The gastrointestinal system and our daily lives are impacted by oxidative stress, ageing, diet, lifestyle, alcohol, trauma, prolonged stress, surgery, nutrient deficiencies, drug use, excessive exercise, starvation, infection, inflammation, hygiene and socioeconomic conditions.[1-3]
Researchers have discovered an abundance of nutrients and herbs that can prevent, assist or alleviate the myriad of gastrointestinal conditions afflicting society today.
Common digestive conditions
- Bacterial/fungal/parasitic infections
- Inflammatory bowel disease (IBD): ulcerative colitis, Crohn’s disease
- Irritable bowel syndrome (IBS)
Treatments for digestive conditions
- Aloe vera
- Artemisia annua (Chinese wormwood)
- Berberis vulgaris (barberry)
- Citrus bioflavonoids
- Citrus x paradisi (grapefruit)
- Colostrum, lactoferrin, lactoperoxidase
- Digestive enzymes – amylase, protease, peptidase, lipase, tilactase/lactase, cellulase, bromelains
- Foeniculum vulgare (fennel)
- Gentiana lutea (gentian)
- Juglans nigra (black walnut)
- Pistacia lentiscus (mastic gum)
- Saccharomyces boulardii
- Ulmus rubra (slippery elm)
Mechanisms of action
Traditionally and through research Aloe vera has demonstrated many benefits to the digestive system, including anti-inflammatory, demulcent, wound healing, antioxidant and antimicrobial properties.
In wound healing, mannose-6-phosphate, a monosaccharide in Aloe vera, activates fibroblast growth factor receptors. This stimulates an increase in proteoglycan and collagen synthesis and cross linking, with an up-regulation in hyaluronic acid and dermatan sulphate production, resulting in wound contraction, tensile strength and healing.
The antimicrobial activity of aloe is thought to be through its glucomannan constituents, in particular acemannan, which prevents pathogenic growth and adhesion to mucosal walls. Aloe vera has been shown to be effective in clinical studies for ulcerative and inflammatory digestive conditions, such as ulcerative colitis.
Artemisia annua (Chinese wormwood)
Artemisia annua is well known for its sesquiterpenoid artemisinin in the treatment of malaria. Malaria is caused by parasites such as Plasmodium falciparum. Studies reveal that this herb can also be used for other parasitic infestations and is classed as an antimicrobial. The essential oil components of Chinese wormwood have shown significant activity against a wide variety of organisms including Candida albicans.
It is believed that the sesquiterpenoids and flavonoids in this herb cause cell membrane disruption, impaired ATP production, release of intracellular contents and disruption of cellular function causing cell death.
Berberis vulgaris (barberry)
Berberis vulgaris has been used traditionally and in contemporary times for its antimicrobial, antioxidant, laxative, cholagogue, hepatic, anti-inflammatory and bitter properties. The primary constituent attributed to these properties is the alkaloid berberine. Numerous studies have demonstrated the antibacterial, antiparasitic, antiprotozoal and antifungal activity of berberine, being effective against numerous organisms including Candida albicans and Giardia lamblia.[9,10]
There is a long history of use for gastroenteritis and diarrhoea with some studies showing berberine reduces diarrhoea volume. The underlying mechanisms to this herb’s activities may not be fully elucidated yet; it is thought that berberine acts by inhibiting the growth of organisms through the inhibition of sterol and cell wall synthesis and by inhibiting adhesion to the mucosal wall.[9,10]
Berberine has many other pharmacological effects in the gastrointestinal tract including inhibition of intestinal ion secretion and smooth muscle contraction, reduction of inflammation and stimulation of hydrochloric acid and bile secretion. The anti-inflammatory activity of barberry is likely due to berberine’s selective inhibition of the COX-2 pathway and the decrease in IL-8.
Citrus bioflavonoids are bioactive substances called flavanones, consisting mainly of naringenin, hesperidin and eriodictyol. They are powerful antioxidant and vitamin C sparing nutrients, with anti-inflammatory, antihistamine, and capillary and collagen strengthening properties.
Hesperidin deficiency has been linked to capillary fragility and permeability, seen in conditions such as haemorrhoids and ulcerations. Supporting this action, citrus bioflavonoids also strengthen collagen by reinforcing cross linking and inhibiting enzymatic cleavage of collagen during inflammation.
Citrus x paradisi (grapefruit)
The bioflavonoid group of flavanones are also found in grapefruit. Additionally, grapefruit contains high levels of nutrients beneficial to the gastrointestinal system including vitamins, carotenoids, pectin and organic acids.
