An Evidence-Based Systematic Review of
Aloe vera by the Natural Standard Research
Catherine Ulbricht, PharmD
Jennifer Armstrong, PharmD
Ethan Basch, MD
Samuel Basch, MD
Steve Bent, MD
Cynthia Dacey, PharmD
Sean Dalton, PhD, MD, MPH
Ivo Foppa, MD, ScD
Nicole Giese, MS
Paul Hammerness, MD
Catherine Kirkwood, MPH, CCCJS-MAC
David Sollars, MAc, HMC
Shaina Tanguay-Colucci, BS
Wendy Weissner, BA
Catherine Ulbricht is afﬁliated to Massachusetts General Hospital, Boston, MA.
Jennifer Armstrong is afﬁliated to University of Rhode Island, Kingston, RI.
Ethan Basch is afﬁliated to Natural Standard Research Collaboration, Cambridge,
Samuel Basch is afﬁliated to Mt. Sinai Medical Center, NY.
Steve Bent is afﬁliated to University of California, San Francisco, CA.
Cynthia Dacey and Nicole Giese are afﬁliated to Natural Standard Research Col-
laboration, Cambridge, MA.
Sean Dalton and Ivo Foppa are afﬁliated to Harvard University, Cambridge, MA.
Paul Hammerness is afﬁliated to Harvard Medical School.
Catherine Kirkwood is afﬁliated to MD Anderson Cancer Center, University of
Tex as , TX.
David Sollars is afﬁliated to New England School of Acupuncture.
Shaina Tanguay-Colucci and Wendy Weissner are afﬁliated to Natural Standard
Journal of Herbal Pharmacotherapy, Vol. 7(3–4), 2007
Available online at http://www.haworthpress.com/web/JHP
2008 by Informa Healthcare USA, Inc. All rights reserved.
doi: 10.1080/15228940802153339 279
280 JOURNAL OF HERBAL PHARMACOTHERAPY
ABSTRACT. An evidence-based systematic review including written
and statistical analysis of scientiﬁc literature, expert opinion, folkloric
precedent, history, pharmacology, kinetics/dynamics, interactions, ad-
verse effects, toxicology, and dosing.
KEYWORDS. Adverse effects, aloe, Aloe vera, dosing, evidence based,
interactions, pharmacodynamics, pharmacology, pharmacokinetics, sys-
SYSTEMATIC AGGREGATION, ANALYSIS, AND REVIEW
OF THE LITERATURE
To prepare each Natural Standard review, electronic searches are con-
ducted in nine databases, including AMED, CANCERLIT, CINAHL, CIS-
COM, the Cochrane Library, EMBASE, HerbMed, International Pharma-
ceutical Abstracts, Medline, and NAPRALERT. Search terms include the
common name(s), scientiﬁc name(s), and all listed synonyms for each
topic. Hand searches are conducted of 20 additional journals (not indexed in
common databases), and of bibliographies from 50 selected secondary ref-
erences. No restrictions are placed on language or quality of publications.
Researchers in the ﬁeld of complementary and alternative medicine (CAM)
are consulted for access to additional references or ongoing research.
All literature is collected pertaining to efﬁcacy in humans (regardless
of study design, quality, or language), dosing, precautions, adverse effects,
use in pregnancy/lactation, interactions, alteration of laboratory assays,
and mechanism of action (in vitro, animal research, and human data).
Standardized inclusion/exclusion criteria are utilized for selection.
Data extraction and analysis are performed by healthcare profession-
als conducting clinical work and/or research at academic centers, using
standardized instruments that pertain to each review section (deﬁning
Ulbricht et al. 281
inclusion/exclusion criteria, and analytic techniques, including validated
measures of study quality). Data are veriﬁed by a second reviewer.
A blinded review is conducted by multidisciplinary research-clinical
faculty at major academic centers with expertise in epidemiology and bio-
statistics, pharmacology, toxicology, CAM research, and clinical practice.
In cases of editorial disagreement, a three-member panel of the editorial
board addresses conﬂicts, and consults experts when applicable. Authors
of studies are contacted when clariﬁcation is required.
Natural standard regularly monitors scientiﬁc literature and industry
warnings. When clinically relevant new data emerge, best efforts are made
to update content immediately. In addition, regular updates with renewed
searches occur every 3 to 18 months, variable by topic.
Synonyms/Common Names/Related Substances:
rAcemannan, Aloe africana,A. arborescens Miller, A. barbadensis,A.
barbadesis,A. capensis,A. ferox,A. latex,A. mucilage,A. perfoliata,
A. perryi Baker, A. spicata, A. vulgari, Barbados aloe, bitter aloe, burn
plant, Cape aloe, Carrisyn, hirukattali, Curac¸ao aloe, elephant’s gall,
ﬁrst-aid plant, Ghai kunwar (Indian), Ghikumar (Indian), Hsiang-
Dan (Chinese), jelly leek, kumari, lahoi, laloi, lily of the desert, Lu-
Hui, medicine plant, Mediterranean aloe, miracle plant, mocha aloes,
musabbar, natal aloes, nohwa, plant of immortality, plant of life, rokai,
sabilla (Spanish), Savila, Socotrine aloe, subr, true aloe, Venezuela
aloe, Za’bila (Swahili), Zanzibar aloe.
rCombination products (example): Mepentol Leche (an emulsion
based on hyper-oxygenated fatty acids, A. barbadensis, and Mimosa
CLINICAL BOTTOM LINE/EFFECTIVENESS
rTransparent gel from the pulp of the meaty leaves of A. vera has been
used topically for thousands of years to treat wounds, skin infections,
282 JOURNAL OF HERBAL PHARMACOTHERAPY
burns, and numerous other dermatologic conditions. Dried latex from
the inner lining of the leaf has traditionally been used as an oral
rThere is strong scientiﬁc evidence in support of the laxative proper-
ties of aloe latex, based on the well-established cathartic properties
of anthroquinone glycosides (found in aloe latex). However, aloe’s
therapeutic value compared with other approaches to constipation
rThere is promising preliminary support from in vitro,animal,and
human studies that topical aloe gel has immunomodulatory properties
that may improve wound healing and skin inﬂammation.
Scientiﬁc Evidence for Common/Studied Uses
See Table 1 for scientiﬁc evidence for common/studied uses.
Natural Standard Evidence-Based Validated Grading RationaleTM
rGrades reﬂect the level of available scientiﬁc evidence in support of
the efﬁcacy of a given therapy for a speciﬁc indication.
TABLE 1. Scientiﬁc evidence for common/studied uses.
Indication Evidence Grade
Constipation (laxative) A
Genital herpes B
Psoriasis vulgaris B
Seborrheic dermatitis B
Aphthous stomatitis C
Cancer prevention C
Diabetes (type 2) C
HIV infection C
Skin burns C
Ulcerative colitis C
Infected surgical wounds D
Pressure ulcers D
Radiation dermatitis D
Ulbricht et al. 283
rExpert opinion and folkloric precedent are not included in this assess-
ment, and are reﬂected in a separate section of each review (“Strength
of Expert Opinion and Historic/Folkloric Precedent”).
rEvidence of harm is considered separately; the grades shown in Table
2 apply only to evidence of beneﬁt.
Historical or Theoretical Uses Which Lack Sufﬁcient Evidence
rAlopecia (hair loss), Alzheimer’s disease, antioxidant,1−3arthri-
tis (osteoarthritis and rheumatoid arthritis), asthma,4bacterial
skin infections,5candidal skin infections,6chronic fatigue syn-
drome, chronic leg ulcers,7congestive heart failure,8corneal
abrasions/ulcers,9coronary artery disease prevention,10 diabetic
ulcers,11 duodenal ulcer, dry skin (aloe gel gloves),12 frostbite,13,14
functional bowel disorders, gastric acid reduction (hyperacidity), gas-
tric ulcer, helminthic infections, hepatitis,15 human papilloma virus16
hyperlipidemia, inﬂammatory bowel disease, lichen planus,17 Parkin-
son’s disease, peptic ulcer,18 periodontal surgical rinse,19 postder-
mabrasion wound healing,20 radioprotection,21 sunburn,22 systemic
lupus erythematosus, tic douloureux,23 untreatable advanced solid
neoplasms,24 urolithiasis (bladder stones), vaginal contraceptive.25
Expert Opinion and Historic Precedent
rTopical aloe ﬁrst gained popularity in the United States in the 1930s
with reports of its success in treating x-ray burns.26−30 Today, A. vera
gel is an ingredient in hundreds of skin lotions and sun blocks,31 and
the gel’s use in cosmetics has been boosted by claims that it possesses
antiaging effects similar to vitamin A derivatives.32
rAloe is popular in traditional Chinese and Ayurvedic medicine. The
Chinese literature describes the skin and the inner lining of aloe leaves
as a “cold, bitter remedy” that can be “downward draining” and used
to clear constipation due to accumulation of “heat” (ﬁre). The gel is
considered “cool and moist.” In Ayurvedic medicine (the traditional
medicine of India), aloe is used internally as a laxative, anthelminthic,
hemorrhoid remedy, and uterine stimulant (menstrual regulator); it is
also used topically, often in combination with licorice root, to treat
eczema or psoriasis. In Arabian medicine, the fresh gel is rubbed
on the forehead as a headache remedy, rubbed on the body to cool
284 JOURNAL OF HERBAL PHARMACOTHERAPY
TABLE 2. Natural Standard Evidence-Based Validated Grading
Level of Evidence Grade Criteria
A (strong scientiﬁc evidence) Statistically signiﬁcant evidence of beneﬁt from
>2 properly randomized trials (RCTs), or
evidence from one properly conducted RCT
and one properly conducted meta-analysis,
or evidence from multiple RCTs with a clear
majority of the properly conducted trials
showing statistically signiﬁcant evidence of
beneﬁt and with supporting evidence in basic
science, animal studies, or theory.
