Aloe vera

What it is

Aloe vera is a succulent, cactus-like plant of the Lily family whose leaves yield two very different materials: the clear inner gel and the bitter yellow latex from the leaf rind. The rind latex contains anthraquinones (hydroxyanthracene derivatives such as aloin, aloe-emodin and emodin), which are the laxative-active constituents; the gel contains sugars, enzymes, vitamins, minerals and amino acids. Oral products range from decolorized gel drinks to non-decolorized whole-leaf extracts, which differ greatly in anthraquinone content. Extracts of the leaf rind latex are used in small amounts as a food flavouring and in larger amounts in dietary supplements.

What the research says

The honest summary is that oral aloe vera has been studied for far more conditions than it has been shown to help. The clearest human signal is a small meta-analysis of three placebo-controlled trials in irritable bowel syndrome (151 people in total), which found a modest improvement in symptom scores; the authors themselves flag unclear randomisation, a high drop-out rate in one trial and only three studies. A 44-patient trial in active ulcerative colitis found a better clinical response than placebo but no difference on sigmoidoscopic scores or laboratory measures. Against that, the anthraquinone fraction is a stimulant laxative with real safety questions: a two-year rodent study found whole-leaf extract carcinogenic to the large intestine of rats, EFSA concluded in 2018 that hydroxyanthracene derivatives should be treated as genotoxic and carcinogenic unless shown otherwise, and about a dozen published cases of clinically apparent liver injury have followed oral use.

Evidence grade: Limited evidence.

What goes wrong

A two-year drinking-water study found non-decolorized Aloe vera whole-leaf extract caused large-intestinal tumours in rats, though not in mice. (Source 1)

• Animal study, Certainty not rated.
• Size: F344/N rats and B6C3F1 mice, 48 per sex per group.
• Who: F344/N rats dosed at 0.5, 1 and 1.5% and B6C3F1 mice dosed at 1, 2 and 3% in drinking water.
• How long: 2 years (13-week study preceded it)
• Result: incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon significantly higher than controls in male and female rats at 1% and 1.5%; no large-intestinal neoplasms in mice or in the 0 or 0.5% rat groups; survival decreased in 1.5% female rats.
• Funding: US National Toxicology Program (government)

These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats.

At least a dozen published cases of clinically apparent liver injury have followed oral aloe vera, typically 3 to 24 weeks after starting it. (Source 2)

• Case series, Low certainty.
• Size: at least a dozen published or mentioned cases.
• Who: people taking oral aloe vera, usually in high doses for constipation, dyspepsia, aging, weight loss or wellness.
• How long: onset typically between 3 and 24 weeks after starting.
• Result: hepatocellular pattern resembling acute viral hepatitis; LiverTox likelihood score B (likely but rare cause of clinically apparent liver injury); rarely severe and no fatal cases reported.
• Funding: independent (US National Institutes of Health)

Liver injury attributable to oral preparations of aloe vera was first reported in 2005 and at least a dozen cases of clinically apparent liver injury have been published or mentioned in the literature.

Chronic use of aloe for constipation can discolour the colonic lining, and diarrhoea, abdominal discomfort and nausea are reported minor effects. (Source 3)

• Expert review, not systematic, Low certainty.
• Size: not stated.
• Who: people using oral aloe vera, particularly long-term for constipation.
• How long: chronic use.
• Result: pseudo-melanosis coli described with chronic use; minor effects diarrhoea, abdominal discomfort, nausea; rare hypersensitivity, skin rash, allergic dermatitis.
• Funding: independent (US National Institutes of Health)

Aloe vera is generally tolerated without adverse events; minor side effects may include diarrhea, abdominal discomfort and nausea. Chronic use for constipation can lead to discoloration of the colon (pseudo-melanosis coli).

EFSA's 2018 position is that hydroxyanthracene derivatives, the laxative constituents of aloe, should be treated as genotoxic and carcinogenic unless specific data show otherwise. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable (review of in vitro, in vivo and epidemiological data)
• Who: not applicable.
• How long: opinion adopted 22 November 2017, published 2018.
• Result: no safe daily intake could be set; aloe-emodin genotoxic in vivo; whole-leaf aloe extract and danthron carcinogenic in animals.
• Funding: European Food Safety Authority (public body)

the Panel concluded that hydroxyanthracene derivatives should be considered as genotoxic and carcinogenic unless there are specific data to the contrary

What the evidence supports

A meta-analysis of three placebo-controlled randomised trials found oral Aloe vera improved irritable bowel syndrome symptom scores compared with placebo. (Source 5)

• Meta-analysis, Low certainty.
• Size: 151 patients with IBS across 3 randomised controlled trials.
• Who: adults with irritable bowel syndrome.
• How long: trials conducted within 5 months.
• Result: standardized mean difference 0.41 (95% CI 0.07 to 0.75), P = 0.020; response rate pooled risk ratio 1.69 (95% CI 1.05 to 2.73), P = 0.030; no significant heterogeneity (P = 0.900, I2 = 0%)
• Funding: not stated.

