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Aloe Vera

GlossarySuccess Chemistry Staff

INTRODUCTION

Aloe vera is one of the oldest known medicinal herbs with

a history of use that spans thousands of years. Today, aloe

vera is cultivated and used in a large variety of commercial

preparations. It is an economic driver in the food, dietary

supplement, and personal care industries worldwide. The

two main commercial materials derived fromaloe vera are

aloe vera juice and aloe latex. Aloe vera juice is used for

various dietary, cosmetic, and medical purposes such as

burn treatment, wound healing, and skincare. It is available

in several forms including liquid juice, juice powder,

and concentrates. Aloe latex was formerly recognized as

an over-the-counter (OTC) laxative drug in the United

States. It has seen limited use in dietary supplements as

a laxative and in the personal care industry as a skin

lightener.

Confusion among consumers, researchers, and regulatory

bodies has arisen from the fact that products from

aloe latex are often referred to as simply “aloe” or “aloe

juice” (including in pharmacopoeias and other official

documents around the world), which is physically, chemically,

and biologically distinct from products made from

the charcoal filtered whole leaf or inner leaf aloe vera juice.

These latex-free juice products represent the vast majority

of aloe products on the market. Regardless, the prominence

of, interest in, and use of aloe vera products for

centuries attests to the plant’s myriad value and benefits.

BACKGROUND

Aloe vera (L.) Burm. f. is one of more than 400 known Aloe

species in the Asphodelaceae family, though it is sometimes

classified in Aloaceae. Because most aloe species

are indigenous to Africa, it is most likely that aloe vera

also originated from that continent. However, because of

its now worldwide cultivation, its origin is difficult to establish.

Linnaeus classified aloe vera as the “true aloe”

hence the name “vera,” meaning true in Latin. Although

it has also been known as Aloe barbadensis, Aloe chinensis,

Aloe indica, Aloe vulgaris, and others, A. vera (L.) Burm.

f. has precedence (1). Its standardized common name is

“aloe vera” though it has also been called Barbados aloe,

Curac¸ao aloe, true aloe, West Indian aloe, Ghrita kumari,

or simply aloe (2).

The plant is cactus-like in appearance with succulent

leaves that grow in a spiral form from a basal rosette

(Fig. 1). An inflorescence is produced annually (typically

December through March) with yellow flowers in a trident

configuration from a single central stalk with many

flowers in each of the three branches. Aloe vera does not

normally reproduce from seeds but from offshoots often

called “pups” that grow out from the mother plant. When

the green outer rind of the leaves is cut or damaged, a

bitter yellow exudate from pericyclic tubules located between

the outer rind and the inner leaf is released. This

sap is commonly referred to as “aloe latex” (3) and contains

several anthraquinone glycosides that have powerful

stimulant laxative properties.

When the rind is completely removed, a semitransparent,

semicrystalline gel-like layer composed of large

thin-walled parenchyma cells is revealed. This inner leaf

material is often called “aloe gel,” or “inner leaf fillet,”

because of its similarity in shape to a fish fillet. When

crushed, it produces a very viscous fluid usually containing

approximately 98.5% water. The solids are composed

mainly of polysaccharides and other carbohydrates,

pectin, and organic acids.

As mentioned earlier, aloe latex–derived products

are used as a laxative agent and the processed leaf or

inner leaf is often employed topically for the treatment

of burns and injury. More recent applications range from

skin-moisturizing agents to the management of cancers in

animals to impregnation in articles of clothing and mattresses

for its softening and moisturizing properties. Aloe

vera juice is also orally ingested to manage digestive ailments

and for its immune-modulating activities and is

sold worldwide in beverage form as a food-based drink

product available in various flavors. Aloe vera is also used

widely in Ayurvedic medicine (4).

CULTIVATION

Aloe vera is cultivated in subtropical regions around the

globe for commercial use and is widely grown by indoor

and outdoor plant enthusiasts as an ornamental plant because

of its hardiness and beauty. The species is resistant

to most insect pests and needs very little maintenance

or care to flourish, given appropriate temperature

conditions (5).

Because of its very low inner leaf solid content of

0.5% to 1.5%, aloe vera plants are highly susceptible to

freezing, which causes extensive damage, even killing

them when the temperature falls below 32◦F. For this reason,

commercial cultivations are typically carried out in

warm weather areas (USDA zones 8–11). Aloe vera is the

most cultivated species of the various Aloe species because

it produces the largest, thickest leaves and therefore yields

the greatest amount of juice. It is cultivated extensively in

removing most of the outer, lower, older leaves. Typically one to

four leaves are removed at a time per plant per harvest.

