Herbs and Nutrients That May Assist

Curcuma longa, (Turmeric) root and rhizome as proprietary BCM-95 ^TM extract
Arabinogalactan from Larix occidentalis (Larch)
Silybum marianum, (St. Mary's Thistle) seed
Glycyrrhiza glabra, (Liquorice) root – deglycyrrhizinised
Glutamine
Glycine
Pectin (Citrus)
Ulmus rubra (Slippery elm) bark powder
Althaea officinalis (Marshmallow) root
Cysteine
Zinc amino acid chelate (Meta Zn – Zinc diglycinate)
Selenomethionine

Actions

Gut Repair & Prebiotic Support
Supports Detoxification

Clinical Applications

• Supports Gastrointestinal Integrity
• Supports Liver Function and Detoxification
• Allergies
• Attention Deficit Hyperactivity Disorder (ADHD)
• Autism

Clinical Overview

Children’s Gut, Liver and Detoxification Support is a combination of herbs and nutrients designed to support healthy digestion, gut integrity, gut flora balance and liver detoxification in children. Glutamine may support intestinal cell nutrition and is combined with traditional herbs which have been used to soothe and heal the gastrointestinal tract. St Mary’s thistle and turmeric also provide support for liver detoxification processes. The formula also has anti-inflammatory and antioxidant benefits. By promoting gut repair and hepatic detoxification, this formula may assist in the support of sensitive, allergic, or reactive children with conditions such as autism, allergies, learning disorders, behavioural issues, and/or bowel problems.

Background Information

Detoxification is the process of “biotransformation” of internally generated (endogenous) and externally acquired (exogenous) toxins into metabolites which can be removed from the body. This process occurs primarily in the liver, but it is worth remembering that some 25% of detoxification takes place in the intestinal tract, as well as in other tissues around the body. So to optimise detoxification it is important to ensure the gut mucosa is intact and working well. Obviously, as everything absorbed from the gut travels through the portal vein to the liver, the better the integrity of the gut lining and the more detoxification that occurs at the gut level, the less antigenic and toxic load is placed on the liver.

In the liver, phase I of detoxification involves the creation (by the appropriate member of the cytochrome p450 family of enzymes) of a reactive site on the toxic molecule to prepare it for the second phase of detoxification, phase II, when conjugation takes place.

This is when the toxic, and now even more reactive, molecule is combined with compounds (e.g. phase II conjugates such as glutathione, glycine, etc.) that make it more water-soluble and easier to excrete. Phase III metabolism then ensures the waste molecule is exported for excretion via urine, or via bile into faeces. It is essential that all three phases of detoxification are functioning well and in balance, as the intermediate metabolites produced may be more harmful or toxic than the original substance. For example, oxidative damage can result if Phase II of detoxification is unable to keep up with Phase I. This imbalance may occur if there is upregulation in Phase I (such as with stress, caffeine, nicotine, alcohol, and various toxins), or inhibition of Phase II, due to lack of required cofactors or insufficient energy in the form of ATP. ^[1] To support the process of detoxification, adequate nutrition is essential – to provide the nutrients necessary for detoxification or biotransformation, particularly Phase II conjugation. As Phase II detoxification is so dependent on an adequate supply of vitamins, minerals and amino acids, fasting may exacerbate toxicity, particularly if fluid intake is low and there is reduced faecal elimination. ^[2] Figure 1 summarises key nutrients required for detoxification.

Figure 1: Key nutrients required for detoxification.

Children Are At Risk of Toxicity

Children are particularly at risk of problems related to toxicity, because their innate detoxification systems are immature and under-functioning. Children are born with an “unfinished”, immature and “leaky” gut, ^[3] and a child’s liver is not functioning at peak efficiency for the first 2 to 3 years of life. ^[4] This has two major consequences:

1. A child is more susceptible to direct toxicity as it will not be able to neutralise and clear toxins efficiently.
2. The diminished clearance of toxins will predispose to toxic accumulation, with potential long-term consequences.

Such risks are multiplied by the inevitable hand-to-mouth behaviour of young children – particularly while they are still crawling.

