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An Evidence-Based Systematic Review of Aloe vera by the Natural Standard Research Collaboration.

February 2007
Journal of Herbal Pharmacotherapy 7(3/4):279-323

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PubMed

Authors:

Catherine Ulbricht

Ethan Basch

University of North Carolina at Chapel Hill

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ABSTRACT An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

. Scientific evidence for common/studied uses.

…

. Jadad score calculation.

…

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An Evidence-Based Systematic Review of

Aloe vera by the Natural Standard Research

Collaboration

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,

MA.

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

Research Collaboration.

Journal of Herbal Pharmacotherapy, Vol. 7(3–4), 2007

Available online at http://www.haworthpress.com/web/JHP

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-

tematic review

SYSTEMATIC AGGREGATION, ANALYSIS, AND REVIEW

OF THE LITERATURE

Search Strategy

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.

Selection Criteria

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 Analysis

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.

Review Process

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.

Update Process

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

tenuiﬂora).

CLINICAL BOTTOM LINE/EFFECTIVENESS

Brief Background

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

laxative.

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

remains unclear.

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

Mucositis 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

RationaleTM.

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,

or theory.

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,

and constipation.

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

use.1

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

2007

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

laxative.34,35

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

DOSING/TOXICOLOGY

General

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.

Standardization

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)

Topical

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

Oral

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

safety.

Intravenous/Intramuscular

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

circumstances.37,46

Pediatric Dosing (Age <18)

Topical

rTopical use in children is common and appears to be well tolerated.

rOral/parenteral, not recommended internally due to lack of safety

data.

288 JOURNAL OF HERBAL PHARMACOTHERAPY

Toxicology

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

effective.

rThe US FDA has approved A.ferox,A.perryi,A.vera, and certain

hybrids for use as natural food ﬂavorings.

PRECAUTIONS/CONTRAINDICATIONS

Allergy

rAvoid if known allergy to plants of the Liliaceae family (garlic, onions,

and tulips).

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

allergy.

Adverse Effects

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

properties.

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

report.63

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

aloe.65

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

Precautions/Warnings/Contraindications

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

lactation.

Ulbricht et al. 291

INTERACTIONS

Aloe/Drug Interactions

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

been destroyed.

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

area.70

rZidovudine (AZT): Preliminary reports suggest that AZT levels may

be boosted by aloe ingestion, although data remain scant in this area.71

Aloe/Herb/Supplement Interactions

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

E.72

Aloe/Food Interactions

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.

Aloe/Lab Interactions

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

Pharmacology

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

α-D-Glcp-(1–>4)-tetra-[6-O-(1-L-maloyl)-α-D-Glcp-(1–>4)]-6-O-

(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

cell proliferation.

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

mannose-6-phosphate.79

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

other organs.2

rWang et al. suggested that aloe polysaccharides might have a radio-

protective effect on nonmalignant cells via its ability to modulate the

cell cycle.82,83

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

levels.62

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

cells.

Ulbricht et al. 295

Pharmacodynamics/Kinetics

rAnthraquinone glycosides, which are absorbed well only after diges-

tion by intestinal bacteria, are eliminated in the urine, bile, feces, and

breast milk.

rThe half-life of aloe-emodin is approximately 48–50 hours.96

HISTORY

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

preparations.

rPenalties have been enforced for illegal marketing of A. vera products

in the United States.38 See Table 3.

EVIDENCE DISCUSSION

See Table 4 for explanation of columns in natural standard evidence

table.

Condition

Refers to the medical condition or disease targeted by a therapy.

TABLE 3.

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

Constipation Randomized,

placebo

controlled,

double blind

Odes, 1991 35 Yes 3 Large NA∗NA Efﬁcacy for treatment of

constipation in

herbal combination.

Genital

herpes

Randomized-

controlled

trial, double

blind

Syed, 1997 60 Yes 3 Large 60% 2 Impressive efﬁcacy of

aloe lotion in ﬁrst

episode of herpes,

methodologically

suspicious.

Genital

herpes

Randomized-

controlled

trial, double

blind

Syed, 1996 120 Yes 2 Large 62.5% 2 Brief report in Letter to

the Editor format.

Found aloe

hydrophilic cream

superior to placebo

or aloe gel.