The essential oil in this fruit has been shown to be antimicrobial and antifungal.[17,18] Grapefruit seed extract has been studied and found effective against bacterial and viral strains, fungi and parasites.
Colostrum, lactoferrin and lactoperoxidase
Colostrum is a rich source of bioactive proteins with wide biological activities that have a direct effect on intestinal and immune health, with particular benefit in pathogenic induced diarrhoea.[20,21] The most characterised proteins include alpha-lactalbumin, beta-lactoglobulin, immunoglobulins, lactoferrin, lactoperoxidase and growth factors.
The immunoglobulins in colostrum (IgA and IgG) play major roles in the heterologous transfer of passive immunity, intestinal immune response to disease and the provision of energy for effective immune responses.
Lactoferrin, an iron-binding glycoprotein, regulates the immune response and cell transcription activation, and has antiviral and antimicrobial activity against a wide number of micro-organisms. Intestinal epithelial cells have receptor mediated binding sites for lactoferrin and it may inhibit intestinal tumours by apoptosis, inhibition of angiogenesis and modulation of carcinogen metabolising enzymes.[21,23]
Lactoperoxidase, an abundant enzyme in colostrum, works synergistically with immunoglobulins and lactoferrin as an antimicrobial.
Digestive enzymes assist in the digestion of starch, proteins, fats, lactose and fibre. They are amylase, protease, lipase, lactase and cellulase, respectively.
Plant-based enzymes from Aspergillus oryzae have high stability and are naturally acid resistant, with activity throughout a wide range of pH conditions (from a pH 3.5-10). This enables the enzymes to be more consistently active and functional throughout the intestinal tract.
When enzymes are taken with a meal they can facilitate healthy digestion, assisting in the absorption and delivery of essential nutrients and aiding in the reduction of symptoms associated with conditions such as indigestion, bloating, flatulence, malabsorption, bacterial overgrowth and maldigestion. When taken between meals these enzymes may be beneficial for inflammatory and allergic conditions.
Proteolytic enzymes, such as proteases and bromelains, cleave protein residues and have significant digestive and anti-inflammatory benefits. Bromelains from pineapple have endoproteolytic and catalytic activity, breaking down peptides, amides and amino acid ester bonds.
A protease peptidase with DDPIV activity is able to cleave allergenic proline containing proteins such as gluten and casein. A group of 22 children with autism had beneficial management of digestive and neurobehavioural symptoms with the intake of DDPIV protease enzyme supplementation.
Foeniculum vulgare (fennel)
Foeniculum vulgare is a herb rich in essential oils, along with flavonoids, phenolic compounds, fatty acids and amino acids. It has been used traditionally and in contemporary times primarily as a carminative and spasmolytic but also possesses antioxidant, antimicrobial, laxative and hepatoprotectant properties. The essential oil component is known to have wide ranging antimicrobial and antifungal activity, while regulating intestinal smooth muscle motility and reducing flatulence. Fennel is therefore indicated for gastrointestinal issues such as colic, colitis, constipation and flatulent dyspepsia.
Gentiana lutea (gentian)
Gentiana lutea contains secoiridoid glycosides and oligosaccharides, which account for its bitter tonic and digestive stimulant properties. Its traditional use in the treatment of digestive disorders dates back centuries and is now also regarded as a tonic and anti-emetic beneficial in loss of appetite, flatulence, anorexia, atonic dyspepsia and gastrointestinal atony.
The action of gentian’s bitter compounds is reported as being due to a reflex on the bitter taste buds causing stimulation of gastrin production via the glossopharyngeal and vagus nerves. This causes an increase in salivary, gastric acid and bile production and therefore leads to digestion stimulation.[12,26]
However, a study of 205 subjects showed a dry extract of gentian root, given over 15 days, had an average level of improvement of 68% in various dyspeptic symptoms, proving that the bitter effect is not just caused by the action on the oral taste buds.
Researchers have discovered bitter taste receptors (called TAS2R) in the gastrointestinal tract including the enteroendocrine cells, which produce the gut hormones and peptides such as gastrin and cholecystokinin (CCK). This in turn stimulates the release of pancreatic enzymes and bile. The bitter compounds may also perform other physiological detoxification functions, through these receptors, in the elimination of absorbed toxins and by having a mild laxative effect.
The main actions of the amino acid glutamine in gut health include: tissue protection; anti-inflammatory and immunological roles; a primary cellular fuel for enterocytes; preservation of metabolic function in stress states; and antioxidant.
When there is a lack of glutamine, atrophy, diarrhoea, decreased gut-associated lymphoid tissue (GALT), increased intestinal permeability, ulceration and necrosis of the intestinal epithelium may occur.
