियामक निकायहरूबीच लामो समयदेखि गहिरो बहस चलिरहेको छ। यस बहसको मुख्य कारण एलोभेरामा पाइने हाइड्रोक्सीएन्थ्रासिन डेरिभेटिभ (HAD) नामक रासायनिक यौगिकहरू हुन्, जसमा एलोइन ए, एलोइन बी, एलो-इमोडिन, इमोडिन, र क्राइसोफानोल जस्ता पदार्थहरू समावेश छन्।

एलोभेराका सबै उत्पादनहरू एउटै हुँदैनन्। कुनै उत्पादन सुरक्षित छ वा असुरक्षित भन्ने कुरा धेरै कुरामा निर्भर गर्दछ: बोटको कुन भाग प्रयोग गरियो (पातको भित्री जेल वा बोक्रा), कसरी प्रशोधन गरियो (HAD हटाइयो कि हटाइएन), अन्तिम उत्पादनमा HAD को कति मात्रा छ, र हामीले कति मात्रामा र कति लामो समयसम्म सेवन गर्छौं।

HAD भनेको के हो र किन यो चिन्ताको विषय हो?

HAD भनेको एलोभेराको पातको बोक्रामा पाइने प्राकृतिक रासायनिक पदार्थ हो। वैज्ञानिक अध्ययनहरूले यी यौगिकहरूको बारेमा केही चिन्ताजनक कुराहरू पत्ता लगाएका छन्। पहिलो कुरा त, केही HAD यौगिकहरूले प्रयोगशालामा कोशिकाको DNA मा क्षति पुर्याउन सक्ने प्रमाणहरू छन्, जसलाई वैज्ञानिक भाषामा जीनोटोक्सिसिटी भनिन्छ। दोस्रो कुरा, उच्च मात्रामा HAD भएका अपरिष्कृत एलोभेरा एक्सट्र्याक्टले पशु अध्ययनहरूमा ठूलो आन्द्राको क्यान्सर निम्त्याएको देखाइएको छ, जसलाई कार्सिनोजेनिसिटी भनिन्छ।

तर, एउटा महत्त्वपूर्ण कुरा बुझ्नु जरुरी छ : सबै HAD हरू एउटै हुँदैनन्, र सबै एलोभेरा उत्पादनहरूमा HAD को मात्रा एउटै हुँदैन। उत्पादनको सुरक्षा मुख्यतया HAD को मात्रामा निर्भर गर्दछ, र यो मात्रा प्रशोधन विधिअनुसार निकै फरक हुन सक्छ।

वैज्ञानिक अध्ययनका मुख्य निष्कर्षहरू

उच्च मात्रामा HAD भएका पूरा-पातको एक्सट्र्याक्टहरूको बारेमा गरिएको एक प्रमुख अध्ययनमा, वैज्ञानिकहरूले मुसाहरूलाई ६० पिपिएम (प्रति मिलियन अंश) सम्मको एलोइन युक्त पानी खुवाए। दुई वर्षको अध्ययनपछि, ती मुसाहरूमा ठूलो आन्द्राको क्यान्सरको घटनामा उल्लेखनीय वृद्धि देखियो। यस अध्ययनको आधारमा, अनुमान गरिएको छ कि यदि कुनै व्यक्तिले दैनिक १ मिग्रा/किग्रा शरीरको तौलको दरमा अपरिष्कृत एलोभेरा एक्सट्र्याक्ट सेवन गर्छ भने, १०,००० मध्ये लगभग ७ जनामा जीवनकालमा क्यान्सर विकसित हुन सक्छ। यदि सेवन ६३.८ मिग्रा/किग्रा/दिनसम्म पुग्छ भने, यो जोखिम १०० मध्ये ५ जनासम्म पुग्न सक्छ।

यसको विपरीत, जब वैज्ञानिकहरूले शुद्धीकृत (डिकोलराइज्ड) एलोभेरा जुसको परीक्षण गरे, जसमा HAD को मात्रा अत्यन्तै न्यून (०.१ पिपिएम भन्दा कम) थियो, तिनीहरूले पूर्ण रूपमा फरक परिणाम पाए। ९०-दिनसम्म मुसाहरूलाई यो जुस खुवाउँदा, १,८४५ मिग्रा/किग्रा शरीरको तौल/दिनसम्मको उच्च मात्रामा पनि कुनै विषाक्तता वा प्रतिकूल प्रभाव देखिएन। यो मात्रा मानवले सामान्यतया सेवन गर्ने भन्दा धेरै गुणा बढी हो। त्यस्तै, १० पिपिएम भन्दा कम एलोइन भएका शुद्धीकृत उत्पादनहरूले DNA क्षति पुर्याउने क्षमता देखाएनन्। यी निष्कर्षहरूले संकेत गर्छन् कि HAD नै एलोभेरा उत्पादनहरूको विषाक्तताको मुख्य कारण हो, र यदि यसलाई हटाइयो भने उत्पादन सुरक्षित हुन सक्छ l