B (good scientiﬁc evidence) Statistically signiﬁcant evidence of beneﬁt from
1–2 properly randomized trials, or evidence of
beneﬁt from ≥1 properly conducted meta-
analysis OR evidence of beneﬁt from >1
cohort/case-control/nonrandomized trials, and
with supporting evidence in basic science,
animal studies, or theory.
C (unclear or conﬂicting scientiﬁc Evidence of beneﬁt from ≥1 small RCT(s)
evidence) without adequate size, power, statistical
signiﬁcance, or quality of design by objective
criteria,∗or conﬂicting evidence from multiple
RCTs without a clear majority of the properly
conducted trials showing evidence of beneﬁt or
ineffectiveness, or evidence of beneﬁt from ≥1
cohort/case-control/nonrandomized trials and
without supporting evidence in basic science,
animal studies, or theory, or evidence of
efﬁcacy only from basic science, animal studies,
D (fair negative scientiﬁc evidence) Statistically sig0niﬁcant negative evidence (i.e.,
lack of evidence of beneﬁt) from cohort/case-
control/nonrandomized trials, and evidence in
basic science, animal studies, or theory
suggesting a lack of beneﬁt.
F (strong negative scientiﬁc evidence) Statistically signiﬁcant negative evidence (i.e.,
lack of evidence of beneﬁt) from ≥1 properly
randomized adequately powered trial(s) of high-
quality design by objective criteria.∗
Lack of evidence†Unable to evaluate efﬁcacy due to lack of
adequate available human data.
*Objective criteria are derived from validated instruments for evaluating study quality, including the 5-
point scale developed by Jadad et al., in which a score below 4 is considered to indicate lesser quality
methodologically (Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized
clinical trials: is blinding necessary? Control Clin Trials 1996;17(1):1–12).
†Listed separately in reviews in the “historical or theoretical uses which lack sufﬁcient evidence” section.
Ulbricht et al. 285
fevers, and is also used for wound healing, conjunctivitis, infection,
rSome naturopaths promote aloe juice as a way to prevent and treat
renal stones.33 Recently, aloe extracts have gained popularity as a
treatment for canker sores, peptic ulcers, and HIV infection. The
inner leaf lining is used orally as a natural laxative.
rMany individuals keep a plant at home (thrives in bright sunlight with
little care), and when faced with a minor burn, gel from a fresh leaf
is applied directly to the affected skin area.
rAloe has been cautiously approved by the expert panel, the German
Commission E, for use in constipation as a second-line agent. A mono-
graph issued by the World Health Organization has also endorsed this
rPreviously, the Food and Drug Administration (FDA) regulated the
use of the laxative component of aloe as a drug, but its topical appli-
cations were not regulated or endorsed. However, because of a failure
to submit further studies on its use as a laxative in 2002, the FDA
recategorized any over the counter “drugs” containing aloe as mis-
branded as a drug. On April 29, 2002, the Federal Register ruled that
aloe products (aloe extract and aloe ﬂower extract) were reclassiﬁed
as category III agents; this ruling became effective on November 5,
2002. As of 2007, there was reported use of aloe extract (aloe species),
and an initial toxicology literature search was in progress. Aloe is not
listed on the FDA’s Generally Recognized As Safe list. Aloe is cur-
rently approved by the US FDA as a food ﬂavoring agent (A. ferox,
A. perryi,A. vera) in accordance with good manufacturing practices.
Brief Safety Summary
rLikely safe: When A. vera gel or extract is used topically to reduce
pain and inﬂammation, enhance healing of skin wounds (abrasions,
cuts, and ulcers), or treat psoriasis, frostbite injury, burns, and HPV I
1Natural Standard Monograph (www.naturalstandard.com). Copyright c
Natural Standard Inc. Commercial distribution or reproduction prohibited.The in-
formation in this monograph is intended for informational purposes only, and is meant
to help users better understand health concerns. Information is based on review of
scientiﬁc research data, historical practice patterns, and clinical experience. This in-
formation should not be interpreted as speciﬁc medical advice. Users should consult
with a qualiﬁed healthcare provider for speciﬁc questions regarding therapies, diagno-
sis and/or health conditions, prior to making therapeutic decisions.
286 JOURNAL OF HERBAL PHARMACOTHERAPY
infections (cold sores). Medical attention should be sought for severe
burns, wounds, or frostbite.
rPossibly safe: When A. vera is taken orally (potential hypoglycemic
properties), or when oral aloe latex is used for short term as a
rLikely unsafe: When oral aloe latex is used as a laxative for prolonged
periods, because of theoretical risk of dehydration and electrolyte im-
balance. Topical aloe gel should be avoided for postoperative wounds,
because of ﬁndings of delayed healing in one trial.36
rRecommended doses are based on those most commonly used in
available trials, or on historical practice. However, with natural prod-
ucts it is often not clear what the optimal doses are to balance efﬁcacy
and safety. Preparation of products may vary from manufacturer to
manufacturer, and from batch to batch within one manufacturer. Be-
cause it is often not clear what the active component(s) of a product
is, standardization may not be possible, and the clinical effects of
different brands may not be comparable.
rStandardized products are not widely available. Although this is likely
not problematic for topical aloe gel, it may pose danger with oral aloe
(because of potential hypoglycemic properties). Oral aloe prepara-
tions often contain 10–30 mg hydroxyanthracene derivatives per daily
dose, calculated as anhydrous aloin.37
rPenalties have been enforced for illegal marketing of A. vera products
in the United States.38
Adult Dosing (Age ≥18)
rGeneral use: Pure A. vera gel is often used liberally on the skin. There
are no available reports of systemic absorption leading to clinically
Ulbricht et al. 287
relevant events. Commercial preparations combined with or without
other active ingredients are available.
rGenital herpes: Hydrophilic cream of 0.5% (by weight) of a 50%
ethanol extract, combined with liquid parafﬁn and castor oil, three
times daily on lesions for ﬁve consecutive days per week, for up to
two weeks has been used.39
rPsoriasis vulgaris: Hydrophilic cream of 0.5% (by weight) of a 50%
ethanol extract of aloe, combined with mineral and castor oils, three
times daily for ﬁve consecutive days per week, for up to four weeks
has been used.40
rConstipation: The dose often recommended is the minimum amount
to maintain a soft stool, typically 0.04–0.17 g of dried juice (corre-
sponds to 10–30 mg hydroxyanthraquinones). As an alternative, in
combination with celandine (300 mg) and psyllium (50 mg), 150 mg
of the dried juice/day of aloe has been found effective as a laxative.41
rDiabetes (type2): 5–15 mL of aloe juice twice daily has been
used.34,35,42 Inconclusive efﬁcacy or safety.
rHIV infection: 1000 mg–1600 mg of acemannan orally in
four equal doses has been used.43,44,45 Inconclusive efﬁcacy or
rNo recommended dosage for injectable acemannan exists to date
because safety has not been sufﬁciently evaluated. Four cases of
death have been associated with A. vera injections under unclear
Pediatric Dosing (Age <18)
rTopical use in children is common and appears to be well tolerated.