In addition, their immune system is compromised. All children are born with their mother’s Th-2 immune bias, which protects the pregnancy, but predisposes infants on the one hand to atopy: allergy, eczema, asthma, etc.; and on the other, to increased susceptibility to infection and infestation through impaired Th-1 immunity. This becomes more of a problem if a child is delivered by caesarean section, and/or is not breast-fed ^[*], both situations that delay the maturation of the more protective Th-1 branch of immunity.

To address these issues, ingredients in Children’s Gut, Liver and Detoxification Support can be seen to consist of two functional groupings:

• Gut repair and prebiotic: turmeric, arabinogalactans, liquorice, glutamine, pectin, slippery elm, marshmallow and zinc; and
• Detoxification support: turmeric, St Mary’s thistle, pectin, cysteine, glycine and glutamine.

Each of the components of the group supports the others, and the groups themselves support each other.

For Gut Repair & Prebiotic Support

Deglycyrrhizinised liquorice (DGL, Glycyrrhiza glabra root). Traditional indications for liquorice in Western herbal medicine include gastritis and peptic ulceration, and it is also used for its anti-inflammatory properties. DGL has been shown to be an effective treatment for both gastric ^[5],[6] and duodenal ulcers. ^[7] DGL is a concentrated extract of liquorice with a glycyrrhizin content of not more than 3%, and high levels of flavonoids. As glycyrrhizin is responsible for much of the mineralocorticoid side effects of liquorice, such as hypertension, sodium and water retention and hyperkalaemia, deglycyrrhizinised liquorice (DGL) is better tolerated. ^[8]

Interestingly, there is a very common – almost universal – misapprehension that liquorice is a demulcent: indeed, most Materia Medica list it as such. Liquorice is anti-inflammatory and mucoprotective – this last action is ascribed to increased mucosal blood flow and mucus secretion. That could be seen as indirect demulcency, perhaps. True demulcent actions are the property of mucilaginous or sometimes oily constituents – such as in slippery elm, below – which form a soothing or softening film over an inflamed mucous membrane. ^[†] Such constituents are not found in significant amounts in liquorice.

Glutamine maintains the gut lining. Glutamine is the preferred fuel for the cells lining the small intestine – it is more important as an oxidative fuel for enterocytes than glucose, ^[9] and it contributes to the maintenance of their integrity. Glutamine also serves as a precursor for nucleotide synthesis in rapidly dividing cells such as lymphocytes and intestinal cells. ^[10] The overall action is to facilitate mucosal growth and repair.

Pectin is a complex plant polysaccharide regarded as a soluble fibre. Typical sources include citrus peels and apples. Arabinogalactans are a type of highly branched polysaccharide fibre derived from the Western larch (Larix occidentalis). Both larch arabinogalactans and pectin have been shown to increase the production of short chain fatty acids, particularly acetate, and also propionate and butyrate. ^[11] These fatty acids are produced when undigested fibre is fermented by colonic bacteria, and have major roles for health: butyrate is a major source of energy for colonocytes, thereby contributing to enterocyte function and mucosal integrity; while acetate and propionate may modulate glucose metabolism in the body. ^[12]

Larch arabinogalactans and pectin are also excellent sources of dietary fibre, and have been reported to have a significant effect on enhancing beneficial gut microflora, such as bifidobacteria and lactobacilli. ^[13] Without doubt, one of the most crucial things that can be done to improve a child’s immune status and gut function is to ensure they are eubiotic – that the gut flora are in balance. Providing fibres such as pectin and arabinogalactans ensures the “good bugs” have plenty of food.

The powdered inner bark of the North American native tree Ulmus fulva (slippery elm) has been used as a herbal remedy for centuries. Native Americans used slippery elm in healing salves for wounds, boils, ulcers, burns, and skin inflammation. It was also taken orally to relieve coughs, sore throats, diarrhoea, and stomach problems.

Slippery elm contains mucilage, a substance that becomes a slick gel when mixed with water. It coats and soothes the mucous membranes of the mouth, throat, stomach, and intestines; it also contains tannin antioxidants, whose astringency helps to relieve inflammatory bowel conditions. Slippery elm also causes reflex stimulation of nerve endings in the gastrointestinal tract leading to increased mucus secretion. This increased mucus production may protect the gastrointestinal tract against ulcers and excess acidity. ^[14]

Marshmallow (Althaea officinalis) root is another herb with a high mucilage content, here combined with flavonoids and phenolic acids, which give it additional and complementary anti-inflammatory and astringent actions on mucous membranes.