This way it is possible to obtain three to six harvests in a

year depending on how many leaves are collected from

each plant at harvest.

Cultivation practices for the industrial production

of aloe extracts made from the yellow latex sap are radically

different from those used to grow aloe vera for juice.

In the case of sap production, plants are not irrigated

and are grown in arid regions. The leaves turn brown

and thin under these conditions but when cut produce

the maximum amount of an anthraquinone glycoside–

rich latex, the principal constituents of which are the

compounds known as “aloins A and B.” The sap exudates

are collected and further processed to produce

two main products, aloe latex concentrate also known as

“aloin paste” and a product commercially known as “aloin

spray dried.”

DESCRIPTION

The leaf of aloe vera is normally described as consisting of

three major parts that are used in commercial products: the

outer mesophyll (rind or cuticle), the interior parenchyma

(inner leaf, gel or gel fillet, inner gel, inner leaf gel fillet),

and the aloe latex (sap, bitter element, yellow sap, yellow

latex). Researchers, raw material manufacturers, and finished

goods manufacturers have utilized all three plant

parts separately or in combination for aloe vera research

and in the formulation of consumer products.

Outer Mesophyll (Rind)

Aloe vera rind or cuticle is the site of photosynthesis and

primarily consists of cellulose, monosaccharides, water

soluble and insoluble carbohydrates, chlorophyll, amino

acids, proteins, and lipids.

Interior Parenchyma (Inner Leaf)

Aloe vera inner leaf is the colorless, mucilaginous

parenchyma of the aloe vera plant leaf consisting of

water, monosaccharides, water-soluble carbohydrates,

water-soluble polysaccharides, and water-insoluble fibrous

pulp. The compound -(1–4)-acetylated mannan,

a polysaccharide also known as “acemannan” or “acetylated

polymannose,” is widely considered to be the biologically

most important component of the inner leaf. After

removal of fibrous pulp from the inner leaf, the resulting

juice contains about 0.5% to 1.5% solids.

Histological examination of aloe vera inner leaf pulp

has shown it to be composed of large cells made up of 16%

cell walls, about 1% microparticles, and 83% of a viscous

gel on a dried weight basis. The carbohydrate portion

of each of these components was distinct, with the cell

walls composed of 34% galacturonic acid (an unusually

high level), the microparticles composed of galactose-rich

polysaccharides, and the liquid gel contained mannan (6).

These findings showed that different pulp structures are

associated with different polysaccharides and may therefore

confer different biological activities.

 

Aloe Vera

Harvest of the

leaf or the

whole plant—

root not used

Cleaning and

sanitation of

the leaves

Reduction of

the leaves to a

puree

consistency

Removal of

the insoluble

pulp and rind

Enzymatic treatment to

reduce viscosity

(not all manufacturers)

Charcoal filtration step to

remove phenolic compounds

(not all manufacturers)

Reduction of

microbial load by

pasteurization

Preservation and packaging

Reduction of water content to

increase the percent juice solids

or to produce juice powder

Flowchart 1 Aloe vera whole leaf processing.

Aloe Latex (Aloe Sap, Aloe Bitters)

Aloe latex is a yellow-green bitter exudate that contains

the anthraquinone glycosides aloins A and B, formerly

known as “barbaloin” and “isobarbaloin,” respectively.

The aloin content of aloe latex changes with the season

and the age of the leaf but usually makes up 10% to 25%

of the dried latex by weight. Products made fromaloe latex

have been used historically as a laxative. The source plant

is most commonly Aloe ferox from Africa or Argentina.

COMMERCIAL RAW MATERIAL PROCESSING

Aloe Vera Juice

Aloe vera juice can be manufactured from raw leaves in

two ways-–from the entire leaf or from only the inner leaf

material. In both cases, the leaves are first processed to

remove the side thorns and tips. For aloe vera juice made

from the entire leaf, the leaves are macerated in a grinder

into what is commonly called “guacamole” and then further

processed by enzymatic treatment (usually with cellulase)

to break up cell walls and then charcoal filtered to

remove anthraquinones and other phenolic constituents.

The resulting aloe vera juice is commonly referred to as

“filtered aloe vera juice” or “purified whole leaf aloe vera

juice.” See flowchart 1 for more detail.

When creating juice from only the inner leaf material,

the inner leaf is separated from the outer rind either

manually with a knife or by machine and then washed to

rinse away any aloe latex present. The remaining material

is crushed and further processed to produce the aloe vera

juice. See flowchart 2 for more detail.