rOral/parenteral, not recommended internally due to lack of safety
288 JOURNAL OF HERBAL PHARMACOTHERAPY
rSubchronic oral use of acemannan has been well tolerated in
animals.47 Systemic toxicity of injectable acemannan has not oc-
curred in mice, rats, or dogs.48
rAlthough anthraquinones are believed to be genotoxic,49 the an-
thraquinones in aloe, including aloe-emodin, do not appear to be
well absorbed, and no detectable levels result from ingestion.50 A
low-molecular-weight fraction from aloe gel has been shown to be
cytotoxic in vitro .51
rMost adverse effects appear to be mediated by potassium depletion
after prolonged oral use, for which supportive care with oral or intra-
venous ﬂuid/electrolyte replacement has been anecdotally reported as
rThe US FDA has approved A.ferox,A.perryi,A.vera, and certain
hybrids for use as natural food ﬂavorings.
rAvoid if known allergy to plants of the Liliaceae family (garlic, onions,
rAfter prolonged use of topical aloe gel, urticaria,52 contact
dermatitis,53,54,55and widespread dermatitis56 have been reported. A
patch test study in 702 patients, however, showed no adverse reactions
when an oily extract from the leaves, Aloe pulvis from the entire plant
or concentrated A. vera gel was applied to the skin.57The authors
suggest that aloe preparations made from the center of leaves con-
tain mostly carbohydrates, and these products are unlikely to cause
rCardiovascular: Theoretically, a risk of arrhythmia may increase
with prolonged use of oral aloe latex, on the basis of anecdotal
reports of potassium depletion, and on the basis of aloe’s laxative
Ulbricht et al. 289
rDermatologic: One randomized trial reported delayed wound healing
with topical aloe gel, applied following complicated gynecological
surgeries.36 Thus, topical aloe may not be advisable for the pro-
motion of postoperative incision healing. Photodermatitis has also
been reported.58 In one case report, a 65-year-old woman who was
2 weeks postdermabrasion applied A. vera leaf juice to her skin,
which produced stinging, induration, and erythema.59The patient was
prescribed hydrocortisone and diphenhydramine ointment, and the
dermatitis subsided over time.59 There is also a case report of aloe-
induced Henoch-Schonlein purpura.60 In one randomized-controlled
study, no serious adverse effects were recorded, although 55% of sub-
jects reported local adverse effects mainly drying up of the skin on
test areas.61 Other symptoms reported were stinging, soreness and, in
a few cases, even ﬁssures that the authors note were probably related
to the dryness. Two persons described erythema after application of
A. vera gel, accompanied by a slight tingling sensation in one of them.
Tingling and tightness of the skin was also reported after use of the
placebo gel, and by-and-large there was no difference regarding the
frequency of adverse effects on the two sides. The proportion of sub-
jects with adverse effects was similar in the group with improvement
and the group without.
rEndocrine: Hypoglycemic effects of oral aloe have been reported in
two methodologically weak human trials, with purported equivalence
to a sulfonylurea antihyperglycemic oral agent (glibenclamide).34,35
Laboratory studies have documented β-cell stimulation and subse-
quent drops in blood glucose in mice (thus, there may be no effect
in type 1 diabetics, in whom βcells have been destroyed).62 In con-
trast, a small randomized trial, published only as a conference ab-
stract, found no evidence of hypoglycemia in 16 type 2 diabetics
given aloe juice (15 ml twice daily).42 Theeffectsofaloeonhu-
man blood glucose levels thus remain inconclusive, although caution
is warranted in patients taking antihyperglycemic agents. Aloe has
also been linked to thyroid dysfunction, on the basis of one case
rGastrointestinal: Occasional abdominal cramping and diarrhea with
oral use have been reported anecdotally by practitioners. Using lax-
atives such as aloe latex for more than 7 consecutive days may ag-
gravate constipation or cause dependency. Chronic use or abuse of
anthranoid-containing laxatives for more than 1 year has been asso-
ciated with increased risk of colorectal cancer, with a relative risk
of 3.04 versus nonanthranoid abusers (triple the risk).64 Thereisa
290 JOURNAL OF HERBAL PHARMACOTHERAPY
single case report of acute hepatitis in a 57-year-old woman taking oral
rHematologic: There is a poorly described single case report of excess
bleeding in a surgical patient receiving the anesthetic agent sevoﬂu-
rane and oral aloe.66
rMusculoskeletal: A risk of muscle weakness may increase with pro-
longed use of aloe latex, on the basis of anecdotal reports of potassium
depletion, and on the basis of aloe’s laxative properties.
rRenal: On the basis of the laxative properties of oral-aloe latex, pro-
longed use may cause potassium depletion; there are anecdotal reports
of low potassium, although scant literature exists in this area. There
is one report of a 27-year-old female who developed an ammonium
acid urate stone because of prolonged use (12 years) of laxatives
(bisacodyl, sennoside, and aloe extract).67
rOral aloe products should be used cautiously in patients with diabetes
or glucose intolerance, and in patients using glucose-lowering agents.
Blood glucose levels should be monitored.
rAvoid oral aloe latex in patients with renal insufﬁciency, car-
diac disease, or electrolyte abnormalities, because of theoretical
risk/anecdotal reports of hypokalemia.
rAvoid use of oral aloe latex in patients with ileus, acute surgical
abdomen, bowel obstruction, fecal impaction, or appendicitis.
rAvo id A. vera injections, which have been associated with four cases
of death under unclear circumstances.37,46
Pregnancy and Lactation
rAlthough topical application is unlikely to be harmful during preg-
nancy or lactation,68 internal use is not recommended because of
theoretical stimulation of uterine contractility by anthroquinones. It
is not known whether pharmacologically active constituents of aloe
may be excreted with breast milk. Consumption of the dried juice
from the pericyclic region of aloe leaves is contraindicated during
Ulbricht et al. 291
rDigoxin, digitoxin: Low levels of serum potassium (because of aloe
latex laxative overuse) theoretically could interfere with cardiac gly-
cosides or other antiarrhythmic agents.
rInsulin: On the basis of the laxative properties of oral aloe latex,
prolonged use may cause potassium depletion and act additively with
insulin to reduce serum potassium levels. Concomitant use of insulin
with oral forms of aloe may increase hypoglycemic effects, based on
preliminary human data.34,35One animal study suggests that stimu-
lation of βcells is responsible for this effect of aloe, and thus the
interaction might not apply to type 1 diabetics, in whom βcells have
rLaxatives: Theoretically, concomitant use of oral aloe latex and other
laxatives may exacerbate hypokalemia, dehydration, metabolic alka-
losis, or other electrolyte abnormalities.
rNonpotassium sparing diuretics (loop diuretics and thiazide diuret-
ics): On the basis of the laxative properties of oral aloe latex, pro-
longed use may cause potassium depletion. Hypokalemia may be
exacerbated by simultaneous applications of thiazide diuretics.
rOral corticosteroids, oral hydrocortisone: Onthebasisofthelaxa-
tive properties of oral aloe latex, prolonged use may cause potassium
depletion. Hypokalemia may be exacerbated by simultaneous appli-
cation of steroids.
rOral hypoglycemic agents: Concomitant use of glucose-lowering
agents with oral forms of aloe may increase hypoglycemic effects. Hy-
poglycemic properties of aloe have been reported in two methodolog-
ically weak human trials, with purported equivalence to an oral hypo-
glycemic sulfonylurea agent (glibenclamide).34,35 Laboratory studies
have documented β-cell stimulation and subsequent drops in blood
glucose in mice.62,69 In contrast, a small randomized trial, published
as a conference abstract, found no evidence of hypoglycemia in 16
type 2 diabetics given aloe juice (15 ml twice daily).42
rSevoﬂurane: There is a poorly described single case report of excess
bleeding in a surgical patient receiving the anesthetic agent sevoﬂu-
rane and oral aloe.66
rThyroid hormones: Aloe has been linked to thyroid dysfunction, based
on one case report.63
292 JOURNAL OF HERBAL PHARMACOTHERAPY
rTopical hydrocortisone: Concomitant topical use of aloe may enhance
absorption of hydrocortisone, although there is limited evidence in this
rZidovudine (AZT): Preliminary reports suggest that AZT levels may
be boosted by aloe ingestion, although data remain scant in this area.71
rHypoglycemic agents: Concomitant use of glucose-lowering agents
with oral forms of aloe may increase hypoglycemic effects, based on
preliminary human data.34,35
rLaxative herbs: Theoretically, concomitant use of oral aloe latex and
other laxatives may exacerbate hypokalemia, dehydration, metabolic
alkalosis, or other electrolyte abnormalities.
rLicorice root (Glycyrrhiza glabra L): On the basis of the laxative
properties of oral aloe latex, prolonged use may result in potassium
depletion. Hypokalemia may be exacerbated by simultaneous appli-
cations of licorice root.