Curcuma longa (turmeric) root/rhizome has been used traditionally in Western herbal and Ayurvedic medicine for its anti-inflammatory, antioxidant, antimicrobial, choleretic and carminative effects. For the gut, turmeric has been commonly used as a traditional remedy for a variety of symptoms such as inflammation, gastritis and gastric ulcer. ^[15] In animal studies, turmeric extract has been found to exert significant protection against ulcerogenic agents and physical stresses. ^[16] One of the mechanisms for the reduction in gastric ulceration observed with C. longa extract seems to be selective and competitive histamine type (H2) receptor antagonistic effects. ^[17] H2 receptors are involved in histamine-induced gastric acid secretion.

Zinc has well known health benefits in areas such as immune function enhancement and detoxification, and is involved in over 350 different enzyme systems. Zinc has numerous beneficial effects on the digestive system, including:

• Playing a vital role in the function and structure of mucous membranes, and is thus essential for proper gut function.
• Zinc has been shown to be beneficial in the treatment of candida. ^[18]
• Patients with Crohn’s Disease have been shown to have depressed zinc status. Zinc deficiency in Crohn’s patients often leads to fistula formation. ^[19] Although multiple mineral deficiencies are common in cases of Crohn’s, zinc status seems to play a vital role in the pathogenesis of the condition improving the clinical outcome of patients. ^[20]
• Connective tissue also requires zinc for proper function. The gut in individuals with microbial overgrowth often becomes “leaky”, allowing toxins to pass into the liver and the blood stream. This puts extra strain on the liver leading to a state of toxic overload. Zinc will help in the healing of the lining of the gut wall thus reducing the toxic load on the liver.

For Detoxification

Curcuma longa (turmeric) has been used in Ayurvedic medicine for a range of liver disorders, including jaundice, due to its liver stimulant effect, increasing the flow of blood through the hepatic system and increasing bile output. The primary actives in turmeric are a family of polyphenols called curcuminoids, and volatile oils. ^[21],[22] Curcumin has been found to be a potent antioxidant, preventing lipid peroxidation. It may do this via free radical scavenging ability or through chelation of metal ions, such as iron, which can initiate lipid peroxidation. ^[23] Curcumin has been found to mediate its liver protecting effects by also inhibiting NF-ĸB, which activates several pro-inflammatory and profibrotic cytokines. ^[24]

BCM-95 ^® is a patent-pending, proprietary, 100% natural turmeric extract containing curcuminoids and various volatile compounds of turmeric. It is a reconstituted, purified and standardised extract that enhances the bioavailability of curcumin. Human studies have shown that, as well as up to 700% enhanced bioavailability, BCM-95 gives enhanced retention of curcumin in the blood when compared with a standard turmeric extract (95% curcuminoids) – as shown in Figure 2. ^[25]

Figure 2: Increased bioavailability and retention of curcumin with a single dose BCM-95 extract

Key: (solid line) compared to a standard curcumin (broken line). ²⁶

Oxidative stress and inflammation are always found together (each causing the other), so it is not surprising that curcumin also has anti-inflammatory action, decreasing many inflammatory mediators. Laboratory studies have identified a number of different molecules involved in inflammation that are inhibited by curcumin, including phospholipase, lipoxygenase, cyclo-oxygenase-2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumour necrosis factor-alpha (TNF-α), and interleukin-12 (IL-12). ^[26]

Silybum marianum (St Mary’s or milk thistle) seed/fruit has a long history of traditional medicinal use for liver health. ^[27] Traditional applications in more recent Western herbal medicine include liver and gallbladder disease such as jaundice, hepatitis and gallstones. The herb is highly regarded as a hepatoprotective, hepatic trophorestorative, antioxidant and choleretic. ^[28] St Mary’s thistle’s flavonoid complex, silymarin, has been found to have hepatoprotective actions by antioxidative, antifibrotic, anti-inflammatory, membrane stabilising, and liver regenerating mechanisms. Silymarin is extracted from the seeds of the milk thistle. Its major flavonolignans include silybin (syn. silibinin) A and B, isosilybin A and B, silychristin A and B, and silydianin, as well as other minor polyphenolic compounds. ^[29] A meta-analysis of studies into the hepatoprotective effects of silymarin has concluded that, from the available clinical evidence, silymarin can be employed as a supportive therapy in situations of alcoholic liver disease, liver cirrhosis, and Amanita phalloides (death cap mushroom) poisoning. ^[30]