The meta-analysis showed a significant difference for patients with AV compared to those with placebo regarding improvement in IBS symptom score (standardized mean difference, 0.41; 95% CI, 0.07–0.75; P = 0.020).

What the evidence does not support

In a randomised, double-blind, placebo-controlled trial in active ulcerative colitis, oral aloe vera gel did not differ from placebo on sigmoidoscopic scores or laboratory variables, and the difference in clinical remission was not statistically significant. (Source 6)

• Randomized trial, Low certainty.
• Size: 44 evaluable patients (30 aloe vera, 14 placebo)
• Who: hospital outpatients with mildly to moderately active ulcerative colitis.
• How long: 4 weeks.
• Result: clinical remission 9/30 (30%) with aloe vera vs 1/14 (7%) with placebo, P = 0.09, odds ratio 5.6 (0.6-49); improvement 11/30 (37%) vs 1/14 (7%), P = 0.06, odds ratio 7.5 (0.9-66); clinical response 14/30 (47%) vs 2/14 (14%), P < 0.05, odds ratio 5.3 (1.0-27); sigmoidoscopic scores and laboratory variables not significantly different.
• Funding: not stated.

Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo.

Where the evidence is mixed

The same meta-analysis states its own evidence base is only three trials and cannot show long-term or rare harms. (Source 7)

• Meta-analysis, Low certainty.
• Size: 151 participants across 3 trials.
• Who: adults with irritable bowel syndrome.
• How long: within 5 months.
• Result: no quantitative estimate; authors' own statement of limitation.
• Funding: not stated.

The long-term safety or rare adverse events of AV could not be demonstrated in this meta-analysis from the 3 prospective RCTs of 151 study participants conducted within 5 months

What official bodies say

In 2002 the US FDA ruled that aloe as a stimulant laxative ingredient in over-the-counter drug products is not generally recognized as safe and effective, because no mutagenicity, genotoxicity or carcinogenicity data were submitted. (Source 8)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: US over-the-counter laxative drug products.
• How long: final rule published 9 May 2002.
• Result: aloe (including aloe extract and aloe flower extract) deemed not generally recognized as safe and effective or misbranded.
• Funding: US Food and Drug Administration (government)

The Food and Drug Administration (FDA) is issuing a final rule stating that the stimulant laxative ingredients aloe (including aloe extract and aloe flower extract) and cascara sagrada

The European Commission prohibited aloe-emodin, emodin, danthron and preparations from aloe leaf containing hydroxyanthracene derivatives in food in 2021. (Source 9)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: foods placed on the EU market.
• How long: Regulation adopted 18 March 2021.
• Result: substances added to Annex III Part A of Regulation (EC) No 1925/2006 (prohibited); EFSA had earlier advised against long-term use and high doses.
• Funding: European Commission (government)

hydroxyanthracene derivatives in food can improve bowel function, but advised against long-term use and consumption at high doses due to potential safety concerns such as the danger of electrolyte imbalance, impaired function of the intestine and dependence on laxatives

Where the research disagrees

Whether oral aloe vera does anything useful for gut symptoms

• Hong et al., meta-analysis in Journal of Neurogastroenterology and Motility (2018), meta-analysis of 3 RCTs, 151 participants, authors note unclear randomisation and a high drop-out rate in one trial: AV is effective and safe for the treatment of patients with IBS compared to placebo. (Source 5)
• Langmead et al., randomised placebo-controlled trial in Alimentary Pharmacology and Therapeutics (2004), randomised, double-blind, placebo-controlled trial, 44 evaluable patients, 4 weeks: Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo. (Source 6)

Whether aloe's laxative anthraquinones pose a cancer risk at dietary exposures

• EFSA ANS Panel (opinion adopted 2017, published 2018), review of in vitro, in vivo animal and epidemiological data; no human outcome trials: the Panel concluded that hydroxyanthracene derivatives should be considered as genotoxic and carcinogenic unless there are specific data to the contrary (Source 4)
• US National Toxicology Program, reported in Toxicological Sciences (2013), 2-year rodent drinking-water carcinogenicity study; effect seen only in rats and only at 1% and above: There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. (Source 1)

How much

• Reference intake: No reference intake (RDA or AI) exists for aloe vera anywhere in the literature we searched, because it is a plant extract used as a food flavouring and dietary supplement rather than a nutrient the body requires. (Source 3)
• Upper limit: EFSA (opinion adopted 22 November 2017, published 2018) was unable to set a safe daily intake for hydroxyanthracene derivatives, the laxative constituents of aloe. In 2021 the European Commission prohibited aloe-leaf preparations containing hydroxyanthracene derivatives in food outright. (Source 4)
• Studied: 100 mL of oral aloe vera gel twice daily for 4 weeks in adults with mildly to moderately active ulcerative colitis. (Source 6)
• Studied: Rodent carcinogenicity study doses were 0.5, 1 and 1.5% non-decolorized whole-leaf extract in drinking water for rats and 1, 2 and 3% for mice, over 2 years. (Source 1)

A common belief, and what the research shows

The belief: Aloe vera juice is a gentle, natural digestive tonic that is safe to drink daily.