rThyroid agents: Aloe has been linked to thyroid dysfunction, based
on one case report.63
rVitamins (C and E): Aloe may slow the absorption of vitamins C and
rAbsorption: The high mucilage content in aloe taken orally may in-
terfere with absorption of foods and orally administered drugs. Mal-
absorption may occur after prolonged oral use of aloe.
rSerum potassium levels: On the basis of the laxative properties of oral
aloe latex, prolonged use may cause potassium depletion, metabolic
alkalosis, and dehydration.
rSerum glucose levels: Preliminary evidence from two poorly con-
ducted human trials and animal data suggests that oral forms of aloe
may lower blood sugar.34,35,62
rThyroid panel: Aloe has been linked to thyroid dysfunction, based on
one case report.63
Ulbricht et al. 293
MECHANISM OF ACTION
rAloe gel: The gel or mucilage obtained from the ﬂesh of the leaf is
99% water at pH 4.5. The constituent polysaccharide glucomannan
is an effective human skin moisturizer, which accounts for its use in
many cosmetics. Acemannan, the major carbohydrate fraction in the
gel, is a water-soluble long-chain mannose polymer, which has been
found in vitro and in animal studies to modulate immune function
(particularly macrophage activation and cytokine production) and to
accelerate wound healing. The macrophage stimulating principle of
acemannan appears to reside in the high molecular weight polysac-
charide Aloeride.73 Acemannan has also been reported to exhibit
antineoplastic and antiviral effects in vitro.
rOther constituents include bradykininase, which possesses anti-
inﬂammatory properties and magnesium lactate, which has antipru-
ritic effects.8A mannose-rich polysaccharide fraction of aloe gel has
been shown in mice, to enhance antibody production.74 Salicylic acid
and other antiprostaglandin compounds may be responsible for aloe’s
local anti-inﬂammatory activity, possibly because of an inhibitory
effect on the arachidonic acid pathway via cyclooxygenase.75
rMaloyl glucan compounds isolated from Aloe babadensis Miller
include 6-O-(1-L-maloyl)-α-; β-D-Glcp (veracylglucan A); α-D-
Glcp-(1–>4)-6-O-(1-L-maloyl)-α;β,-D-Glcp (veracylglucan B); and
(1-L-maloyl)-α;β-D-Glcp (veracylglucan C).76 On the basis of in
vitro study, veracylglucan B demonstrated potent anti-inﬂammatory
and antiproliferative effects, while veracylglucan C exhibited signiﬁ-
cant cell proliferative and anti-inﬂammatory activities. Veracylglucan
B and C appeared antagonistic and competitive in their effects on
rAntioxidant properties have been attributed to aloesin derived from A.
vera .1,2,3On the basis of cell-line research, APS-1, a polysachararide
from A. vera var, chinesis, also showed free radical scavenging and
other antioxidant properties.77
rTopical aloe’s anti-inﬂammatory properties do not appear to
interfere with wound healing, but rather increase wound tensile
strength,78 possibly because of the ﬁbroblast stimulating activity of
294 JOURNAL OF HERBAL PHARMACOTHERAPY
rAntileukemic and antimutagenic effects of aloe in vitro have been
attributed to di (2-ethylhexyl) phtalate.80 Promotion of apoptosis has
been reported in vitro as a possible antineoplastic mechanism.81 Aloe
appears to affect detoxiﬁcation of reactive metabolites by liver and
rWang et al. suggested that aloe polysaccharides might have a radio-
protective effect on nonmalignant cells via its ability to modulate the
rCalcium isocitrate, isolated from Aloe sponaria, has been shown to
be inotropic in rat and rabbit hearts.8
rConstituents of kitachi aloe leaf pulp and skin have been found to
stimulate β-cells in diabetic mice, thereby lowering blood glucose
rAloe latex: Aloe latex contains anthraquinone glycosides (aloin, aloe-
emodin, and barbaloin) that act as potent stimulant laxatives.50,84−89
These water soluble glycosides are split by intestinal bacteria into
aglycones, which are believed to exert a more powerful laxative
effect than other herbs, including senna, cascara, or rhubarb root.
One of these compounds, aloe-emodin-9-anthrone, has been shown
to increase the water content in rat large intestines.90 This appears
to be a more important cathartic mechanism than increased intestinal
motility (which has also been proposed).85,86
rThe anthraquinone glycosides have been studied for their cytotoxic
effects.91 For instance, aloe-emodin induced apoptosis in T24 human
bladder cancer cells, which is thought to be mediated through the
activation of p53, p21, Fas/APO-1, Bax, and caspase-3.92 In human
malignant melanoma cells, aloe-emodin inhibited NAT1 activity in
intact cells in a dose-dependent manner.93 In human lung carcinoma
cells, aloe-emodin is thought to induce DNA damage through
generation of reactive oxygen species.94
rOn the basis of in vivo angiogenesis assays, C´
ardenas et al.
report that aloe-emodin may behave both as an antitumor and an
antiangiogenic compound.95 Aloe-emodin is thought to inhibit
endothelial cell proliferation, but this effect is not cell speciﬁc,
because aloe-emodin also inhibits tumor cell proliferation. Cell
migration and invasion are not remarkably affected by aloe-emodin.
On the other hand, aloe-emodin has different effects on endothelial
and tumor cell gelatinases. Two main targets of the pharmacolog-
ical action of aloe-emodin as an antiangiogenic compound seem
to be urokinase secretion and tubule formation of endothelial
Ulbricht et al. 295
rAnthraquinone glycosides, which are absorbed well only after diges-
tion by intestinal bacteria, are eliminated in the urine, bile, feces, and
rThe half-life of aloe-emodin is approximately 48–50 hours.96
rAloe is depicted as the “plant of Immortality” in 6000-year-old Egyp-
tian stone carvings, and was a traditional funerary gift to the pharaohs.
The ancient Egyptian Book of Remedies notes the use of aloe to
cure infections, treat the skin, and prepare laxatives. The New Tes-
tament (John 19:39–40) refers to a mixture of myrrh and aloes for
the preparation of Jesus’ body. Alexander the Great is said to have
conquered Socotra to secure control of aloe. The Greek physician
Dioscorides recorded its use in 74 AD for wounds, hair loss, gen-
ital ulcers, and hemorrhoids. Arab traders found willing buyers for
aloe transported to Asia in the sixth century AD, and the Spanish
brought aloe to the Americas in the 16th Century. In the 1930s, top-
ical aloe gel was hailed as a treatment of roentgen (radiation) der-
matitis and has since been widely used in cosmetic and dermatologic
rPenalties have been enforced for illegal marketing of A. vera products
in the United States.38 See Table 3.
See Table 4 for explanation of columns in natural standard evidence
Refers to the medical condition or disease targeted by a therapy.
Quality of Study 0–2
Study Statistically =poor; 3–4 =good; Magnitude
Condition Design Author, Year
Signiﬁcant? and 5 =excellent of Beneﬁt ARR∗NNT Comments
Odes, 1991 35 Yes 3 Large NA∗NA Efﬁcacy for treatment of
Syed, 1997 60 Yes 3 Large 60% 2 Impressive efﬁcacy of
aloe lotion in ﬁrst
episode of herpes,
Syed, 1996 120 Yes 2 Large 62.5% 2 Brief report in Letter to
the Editor format.
superior to placebo
or aloe gel.
Paulsen, 2005 41 No 4 None NA NA
has no effect
when compared with
Syed, 1996 60 Yes 3 Large 77% 2 Impressive efﬁcacy of
Vardyn, 1999 46 Yes 3 Large 43% 3 Impressive efﬁcacy of
aloe lotion; only
known study for this
Garnick, 1998 40 Yes 2 Medium NA NA Combination of aloe,
allantoin, and silicon
dioxide vs. silicon
Plemons, 1994 83 Yes 2 Large NA NA Acemannan (topical)
ulcer healing vs.
Ty p e 2
Yongchaiyudha, 1996 72 Yes 1 Large NA NA Poor quality design and
Ty p e 2
Bunya praphatsara, 1996 72 Yes 1 Large NA NA Poor quality design and
Ty p e 2
Chalaprawat, 1997 16 No 2 None NA NA Conference abstract.