Modified Citrus Pectin (MCP) Can Help Remove Heavy Metals

Ordinary fruit pectin is in a molecular form which is too large to pass through the intestinal wall, so it cannot be absorbed into the bloodstream. However, Children’s Gut, Liver and Detoxification Support contains modified citrus pectin (MCP), which has been specially treated so that the pectin molecules are broken down to sizes small enough for them to pass through the intestinal wall and enter the bloodstream. Once in the blood stream, the modified pectin molecules have a couple of very useful properties:

• They can act as “decoys” for lectins (sugar-binding proteins that can function as immune triggers, or as facilitators for infection or metastasis), which seek out a sugar called galactose in human cells. When lectins encounter pectin, which also contains galactose, they adhere to it instead of adhering to host cells. By attaching to these lectins, MCP keeps them from adhering to healthy tissues in the body. ^[31]
• They can also bind many heavy metal ions and facilitate their removal from the body. ^[32]

Glutamine Can Enhance Gut Glutathione Production and Immunity

The gut is a major producer of glutathione and oral glutamine supplementation has been found to increase the production of gut glutathione. ^[33] In addition, glutamine is a source of energy for immune cells – and 70% of the human immune system is centred around the gut in the gut-associated lymphatic tissue (GALT). Because of the relative immaturity of a child’s gut and immune system, glutamine supplementation is of enormous importance in keeping them well.

Glutamine, cysteine and glycine combine to form glutathione (chemical name gamma-glutamyl-cysteinyl-glycine), a crucial intracellular antioxidant, heavy metal chelator, and a vital phase II conjugating agent. [34] Selenium is an essential element for the correct structure and function of the enzyme glutathione peroxidase (GPx) ^[‡], which facilitates glutathione’s activity.

GSH Works Alongside Metallothioneins (Mts) in Detoxification And Removal of Heavy Metals (Figure 3)

MTs are a family of cysteine-rich, low molecular weight proteins made up of 14 amino acids arranged into molecules of between 61 and 68 total peptides. They are localised to the membrane of the Golgi apparatus in the cells of most living creatures: bacteria, yeasts, higher plants, protozoa, invertebrates, insects, molluscs, birds, animals and humans. Their function is primarily to protect living cells from toxic metals. MTs have the capacity to bind both physiological (such as zinc, copper, selenium) and xenobiotic (such as cadmium, mercury, silver, arsenic) metals through the thiol group of their cysteine residues, which represent nearly 30% of their amino acidic residues. ^[35] So obviously cysteine is an important nutrient for MT synthesis.

In addition, most of the body's MT is induced by zinc, ^[36] with glutathione (GSH) needed for loading apo-MT with zinc, and glutathione disulfide (GSSG) required for redox exchange. Selenium and the GSH/GSSG redox couple enhance delivery of zinc to cells, and the sequestering of mercury and other heavy metals. Selenium is also capable of binding directly with mercury to facilitate its removal. ^[37] Human studies have found that zinc supplementation increased MT levels. ^[38],[39]

Gastrointestinal Healing, Supporting Gastrointestinal Integrity

Animal studies also indicate that when the gastrointestinal tract is under stress, such as that precipitated by hypoxia or surgical manipulation, oral glutamine supplementation has multiple protective effects:[40]

• Reduces intestinal injury by ameliorating inflammatory cytokine release;
• Prevents decreases in the activity of the superoxide- and hydrogen peroxide-scavenging enzymes catalase and superoxide dismutase; and thereby
• Prevents mitochondrial damage, maintaining all-important energy supplies.

Children are notorious for “tummy upsets”, and glutamine, with its protective and restorative actions, could go a long way towards preventing and ameliorating such episodes.