At this stage, regardless of starting material, the

now-processed aloe vera juice is typically called “single strength.”

The juice from the leaf or inner leaf can also be

further processed to produce concentrates and powders

and are often spray or freeze dried. Some heat is usually

applied in the industrial production of aloe vera juice to

deactivate enzymes that would break down the mannans

into oligosaccharides and simple sugars. Heating also

serves to control the normal microbial load present on the

plant. Enzymatic treatment can be used to further break

down cell walls, with filtration removing any remaining

insoluble fiber. The resulting filtered juice contains all the

major groups of components from the original aloe vera

inner leaf.

Aloin-Rich Materials

The commercial production of aloin-rich materials starts

with the specialized cultivation practices mentioned earlier.

In contrast to aloe juice production, the leaves are

  • Leaf harvest

  • Cleaning and sanitation of the leaves

  • Removal of most of the rind

  • eduction of fillet to puree

  • Removal of the insoluble pulp and rind Enzymatic treatment to

  • reduce viscosity

  • Reduction of microbial load by pasteurization

  • Preservation and packaging

  • Reduction of water content to increase the percent juice solids or to produce juice powder

  • Dicing/slicing of fillet typically for use in beverage or food, the pulp is not removed

  • Reduction of microbial load by pasteurization

  • Preservation and packaging

Aloe vera inner leaf processing.

Acemannan

Mannan is a generic name for polysaccharides that are

polymers of the sugar mannose. In aloe vera juice, the

mannose moieties are connected by -(1–4) linkages,

which are partially substituted with acetate units and with

galactose-rich side chains on the mannose backbone. This

-(1,4)-acetylated-polymannose material is also known by

other names such as “aloverose” and “acemannan”; the

latter is also a name given to a proprietary substance

covered by many patents (7) and has been assigned as a

generic name by the United States Adopted Names Council

(8). It is based on the chemical name as it refers to the

acetylated mannan found in all aloe vera inner leaf fillets

(Fig. 3).

Acemannan is not sold as a pure material; however,

many commercial products contain varying amounts of it

depending on the processing of the aloe vera leaf as mentioned

earlier. The therapeutic properties of aloe vera juice

have been largely attributed to its polysaccharide component

and acemannan in particular. This high-molecularweight

material is perhaps the most studied component

of the aloe vera plant aside from the anthraquinone glycosides.

Many industrial methods have been developed

to stabilize the aloe vera juice and prevent polysaccharide

degradation. Drying the juice at temperatures over 60◦C

has been shown to cause deleterious changes in acemannan

and also pectin from the cell walls (9).

ANALYSIS OF COMMERCIAL PRODUCTS

Analysis of 32 commercial products showed wide variations

in polysaccharide content when compared by molecular

weight (10), which was attributed to different manufacturing

procedures. A second study of nine commercial

powders used a method that hydrolyzed the mannan into

mannose as a rapid way to measure the total polysaccharide

content in the powder. One sample was found to have

an abnormally high concentration of free glucose, four

showed signs of spoilage, and all but three were found to

have low levels of polymannose present (11). Both studies

found all samples to have a significantly lower amount

of aloins than the raw unwashed inner leaf fillet, with a

high of 16 ppm of aloin A found in one sample in one of

the studies. Because of the widespread use of aloe vera

juice in personal care products, a voluntary industry limit

of 50ppm aloin content for use in cosmetics as a topical

agent has been established (12).

PRECLINICAL STUDIES

General

Manyof the biological properties of aloe vera have been attributed

to acemannan. This compound has been studied

precipitate

fraction demonstrated wound healing activity (17),

suggesting that more than one aloe compound could be

useful in treating both inflammation and wounds.

 

Skin Moisturizing

Aloe vera applied topically has a moisturizing effect on

skin (18) and has been used for this purpose and as a

conditioning agent.

Antidiabetic Activity

Rodent studies have shown blood glucose regulating activity

of an aloe vera alcoholic extract (19) and processed

aloe vera inner leaf juice (20), suggesting its utility in treating

non–insulin-dependent diabetes.

Antitumor Activity

Acemannan has shown significant antitumor activity via

immune system activation. In a mouse model, IP injection

of acemannan at the time of implantation of sarcoma cells

resulted in a 40% survival rate in the treated animals versus

0% of the controls, most likely because of the production

of monokines from macrophage peritoneal stimulation.