No effect of aloe
juice on mean
(Continued on Next Page)
Quality of Study 0–2
Study Statistically =poor; 3–4 =good; Magnitude
Condition Design Author, Year
Signiﬁcant? and 5 =excellent of Beneﬁt ARR∗NNT Comments
Montaner, 1996 63 No 5 None NA NA Acemannan ineffective
Skin burns Randomized-
Puvabanditsin, 2005 20 No 2 None NA NA 70% A. vera cream had no
suntan or sunburn
protection and no
efﬁcacy in sunburn
Skin burns Non-blinded, not
Visuthikosol, 1995 27 Yes 2 Large NA NA Study used “within subject”
Skin burns Equivalence trial Heck, 1981 18 NA 1 Medium NA NA Faster healing with aloe vs.
Langmead, 2004 44 Yes 3 Medium 23% 4 Clinical improvement in
30% of patients treated
with oral aloe, but no
Schmidt, 1991 21 Yes 4 Negative NA NA Signiﬁcant delay in wound
healing by second
phase II study
Su, 2004 58 No 3 None NA NA No improvements in
with oral aloe gel during
radiation therapy for
head and neck cancers.
ressure ulcers Randomized-
Thomas, 1998 30 No 2 None NA NA No effect of acemannan on
Systematic review Richardson, 2005 7 trials No NA None NA NA No effect.
Comparison trial Bosely, 2003 45 Yes 2 None NA NA Aloe gel less effective than
cream in prevention and
treatment of radiation
dermatitis in children.
Williams, 1996 194 No 4 None NA NA No prevention of radiation
dermatitis by aloe gel.
Heggie, 2002 225 Yes 3 None NA NA Aloe gel less effective than
aqueous cream for
prevention of pain or
radiation therapy for
Olsen, 2001 70 Yes 1 Medium NA NA Delay in development of
Systematic review Vogler, 1999 10 studies NA NA NA NA NA 10 studies of various
∗ARR, absolute risk reduction; NA, not applicable.
TABLE 4. Explanation of Columns in Natural Standard Evidence Table
12345 678 910
Condition Study Author,
Statistically Quality of Magnitude Absolute Number Comments
Design Year Signiﬁcant? study 0–2 =
of Beneﬁt Risk
study 0–2 =
poor; 3–4 =
good; and 5
Ulbricht et al. 301
Common Types Include
rRandomized-controlled trial (RCT): An experimental trial in which
participants are assigned randomly to receive either an intervention
being tested or placebo. Note that Natural Standard deﬁnes RCTs as
being placebo controlled, whereas studies using active controls are
classiﬁed as equivalence trials (see below). In RCTs, participants and
researchers are often blinded (i.e., unaware of group assignments),
although unblinded and quasi-blinded RCTs are also often performed.
True random allocation to trial arms, proper blinding, and sufﬁcient
sample size are the basis for an adequate RCT.
rEquivalence trial: An RCT that compares two active agents. Equiv-
alence trials often compare new treatments to usual (standard) care,
and may not include a placebo arm.
rBefore and after comparison: A study that reports only the change in
outcome in each group of study, and does not report between-group
comparisons. This is a common error in studies that claim to be RCTs.
rCase series: A description of a group of patients with a condition,
treatment, or outcome (e.g., 20 patients with migraine headache un-
derwent acupuncture and 17 reported feeling better afterwards). Case
series are considered weak evidence of efﬁcacy.
rCase-control study: A study in which patients with a certain out-
come are selected and compared with similar patients (without the
outcome) to see if certain risk factors/predictors are more common in
patients with that outcome. This study design is not common in the
complementary and alternative medicine literature.
rCohort study: A study that assembles a group of patients with certain
baseline characteristics (for example, use of a drug), and follows them
forward in time for outcomes. This study design is not common in the
complementary and alternative medicine literature.
rMeta-analysis: A pooling of multiple trials to increase statistical
power (often used to pool data from a number of RCTs with small sam-
ple sizes, none which demonstrates signiﬁcance alone but in aggregate
can achieve signiﬁcance). Multiple difﬁculties are encountered when
designing/reviewing these analyses; in particular, outcomes measures
or therapies may differ from study to study, hindering direct compar-
rReview: An author’s description of his or her opinion on the basis of
personal, nonsystematic review of the evidence.
302 JOURNAL OF HERBAL PHARMACOTHERAPY
rSystematic review: A review conducted according to prespeciﬁed cri-
teria in an attempt to limit bias from the investigators. Systematic
reviews often include a meta-analysis of data from the included stud-
rP: Pending veriﬁcation.
Identiﬁes the study being described in a row of the table.
The total number of subjects included in a study (treatment group plus
placebo group). Some studies recruit a larger number of subjects initially,
but do not use them all because they do not meet the study’s entry criteria.
In this case, it is the second, smaller number that qualiﬁes as N.Nincludes
all subjects that are part of a study at the start date, even if they drop out,
are lost to follow-up, or are deemed unsuitable for analysis by the authors.
Trials with a large number of dropouts that are not included in the analysis
are considered to be weaker evidence for efﬁcacy. (For systematic reviews
the number of studies included is reported. For meta-analyses, the number
of total subjects included in the analysis or the number of studies may be
reported.) P =pending veriﬁcation.
Results are noted as being statistically signiﬁcant if a study’s authors
report statistical signiﬁcance, or if quantitative evidence of signiﬁcance is
present (such as Pvalues). P =pending veriﬁcation.
Quality of Study
A numerical score between 0 and 5 is assigned as a rough measure of
study design/reporting quality (0 being weakest and 5 being strongest).
This number is based on a well-established and validated scale developed
by Jadad et al. (Jadad AR, Moore RA, Carroll D, et al. Assessing the
quality of reports of randomized clinical trials: is blinding necessary?
Control Clin Trials 1996;17(1):1–12). This calculation does not account
for all study elements that may be used to assess quality (other aspects of
Ulbricht et al. 303
TABLE 5. Jadad score calculation.
Was the study described as randomized (this includes
words such as randomly, random, and
Was the method used to generate the sequence of
randomization described and appropriate (table of
random numbers, computer generated, etc)?
Was the study described as double blind? 0/1
Was the method of double blinding described and
appropriate (identical placebo, active placebo,
Was there a description of withdrawals and dropouts? 0/1
Deduct one point if the method used to generate the
sequence of randomization was described and it
was inappropriate (patients were allocated
alternately, or according to date of birth, hospital
Deduct one point if the study was described as double
blind but the method of blinding was inappropriate
(e.g., comparison of tablet vs. injection with no
study design/reporting are addressed in the “evidence discussion” sections
rA Jadad score is calculated using the seven items in the table below.
The ﬁrst ﬁve items are indications of good quality, and each counts
as one point towards an overall quality score. The ﬁnal two items
indicate poor quality, and a point is subtracted for each if its criteria
are met. The range of possible scores is 0 to 5 (see Table 5).
Magnitude of Beneﬁt
This summarizes how strong a beneﬁt is: Small, medium, large, or none.
If results are not statistically signiﬁcant “NA” for “not applicable” is en-
tered. To be consistent in deﬁning small,medium,andlarge beneﬁts across
different studies and reviews, Natural Standard deﬁnes the magnitude of
304 JOURNAL OF HERBAL PHARMACOTHERAPY
beneﬁt in terms of the standard deviation (SD) of the outcome measure.
Speciﬁcally, the beneﬁt is considered
rLarge: if >1SD
rMedium: if 0.5 to 0.9 SD
rSmall: if 0.2 to 0.4 SD
In many cases, studies do not report the SD of change of the outcome
measure. However, the change in the SD of the outcome measure (also
known as effect size) can be calculated, and is derived by subtracting the
mean (or mean difference) in the placebo/control group from the mean (or
mean difference) in the treatment group, and dividing that quantity by the
pooled SD (effect size =[mean treatment — mean placebo]/SD P).
Absolute Risk Reduction
This describes the difference between the percent of people in the
control/placebo group experiencing a speciﬁc outcome (control event rate),
and the percent of people in the experimental/therapy group experiencing
that same outcome (experimental event rate). Mathematically, absolute risk
reduction (ARR) equals experimental event rate minus control event rate.
Absolute risk reduction is better able to discriminate between large and
small treatment effects than relative risk reduction, a calculation that is of-
ten cited in studies ([control event rate — experimental event rate]/control
event rate). Many studies do not include adequate data to calculate the
ARR, in which cases “NA” is entered into this column. P =pending
Number Needed to Treat
This is the number of patients who would need to use the therapy under
investigation, for the period of time described in the study, in order for one
person to experience the speciﬁed beneﬁt. It is calculated by dividing the
ARR into 1 (1/ARR). P =pending veriﬁcation.
