Aloe vera review

Aloe vera also known as Aloe barbadensis Miller, Aloe indica Royle, Aloe perfoliata L. var. vera, Aloe vulgaris Lam or Aloe, is a plant belonging to the Liliaceae family, of which there are over 360 known species ¹. Aloe vera are cactus-like perennial succulents and are characterised by stem less, large, thick, fleshy leaves that are lance-shaped and have a sharp apex and a spiny margin ². Aloe vera plant provides two distinct products: the yellow latex, which is referred to as aloe juice, and the leaf pulp which is the innermost portion of the Aloe vera leaf and is composed of the parenchyma cells whose baseline function is for storage of food and nutrients that contain the Aloe vera gel. The raw pulp contains about 98.5% water with the remaining 1.5% containing a range of compounds including water-soluble and fat-soluble vitamins, minerals, enzymes, polysaccharides, phenolic compounds and organic acids ³. Aloe vera exhibits many pharmacological activities such antioxidant, antimicrobial, immune boosting, antitumor, hypoglycemic, hypolipidemic, wound healing, and antidiabetic ⁴. Aloe vera leaf pulp is commonly delivered as a topical ointment on wounds in a gel, cream or mucilage form (the mucilage being the thick, glue-like gel substance that is derived from the leaf pulp of the Aloe vera plant). Traditionally, the clear gel from Aloe vera plant is rubbed on the skin as an ointment to treat wounds and burns. The green part of Aloe vera leaf can be made into a juice or dried and taken orally as a laxative. Aloe vera is used in many commercial products in various forms, including drinks, concentrates, capsules, powders, and as a flavoring.

Aloe vera’s use can be traced back 6,000 years to early Egypt, where the plant was depicted on stone carvings. Known as the “plant of immortality,” aloe vera was presented as a funeral gift to pharaohs ⁵. Historically, aloe vera has been used for a variety of purposes, including treatment of wounds, hair loss, and hemorrhoids; it has also been used as a laxative. Aloe vera has a long history of use as an anti-inflammatory herbal application for burns and for a variety of conditions in traditional medicine ⁶. Today, Aloe vera is still used as a herbal medicine. Aloe vera is used either internally or externally in humans and has some medicinal effects which have been supported by scientific and medical research ⁷. As a herbal medicine, Aloe vera juice is commonly used internally to relieve digestive discomfort ⁸ and externally to relieve skin discomforts such as minor burns, wounds and various skin conditions such as eczema and scabies ⁹. The topical or external applications usually use aloe-derived products, which include aloe vera cream, aloe vera mucilage, aloe vera gel etc. ⁷. However, crude aloe vera components such as fresh aloe vera leaf, fresh aloe vera stem, and aloe vera juice are also used as adjuvant treatment to treat skin disorders ¹⁰.

Aloe vera contains 75 potentially active constituents including vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids and amino acids ¹¹, some of which have several pharmacological actions. These include the carboxypeptidase that inactives bradykinin, salicylates and substances that inhibit local vasoconstriction ¹². The anti-inflammatory compound called C-glucosyl chromone has been isolated from gel extracts ⁶. It has been proven that fresh Aloe vera can promote the attachment and growth of normal human cells in vitro and enhance the healing of wounded monolayers of cells ¹³ whereby Aloe vera gel not only increased the collagen content of the wound but also changed the collagen composition and increased the degree of collagen cross linking ¹⁴. Some studies have shown that pure Aloe vera is effective in preserving skin circulation following frostbite injury ¹⁵ and in accelerating wound healing ¹⁶ and increasing the breaking strength of resulting scar tissue in patients ¹⁷. In addition, Aloe vera can stimulate fibroblasts, which produce the collagen and elastin fibres, making the skin more elastic and less wrinkled; and Aloe vera has cohesive effects on the superficial flaking epidermal cells by sticking them together, to soften the skin ¹⁸. To summarise, the mechanism of action of Aloe vera includes healing properties, anti-inflammatory activity, effects on the immune system, moisturising and anti-aging effects and antiseptic effects ⁵.

Two substances from aloe vera- the clear gel and the yellow latex, are used in health products today. Aloe gel is primarily used topically (applied to the skin) as a remedy for skin conditions such as burns, frostbite, psoriasis, and cold sores, but it may also be taken orally (by mouth) for conditions including osteoarthritis, bowel diseases, and fever. Aloe latex is taken orally, usually for constipation.