Psoriasis

vulgaris

Randomized-

controlled

trial, double

blind

Paulsen, 2005 41 No 4 None NA NA

Aloe vera

has no effect

when compared with

placebo

Psoriasis

vulgaris

Randomized-

controlled

trial, double

blind

Syed, 1996 60 Yes 3 Large 77% 2 Impressive efﬁcacy of

aloe lotion,

methodologically

suspicious.

296

Seborrheic

dermatitis

Randomized-

controlled

trial, double

blind

Vardyn, 1999 46 Yes 3 Large 43% 3 Impressive efﬁcacy of

aloe lotion; only

known study for this

indication.

Aphthous

stomatitis

Randomized-

controlled

trial, double

blind,

modiﬁed

crossover

Garnick, 1998 40 Yes 2 Medium NA NA Combination of aloe,

allantoin, and silicon

dioxide vs. silicon

dioxide alone.

Aphthous

stomatitis

Equivalence

trial, double

blind

Plemons, 1994 83 Yes 2 Large NA NA Acemannan (topical)

accelerated oral

ulcer healing vs.

Orabase-Plain.

Ty p e 2

diabetes

Placebo

controlled,

single-blind

Yongchaiyudha, 1996 72 Yes 1 Large NA NA Poor quality design and

reporting.

Ty p e 2

diabetes

Placebo

controlled,

single-blind

Bunya praphatsara, 1996 72 Yes 1 Large NA NA Poor quality design and

reporting.

Ty p e 2

diabetes

Randomized-

controlled

trial, double

blind,

crossover

Chalaprawat, 1997 16 No 2 None NA NA Conference abstract.

No effect of aloe

juice on mean

plasma glucose

levels.

(Continued on Next Page)

297

TABLE 3.

(Continued)

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

Advanced HIV

Infection

Randomized-

controlled trial,

double blind

Montaner, 1996 63 No 5 None NA NA Acemannan ineffective

against HIV.

Skin burns Randomized-

controlled trial,

double blind

Puvabanditsin, 2005 20 No 2 None NA NA 70% A. vera cream had no

suntan or sunburn

protection and no

efﬁcacy in sunburn

treatment.

Skin burns Non-blinded, not

controlled

Visuthikosol, 1995 27 Yes 2 Large NA NA Study used “within subject”

controls.

Skin burns Equivalence trial Heck, 1981 18 NA 1 Medium NA NA Faster healing with aloe vs.

silvadene.

Ulcerative

colitis

Placebo- controlled

trial

Langmead, 2004 44 Yes 3 Medium 23% 4 Clinical improvement in

30% of patients treated

with oral aloe, but no

changes on

sigmoidoscopy. Small

study.

Infected

surgical

wounds

Randomized-

controlled trial,

nonblinded

Schmidt, 1991 21 Yes 4 Negative NA NA Signiﬁcant delay in wound

healing by second

intention after

gynecological

laparotomy.

Mucositis

(radiation

induced)

Double-blind,

placebo-

controlled

phase II study

Su, 2004 58 No 3 None NA NA No improvements in

mucositis symptoms

with oral aloe gel during

radiation therapy for

head and neck cancers.

298

ressure ulcers Randomized-

controlled

trial

Thomas, 1998 30 No 2 None NA NA No effect of acemannan on

pressure ulcers.

Radiation

induced

dermatitis

Systematic review Richardson, 2005 7 trials No NA None NA NA No effect.

Radiation

induced

dermatitis

Comparison trial Bosely, 2003 45 Yes 2 None NA NA Aloe gel less effective than

1% anionic

phospolipid-based

cream in prevention and

treatment of radiation

dermatitis in children.

Radiation

induced

dermatitis

Randomized-

controlled trial,

double blind

Williams, 1996 194 No 4 None NA NA No prevention of radiation

dermatitis by aloe gel.

Radiation

induced

dermatitis

Randomized-

controlled trial,

double blind

Heggie, 2002 225 Yes 3 None NA NA Aloe gel less effective than

aqueous cream for

prevention of pain or

desquamation from

radiation therapy for

breast cancer.

Radiation

induced

dermatitis

Randomized-

controlled trial,

partially blinded

Olsen, 2001 70 Yes 1 Medium NA NA Delay in development of

radiation-associated

skin changes.

Multiple

indications

Systematic review Vogler, 1999 10 studies NA NA NA NA NA 10 studies of various

indications analyzed.

∗ARR, absolute risk reduction; NA, not applicable.