When appropriate, this brief section may comment on design ﬂaws
(inadequately described subjects, lack of blinding, brief follow up, not
intention-to treat, etc.), notable study design elements (crossover, etc.),
Ulbricht et al. 305
dosing, and/or speciﬁcs of study group/subgroups (age, gender, etc). More
detailed description of studies is found in the evidence discussion section
that follows the “Evidence Table” in Natural Standard reviews.
rSummary: Few clinical studies have been conducted to evaluate the
laxative effect of aloe latex in humans. However, the laxative effect of
anthraquinone glycosides found in aloe, such as aloin, aloe-emodin,
and barbaloin, is well established scientiﬁcally.50,84,85,86,87,88,89 The
question of whether aloe latex may offer a reasonable approach to
treating constipation remains to be answered. Further study is war-
ranted to establish dosing, and to compare efﬁcacy and safety with
commonly used laxative agents.
rEvidence: Chapman and Pitelli compared the laxative effect of aloin
(1 grain [ =0.0648 g] once) with phenolphtalein (2 grain once), phe-
nolphtalein +aloin (1 grain and 0.5 grain, respectively), and placebo
in 28 healthy adults.97 Study subjects were randomly allocated to
different treatment sequences; stool frequency and transit time were
compared for all treatments. Aloin had a laxative effect (compared
with placebo), which was reported as stronger than phenolphtalein
and slightly weaker than the combination. However, no statistical
analysis was presented in the article.
rA randomized double-blind placebo-controlled study found that aloe
(in combination with celandine and psyllium) was an effective lax-
ative in patients suffering from chronic constipation.41 Thirty-ﬁve
such patients were randomly allocated to either celandine +aloe +
psyllium (starting with one 500mg capsule per day containing these
ingredients in ratios 6:3:1 and increasing up to three capsules per day
as required) or placebo. Three subjects in the placebo group dropped
out because of lack of effect, whereas all subjects in the celandine
+aloe +psyllium group remained in the study. All indicators of
constipation improved in the experimental group versus placebo with
statistical signiﬁcance. The mean number of stools increased to 7.9
in the aloe group versus 4.3 in the placebo group. Stool consistency
scores (1 =soft/liquid, 2 =normal, 3 =hard) improved to 1.6 and
2.4, respectively. The number of capsules taken was a third lower in
the experimental group versus placebo (10.1 and 15.8, respectively).
Pain scores remained unchanged in both groups. Although this study
demonstrated the efﬁcacy of an herbal combination containing aloe
306 JOURNAL OF HERBAL PHARMACOTHERAPY
as a laxative, the effect of aloe cannot be separated from the other
rSummary: Limited evidence suggests that 0.5% extract from A.vera
in a hydrophilic cream is an effective treatment of genital herpes in
men (superior to both aloe gel and placebo). The best available study
(Syed, 1997), although seemingly well designed and reported, reports
a high degree of efﬁcacy that is suspicious from a methodological
standpoint. Additional research is warranted in this area.
rEvidence: Syed et al. randomized 60 men with a ﬁrst episode of
genital herpes to receive topical aloe or placebo.39 Aloe treatments
consisted of three daily applications of a 0.5% cream for ﬁve days
versus applications of a cream without active ingredients. Two-thirds
were cured of lesions in the aloe group after one week compared with
only 2/30 in the placebo group (P<.001). It is unlikely that this
strong effect was accounted for by ﬂawed randomization or blinding
procedures (neither was disclosed in the paper). From methodological
and clinical perspectives, such highly effective results in an isolated
study are suspicious. However, without further evaluation in a follow-
up randomized trial, a ﬁrm conclusion cannot be made.
rIn a prior published Letter to the Editor, Syed et al. described a ran-
domized, double-blind controlled trial in 120 men in Pakistan, in
which 0.5% topical aloe extract gel or cream, or placebo, was applied
to male patients with ﬁrst episode of genital herpes.98 Treatment was
administered three times/day, for ﬁve consecutive days/week, for two
weeks. Aloe in hydrophyllic cream was noted to signiﬁcantly shorten
the duration of lesions versus gel or placebo (4.8 days, 7.0 days, and
14.0 days respectively). With cream, 70% of patients were cured, ver-
sus 7.5% in placebo. Although promising, the abbreviated format of
this publication neither describe blinding, randomization, and method
of statistical analysis, nor measurement criteria for classifying lesions.
Therefore, the evidence remains inconclusive.
rSummary: Evidence from one randomized trial suggests that 0.5%
extract from A.vera in a hydrophilic cream is an effective treatment
Ulbricht et al. 307
of psoriasis vulgaris. Although well designed and reported, the high
degree of efﬁcacy in this study is suspicious from a methodological
standpoint. Additional research is warranted in this area.
rEvidence: Paulsen et al. conducted a randomized, double-blind,
placebo-controlled, and right/left comparison study to assess the ef-
fects of a commercial, preserved, but otherwise untreated A. vera gel
in the treatment of psoriasis.61 Forty-one patients (at least 18 years
of age) with stable plaque psoriasis were included. Patients were ex-
cluded if they were pregnant, expectedly noncompliant, had received
systemic antipsoriatic treatment recently, had known allergy to any
ingredients of the gels, or had severe concomitant disease, demanding
the use of immunosuppressive or immunomodifying drugs. Certain
medication use also qualiﬁed as exclusion criteria. Subjects were ad-
ministered a commercial Aloe Vera Gel
R(Aloe Vera Group ApS,
Søborg, Denmark), which consisted of 98% A. vera leaf gel, with
less than 100 p.p.m. of anthraquinones, and the additives xanthan
gum, potassium sorbate, sodium benzoate, sodium sulphite, and citric
acid. The placebo gel contained the same ingredients except that the
liquid A. vera gel was replaced by water. There was a two-week wash-
out period followed by a four-week treatment period with two daily
applications and follow-up visits after one and two months. Statisti-
cal analysis included all randomized patients with at least two post
start-of-treatment measurements (N=40). The difference between
the changes on the two sides was assessed with Wilcoxon’s matched-
pairs signed-ranks test and the level of signiﬁcance chosen at 5%.
There was one drop out in this study, but the authors did not state a
reason for dropping out. No serious adverse effects were recorded,
although 55% of subjects reported local adverse effects mainly drying
up of the skin on test areas. The score sum of erythema, inﬁltration,
and desquamation decreased in 72.5% of the A. vera-treated sites
compared with 82.5% of the placebo-treated areas from week 0 to
week 4, which was statistically signiﬁcant in favor of the placebo
treatment (P=0.0197). Overall, this was a well-designed study, but
the description of randomization was unclear. The lack of observed
effect may be attributable to the small sample size of the study; fur-
thermore, it is unclear whether the large placebo response can be
explained by the short duration of the study; longer studies would
help clarify this limitation.
rSyed et al. randomized 60 patients with long-standing psoriasis to re-
ceive aloe treatment or placebo.40 Aloe treatments consisted of three
daily topical applications of a 0.5% cream for four weeks versus
308 JOURNAL OF HERBAL PHARMACOTHERAPY
applications of a cream without active ingredients. Patients were fol-
lowed over eight months and compared in terms of proportion cured
and proportion of plaques cured. More than 80% of plaques and pa-
tients were cured in the treatment group versus <10% in the placebo
group (for both comparisons, P<.001). It is unlikely that such a
strong effect is attributable to ﬂawed randomization or blinding. The
high degrees of efﬁcacy and compliance reported in this study, and
lack of reporting of blinding or randomization, raise questions about
the accuracy of these results. However, no ﬁrm conclusion can be
made without further study.
rSummary: Preliminary evidence from one randomized trial supports
aloe’s efﬁcacy in the treatment of seborrheic dermatitis. Corroboration
by studies from independent groups is warranted before a strong
recommendation can be made.
rEvidence: Vardyn et al. examined the efﬁcacy of aloe emulsion for
the treatment of seborrheic dermatitis.99 Forty-six patients were
randomly allocated to treatment with 30% A. vera emulsion topically
twice per day or to placebo for 4–6 weeks. At the end of the treatment
period, global improvement was seen in the aloe group (58% and 62%
according to dermatologist and patient ratings scales, respectively)
versus placebo (15% and 25%, respectively). This study was well
designed and reported, and the dramatic results are unlikely because
of bias. However, because this is an isolated study, further evaluation
is warranted to provide additional support.
rSummary: There is equivocal evidence from two studies that treatment
of recurrent aphthous ulcers with aloe gel reduces pain and prolongs
ulcer-free intervals. Further study is warranted.
rEvidence: Garnick et al. examined the effectiveness of a gel containing
aloe, in addition to silicon dioxide and allantoin, on the healing of
recurrent aphthous ulcers (100). First, a gel containing aloe, allantoin,
and silicon dioxide was compared with a gel containing only silicon
dioxide in 40 patients. The mean duration of lesion-free intervals was
ﬁve days in the experimental group versus 18 days in the silicon
dioxide group. However, this trend was not statistically signiﬁcant.