The data suggested that this acemannan-stimulated

synthesis “resulted in the initiation of immune attack,

necrosis, and regression of implanted sarcomas in mice”

(21). A study involving acemannan treatment as an adjunct

to surgery and radiation in confirmed fibrosarcoma

in dogs and cats showed tumor shrinkage in one-third

of the animals after four to seven weeks of treatment administered

by intraperitoneal and intralesional injections

(22). An earlier study by the same group showed similar

results (23).

Studies on Aloin-Rich Materials

Aloin-rich extracts derived from aloe latex belong to the

stimulant laxatives drug class. Aloins are inactive until

deglycosylated by intestinal flora to form aloe-emodin, the

putative active compound (24). Their mechanism of action

is believed to involve increasing peristalsis and water accumulation

in the colon (25). Aloe latex has been subjected

to a human clinical trial as a laxative in combination with

other ingredients (26).

The potential toxicities of aloin and its metabolites

are not well established though studies have shown it

does not promote colon cancer in a mouse model (27) and

induces cell changes that could be a sign of anticancer

activity (28). Selective activity against certain cancers has

also been demonstrated by aloe-emodin, a metabolite of

aloins A and B (29,30).

 

CLINICAL STUDIES

Wound Healing

Although one study showed a delay in healing wound

complications after cesarean delivery or gynecological

surgery following treatment with “aloe vera dermal

wound gel” (31), another recorded a 6-day statistically

significant reduction (from 18 to 12 days) in the healing

time of partial thickness burns. A systematic review of

the literature for the use of topical aloe vera in treating

burn wounds included four controlled clinical trials involving

371 patients. A meta-analysis based on the time

for healing showed almost nine fewer days required for

the aloe vera–treated group over the controls (32). No specific

conclusions could be drawn because of the difference

in preparations and outcome measures. Further studies

with well-characterized materials were called for by the

authors as cumulative evidence tended to support the use

of aloe vera for the treatment of first- and second-degree

burns. A bioadhesive patch of an aloe vera preparation

was evaluated in an open uncontrolled trial for the management

of mouth ulcers in children with apparent good

results (33).

 

Ulcerative Colitis and Irritable Bowel Syndrome (IBS)

Ulcerative colitis is caused by a dysfunction of the immune

system (34). A 2004 clinical trial involving 44 patients

with mild or moderately active ulcerative colitis compared

100 mL twice-daily oral aloe vera juice treatment

with placebo for four weeks. The aloe vera–consuming

patients showed positive clinical responses more often

than placebo. Clinical remission was seen in 30% of the

active group, clinical improvement in 37%, and a clinical

response in 47% of patients compared with 7%, 7%,

and 14% in the placebo group, respectively. Histological

scores and the Simple Clinical Colitis Activity Index did

not change in the placebo group but decreased significantly

for those who consumed aloe vera. No significant

differences were seen between the two groups with regard

to laboratory values or sigmoidoscopic scores (35).

Ahuman clinical study using aloe vera for treatment

of irritable bowel in refractory secondary care patients

failed to show a benefit, though the authors could not rule

out that diarrhea-predominant patients were helped (36).

Antidiabetic Activity

Aloe dried sap has demonstrated hypoglycemic activity

in a study involving five patients with non–insulindependent

diabetes (37).

Antitumor Activity

A preliminary clinical trial on the use of orally administered

“aloe vera tincture” for untreatable metastatic solid

tumor patients with and without melatonin treatment

showed a significantly higher percentage of nonprogressing

patients in the group that received the aloe treatment

(50% vs. 27%, P < 0.05) (38). Another human trial on 240

patients treated with Aloe aborescens (used because of purported

immunostimulating activity from this plant owing

to its acemannan component) suggested that oral aloe

therapy may be a successful adjunct to chemotherapy in

patients with metastatic solid tumors. Tumor regression

rate and survival time were improved in this study (39).

No conclusions can be drawn from this study because

details on characterization of the test material were not

provided.

SAFETY

A four-week subacute oral toxicity study in mice administered

a freeze-dried aloe juice product reported no remarkable

subacute toxic effects but did note a decrease

in male kidney weights. The report also provided a review

of several adverse reaction case studies associated

with aloe vera (40). They ranged from skin irritation from

topical use to one report of acute hepatitis in a 73-yearold

female taking oral aloe vera capsules for constipation.

A second case of acute hepatitis involving a 26-year-old

man who had been drinking “aloe vera tea” has also been

reported (41).

The National Toxicology Program of the U.S. government

nominated “aloe vera gel” for study in 1998 (42).