बजारमा पाइने एलोभेरा जुसहरूको विश्लेषण गर्दा, वैज्ञानिकहरूले एलोइनको मात्रा निकै फरक-फरक पाए। कुनै जुसमा एलोइनको मात्रा ६.०५ नेनोग्राम प्रति मिलिलिटर जत्तिकै कम थियो भने कुनैमा ३३७.९८ नेनोग्राम प्रति मिलिलिटरसम्म पाइयो। यसको अर्थ हो, बजारमा पाइने केही उत्पादनहरूमा HAD को मात्रा अत्यन्तै कम छ भने केहीमा उच्च। त्यसैले, एउटै ब्रान्डको उत्पादन अर्को भन्दा धेरै सुरक्षित हुन सक्छ, र यो कुरा उपभोक्ताले लेबल हेरेर मात्र थाहा पाउन सक्छ।

सन् २०२४ मा गरिएको एउटा अध्ययनमा, पाँच वटा व्यावसायिक एलोभेरा जेल पेय पदार्थहरूको एम्स परीक्षण गरियो, जुन ब्याक्टेरियामा उत्परिवर्तन हुन्छ कि हुँदैन भनेर जाँच गर्ने विश्वसनीय प्रयोगशाला विधि हो। अचम्मको कुरा, सबैभन्दा धेरै एलोइन भएको नमूनाले पनि कुनै उत्परिवर्तनशीलता देखाएन। यसले संकेत गर्छ कि उचित प्रशोधन विधि अपनाएर उत्पादन गरिएका एलोभेरा जुसहरू सुरक्षित हुन सक्छन्, तर यसको लागि निर्माताहरूले कडा गुण नियन्त्रण बिधि अपनाउनु अत्यन्तै आवश्यक छ।

वैज्ञानिकहरूले जोखिमको मार्जिन (Margin of Exposure - MOE) नामक विधि प्रयोग गरी एलोभेरा उत्पादनहरूको सुरक्षा मूल्यांकन गर्दछन्। यो विधि निकै सरल छ: पशु अध्ययनबाट प्राप्त हुने त्यो मात्रा (जसमा १०% जनसंख्यामा प्रतिकूल प्रभाव देखिन्छ) लाई मानवले दैनिक सेवन गर्ने मात्राले भाग गरिन्छ। यदि यो गणना गर्दा १०,००० भन्दा बढी आउँछ भने, त्यो जोखिम स्वीकार्य मानिन्छ। शुद्धीकृत, कम-HAD उत्पादनहरूको लागि, यो मान १०,००० भन्दा धेरै बढी हुने अनुमान गरिएको छ, जसको अर्थ ती उत्पादनहरू सुरक्षित हुन सक्छन।

युरोपेली संघमा कानूनी अवस्था

सन् २०१८ मा, युरोपेली खाद्य सुरक्षा प्राधिकरण (EFSA) ले एउटा महत्त्वपूर्ण वैज्ञानिक राय प्रकाशित गर्यो। तिनीहरूले निष्कर्ष निकाले कि HAD हरू जीनोटोक्सिक र कार्सिनोजेनिक मानिनुपर्छ, र त्यसैले यसको "सुरक्षित दैनिक सेवन" स्थापित गर्न सकिदैन। यस रायको आधारमा, युरोपेली आयोगले सन् २०२१ मा एउटा कानून (नियमन २०२१/४६८) जारी गर्यो, जसले HAD युक्त एलो प्रजातिका सबै तयारीहरूलाई खाद्य पदार्थमा प्रयोग गर्न प्रतिबन्ध लगायो। यसको मतलब, चाहे HAD को मात्रा जति सुकै कम किन नहोस्, सबै एलोभेरा उत्पादनहरू युरोपेली बजारबाट हटाइयो।

तर, नोभेम्बर २०२४ मा, युरोपेली संघको सामान्य अदालतले यो प्रतिबन्ध खारेज गर्यो। अदालतले के तर्क गर्यो भने आयोगले "पदार्थ" को सट्टा "तयारीहरू" प्रतिबन्ध गरेर आफ्नो अधिकारको दायरा नाघ्यो। अदालतले यो पनि भन्यो कि सबै तयारीहरूमा HAD को मात्रा एउटै हुँदैन; केही तयारीहरूमा HAD को मात्रा अत्यन्तै न्यून (ट्रेस) हुन्छ, र तिनीहरूलाई पनि प्रतिबन्ध लगाउनु अनुपयुक्त थियो। साथै, EFSA ले "सामान्य उपभोग अवस्थाहरूमा सम्भावित जोखिम" स्थापित गरेको थिएन, जुन कानूनले प्रतिबन्ध लगाउन अनिवार्य गरेको थियो।