Figure 3: Detoxification of heavy metals requires metallothioniens and glutathione.

Take Glutamine With Your NSAID

Oral glutamine has also been found to significantly ameliorate the effects of nonsteroidal anti-inflammatory medications on the small intestinal mucosa. ^[41] In healthy human volunteers, glutamine has been found to have protective effects on the gastrointestinal mucosa. In a controlled study, glutamine administered at a dose of 7g half an hour prior to NSAID administration and several doses of 1g, both with and following NSAID dosing, were found to significantly moderate the increased intestinal permeability associated with NSAID use. ^[42] Given the current medical/media recommendations for NSAID use for children (the most common being ibuprofen), this becomes a very important reason for glutamine supplementation.

Turmeric Heals The Gut

In an uncontrolled study, turmeric (600mg five times daily) was given to twenty-five individuals with either gastric or duodenal ulcers, measuring 0.5 to 1.5cm in diameter, or erosions, gastritis and dyspepsia. Within 4 weeks, 48% of the ulcers had healed, and by 8 weeks, resolution had been achieved in 72%. In the non-ulcer patients, their abdominal pain and dyspepsia symptoms subsided in the first and second weeks. ^[43] While children are unlikely to be developing ulcers, these studies point out the potent, yet safe, protective and restorative actions turmeric can bring to the gastrointestinal system.

Deglycyrrhizinised Liquorice, DGL, A Healer of the Gut

In animal studies, DGL was found to prevent ulcer development, ^[44] inhibit gastric acid secretion, ^[45] and protect the gastric mucosa from aspirin and bile. ^[46] It also reduces the number and size of ulcers. In well-controlled clinical trials, DGL was shown to be as effective as the drugs carbenoxolone, cimetidine and ranitidine. ^{[47].[48],[49]} A DGL mouthwash produced rapid improvements in humans with aphthous ulcers. ^[50] Faecal blood loss induced by aspirin consumption was reduced with coadministration of DGL (350mg), and animal studies with aspirin confirmed DGL use was associated with reduced gastric mucosal damage. ^[51] DGL provides safe, soothing anti-inflammatory and muco-protective ^[52] actions to a child’s irritated gut mucosa.

Zinc Promotes Healing

Zinc has been found to aid in gastric mucosal healing in patients with benign gastric ulceration. In a double-blind placebo-controlled trial of 18 individuals with benign gastric ulcers, 220mg zinc sulphate or placebo was administered three times daily for 3 weeks. Patients taking zinc sulphate had an ulcer healing rate three times that of patients treated with placebo (p<0.05). ^[53]

Supporting Liver Function and Detoxification

St Mary’s Thistle Protects and Restores the Liver

Researchers believe that the hepatoprotective action of silymarin is largely due to its antioxidant properties. Oxidative stress has been implicated in the development of liver disease, as reactive oxygen species (ROS) can damage membrane lipids, proteins, DNA and RNA. Silymarin has been found to directly inhibit lipid peroxidation of cell membranes, which can prevent a chain reaction of oxidative stress that leads to cell damage. ^[54]

In addition to being a potent antioxidant, silymarin also has several other actions that make it an important compound for promoting healthy liver function: ^[55]

• Recent research has discovered that silymarin has anti-inflammatory properties through the inhibition of the potent proinflammatory mediator nuclear factor kappa B (NF-ĸB). NF-ĸB appears to play a key role in liver inflammation and the development of fibrosis.
• Silymarin has demonstrated significant anti-fibrotic action, also through the inhibition of NF-ĸB.
• There is evidence that silymarin can promote liver repair and regeneration. Silymarin has been shown to enter the cell nucleus and stimulate DNA replication mechanisms, such as augmenting RNA polymerase, which in turn hastens protein and DNA synthesis. ^[56]

Curcuma Longa (Turmeric) Supports Liver Function

Like St Mary’s thistle, turmeric has demonstrated laboratory evidence of liver protection and acts upon similar pathways to reduce inflammation and oxidative stress. Research has shown that curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl ₄) intoxication. ^[**] Furthermore, some research has shown that curcumin reverses cirrhosis in animal models. ^[57] This hepatoprotective action is mediated through cucumin’s capacity to reduce the activity of liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP); and attenuate oxidative stress by increasing the amount of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Animal studies utilising very high doses of curcumin have suggested that curcumin can modify both phase I and phase II detoxification pathways, downregulating activity of cytochrome P450 enzymes CYP1A and CYP3A, and increasing glutathione S-transferase activity. ^[58]