299

TABLE 4. Explanation of Columns in Natural Standard Evidence Table

12345 678 910

Condition Study Author,

Year

Statistically Quality of Magnitude Absolute Number Comments

Design Year Signiﬁcant? study 0–2 =

poor;

of Beneﬁt Risk

Reduction

Needed Comments

Study

Design

Author,

Year

Statistically

Signiﬁcant?

Quality of

study 0–2 =

poor; 3–4 =

good; and 5

=excellent

Magnitude

of Beneﬁt

Absolute

Risk

Reduction

Number

Needed to

Treat

Comments

300

Ulbricht et al. 301

Study Design

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-

ison.

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-

ies.

rP: Pending veriﬁcation.

Author, Year

Identiﬁes the study being described in a row of the table.

“N”

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.

Statistically Signiﬁcant?

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.

Item Score

Was the study described as randomized (this includes

words such as randomly, random, and

randomization)?

0/1

Was the method used to generate the sequence of

randomization described and appropriate (table of

random numbers, computer generated, etc)?

0/1

Was the study described as double blind? 0/1

Was the method of double blinding described and

appropriate (identical placebo, active placebo,

dummy, etc)?

0/1

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

number, etc).

0/−1

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

double dummy).

0/−1

study design/reporting are addressed in the “evidence discussion” sections

of reviews).

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

P=pending veriﬁcation.

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

veriﬁcation.

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.

Comments

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.

Constipation

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

ingredients.

Genital Herpes

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.

Psoriasis Vulgaris

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.

Seborrheic Dermatitis

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.

Aphthous Stomatitis

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

Orabase-Plain

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

inappropriate).

Cancer Prevention

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

be drawn.

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

practice.

HIV Infection

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

aloe.

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,

support.

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

correlation.

Skin Burns

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

Silvadene

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.

Ulcerative Colitis

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

topical aloe.

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

results.

rA. vera rinses have also been used on periodontal surgical sites.19

Mucositis

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

Pressure Ulcers

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.

Radiation Dermatitis

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

drawn.

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.

PRODUCTS STUDIED

Brands Used in Statistically Signiﬁcant Clinical Trials

rCarrisyn

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

aphthous ulcers/stomatitis).

Brands Shown to Contain Claimed Ingredients Through Third-Party

Testing

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

rNot applicable.

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WHAM evidence summary: Aloe vera for treating burns

Article

Jun 2022

Emily Haesler

Aloe vera: A contemporary overview on scope and prospects in food preservation and packaging

Article

Mar 2022
PROG ORG COAT

Wastage of perishable foods is an enormous challenge in the food sector, and it requires effective mitigation strategies. Aloe vera is one of the oldest remedies for numerous human ailments because of its antimicrobial, antioxidant, anti-inflammatory and other functional properties. Thus, it has been popular for applications in various fields including food preservation, sustainable packaging, cosmetics and pharmaceutical industries. This paper is a contemporary review on A. vera, its bioactive components, processing, and applications in food especially in preservation and packaging. A. vera and its various active components are being used as natural antimicrobial, antioxidants, and preservative in biopolymer-based edible films and coatings for extending shelf life of perishable food items as sustainable alternatives to synthetic chemicals. A. vera is also used in health drinks and other beverages in the form of powder, as a functional bioactive component. Processing of A. vera by conventional thermal techniques at elevated temperature can degrade major bioactive compounds, and therefore , non-thermal processing technologies such as sonication, high pressure processing and membrane processing are preferred. As a natural food preservative, A. vera can protect food products from oxidative and microbial deteriorations, improve their texture, and enhance nutritional/health-promoting value. A. vera is non-toxic to environment and human at the concentrations required for food preservation and packaging applications, and thus it can be a promising sustainable alternative to synthetic chemical-based preservatives, antioxidants, and antimicrobial agents.