People primarily use aloe’s clear gel topically in creams and ointments to treat burns, the skin condition psoriasis and even acne. Some also take the gel orally to treat certain conditions. Aloe latex, a laxative, has been taken orally to treat constipation.

While aloe gel is generally safe when used as recommended, oral use of aloe latex poses safety concerns. In fact, taking 1 gram a day of aloe latex for several days can cause kidney damage and might be fatal. In rodents, aloe vera caused intestinal tumors ¹⁹, ²⁰.

Aloe vera benefits

Based on various preclinical studies, Aloe vera constituents have enormous potential to prevent and treat various diseases ²¹. Various biological and pharmacological activities of Aloe vera, such as antioxidant, anti-inflammatory, immuno-modulatory, antimicrobial, antiviral, antidiabetic, hepatoprotective, anticancer, and skin-protective and wound-healing responses, have been attributed to the presence of many active compounds, including anthraquinones, anthrones, chromones, flavonoids, amino acids, lipids, carbohydrates, vitamins and minerals ²¹. However, randomized clinical trials are needed to understand the full therapeutic potential of this unique medicinal plant. Applying Aloe vera gel on the skin is not likely to cause harm.

Aloe vera leaves are the most used part of the plant, with bioactive acetylated glucomannan and anthraquinone glycosides being obtained from the Aloe gel, while the latex contains too high an anthraquinoids content (aloin A and B); an excessive consumption of these compounds presented in aloe juice can have toxic effects, and therefore, its consumption must be limited ²². Recently, some studies have reported the antioxidant properties ²³ or carotenoids content, composition of phenolic compounds, and fatty acid profile of Aloe vera flowers ²⁴. In some countries, Aloe vera flowers have become a new crop with great popularity in the culinary field, as they are rich in nutrients and bioactive compounds ²⁵. Quispe et al. ²⁶ described an antioxidant activity four to eight times greater in Aloe vera flowers than in Aloe vera gel. Furthermore, some bioactive compounds such as gentisic acid with anti-inflammatory, antirheumatic, and antioxidant properties have been detected mainly in Aloe vera flowers (101 mg/100 g freeze-dried) rather than in Aloe vera leaf skin (6 mg/100 g freeze-dried) ²⁷. Aloe vera flowers presented an important content of apigenin glycoside derivatives (4.48 mg/g), and no anthraquinone glycosides have been detected in that part of the plant ²⁴. Additionally, the important antimicrobial activity of Aloe vera flower against the multidrug-resistant Pseudomonas aeruginosa (Minimum Inhibitory Concentration (MIC) = 0.025 mg/mL and Minimum Bactericidal Concentration (MBC) = 0.05 mg/mL) and the powerful antifungal activity against Aspergillus flavus, Aspergillus niger, Penicillium funiculosum and Candida albicans, higher than that of ketoconazole ²⁴. Therefore, Aloe vera flowers could be considered as a valuable byproduct for the food, cosmetic, or pharmaceutical industries. However, the Aloe vera flower is not a plant material that has been studied to the same extent as the leaves. The optimal time to harvest aloe vera leaves is reportedly after three years of the plant’s growth, because then it has the highest content of bioactive compounds ²³, but the best maturity stage to harvest Aloe vera flowers remains unknown.

What scientists have learned about Aloe Vera

• Aloe latex contains strong laxative compounds. Products made with aloe were at one time regulated by the U.S. Food and Drug Administration (FDA) as over-the-counter (OTC) laxatives. In 2002, the FDA required that all OTC aloe laxative products be removed from the U.S. market or reformulated because the companies that manufactured them did not provide the safety data necessary for continued approval.
• Research suggests topical use of aloe also may help people with herpes simplex, lichen planus, or psoriasis.
• Clinical research suggests that topical application of an aloe-based gel twice daily (along with medical soap and tretinoin gel) may improve acne.
• There’s not enough high-quality scientific evidence to show whether topical use of aloe helps to heal wounds ²⁸.
• Clinical research suggests topical application of aloe gel may speed burn healing. There also is evidence that treatment with aloe vera may reduce pain from burns.
• Three trials (with a total of 236 adult participants) have evaluated the use of oral doses of aloe vera for symptoms of irritable bowel syndrome. Results from one trial showed a benefit; the other two trials showed no benefit of aloe vera over placebo.
• In a small European study, 44 adults with ulcerative colitis were randomly assigned to receive aloe vera gel or a placebo twice daily for a month. Almost half of the people treated with aloe vera responded to the treatment whereas 14 percent of those treated with placebo responded.
• Aloe vera has been studied in clinical (human) trials for diabetic foot ulcers and dental plaque, but there’s not enough scientific evidence to show whether aloe vera is helpful for these conditions. A 2009 review article examined data from a mix of laboratory, animal, and clinical trials and concluded that more research is necessary to explore aloe’s clinical effectiveness for a number of different skin conditions.