No long-term carcinogenicity studies of aloe vera gel in

animals were identified at that time. NTP subsequently

chose to conduct a two-year carcinogenicity study on mice

and rats with a “whole leaf extract” (43) that includes a

considerable amount of latex aloins. The majority of aloe

vera juice products intended for long-term internal use

are either charcoal filtered whole leaf preparation or are

made from washed inner leaf juice with aloin concentrations

typically under 10 parts per million. The NTP

report was still in progress at the time of publication of

this chapter.

REGULATORY STATUS

United States

Aloe and aloin are present in the first approved food additives

list published by the U.S. Food and Drug Administration

in 1959. Although initially approved in the United

States in 1975 as an OTC drug to treat chronic constipation,

aloe latex is no longer approved for such use in the

United States as of May 9, 2002 (44). Standard quality tests

for aloe latex have been described in detail in many official

pharmacopeias including the United States Pharmacopeia,

Japanese Pharmacopoeia, and the European Pharmacopoeia,

though, as mentioned in the introduction, these texts typically

define aloe latex as simply “aloe” or incorrectly as

“aloe juice.”

Aloe vera juice products can be labeled and marketed

as dietary supplements. Aloe latex may also be used

in dietary supplements in the United States with laxative

or constipation claims as long as such claims are not for

the treatment of chronic constipation.

Australia

Aloe vera inner leaf (called “aloe barbadensis”) is eligible

for use as an active or excipient ingredient in Australia

in “Listed” medicines in the Australian Register of Therapeutic

Goods. Acemannan is approved as a component.

Components are not approved as substances for use in

their own right and can only be used in conjunction with

an approved source.

Some aloe vera juice and juice concentrate beverages

are viewed as “nontraditional foods” and not as “novel

foods” and there are some listed medicines described as

“aloe vera drinking gel” or as “aloe vera juice.”

Canada

Aloe vera inner leaf, when included as a Natural Health

Product (NHP) active ingredient, requires premarket authorization

and a product license number for OTC human

use. Such products must comply with the minimum specifications

outlined in the current NHPD Compendium of

Monographs (45).

European Community

Aloe vera inner leaf was listed as “currently not on the

priority list” in the inventory of herbal substances for assessment

by the European Medicines Agency as of March

2009. There is an EU regulatory limit established for aloin

content of 0.1 ppm in orally ingested products based on

a flavoring regulation in which the aloin is defined as an

added ingredient as opposed to naturally occurring. The

International Aloe Science Council (IASC) (a trade association)

has taken a position that these regulations are not

applicable to aloe vera juice products.

Japan

Aloe vera juice is regulated as a food beverage product in

Japan and is not to contain more than 0.60 mg/kg of benzoic

acid. Various forms of aloe vera and extracts thereof

are used as components of functional food products or in

Foods for Specified Health Use such as in fortified waters

and fermented yogurt drinks.

South Korea

Aloe products, known as “edible aloe concentrate” and

“edible aloe gel,” are regulated as food products by the

Korean Food and Drug Administration. Juice or concentrate

from the inner leaf or dried and powdered inner

leaf material containing not-less-than 30 mg/g of total

aloe polysaccharides is able to carry the health claim

of “smoothing the evacuation” on the basis of 20 to

30 mg delivered as aloe polysaccharides. Processed aloe

vera leaf or concentrates thereof, after removal of the

inedible parts, and containing 2.0 to 50 mg/g of anthraquinones

(as anhydrous barbaloin), is permitted to

make the same health claim at the specified daily intake.

Aloe vera is also one of the four botanical ingredients allowed

to make immune system enhancement claims in

South Korea.

CONCLUSION

Of the 400 known species of aloe, Aloe vera is the most

commonly used in commerce and is cultivated in many

different areas of the world. The plant yields two raw

materials for use in various consumer products including

foods, dietary supplements, cosmetics, and drugs, namely

aloe vera juice and aloe latex. Aloe vera juice can be made

from processing either the entire leaf or only the inner leaf

material. Aloe vera juice is often further processed into a

powder or concentrate.

Preliminary scientific evidence suggests that aloe

vera has therapeutic benefits; however, more studies need

to be conducted to definitively demonstrate efficacy. Consumers

should be aware and informed when buying aloe

vera products; although there are many quality products

on the market, there are also many products that may

bring little or no benefit to the user. The IASC maintains a

certification program using validated analytical methods

to determine and ensure products displaying the IASC

program seal contain aloe vera of a particular quality. It

is recommended that consumers verify that products displaying

the IASC seal are current participants in the IASC

certification program.

 

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