Experts cool concerns over FDA Aloe vera carcinogenicity study

Scientists from the US Food and Drug Administration published data in the January edition of the journal Toxicological Sciences​ from a toxicology study with Aloe barbadensis​ Miller.

The study was performed because “only limited data are available on the safety of this dietary supplement”​.

The two-year rat study found 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”​.

Unlike products on the market​

However, Roy Upton, executive director of the American Herbal Pharmacopeia, noted that the study used large quantities of high-aloin-yielding products.

“Some of these products averaged 6300 ppm of aloin A and are completely different than many aloe vera juice products on the market that limit aloin to less than 5 ppm,” ​he said. “Additionally, these preparations were administered every day for 2 years.”​

AHP recently published the first pharmacopoeial standard developed for aloe vera leaf and inner leaf juice.

“I am happy that we can clarify the distinctions between the high-aloin-containing products for which safety concerns have been noted and help establish the standards for ensuring the identity, purity, quality, and safety of aloe juice products,” ​he added.

Limit the anthraquinones​

Alexander Schauss, PhD, senior research director at AIBMR Life Sciences, pointed to the anthraquinones and other phenolic substances in parenchyma cells in whole leaf Aloe vera.

“When these cells are included in a gel and ingested they can serve as chemical irritants in the lower intestinal tract since mammals lack an enzyme (beta-glycosidase) necessary to hydrolyze the beta-1 to 4-glycosidic bonds in the gel.” ​

Dr Schauss told NutraIngredients-USA that other recent studies have shown no significant toxicological effect from ingestion of an Aloe vera gel product, which significantly lowered the content of compounds that might induce goblet cell hyperplasia.

A study in the Journal of Food Science​ (2012; Vol. 71, pp. T2-T9) reported a supercritical extraction of aloe gel with significantly lower levels of compounds such as anthraquinones.

“It is also noteworthy to mention that the same investigators studying the same extract [used in ​J. Food Sci. study] found no evidence of mutagenicity in the Ames test or chromosomal aberration test, or the in vivo bone marrow micronucleus test,” ​he said.

“This may suggest that whereas whole-leaf extracts, such as used in the FDA study, can induce gastrointestinal tract insult, Aloe preparations containing low levels of anthraquinones and other GI tract chemical irritants, may not. ​

“Realizing this possibility FDA have indicated that they plan on determining whether decolorized whole-leaf extracts, which are low in anthraquinones and certain phenolics, elicit similar responses to that seen in the GI tract with Aloe whole-leaf extracts. ​

ABC​

Mark Blumenthal, founder & executive director, of the American Botanical Council, concurred that one of the key issues is whether the whole aloe vera leaf extract used in these rat studies is representative of the bulk of the aloe vera material used in the cosmetic and dietary supplement industries.

“From my experience, it is not. ​

“Whole leaf aloe vera extract used here seems to refer to the actual grinding of the entire aloe leaf and the gel contained therein a slurry containing leaf pulp and gel. ​

“When I have visited aloe farms and processing plants in South Texas and Mexico, the aloe leaf is filleted, whereby the gel was cut out from the enclosing green leaf material. As I understand the anatomy of the aloe plant, the aloin and other anthrone compounds (pro-drug compounds with a stimulant laxative effect) that are implicated in the toxicology studies, are found in the inner leaf material, but ​notin the gel. ​

“Most commercial aloe raw materials used for aloe juice, aloe dietary supplements, and aloe-based cosmetics, are usually made from the aloe gel, devoid of the whole leaf material and thus the anthrone compounds,” ​added Blumenthal. 

Erroneous​

Steven Dentali, PhD, Chief Science Officer for the American Herbal Products Association (AHPA) said the the "incorrect test material description by the authors erroneously implies that the common juice-based marketplace aloe products were tested when what was in fact studied were latex-rich materials.​

"In brief, the difference between a decolorized whole leaf extract and a nondecolorized one is that anthraquinones, some of which have been shown to be carcinogenic, have been removed in decolorized whole leaf extracts of aloe vera, which along with inner leaf aloe juice materials, represent the majority of marketplace products.​

"The test material reported on in the published research, as has been well recognized in all previous published accounts, is not representative of the marketplace standard. The marketplace products are charcoal-processed to decolorize them as mentioned in this study, and that material did not cause the effects reported here."​

FDA study ​

Led by Mary Boudreau from the FDA’s Division of Biochemical Toxicology, the researchers spiked the drinking water of lab rats with different levels of extracts from Aloe barbadensis​ Miller

A 13-week study resulted in irritation of the lab animals’ intestine, while a two-year study revealed a decrease in the survival rates of some females receiving drinking water spiked with 1.5% aloe. Both male and female displayed increases in tumors in various parts of the intestine. The carcinogenicity of the aloe used in the study was greater for male animals than females, they added.

The take home message from the study, said Dr Schauss, is that, “consumers should consider limiting chronic ingestion of whole-leaf Aloe extracts and consider extracts low in anthraquinones and phenolics to reduce the risk of adenomas and adenocarcinomas of the large intestine. ​

“Companies manufacturing Aloe vera products have an obligation to provide experimental evidence of safety rather than rely on faith,” ​he added.

Source: Toxicological Sciences​
Volume 131, Number 1, Pages 26-39, doi:10.1093/toxsci/kfs275
“Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats”
Authors: M.D. Boudreau, P.W. Mellick, G.R. Olson, R.P. Felton, B.T. Thorn, F.A. Beland