Research on the use of aloe for specific conditions shows:

Burns and wounds. Application of aloe gel appears to shorten the duration of wound healing for first- and second-degree burns. Aloe gel might also promote wound healing.

Acne. Research suggests that aloe gel, applied in the morning and evening in addition to the use of the topical prescription acne medicine tretinoin (Retin-A, Atralin, others), might be more effective in reducing acne than using a topical prescription alone.

Psoriasis. Aloe extract cream might reduce redness, scaling, itching and inflammation caused by mild to moderate psoriasis. You might need to use the cream several times a day for a month or more to see improvements in your skin.

Herpes simplex virus. Applying a cream containing aloe extract might help lesions heal sooner.

Oral lichen planus. Research suggests that twice-daily application of aloe gel for eight weeks might help reduce symptoms of this inflammatory condition that affects the inside of the mouth.

Burn wound healing effect

In vitro (test tube) extracts of aloe vera stimulate the proliferation of several cell types. Many studies have shown that treatment with whole Aloe vera gel extracts resulted in faster healing of wounds ²⁹. Aloe vera may have a direct effect on the wound healing process as a whole, which is manifested by increase in rate of contraction of wound area ³⁰ and has confirmed the effect of Aloe vera on increasing wound contraction and collagen synthesis. This property is attributed to the mannose-6-phosphate known to be present in Aloe vera gel ³¹. Polysaccharides from Aloe promote both the proliferation of fibroblasts and the production of hyaluronic acid and hydroxyproline in fibroblasts, which play important roles in extracellular matrix remodeling during wound healing ³². Acemannan, significantly increases periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, type I collagen and alkaline phosphatase activity in primary human periodontal ligament cells ³². In a clinical study, to check the efficacy of Aloe vera gel compared with 1% silver sulfadiazine cream as a burn dressing for the treatment of superficial and partial thickness burns, healing of burn wounds were remarkably early in Aloe vera treated patients than those patients treated with 1% silver sulfadiazine ³³. Polysaccharides isolated from Aloe vera induce matrix mellatopeptidase (MMP)-3 and metallopeptidase inhibitor-2 gene expression during the skin wound repair of rat, which directly helps to regulate the wound healing activity of Aloe vera gel ³⁴.

Constipation

Whether oral use of aloe latex is effective at treating constipation is unclear. While it acts as a laxative, aloe latex can also cause abdominal cramps and diarrhea.

What makes Aloe act like a laxative ?

An organic component in the outer leaf pulp of Aloe leaves, known as the latex, contains anthraquinones. Aloin is an example of an anthraquinone found in the latex that may give the plant its laxative qualities.

How much aloin is in products in the U.S. that may be consumed by the public ?

There are very little data about what the levels of aloin are in the consumer products. According to published research, levels of aloin in most liquid products are less than 1 part per million (ppm); however, levels in solid or semi-solid products may be 10-100 times higher.

How much aloin is in a typical drink ?

This is not clear. Industry usually processes the Aloe vera leaf to make a decolorized whole leaf extract to remove aloin. Industry has a self-regulated upper limit standard of 10 ppm of aloin in orally ingested products, but there are no labeling requirements for aloin content.