तर, कथा यहाँ सकिएको छैन। जनवरी २०२५ मा, युरोपेली आयोगले सामान्य अदालतको निर्णयको विरुद्ध उच्च अदालतमा अपील गर्यो। अहिले यो मुद्दा युरोपेली संघको अदालतमा विचाराधीन छ, र अन्तिम निर्णय आउन अझै केही समय लाग्नेछ। यसको अर्थ हो, युरोपमा एलोभेरा उत्पादनहरूको कानूनी स्थिति अहिले अनिश्चित छ।

उपभोक्ताहरूको लागि सुझावहरू

यदि तपाईं एलोभेरा जुस वा खाद्य पूरक सेवन गर्दै हुनुहुन्छ भने, केही कुराहरूमा विशेष ध्यान दिनु आवश्यक छ।

सबैभन्दा पहिले, उत्पादनको लेबल राम्रोसँग पढ्नुहोस्। शुद्धीकृत उत्पादनहरूमा HAD को मात्रा अत्यन्तै कम हुन्छ, त्यसैले ती सुरक्षित हुन्छन्। यदि सम्भव छ भने, उत्पादनमा एलोइन र एलो-इमोडिनको मात्रा कति छ भनी पनि हेर्नुहोस्।

त्यस्तै, निर्माताले सिफारिस गरेको मात्रा भन्दा बढी सेवन नगर्नुहोस्। "धेरै राम्रो" भन्दै बढी मात्रामा सेवन गर्नु कहिल्यै राम्रो हुँदैन। गर्भवती महिला, स्तनपान गराउने आमा, र पाचन समस्या भएका व्यक्तिहरूले त झन् विशेष सावधानी अपनाउनु पर्छ।

अन्त्यमा, पूरा-पातको वा बोक्रा सहितको उत्पादनहरू कहिल्यै नलिनुहोस्। यी उत्पादनहरूमा HAD को मात्रा उच्च हुन्छ र तिनीहरू असुरक्षित हुन सक्छन्। सधैं भित्री जेलबाट मात्र बनेका उत्पादनहरू खोज्नुहोस्।

निष्कर्ष

एलोभेरा आफैंमा खतरनाक होइन, तर यसको प्रशोधन र HAD को मात्राले यसको सुरक्षा निर्धारण गर्दछ। अपरिष्कृत, पूरा-पातका उत्पादनहरूमा क्यान्सरको जोखिम हुन सक्छ र ती प्रयोग नगर्नु नै उत्तम हो। तर, एलोभेरालाई सही तरिकाले प्रशोधन गरियो र HAD को मात्रा न्यूनतममा राखियो भने, यो सुरक्षित रूपमा सेवन गर्न सकिन्छ भन्ने वैज्ञानिक प्रमाणहरूले संकेत गर्दछ । उपभोक्ताको रूपमा, हामीले लेबल ध्यानपूर्वक पढेर मात्र गुणस्तरीय, शुद्धीकृत उत्पादनहरूको सेवन गर्नुपर्छ, र सधैं सिफारिस गरिएको मात्रालाई पालना गर्नुपर्छ।

मुख्य सन्देश

एलोभेराको सुरक्षा यसको प्रशोधनमा निर्भर गर्दछ। शुद्धीकृत, कम-HAD उत्पादनहरू सुरक्षित छन् भने अपरिष्कृत, उच्च-HAD उत्पादनहरू असुरक्षित हुन सक्छन्। सधैं लेबल पढ्नुहोस्, सिफारिस गरिएको मात्रा पालना गर्नुहोस्, र गुणस्तरीय उत्पादन मात्र सेवन गर्नुहोस्।

सन्दर्भहरू

यो सारांश निम्न वैज्ञानिक अध्ययनहरूमा आधारित छ:

Boudreau, M. D., et al. (2013). Toxicological Sciences, 131(1), 26-39.

Di Minno, A., et al. (2024). Food Safety and Health, 2(4), 489-496.

European Commission. (2021). Regulation (EU) 2021/468.

European Commission. (2025). Appeal C-38/25 P.

European Food Safety Authority. (2005). EFSA Journal, 3(3), 282.

European Food Safety Authority. (2022). EFSA Supporting Publications, 19(10), EN-7636.

General Court of the European Union. (2024). Case T-189/21.

Hu, J., et al. (2021). Toxicology Reports, 8, 511-519.

National Toxicology Program. (2013). NTP TR 577.

Ren, Q., et al. (2024). Journal of Agricultural and Food Chemistry, 72(29), 16163-16176.

Shao, A., et al. (2013). Food and Chemical Toxicology, 57, 161-170.

Younes, M., et al. (2018). EFSA Journal, 16(1), 5090.