Ulbricht et al. 309
When comparing the experimental treatment with a control gel (N=
18), mean intervals were 9 versus 2 days (P=.0335). Because of
the multiple agents involved in this study, it is not possible to draw
conclusions about the efﬁcacy of aloe itself.
rPlemons et al. randomized 53 patients suffering from recurrent oral
ulcers to topical treatment with either the aloe constituent aceman-
nan (Carrisyn Gel Wound Dressing
R, modiﬁed for oral lesion use) or
R(oral analgesic) four times daily. A third group was
treated with freeze-dried acemannan (Carrisyn Gel Wound Dressing
cut into small pieces). The average healing time was shorter in the
acemannan groups (5.7 days) than in the control group (7.8 days;
P=.0031), whereas other parameters (erythema and discomfort)
were only marginally affected. These results suggest that topical ace-
mannan accelerates the healing of ulcers in aphthous stomatitis, but
interpretation of the results must take methodological weaknesses
into account (randomization inadequately reported, blinding methods
rSummary: There is preliminary evidence from a small case-control
study that aloe consumption may reduce the risk of developing lung
cancer. Further evidence is warranted in this area to clarify whether it
is aloe itself or other factors that mediate this beneﬁt.
rEvidence: In a multi-center Japanese case-control study of 192 sub-
jects (1 case per 2 controls), a questionnaire was administered to
determine the potential correlations between lung cancer incidence,
smoking, and consumption of 17 different types of plants.101 Odds
ratios were calculated via an established method (Mantel-Haenszel
analysis). A subgroup of 132 subjects (44 “pairs”) was analyzed
speciﬁcally for plant food intake, and it was determined that the odds
ratio for the aloe species Aloe arborescens Miller was 0.5 (P<.1),
suggesting half the incidence of cancer in regular consumers of aloe
versus nonaloe consumers. Although compelling, the methodological
difﬁculties of case-control studies apply to this report. The possi-
ble effect of confounders not detected by the study questionnaire is
prominent. For example, aloe/plant eaters may be more likely to ex-
ercise than nonplant eaters, which may exert an independent effect on
outcome. In addition, it is not clear whether this effect is generalizable
to other species of aloe.
310 JOURNAL OF HERBAL PHARMACOTHERAPY
Diabetes (Type 2)
rSummary: Laboratory studies have documented β-cell stimulation
by aloe, as well as drops in blood glucose in mice.62 Results from
two poorly conducted human trials suggest that oral aloe gel may be
effective in lowering blood glucose levels, although a third, smaller
study found no effect. More deﬁnitive studies are needed to explore
efﬁcacy and safety of aloe in diabetics.
rEvidence: Two nonrandomized studies conducted by the same group
concluded that aloe gel might be as effective as glibenclamide (a
sulfonylurea antihyperglycemic oral agent) to lower blood glucose in
type 2 diabetes mellitus.34,35 However, methodology, statistics, and
results were incompletely described. Thus, ﬁrm conclusions cannot
rIn a randomized double-blind placebo-controlled crossover study
published only as a conference abstract, Chalprawat found no hy-
poglycemic effect of aloe juice (15mL twice daily) in 16 type 2
diabetics.42 Although the statistical power of this study was low, a
large hypoglycemic effect is unlikely given the results.
rOral dried aloe gel was studied in ﬁve patients with type 2 diabetes.102
Half a teaspoon of aloe was administered daily over 4–14 weeks,
after which time fasting glucose was noted to have fallen from a
mean of 273 to 151 (P<.05). In a simultaneous mouse study,
both glibenclamide (10 mg/kg twice daily) and aloe (500 mg/kg
twice daily) were found to induce hypoglycemia after ﬁve days
(blood sugar reduced by 40%). However, only glibenclamide was
effective after three days. Although compelling, this study is too
preliminary and methodologically weak (small, no controls, and
poor description of methods) to be of direct relevance to clinical
rSummary: Acemannan, the major carbohydrate fraction in aloe gel,
has been shown in vitro to possess immunostimulant and antiretro-
viral activities. Preliminary data from human trials are equivocal;
because of methodological weaknesses of available studies, ﬁrm con-
clusions are not possible. Without further human trials, the evidence
cannot be considered compelling either in favor or against this use of
Ulbricht et al. 311
rEvidence: Montaner et al. conducted a randomized double-blind study
to evaluate the efﬁcacy of acemannan as an adjuvant antiretroviral
agent for HIV.43 In this trial, 63 patients were randomized to receive
either 400 mg oral acemannan four times daily or placebo. No differ-
ence in CD4 counts, CD4/CD8 ratios, P24 antigen, β2-microglobulin
concentration, or viral load was found between the two treatment
groups. Although these results are discouraging, because no power
calculation was performed, it is not clear that the sample size was ad-
equate to properly measure differences between groups. Descriptions
of blinding and randomization are limited.
rTwo non-randomized studies evaluating the efﬁcacy of oral aceman-
nan in the treatment of HIV infection have been published as confer-
ence abstracts.44,45 Both studies found clinical improvement and large
increases in circulating monocytes/macrophages. The observational
character of these reports provides compelling, albeit preliminary,
rIn a case report, McDaniel and McAnalley found improvement in
several serologic and clinical indicators of HIV infection in eight
patients treated with acemannan (Carrisyn
R) for 90 days (unclear if
subjects received four doses of 250 mg or 250 mg in four divided
doses).44 Beneﬁts included decline in HIV core antigen, elimination
of diarrhea, fever, diaphoresis, and “loss of culturability.”
rIn a nonrandomized controlled study, McDaniel et al. found circu-
lating monocytes/macrophages to be signiﬁcantly more numerous in
14 HIV patients treated with 800 mg acemannan per day (365 per
smear) than in 35 patients not receiving acemannan (68 per smear,
P=.00027).45 These surrogate serologic endpoints require clinical
rSummary: Preliminary evidence suggests that aloe may be effective
in promoting healing of partial thickness skin burns. However, the
existing studies are small and poor in quality, and therefore no clear
conclusion can be drawn. Further study is warranted in this area.
rEvidence: Puvabanditsin et al. conducted a double-blind, random-
ized, placebo-controlled study to assess the efﬁcacy of A. vera cream
in prevention of burn and tan from ultraviolet light.103 Patients were
excluded from this study if they were pregnant or taking photosen-
sitizing medications. Twenty volunteers were included in this study,
312 JOURNAL OF HERBAL PHARMACOTHERAPY
who were at least 18 years of age with no history of sun sensitivity or
skin cancers in the family. Patients were randomized to received 70%
A. vera cream on the test sites 30 minutes before, immediately after, or
both before and after then the serial ultraviolet UVB 40,50,60,70,80
mj were radiated. The minimal erythema dose reading was taken at
24 hours for sunburn evaluation, and both erythema and pigmentation
were evaluated using a visual grading 1–4 score. The A. vera cream
application was continued at the test sites twice daily for the next
three weeks. Twenty volunteers completed with study, although the
results suggested that that the A. vera cream has no sunburn or suntan
protection and no efﬁcacy in sunburn treatment when compared with
placebo (P>.05). The A. vera cream had no bleaching effect ei-
ther. It is unclear whether the study size was large enough to produce
statistically signiﬁcant results. Limitations of this study include an
incomplete description of randomization and blinding.
rVisukitosol et al. examined the effect of a topical aloe gel preparation
on skin burns in comparison to Vaseline
Rgauze.104 They found in 27
patients with partial thickness skin burns that the mean healing time
was 12 days with aloe gel treatment versus 18 days with Vaseline
gauze. Although the ﬁndings from this trial are suggestive, the lack
of true controls (only the distal part of each wound was treated with
aloe) or blinding prohibits ﬁrm conclusions.
rHeck et al. topically treated 18 patients with second-degree burns
(2%–12% of total body surface area) with either aloe extract or with
R105. The average wound healing time was 13 days with aloe
versus 16 days with Silvadene
R. No statistical analysis was presented
and results were not stratiﬁed by burn severity. Therefore, a deﬁnitive
conclusion cannot be made.
rIn a poorly described study, silver suﬂadiazine cream was found to
be more effective than aloe in the treatment of experimental second
degree burns, with a suggestion that aloe may in fact disrupt the
healing process.106 These conﬂicting results cannot be considered
conclusive, but must be considered.
rSummary: There is promising preliminary evidence from a small ran-
domized placebo-controlled trial in 44 individuals suggesting that
oral A. vera gel (100 mL twice daily for 4 weeks) is beneﬁcial in the
Ulbricht et al. 313
management of ulcerative colitis.107,108 Clinical improvement (“re-
mission”) was seen in 30% of aloe patients compared with 7% of
placebo patients (i.e., one patient), although no sigmoidoscopic im-
provements were seen in either group. Comparisons to standard ther-
apies have not been conducted, and additional research is warranted
in this area before a ﬁrm conclusion can be drawn.