Anticancer activity

Aloin, an anthraquinone being a natural compound and the main ingredient of Aloe, has been documented for its remarkable potential therapeutic options in cancer, wherein it showed chemoprotective effects against 1,2-dimethylhydrazine-induced preneoplastic lesions in the colon of Wistar rats ³⁵. Aloin, derived from aloe vera leaves, has been shown to possess anticancer potential activities ³⁶ as it inhibits tumor angiogenesis and growth via blocking signal transducer and activator of transcription 3 activation, with the potential of a drug candidate for cancer therapy ³⁷. Aloin treatment could inhibit the secretion of VEGF in cancer cells. VEGF is one of the most important proangiogenic cytokines known and well characterized as an inducer of tumor neovascularization. Aloin treatment significantly inhibited in vitro VEGF-induced angiogenic response of human endothelial cells, causing an inhibition of proliferation and migration of endothelial cells ³⁸. Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione) is also a subtype of anthraquinone, a natural compound that has traditionally been found to have diverse biological activities including anticancer functions ³⁹. Aloe-emodin is an herbal anthracenedione derivative from aloe vera leaves. Recent reports have shown that Aloe-emodin possesses antiproliferation effects on some types of cancer cells, such as lung, squamous, glioma, and neuroectodermal cancer cells ⁴⁰. The inhibitory effect of Aloe-emodin on the activity and gene expression of N-acetyl transferase, which plays an initial role in the metabolism of aryl amine carcinogens, was found in human malignant melanoma cells ³⁶. Recently, Lin et al ³⁶ demonstrated that Aloe-emodin-induced apoptosis in T24 human bladder.

Anthraquinone derivatives such as emodin-like natural (emodin, rhein, and aloin) and synthetic (anthraquinone-2-sulfonic acid) anthraquinones have recently been shown to protect in models of amyloid β and τ aggregation-induced cell death through antiaggregation properties, and/or enhancing the phosphatidylinositol-3-kinase/protein kinase B survival mechanism, which suggests that anthraquinone-2-sulfonic acid could be a new neuroprotective compound and a novel caspase inhibitor ⁴¹.

Immunomodulatory effect

Aloe vera gel has strong immunomodulatory activity wherein it downregulates lipopolysaccharide-induced inflammatory cytokine production and expression of NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome in human macrophages ⁴². Aloe vera could inhibit the inflammatory process following burn injury, as characterized by the reduction of leukocyte adhesion, as well as proinflammatory cytokines ⁴³. Liu et al ⁴⁴ have shown that Aloe polysaccharides pretreatment can attenuate the cerebral ischemia and reperfusion injury in severe traumatic–hemorrhagic rats by first entering high altitude through inhibiting systemic inflammatory response and leukocyte aggregation and lipid peroxidation in the brain. Administration of aloe vera has been universally demonstrated to result in marked increase in phagocytic and proliferative activity of the reticuloendothelial system ⁴⁵. Aloe vera directly inhibits the cyclooxygenase pathway and reduces prostaglandin E2 production, which plays an important role in inflammation ⁴⁶. Aloe also contains anthraquinones and chromone in the inner gel, which possess strong anti-inflammatory effects as shown in murine macrophages ⁴⁷. This report ⁴⁸ suggests that Aloe as a whole has anthraquinones (aloin) and chromone (aloesin) components, and Aloe gel has pharmacological activity to alleviate inflammatory responses in inflammatory bowel disease. A recent report of a clinical study evaluated the therapeutic effect of aloe vera gel wherein 2% oral gel is not only effective in decreasing the pain score and wound size in recurrent aphthous stomatitis patients but also decreasing the aphthous wound healing period ⁴⁹.

Intestinal absorption

Aloe material has been used for drug absorption enhancement for drugs with low bioavailability due to extensive efflux ⁵⁰. Lactobacillus brevis strains were isolated from naturally fermented aloe vera gel which inhibited the growth of many harmful enteropathogens without restraining most normal commensals in the gut and hence were named POAL (probiotics originating from Aloe leaf) strains; these and exhibit discriminative resistance to a wide range of antibiotics ⁵¹. Aloin, present in the gel, is metabolized by the colonic flora to reactive Aloe-emodin, which is responsible for the purgative activity. Aloe-emodin isolated from aloe vera inhibits colon cancer cell migration by downregulating MMP-2/9 and also inhibits ras a homolog family member B and vascular endothelial growth factor (VEGF) via reducing DNA binding activity of nuclear factor κ-light-chain-enhancer of activated B cells ⁵². Aloe vera gel has been shown to contain five phytosterols, which are able to reduce visceral fat accumulation, and influences the metabolism of glucose and lipids in animal model experiments, where they reduced large-sized intestinal polyps and ameliorated reduction in plasma. High molecular weight adiponectin levels in adenomatous polyposis coli gene-deficient multiple intestinal neoplasia mice fed high-fat diet. Furthermore, an in vitro study has shown that aloe vera gel and whole leaf extract were able to reduce significantly the transepithelial electrical resistance of the Caco-2 cell monolayers and thereby showed the ability to open tight junctions between adjacent cells. Hence, aloe vera gel and whole leaf extract solutions significantly enhanced the transport of insulin across the Caco-2 cell monolayers ⁵³.