Juglans nigra (black walnut)
Juglans nigra has a traditional history as an antiparasitic. In contemporary times, in vitro testing shows black walnut to also be antimicrobial and antifungal.[31,32] These properties are accredited to the naphthoquinone constituent juglone and its rich source of antioxidant phytochemicals.[31,33] The bioactivity of juglone appears to be through the inhibition of enzymes required for metabolic function of the microorganism.
Pectin is a non-starch polysaccharide that is indigestible due to a lack of pectic enzymes. This dietary fibre delays gastric emptying and is metabolised by colonic bacteria to produce the vitally important short chain fatty acids (SCFAs). These are required to promote microbial diversity and provide energy for the commensal bacteria in the gut.
Pectin’s production of SCFAs stimulates epithelial growth, thereby reducing intestinal permeability, and increasing colonic absorption. These are important mechanisms to reduce diarrhoea incidence and may make pectin a useful therapy in inflammatory bowel disease.
One study showed pectin stimulated the growth of bifidobacteria and lactobacillus in vitro. In children, pectin was found to effectively reduce acute intestinal infections, significantly slow diarrhoea and improve small intestinal permeability.[36,37] Pectin also contributes to heavy metal detoxification and related inflammation.
Pistacia lentiscus (mastic gum)
The resin from the tree Pistacia lentiscus, called mastic gum, has been used traditionally in gastrointestinal health for 5,000 years. Mastic gum has been proven as an effective antioxidant, antimutagenic, anti-inflammatory and antimicrobial against a wide variety of organisms. The resin is rich in volatile oils, the main active constituents.
Studies show mastic gum benefits the gastrointestinal system by:
- reducing gastric mucosal damage and ulcerations, through antisecretory and cyproprotectant activities
- significantly improving functional dyspepsia symptoms
- exerting a significant antibacterial effect on Helicobacter pylori and other bacteria[38,40]
- delaying the onset and progression of colitis
- significantly reducing the symptoms and inflammation of mild-moderate Crohn’s disease.[41,42]
The collective research shows mastic gum is a wide-range therapeutic agent and a potential treatment for many gastrointestinal complaints.
The gastrointestinal tract holds a unique bacterial microbiota containing 100-1000 bacterial species. The main roles of the commensal bacteria are generalised as:
- metabolic – supporting digestion
- protective – supporting host immunity and defenses
- trophic – involved in cross-talk with the immune system and influencing cell growth and differentiation.
Research has identified the mechanisms of action of probiotics to be widespread across bacteria, be specific to the bacterial species or be strain specific. An example of researched strain-specific benefits includes the LAB4 probiotics. LAB4 includes Lactobacillus acidophilus CUL60 and CUL21, Bifidobacterium lactis CUL34 and B. bifidum CUL20. Studies have shown this combination of specific strains to be beneficial in relieving IBS symptoms and for the prevention of antibiotic-associated Clostridium difficile infections.[45,46]
Additionally, LAB4, L. paracasei Lpc-37, L. plantarum Lp-115, L. salvarius Ls-33, L. rhamnosus HN001, L. acidophilus La-14, and B. lactis Bl-04 and HN-019 have all shown gastrointestinal immune modulation activity in research.[47-50]
Saccharomyces boulardii (SB) is a probiotic, non-colonising yeast species. It is resistant to gastric acidity and proteolysis and when taken orally becomes quickly established.
In the gastrointestinal tract SB has a multitude of beneficial actions including regulation of intestinal microbial homeostasis, interference with the pathogenic colonisation and infection, modulation of local and systemic immune responses, stabilisation of the gastrointestinal barrier function and induction of absorption and nutrition enzymatic activity.
SB has been researched for its benefits in numerous gastrointestinal diseases, especially those with a predominate inflammatory component, including infectious diarrhoea, candidiasis, IBD, parasitic infections and IBS. One randomised controlled trial showed SB taken daily for four weeks improved the IBS quality of life score.
Curcumin is an active substance in the herb turmeric. It exerts a wide range of pharmacological bioactivities, such as antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and antimicrobial properties.
Curcumin has been researched in numerous cancer and inflammatory disease trials. Its ability to inhibit the expression of COX-1, COX-2, lipoxygenase, TNF, IFN-gamma, iNOS and NFkB activation has made it a candidate for ulcerative colitis and experimental colitis research.[4,55]
Ulmus rubra (slippery elm)
Slippery elm is a highly mucilaginous and nutrition rich plant. It stimulates the nerve endings in the gastrointestinal tract to increase mucin production which improves barrier function against ulcers, excess acidity, ingested irritants and toxins of the gastrointestinal tract.[6,9]
It is a nutritive demulcent for soothing irritated and inflamed tissue. A mucosal biopsy study showed slippery elm reduced oxygen free radicals in ulcerative colitis. Traditionally, this herb is indicated for diarrhoea, constipation, gastritis, acid dyspepsia, gastric reflux, peptic ulcers, IBS and Crohn’s disease.