Pharmacodynamics of Aloe vera and acemannan in therapeutic applications for skin, digestion, and immunomodulation

Article

Full-text available

Aug 2021

Scientific studies of Aloe vera have tentatively explained therapeutic claims from a mechanistic perspective. Furthermore, in vitro outcomes demonstrate that the breakage of acemannan chains into smaller fragments enhances biological effects. These fragments can intravenously boost vaccine efficacy or entrain the immune system to attack cancer cells by mannose receptor agonism of macrophage or dendritic cells. With oral consumption, epithelialisation also occurs at injured sites in the small intestine or colon. The main advantage of dietary acemannan is the attenuation of the digestive process, increasing satiety, and slowing the release of sugars from starches. In the colon, acemannan is digested by microbes into short-chain fatty acids that are absorbed and augment the sensation of satiety and confer a host of other health benefits. In topical applications, an acemannan/chitosan combination accelerates the closure of wounds by promoting granular tissue formation, which creates a barrier between macrophages or neutrophils and the wound dressing. This causes M2 polarisation, reversal of inflammation, and acceleration of the re-epithelialisation process. This review summarises and explains the current pharmacodynamic paradigm in the context of acemannan in topical, oral, and intravenous applications. However, due to contradictory results in the literature, further research is required to provide scientific evidence to confirm or nullify these claims.

An Adjunct In Periodontal Management A Review On Phytotherapy

Article

Full-text available

Jan 2021

Jaideep Mahendra

An additional therapeutic method for the treatment of various oral diseases is Phytotherapy, General health and immunity is enhanced by Phytotherapy. Herbs and their extracts has antimicrobial, antioxidative and anti-inflammatory properties. Aim of this review is to offer a basic overview of usage of herbal species in treatment of periodontitis. Besides routine treatment for periodontitis, the surgical and non-surgical periodontal therapy, the right combination of herbal plants and their extracts can improve the standard therapeutic procedure in patients with gingivitis and periodontal disease.

Functional Applications of Aloe vera on Textiles: A Review

Article

Full-text available

Apr 2021

Aloe vera is one of the oldest medicinal plants in human history. It exhibits 200 or more different biologically-active substances and has attracted many researchers into its potential applications. Researchers have also noted that Aloe vera has fewer adverse effects on human health than other alternative herbal medicines. Aloe vera leaves contain acemannan which is the key functional component. Acemannan is a long-chain polymer consisting of randomly acetylated linear d-mannopyranosyl units and has immune modulation, antibacterial, antifungal and antitumor properties. Due to this functional attribute, the Aloe vera plant is known as a “healing plant”. Researchers claim that Aloe vera treatment can speed wound healing, offer UV protection, and has anti-oxidant and anti-microbial properties. Historically, Aloe vera has been used for a variety of medicinal purposes. Aloe vera contains a moisturizing agent for which it is used in cosmetics. Aloe gel is also used in computer memory hardware to reduce electronic waste. Recently Aloe vera are extensively used to prepare the different types textile composite which are involved in the field of wound healing, tissue engineering, medical textile, health care textiles, curative garments, cosmetotextiles, UV protective textiles, wearable electronic textiles and so on. Aloe vera is used in pre-treatment and printing due to its succulent enzymatic and gummy characteristics. Aloe gel also contains a salty substance that allows its use in natural, eco-friendly dyeing. This review considers the many actual and potential applications of Aloe vera based textile composite materials for therapeutic and other purposes. Graphic Abstract

Herbal Remedies

Chapter

Jan 2023

Colin G. Rousseaux

USE OF PHYTO-TOXINS IN THE NOVELS AND SHORT STORIES OF AGATHA CHRISTIE

Article

Sep 2022

Agnita Kundu

Agatha Christie is known as the queen of crime. She has written numerous novels, short stories, plays and travelogue. Her work has been translated in several languages across the world, holding a Guiness World Record of maximum sold novelist. Her uniqueness as a novelist was partly due to her innovative and realistic ways of committing a murder. Poison was her favourite method. In order to be creative she has used various plant based poisons. This article takes a quantitative and objective look at the extensive use of phyto toxins in her work in a comprehensive way.

Sensitive and selective determination of aloin with highly stable histidine-capped silver nanoclusters based on the inner filter effect

Article

Oct 2021
COLLOID SURFACE A

Aloin is a natural medicine, which possesses the functions of enhancing immune function, anti-tumour, detoxification, anti-bacterial, anti-stomach damage, liver protection and skin protection. Excessive use will cause side effects. Thus, sensitive aloin determination is very necessary in daily life. As far as we know, there are rare reports about aloin sensing through fluorescent methods. In this work, a simple method for the synthesis of fluorescence silver nanoclusters (Ag NCs) was demonstrated by using histidine (His) as the templating agent and ascorbic acid as the reducer. The as-prepared silver nanoclusters (Ag [email protected]) possessed excellent water solubility and dispersion. Detailed research illustrated that the FL intensities of Ag [email protected] were linearly quenched in the presence of aloin (varying from 0.5 to 200 µM). The corresponding detection limit reached 0.052 µM. The static quenching and inner filter effect were the main fluorescence quenching mechanisms. This fluorescent sensor has been successfully employed for the detection of aloin in natural samples.