Antidiabetic effect

Clinical studies have suggested that aloe vera gel may act as a safe antihyperglycemic and antihypercholesterolemic agent for type 2 diabetic patients without any significant effects on other normal blood lipid levels or liver/kidney function ⁵⁴. In vivo (animal study) and in vitro (test tube) studies strongly demonstrate that the water soluble fraction of Aloe spp. possesses glucose-lowering activities and some of its components modulate glucose transporter-4 mRNA expression ⁵⁵. In a randomized controlled trial, aloe vera gel complex reduced body weight, body fat mass, and insulin resistance in obese prediabetes and early nontreated diabetic patients ⁵⁶. Furthermore, in a pilot study, two Aloe products in patients with prediabetes over an 8-week period, tended to revert the impaired fasting glucose and impaired glucose tolerance observed in conditions of prediabetes/metabolic syndrome ⁵⁷. One study discussed the efficacy of aloe-emodin-8-O-glycoside isolated from aloe vera gel in enhancing glucose transport by modulating the proximal and distal markers involved in glucose uptake and its transformation into glycogen ⁵⁸. Tanaka et al ⁵⁹ reported reductions in both fasting and random blood glucose levels of db/db diabetic mice chronically treated with the same phytosterols from aloe vera gel. Jain et al ⁶⁰ found that aloe vera gel has significant antidiabetic and cardioprotective activity as it significantly reduced oxidative stress in streptozocin induced diabetic rats and improved antioxidant status. Aloe vera gel also helps to improve the carbohydrate metabolism, with a recent report suggesting that it helps to improve metabolic condition in obese prediabetes and early nontreated diabetic patients by reducing body weight, body fat mass, fasting blood glucose, and fasting serum insulin in obese individuals ⁵⁶. Shin et al ⁶¹ shown that dietary Aloe formula also reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the white adipose tissue and liver, both of which are important peripheral tissues affected by insulin resistance. Aloe vera also has shown improvement in the function of isolated rat pancreatic islets wherein it increased survival of the islet cells, their mitochondrial activity, and insulin levels at the same time as reducing production of reactive oxygen species ⁶².

Antioxidant effect

Aloe vera contains substantial amounts of antioxidants including α-tocopherol (vitamin E), carotenoids, ascorbic acid (vitamin C), flavonoids, and tannins and it has been suggested that antioxidant action may be an important property of plant medicines used in treatment of various diseases ⁶³. Topical Aloe saponaria treatment has shown antinociceptive and anti-inflammatory effects in ultraviolet B-induced sunburn model via its antioxidant components present in gel ⁶⁴. Aloe gel is able to scavenge the free radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)+•, and nitric oxide in a concentration-dependent manner, as seen in an in vitro study of the radioprotective efficacy of aloe vera gel ⁶⁵. Administration of ethanolic extract of aloe vera gel on tissue antioxidants led to reduction in blood glucose level in diabetic rats, which helps to prevent excessive formation of free radicals through various biochemical pathways and also reduces the potential glycation of the enzymes ⁶⁶. In vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel using 10 digestive enzymes including five carbohydrases and five proteases. Results suggested that Aloe polysaccharides exhibited a protective effect against 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidative stress and cell death in kidney epithelial cells (Vero cells) as well as in an in vivo zebrafish model ⁵¹. One study determined the total phenolic content of aloe vera leaf skin extracts and a significant correlation was established between the total phenolic content and the antioxidant capacity ⁶⁶. The methanol extracts of leaf skins and flowers of aloe vera were also screened for their antioxidant and antimycoplasmic activities, and in vitro antioxidant activities of both extracts exhibited antioxidant activity, with the leaf skin extract being the most active ⁶⁷.