Use of mastic gum in Crohn’s disease
Background: Crohn’s disease (CD) is a chronic inflammatory disease that may affect any level of the gastrointestinal tract. It is well established that immunological mechanisms are involved in the pathogenesis of the CD. Mastic gum has been reported to have significant antioxidant, antimicrobial properties but also regulates inflammatory biomarkers. These are the first studies to report the effectiveness of mastic gum in CD.
Subjects/Method: A 4-week placebo controlled trial of 10 adults with mild to moderately active CD and 8 healthy controls.
Intervention: Patients and healthy controls were subjected to supplementation with mastic gum (6 capsules per day providing a total of 2.2 grams).
Results: Mastic gum significantly decreased the CD activity index and levels of plasma inflammatory mediators IL-6 and CRP, while modulating the immune system through the reduction of TNF-alpha and enhanced macrophage migration inhibitory factor, without side effects.
Kaliora AC, Stathopoulou MG, Triantafillidis JK, et al. Alterations in the function of circulating mononuclear cells derived from patients with Crohn’s disease treated with mastic. World J Gastroenterol 2007;13(45):6031-6036.
Efficacy of SB for acute diarrhoea
Background: Research has been unclear of the efficacy of Saccharomyces boulardii in the treatment of childhood diarrhoea.
Subjects/Method: Systematic review and meta-analysis of all trials for safety and efficacy within Medline, Embase, CINAHL, Scopus, and The Cochrane Library up to September 2013.
Intervention: In total, 1248 articles were identified, of which 22 met the inclusion criteria.
Results: SB is safe and has clear beneficial effects in children with acute diarrhoea. Pooling data from trials showed that SB significantly reduced the duration of diarrhoea, stool frequency on day 2 and day 3, the risk for diarrhoea on day 3 and day 4.
Probiotics alter immune response
Background: The immunological activity of probiotics has been well researched but there are very few studies examining probiotic supplementation for this function in healthy populations.
Subjects/Method: A 12-week trial involving 20 healthy volunteers.
Intervention: LAB4 probiotic supplement (containing L. acidophilus CUL21 and CUL60, B. bifidum CUL20, B. lactis CUL34) at a total daily dose of 25 billion CFU with 2g of fructooligosaccharide (FOS).
Results: The probiotic combination had a potentially beneficial alteration to the immune response as shown by ex vivo alterations in cytokine production.
Hepburn NJ, Garaiova I, Williams EA, et al. Probiotic supplement consumption alters cytokine production from peripheral blood mononuclear cells: a preliminary study using healthy individuals. Benef Microbes 2013;4(4):313-317.
Dosage range according to clinical studies
Cautions and contraindications
- Due to the antiplatelet activity of turmeric, suspend use of curcumin one week prior to major surgery.
- Turmeric can cause gallbladder contractions and should not be used by individuals with gallstones or bile duct obstruction.
- Bromelain is contraindicated in people who are hypersensitive to pineapple.
- Bromelains may potentiate bleeding when used simultaneously with anticoagulant/platelet medications.
- L-glutamine is contraindicated in patients with hypersensitivity to glutamine or hepatic disease, or any condition where there is a risk of accumulation of nitrogenous wastes in the blood thus increasing the risk of ammonia-induced encephalopathy and coma.
- Theoretically glutamine, which is metabolised to the excitatory neurotransmitter glutamate, might antagonise the anticonvulsant effects of medications taken for epilepsy.
- Slippery elm (mucilage) forms an inert barrier over the intestinal lining and may theoretically alter the rate and/or extent of absorption of medicines with narrow therapeutic indexes (such as barbiturates, digoxin, lithium, phenytoin and warfarin). It is advisable to separate doses by at least two hours.
- Pectin may interfere with the intestinal absorption of digoxin, lovastatin and tetracyclines.
- Aloe vera may have hypoglycaemic activity, therefore additive effects are theoretically possible when taken in conjunction with hypoglycaemic agents.
- Berberis vulgaris is contraindicated in pregnancy.
- The use of Artemisia annua in pregnancy or lactation is not recommended.
- Patients with true (IgE-mediated) yeast allergy may be allergic to products containing S. boulardii.
- Since S. boulardii is a yeast, antifungal medications/herbal supplements may decrease its effectiveness. Take 2 hours before or 4-6 hours after antifungals.
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