An overview on indications and chemical composition of aromatic waters (hydrosols , distillate ; essential oil ) as functional beverages in Persian nutrition culture and traditional Persian medicine for hyperlipidemia and cardiovascular conditions ( plus a review on related plants and essential oils)

Article

Full-text available

Feb 2017

Azadeh Hamedi

Characterization of Corosolic Acid as a KPC-2 Inhibitor That Increases the Susceptibility of KPC-2-Positive Bacteria to Carbapenems

Article

Full-text available

Jul 2020

The emergence of KPC-producing Gram-negative bacteria in clinical practice highlights the need to search for novel antimicrobials and new anti-infection strategies. In this study, we constructed a laboratory KPC-2-positive strain, E. coli BL21(DE3) (pET28a-KPC-2) and identified the activity of KPC-2 in this strain. Using enzyme inhibition assays, checkerboard MIC assays, growth curves, time-killing assays and combined disk test, we found that the natural compound corosolic acid (CA) significantly inhibited the activity of the class A β-lactamase KPC-2, which is common among clinical isolates. CA treatment increased the antibacterial or bactericidal activity of imipenem and meropenem against E. coli BL21(DE3) (pET28a-KPC-2) in vitro (FIC index = 0.17 ± 0.03 for both carbapenems). In addition, the mouse intraperitoneal infection model confirmed that the combination therapy significantly reduced the bacterial load in the livers and spleens following subcutaneous administration. Our results showed that CA can be used to extend the life of carbapenems, providing a viable strategy for severe infections caused by KPC-2-positive bacteria.

Radioprotective Efficacy of Aloe vera Leaf Extract

Article

Full-text available

Jan 1998

Radiomodifying effects of the leaf extract of Aloe vera were observed on the testes of Swiss albino mice at 50 and 100 mg/kg dose levels. This extract was non-toxic when injected up to 800 mg/kg, and significant enhancement in survival time of the irradiated group was observed. In addition, treatment reduced radiation-induced damage to germ cells and loss in body weight.

Studies of Aloe. II. : Mechanism of Cathartic Effect. (1)

Article

Sep 1988

The mechanism of cathartic effect of barbaloin, representative of Aloe, was investigated by using male rats. Barbaloin administered orally was demonstrated to decompose to aloe-emodin-9-anthrone and aloe-emodin in the rat large intestine. And, these decomposed compounds were likely to change each other in the large intestine. Any compound of barbaloin, aloe-emodin-9-anthrone and aloe-emodin administered orally to rats was found to cause an obvious increase of water content in the large intestine, and only aloe-emodin-9-anthrone administered orally caused a significant increase of water content in the small intestine. Furthermore, the clear increase of water content and abnormality of electrolytes (Na⁺, K⁺) in the colon segment of rat were observed only by aloe-emodin-9-anthrone when compounds tested were injected directly into the colon segment. Therefore, it seemed that aloe-emodin-9-anthrone, a decomposition product of babaloin in the rat large intestine, caused an increase of water content in the large intestine by a different mechanism from the stimulation of peristalsis and this played an important role in cathartic activity of barbaloin.

Safety of herbal medications in pregnancy

Article

Jan 1997

K. Lepik

Aloe vera in the treatment of roentgen ulcers and telangiectasis

Article

C.S. Wright

The use of the fresh whole leaf of aloe vera in the treatment of roentgen dermatitis was suggested by C. E. and Creston Collins.¹ Early in 1935 they reported the case of a woman, aged 31, who had had a severe roentgen dermatitis of the left forehead following a depilating roentgen treatment. Various local treatments were tried without effect, and exfoliation and severe itching persisted at the treated site. The patient received a local application of the fresh whole leaf of aloe vera to allay the itching. Within twenty-four hours the sensation of itching and burning subsided and the condition progressively improved within the next five weeks and showed "complete regeneration of skin of the forehead and scalp, new hair growth, complete restoration of sensation, and absence of scars." Radiation sequelae have been classified by Wise and Sulzberger² as "(1) pigmentation, (2) telangiectasis, (3) sclerosis, (4) keratoses, (5)