Effect on estrogen status

Isolated emodin and aloe-emodin from aloe vera gel specifically suppress breast cancer cell proliferation by targeting estrogen receptor-alpha protein stability through distinct mechanisms, which suggests a possible application of anthraquinones in preventing breast cancer cell proliferation through estrogen receptor-alpha inhibition ⁶⁸. Aloe vera gel also helps to maintain ovarian steroid status in polycystic ovary-like condition wherein steroidogenesis altered and disturbed estrogen:testosterone ratio ⁶⁹.

Antihyperlipidemic activity

Aloe vera is known for its antihyperlipidemic property wherein it has beneficial effects on the prevention of fatty streak development and may help to reduce the development of atherosclerosis through modification of risk factors ⁵⁴. Aloe vera leaf gel efficacy has been checked in hyperlipidemic type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial wherein it reduced total cholesterol and LDL (low density lipoprotein or “bad” cholesterol) levels significantly ⁵⁴. A recent study also demonstrated that administration of phytosterols isolated from aloe vera gel reduces visceral fat mass and improves hyperglycemia in Zucker diabetic fatty rats ⁷⁰. Dried pulp of Aloe succotrina leaves produced significant antihyperlipidemic effect in high-fat diet- and fructose-induced hyperlipidemic rats, where it significant decreased serum levels of total cholesterol, total triglycerides, low-density lipoprotein–cholesterol, very low-density lipoprotein, and high-density lipoprotein–cholesterol ⁷¹. Previous reports also suggested that aloe vera gel-treated polycystic ovarian syndrome (PCOS) rats exhibited significant reduction in plasma triglyceride and LDL cholesterol levels, with an increase in high-density lipoprotein–cholesterol PCOS condition wherein hyperlipidemia is one of main consequences. The Aloe vera gel treatment also caused reversion of abnormal estrous cyclicity, glucose intolerance, and lipid metabolizing enzyme activities, bringing them to normal. It has phytocomponents with antihyperlipidemic effects and has shown efficacy also in management of PCOS but also the associated metabolic complications ⁷².

Antiulcer activity

Aloe vera leaf extracts have been promoted for digestion and are used in the treatment of peptic ulcer for cytoprotective action whereby aloe vera gel expresses antibacterial properties against both susceptible and resistant Helicobacter pylori strains and acts as a novel effective natural agent for combination with antibiotics for the treatment of Helicobacter pylori gastric infection ⁴⁹. One study demonstrated that newly formulated aloe- and myrrh-based gels proved to be effective in topical management of minor recurrent aphthous stomatitis and was superior in decreasing ulcer size, erythema, and exudation; myrrh resulted in more pain reduction in a randomized, double-blind, vehicle-controlled study ⁷³.

Liver protective effect

Isolated phytosterols, namely lophenol and cycloartanol, have the ability to induce the downregulation of fatty acid synthesis and a tendency for upregulation of fatty acid oxidation in the liver, which favors the reduction in intra-abdominal fat and improvement of hyperlipidemia. Furthermore, addition to sterol regulatory element-binding transcription factor 1/peroxisome proliferator-activated receptor (PPAR)-α ratio was decreased; metabolic syndrome-related disorders were improved and liver steatosis in Aloe-sterol-treated Zucker diabetic fatty rats ⁷⁴. Aloe formulas also suppress obesity-induced inflammatory responses by reducing levels of the proinflammatory cytokines, PPARγ/liver X receptor α, and 11β-hydroxysteroid dehydrogenase 1, and enhance anti-inflammatory cytokines in white adipose tissue and liver. The beneficial effects of Aloe formula with respect to obesity-induced insulin resistance and hepatic steatosis have been associated with its action on PPARγ/liver X receptor α ⁶². Saito et al ⁷⁵ showed that aloe vera gel extract prevents ethanol-induced fatty liver by suppressing mRNA expression of lipogenic genes in the liver. The combination of probiotic Lactobacillus rhamnosus GG and aloe vera gel have a therapeutic potential to decrease cholesterol levels and the risk of cardiovascular diseases ⁷⁵.