Infected Surgical Wounds
rSummary: In one study, topical aloe gel was found to prolong wound-
healing time following gynecological or obstetrical laparotomy. Fur-
ther study is warranted, because wound healing is a popular use of
rEvidence: Schmidt et al. examined the effect of aloe gel on the heal-
ing of complicated surgical wounds (healing by second intention).36
In this study, 21 women with complicated wounds after gynecolog-
ical or obstetric surgery were stratiﬁed according to incision type
and randomized to either standard treatment (debridement and irriga-
tion), or standard treatment plus aloe gel. Wounds in the experimental
group healed in 83 days on average versus 53 days with standard
treatment (P=.003). Because of the clearly prolonged healing in
the group treated with aloe, patient recruitment was terminated be-
fore the desired sample size (n=114) was reached. This otherwise
well-designed trial was not placebo-controlled. However, the effect of
size was unlikely because of a placebo effect. Further study of aloe’s
role in the healing of wounds of varying severity may be warranted
before this traditional use can be strongly discouraged, although use
in complicated surgical wounds may not be advisable in light of these
rA. vera rinses have also been used on periodontal surgical sites.19
rSummary: There is preliminary evidence from a double-blind
placebo-controlled phase II trial in 58 patients with head-and-neck
cancers suggesting that oral A. vera gel does not improve radiation
induced mucositis.109 No improvements were observed in soreness,
tolerance of therapy, or overall well-being.
314 JOURNAL OF HERBAL PHARMACOTHERAPY
rSummary: One well-designed randomized trial found no beneﬁt of
topical acemannan hydrogel (the major carbohydrate fraction in aloe
gel) in the treatment of pressure ulcers.
rEvidence: Thomas et al. conducted a randomized-controlled trial in
which 30 patients with pressure ulcers were randomly allocated to
receive either acemannan hydrogel (daily dressings with 0.25-inch
layer) or saline dressing.110 Ulcers were evaluated weekly for 10
weeks or until ulcers healed. Both the proportion of healed ulcers
(63% versus 64%) and the mean time to healing (5.3 vs. 5.2 weeks)
were similar in the two groups. This study had sufﬁcient (80%) power
to detect a 25% difference between treatment arms. These results
suggest that acemannan hydrogel may not be effective in the treatment
of pressure ulcers.
rSummary: Reports, during the 1930s, of topical aloe’s beneﬁcial ef-
fect on postradiation dermatitis triggered widespread use in dermato-
logical and cosmetic products.26,27,28,29,30 Aloe gel is currently rec-
ommended by some practitioners for radiation-induced dermatitis.
However, preliminary scientiﬁc evaluation suggests that topical aloe
may not signiﬁcantly improve pain or desquamation related to ra-
diotherapy, and may be inferior to topical aqueous gel. Additional
well-designed studies are necessary before a ﬁrm conclusion can be
rSystematic review: Richardson et al. conducted a systematic review
to assess the effectiveness of A. vera gel for radiation-induced skin
reactions.111 Major biomedical databases, specialist CAM databases,
and unpublished and ongoing research were searched. Seven trials
were found. The authors conclude that there is no evidence from clin-
ical trials to suggest that topical A. vera is effective in preventing or
minimizing radiation-induced skin reactions in cancer patients. Fur-
ther methodologically rigorous, sufﬁciently powered research studies
should be conducted to evaluate the effectiveness of currently used and
novel therapies for the prevention, minimization, and management of
radiation-induced skin reactions.
rEvidence: Olsen et al. prospectively studied 70 cancer patients
receiving radiation doses greater than 2000cGy.112 Patients were
Ulbricht et al. 315
randomized to either pure A. vera gel (applied liberally to the irra-
diated skin area throughout the day) or no speciﬁc topical treatment.
All patients were instructed to wash the irradiated skin area with mild
soap. Skin changes were evaluated by a clinician, blinded to the treat-
ment, at weekly intervals. The only statistically signiﬁcant difference
found between treatment arms was skin texture, which at a cumulative
dose below 2700cGy was rare in the nontreated group than in the aloe
group (P<.012). No signiﬁcant differences were seen for erythema,
itching, or tanning. However, in a subgroup receiving higher cumula-
tive radiation doses, onset of skin changes was signiﬁcantly delayed
in the aloe group. Although this study found some beneﬁcial effects
of aloe on radiation-associated skin changes, lack of patient blinding
or placebo weakens the results.
rWilliams et al. conducted a randomized trial addressing the efﬁcacy of
aloe gel for radiation-induced dermatitis.113 In this study, 184 women
undergoing treatment for breast cancer were stratiﬁed according to
age, planned target radiation dose, dose fraction, and skin complexion.
Subjects were randomized in a double-blind manner to topical aloe
(applied twice/day on the treatment ﬁeld) versus placebo (inert gel).
No difference was found between groups or within strata. Although
this was a fair-sized trial, no power calculation was performed at
the onset, and description of methodology was limited. Nonetheless,
these results are discouraging.
rHeggie et al. conducted a randomized-controlled trial (phase III) in
225 women undergoing radiation therapy for breast cancer.114 Sub-
jects received either topical A. vera gel or aqueous cream three times
per day throughout radiotherapy and for two weeks following therapy.
Assessments were made by nursing staff at weekly visits. The authors
report that patients receiving aqueous cream experienced signiﬁcantly
less pain and desquamation compared to aloe patients. These results
suggest that aqueous gel may be a superior choice in such patients,
although because of lack of use of validated evaluation instruments
and incomplete reporting of analysis, these results cannot be consid-
ered deﬁnitive. Comparison of aloe to a nonactive intervention would
provide additional information about the efﬁcacy of aloe.
rBosley et al. conducted a randomized-controlled trial (phase III) com-
paring a 1% anionic phospholipid-based cream with an A. vera-based
gel in the prevention and treatment of radiation dermatitis in 45 pe-
diatric patients treated with radiation therapy.115 The mean age of
subjects was 11 years with Hodgkin’s disease being the most com-
mon diagnosis, and the thorax being the most common treatment
316 JOURNAL OF HERBAL PHARMACOTHERAPY
ﬁeld. Chemotherapy was either used before or during radiation treat-
ment. Patients were excluded if they had received prior irradiation
for their disease, had coincident dermatological conditions, or if there
was planned use of other topical products. Treatments were applied
topically, symmetrically, and adjacent within the ﬁeld of irradiation
once daily after radiation treatment. Skin comfort was evaluated by
a questionnaire and dermatological assessments were made using a
15-item score on a 4-level scale before and weekly during treatment,
and up to six weeks after radiation. The authors reported statistically
signiﬁcant results favoring the cream-on-skin assessment variables
such as dryness (P=.002), comfort (P=.002), erythema (P=
.002), and peeling (P=.008). Limitations of the study include a lack
of description of randomization, lack of blinding, and the lack of re-
ported mean duration of treatment between the two treatment groups.
In addition, the skin comfort assessment was based on subjective data.
Brands Used in Statistically Signiﬁcant Clinical Trials
R(internal preparations have been used in HIV with unproven
efﬁcacy); Carrisyn Gel Wound Dressing
R(preparation of acemannan,
the major carbohydrate fraction of aloe gel, found efﬁcacious for oral
Brands Shown to Contain Claimed Ingredients Through Third-Party
rConsumer Lab: Recalls and warnings—Marketers of Seasilver Or-
dered to Pay Almost $120 Million (Posted: 7/24/2006); Aloe Producer
Recalls Product Due to Toxic Levels of Vitamin D (Posted: 4/1/2004);
Federal Trade Commission Charges Marketers of Seasilver with False
and Deceptive Claims (Posted: 6/20/2003).
rConsumer Reports: NA. last accessed 6/1/07.
rNatural Products Association: NA. last accessed 6/1/07.
rNSF International: NA. last accessed 7/30/07.
rU.S. Pharmacopeia (February 2005): In an expert committee meeting
summary, aloe was assigned a class 1 safety rating.
Ulbricht et al. 317
U.S. Equivalents of Most Commonly Recommended European Brands
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