What the research shows: The literature separates the inner gel from the bitter leaf-rind latex, and it is the latex anthraquinones that act as a stimulant laxative: LiverTox records that "Chronic use for constipation can lead to discoloration of the colon (pseudo-melanosis coli)." The same source records that "Liver injury attributable to oral preparations of aloe vera was first reported in 2005 and at least a dozen cases of clinically apparent liver injury have been published or mentioned in the literature." A two-year rodent study concluded that "These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats." That is an animal result and not a human finding, but it is why EFSA concluded that hydroxyanthracene derivatives "should be considered as genotoxic and carcinogenic unless there are specific data to the contrary".

Questions and answers

What is it?

Aloe vera is a succulent plant grown in dry climates. Its leaves give two different materials: a clear inner gel and a bitter yellow latex from the leaf rind. Oral products are made from either or both, and the rind latex carries the laxative anthraquinones. (Source 3)

What does it do in the body?

Swallowed aloe acts mainly through the anthraquinones in the leaf rind latex, which are phenolic compounds with laxative actions. Aloe leaf material also contains vitamins, enzymes, minerals, sugars, fatty acids and amino acids, but no nutritional role for it in the body has been established. (Source 3)

Is it good or bad for you?

It depends heavily on which preparation and for how long. Short-term, small trials suggest a modest benefit for irritable bowel symptoms, while a trial in ulcerative colitis found no difference from placebo on objective measures. Long-term or high-dose use of the anthraquinone-containing preparations is where the harm sits: European regulators treat those constituents as genotoxic and carcinogenic in the absence of data to the contrary. (Source 4)

How do you get more of it?

Aloe reaches people as a dietary supplement, as a drink, and in very small amounts as a food flavouring. It is not a nutrient, so there is no intake target to reach; the documented routes are simply supplement or flavouring use. (Source 3)

If it is harmful, what reduces it?

The only measure described in the literature is stopping intake, which is also how regulators have acted. The US FDA removed aloe as an over-the-counter stimulant laxative ingredient in 2002, and the European Commission prohibited aloe-leaf preparations containing hydroxyanthracene derivatives in food in 2021. (Source 8)

Why might someone be low in it or missing it?

This does not apply. Aloe vera is a plant extract taken by choice, not a substance the body makes or requires, so nobody can be deficient in it. The only reason someone would have none is that they have not taken any. (Source 3)

Which whole foods contain it or feed it?

Aloe appears in the food supply as a flavouring used in small amounts, and as gel or juice drinks. No ordinary whole food contains it other than the aloe leaf itself. (Source 3)

What happens if you do not have it?

Nothing is known to happen. No deficiency state has been described, and the health claims made for aloe have not been substantiated; the supportive work is largely in vitro and animal research. (Source 3)

How can you test for it?

No blood or stool test measures aloe vera status, and we found none in the literature searched. The only relevant testing is for harm: when aloe-related liver injury occurs, it shows up as a hepatocellular pattern of raised liver enzymes that resembles acute viral hepatitis, which is a test for the injury and not for the substance. (Source 2)

We searched: LiverTox aloe vera monograph, EFSA 2018 hydroxyanthracene opinion, NTP/Toxicological Sciences carcinogenicity report and web searches for aloe vera biomarker or status test; none describes a validated measure of aloe intake or body level

References

1. Toxicological Sciences. Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats. 2013. PMID 22968693, DOI 10.1093/toxsci/kfs275. Read the source
2. National Institute of Diabetes and Digestive and Kidney Diseases, NCBI Bookshelf. Aloe Vera — LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Hepatotoxicity and Mechanism of Injury sections). 2022. Read the source
3. National Institute of Diabetes and Digestive and Kidney Diseases, NCBI Bookshelf. Aloe Vera — LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Background section). 2022. Read the source
4. EFSA Journal, European Food Safety Authority. Safety of hydroxyanthracene derivatives for use in food (EFSA ANS Panel scientific opinion, abstract). 2018. DOI 10.2903/j.efsa.2018.5090. Read the source
5. Journal of Neurogastroenterology and Motility. Aloe vera Is Effective and Safe in Short-term Treatment of Irritable Bowel Syndrome: A Systematic Review and Meta-analysis. 2018. DOI 10.5056/jnm18077. Read the source
6. Alimentary Pharmacology and Therapeutics. Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis. 2004. PMID 15043514, DOI 10.1111/j.1365-2036.2004.01902.x. Read the source
7. Journal of Neurogastroenterology and Motility. Aloe vera Is Effective and Safe in Short-term Treatment of Irritable Bowel Syndrome: A Systematic Review and Meta-analysis (discussion, limitations). 2018. DOI 10.5056/jnm18077. Read the source
8. US Food and Drug Administration, Federal Register 67(90):31125. Status of Certain Additional Over-the-Counter Drug Category II and III Active Ingredients. Final rule (SUMMARY). 2002. PMID 12001972. Read the source
9. European Commission, Official Journal of the European Union. Commission Regulation (EU) 2021/468 amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivatives (recital 3). 2021. Read the source