Antibacterial activity

Aloe vera has been described as an antibacterial agent. The Aloe protein of 14 kDa from the aloe vera leaf gel was isolated and the purified Aloe protein exhibited a potent antifungal activity against Candida paraprilosis, Candida krusei, and Candida albicans ⁷⁶. Aloe vera has anthraquinones as an active compound, which is structural analogue of tetracycline. The anthraquinones acts like tetracycline that inhibits bacterial protein synthesis by blocking the ribosomal A site (where the aminoacylated tRNA enters). Therefore, the bacteria cannot grow in the media containing aloe vera extract. Pandey and Mishra ⁷⁶ established the susceptibility of Gram-positive and Gram-negative bacteria to an extract of the inner gel of aloe vera. Polysaccharides of aloe vera gel have been attributed direct bacterial activity through the stimulation of phagocytic leucocytes to destroy bacteria ⁷⁷. Aloe vera contains pyrocatechol a hydroxylated phenol, known to have toxic effect on microorganisms ⁷⁸. A recent study demonstrated that the aloe vera inner gel expresses antibacterial properties against both susceptible and resistant Helicobacter pylori strains and impact on the antimicrobial resistance phenomenon of Helicobacter pylori, proposing the aloe vera inner gel as a novel effective natural agent for combination with antibiotics for the treatment of Helicobacter pylori gastric infection ⁷⁹.

Antiviral activity

Many reports have suggested that aloe vera gel has antiviral activity that prevent virus adsorption, attachment, or entry to the host cell. An in vitro study has shown that crude extract of aloe vera gel has antiviral activity against herpes simplex virus type 2 strain ⁸⁰. Anthraquinone derivatives, such as Aloe-emodin, emodin, and chrysophanol, reportedly exhibit antiviral activity wherein their inhibitory mechanism and effect against influenza A virus with reducing virus-induced cytopathic effect and inhibiting replication of influenza A ⁸¹. Preliminary trials have suggested that aloe vera consumption may be of help to HIV-infected individuals as it improves the immune system by increasing the CD4 count ⁸². Many methods have been developed for the successful transformation and regeneration of aloe vera wherein Aloe able to produce interferon alpha 2 (IFNα2). This experiment was assessed using an antiviral assay with A549 cells wherein these cells treated with extracts from both the rind and pulp fractions of the shoot and subsequently infected with the lytic Encephalomyocarditis virus. This experiment demonstrated that aloe vera was capable of expressing a human protein with its biological activity namely interferon alpha 2 (IFNα2) ⁸³.

Aloe vera Safety and Side Effects

Aloe vera both in gel and latex form when taken by mouth may be unsafe during pregnancy and while breastfeeding. Aloe vera gel is generally considered safe and can be effective when appropriately applied to the skin for burns and psoriasis ⁸⁴, ⁸⁵. Some patients experienced burning after topical application ⁸⁶, contact dermatitis ⁸⁷ and mild itching ⁸⁸.

Topical use of aloe gel is generally well tolerated. However, there have been occasional reports of burning, itching, and eczema with topical use of aloe gel. Oral use of aloe latex can cause abdominal pain and cramps. Oral consumption of aloe leaf extracts (for as little as 3 weeks and as long as 5 years) has been related to cases of acute hepatitis. Animal studies have noted an association between aloe vera leaf extract taken orally and gastrointestinal cancer in rats and mice; however, concerns were expressed about the differences in the product used in that study and those commonly used by consumers. Thus, more research is needed to assess the relevance to human health. Overuse of aloe latex may increase the risk of adverse effects from the drug digoxin, used for some heart problems.

It might be safe when appropriate doses are taken orally for a short time. More research is needed to answer this question. However, avoid using aloe latex or or whole-leaf extract orally. Unprocessed aloe latex contains chemicals that appear to have the potential to cause cancer ¹⁹ and processed aloe latex might have cancer-causing compounds. In rodents, it caused intestinal tumors ¹⁹, ²⁰. A 2-year National Toxicology Program study ¹⁹ on oral consumption of nondecolorized whole leaf extract of aloe vera found clear evidence of carcinogenic activity in male and female rats, based on tumors of the large intestine. Another study ⁸⁹ in rats showed that decolorized whole leaf aloe vera did not cause harmful effects. This suggests that a component called aloin, most of which is removed by the decolorization process, may be responsible for the tumors seen in rats fed nondecolorized whole leaf aloe vera. More information, including what products are actually in the marketplace and how individuals use different types of aloe vera products, is needed to determine the potential risks to humans.