Aloe vera in the treatment of radiation ulcers of mucous membranes

Article

F.B. Mandeville

Hypoglycaemic and antidiabetic effects in mice of Aloe arborescens Miller var. natalensis Berger

Article

Mar 1993
PHYTOTHER RES

Two different components were separated from Aloe arborescens var. natalensis Berger (Kidachi aloe in Japanese), which exhibit hypoglycaemic activity in spontaneously diabetic mice and normal mice. One component was separated from the succulent layer of the Aloe leaf (leaf pulp). This component, when administered to mice intraperitoneally or orally, decreased the blood glucose level, and maintained the lower level for about 24 h. On the other hand, administration of the superficial layer of the Aloe leaf (leaf skin) to streptozotocin (pancreatic islets beta-cells toxin) –- induced diabetic mice, significantly depressed hyperglycaemia and examination of the tissue section under the light microscope revealed less denaturation and necrosis of islets beta-cells. These results indicate that Kidachi aloe relieves the diabetic condition by direct hypoglyceration (blood glucose lowering activity) and activates beta-cells.

Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: Topoisomerase II-alpha coamplification

Article

Jan 2006

In the present study the cytotoxic activity of aloin, a natural anthracycline from Aloe plant, is reported against two human breast cancer cell lines; without (MCF-7) and with (SKBR-3) erbB-2-topoII? co-amplification. MCF-7cell line was shown to be more sensitive to aloin than SKBR-3 demonstrated by MTT and clonogenic assays, from which IC50 and 50% ICF values are reported to be 60?g/ml, respectively, in the former cell line and as high as 150 and 80?g/ml,respectively, in the latter, which are still far below the maximum tolerated dose of the compound. The effect of aloin is suggested to be brought about by more than one mechanism depending on the dose level and tumor phenotype. This was demonstrated by flow cytometric analysis, fluorescence microscopy and western blot analysis, which revealed that aloin at higher concentrations caused a reduction in the proportion of cells undergoing mitosis, induction of apoptosis, inhibition of topo II? protein expression and down regulation of cyclin B1 protein expression in MCF-7 cell line, whereas erbB-2 protein expression was not affected. Topo II? protein expression was mildly down-regulated in SKBR-3 cell line at higher concentrations only.

The hypoglycemic effects of Aloe Vera in Thai diabetic patients

Article

Jan 1997
J CLIN EPIDEMIOL

Montchai Chalaprawat

Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophilic cream: A placebo-controlled double-blind study

Article

Jun 1997

BACKGROUND Genital herpes simplex virus infection is unique to humans, and is one of the commonest sexually transmitted diseases worldwide. OBJECTIVE The purpose of this double-blind placebo-controlled study was to determine the clinical efficacy and tolerability of Aloe vera extract 0.5% in a hydrophilic cream to cure patients afflicted with the first episodes of genital herpes. METHODS Preselected patients (n=60), aged 18–40 years (mean 23.6), with culture-confirmed diagnosis of herpes simplex genitalis, harboring 738 lesions (mean 12.3), were randomized to active or placebo treatment. Patients entered the study within 7 days (mean 4.1) of the onset of the lesions. Each patient was provided with a precoded 40-g tube, containing placebo/active preparation with instructions on self-application of the trial medication to their lesions three times daily for 5 consecutive days (maximum 15 topical applications per week). To assess the clinical efficacy and other beneficial effects patients were examined twice weekly and reepithelialized lesions with some residual erythema were considered as healed. Patients whose lesions resolved during the active treatment period (1 or 2 weeks) were spared further medication, and were requested to report to the clinic as scheduled for review and recurrence control. Empty tubes were collected from the remaining patients, and similarly coded replacement tubes were given to continue the treatment (in total 102 tubes were used). RESULTS The group treated with Aloe vera extract cream had both significantly shorter mean time to healing than the placebo group (4.9 days vs 12 days; P CONCLUSION The clinical results suggest that Aloe vera extract (0.5%) in a hydrophilic cream is more efficacious than placebo, thus supporting the benefits of Aloe vera therapy as an alternative, reliable and effective treatment to cure the first episodes of genital herpes in men.

Investigations on the Laxative Action of Aloin in the Human Colon

Article

Dec 1993

A. Koch

An Evidence-Based Systematic Review of Aloe vera by the Natural Standard Research Collaboration.

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