Taking 1 gram a day of aloe latex for several days can also cause acute kidney failure and can be fatal.

There have been a few reported cases of acute toxic hepatitis in people who took aloe vera supplements orally since 2005. In particular, there have been one each in Germany ⁹⁰, Turkey ⁹¹, USA ⁹², 10 cases in Switzerland ⁹³ and 3 cases in South Korea ⁹⁴.

Other side effects include abdominal cramps and diarrhea. Oral use of aloe latex and whole-leaf extract isn’t recommended for children younger than age 12.

People with diabetes who use glucose-lowering medication should be cautious if also taking aloe orally because aloe may lower blood glucose levels.

If you are concerned, have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with your physician before altering existing treatments or starting any new treatment.

How similar are the doses of aloin in the drinking water fed to the animals to those found in Aloe vera products ?

This is not clear, as there are no labeling requirements to list aloin content. The concentration of aloin in the water that the rodents drank in the study ¹⁹ is similar to that found in some Aloe vera products, but higher than in other products. The National Toxicology Program wanted to test an Aloe preparation that includes all components that may be in the products on the market. The study used a whole leaf extract of Aloe barbadensis Miller that did not undergo charcoal filtration during processing ¹⁹. Many commercial producers of Aloe vera beverages use charcoal filtration to reduce the levels of aloin in their products.

What do the National Toxicology Program rodent studies mean for humans ?

The National Toxicology Program rat studies give cause for serious concern. Some questions that need to be answered before their importance can be fully appreciated include ⁹⁵:

• What products are actually in the market place ?
• What are the aloin levels across a broad spectrum of products ?
• What are the patterns of human exposure ?

There is not enough information currently available to know how much Aloe vera people are consuming or for how long. Based on what scientists know right now, there is nothing that would lead them to believe that this finding would not be relevant to humans ⁹⁶.

Do scientists at the National Toxicology Program have any idea what may be causing the tumors and the other effects ?

Scientists suspect it may be the aloin, but they don’t know for sure ⁹⁶ . They hope to do more studies to determine what may be causing the tumors.

Should I stop drinking Aloe ?

That is a decision you might want to make with your health care provider. Like any personal decision, the more information you have the better ⁹⁵. Currently, manufacturers of these products are not required to label aloin concentration in Aloe vera products. If aloin is the cause of the tumors in rats then, generally speaking, the lower the concentration of aloin in a product, the lower the possibility that it may cause harm. Tumors developed in animals that drank water containing 60 ppm of aloin daily for nearly their entire lifetime ⁹⁶.

Aloe vera gel and Medicine Interactions

Possible interactions include:

• Anticoagulants and anti-platelet drugs, herbs and supplements. These types of drugs, herbs and supplements reduce blood clotting. Oral use of aloe might also slow blood clotting. Taking aloe orally with either of these types of medications might lead to increased bleeding.
• Digoxin (Lanoxin). Oral use of aloe latex can decrease potassium levels. Low potassium might increase the side effects of digoxin. Don’t take aloe latex and digoxin together.
• Diabetes drugs. Oral use of aloe gel, when taken in combination with diabetes drugs, might increase the risk of a condition characterized by an abnormally low level of blood sugar (hypoglycemia).
• Oral drugs. Oral use of aloe latex can decrease your body’s absorption of other drugs. This might reduce their effectiveness.
• Sevoflurane (Ultane). This anesthesia used during surgery might slow blood clotting. Oral use of aloe might have a similar effect. When used in combination, excessive bleeding during surgery is possible.
• Stimulant laxatives. Oral use of aloe latex with stimulant laxatives might overstimulate your bowels. This can lead to dehydration.
• Warfarin (Coumadin, Jantoven). Oral use of aloe latex can cause diarrhea. This can increase the effects of warfarin, a blood-thinning drug, and the risk of bleeding.
• Water pills (diuretics). Oral use of aloe latex, a laxative, in combination with use of diuretics might decrease potassium levels too much. Potassium supplementation might be needed.

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