Allergies

The Connection Between Atopy (i.e Allergies, Eczema, Asthma, etc.) and Gut Dysfunction is Well-Established

Researchers report that “minor morphological abnormalities of the gastrointestinal tract are common in children with atopy”. ^[59] Interestingly, the histological changes in the gut appear to mimic those seen in the bronchial mucosa, ^[60] which is suggestive of a systemic (possibly immunological) problem affecting mucosal function generally. In the same vein, we find that patients with atopic dermatitis may have a predisposition to develop chronic inflammation of the large intestine. ^[61]

Intestinal Permeability is a Feature of Asthma, ^[62] Eczema, ^[63] And, Of Course, Food Allergies ^[64] (e.g. Coeliac Disease) and Sensitivities (e.g. Dairy or Salicylate Intolerance). In a series of gastric biopsies of atopic children, the most striking feature was epithelial degeneration (in 13 out of 21 samples). In the same study, jejunal biopsies revealed increased eosinophilic infiltration of the lamina propria ^[††] in 10 out of 28 diagnostic samples, with 4 subjects showing partial villous atrophy. It was concluded that in atopic children, gastric hyposecretion and epithelial degeneration may promote the passage of undigested food allergens through the jejunal mucosa, predisposing to more severe changes, as seen, for instance, in cow's milk intolerance. ^[65]

It has been suggested that gastrointestinal abnormalities could precede atopic eczema and perhaps play a part in the aetiology of the skin disease by allowing allergic sensitisation, as a result of increased antigen entry through the damaged mucosa. In this respect it may be relevant that gastrointestinal symptoms were reported to have preceded evidence of skin disease in most children with atopic eczema. ^[66] Dysbiosis typically leads to leaky gut. Whether from hyphal invasion by fungal forms of Candida spp., or reactive inflammatory damage to the tight junctions between cells, impairment of the intestinal mucosal barrier appears to be involved in the pathogenesis of atopic dermatitis.[67] For these reasons that Children’s Gut, Liver and Detoxification Support may be suitable in children with atopy and concomitant leaky gut, dysbiosis and/or toxicity.

Attention Deficit Hyperactivity Disorder (ADHD)

There is a very strong connection between ADHD, toxicity and allergies, which was made very clear by the work of Dr Ben Feingold, who in 1973 claimed that food additives and colours were responsible for 40-50% of the hyperactive children he had seen in practice. Feingold pointed out that over 3000 food additives had been introduced into the food supply with no testing on behavioural effects. His hypothesis developed into what is known as the Feingold Diet which focuses on eliminating a variety of food colours, artificial flavours, particular preservatives and naturally occurring salicylates from the diet. ^[68]

Much progress has been made in the understanding of ADHD since Feingold first proposed his theory, and we now know that, while food additives are certainly a factor, many more substances can trigger behavioural problems in children. Food-derived neurotoxins include the exorphins from gliadin (wheat) and casein (dairy), amines from chocolate and oranges, and salicylates from many fruits and vegetables.

We also find heavy metals, such as lead, to be potential contributors to this condition. A dose-response relationship between childhood lead exposure and ADHD has been found in many studies. ^{[69],[70],[71]} One particular study of 97 children with ADHD and 53 controls found that higher blood lead levels correlated with significantly higher levels of ADHD symptoms. Interestingly, mean blood lead levels were only 1.04 µg/dL and maximum levels were 3.4 µg/dL, still far below the supposed “acceptable” level of 10µg/dL. ^[72]

While dietary control is obviously important, the question remains of why these children are reacting to what for others are perfectly innocuous foods? Part of the answer lies in gut permeability and the capacity to detoxify substances absorbed from the gut: factors which are well addressed by the herbs and nutrients in Children’s Gut, Liver and Detoxification Support, as delineated previously.

Autism

Although autism is primarily a neurodevelopmental disorder, the association of gastrointestinal symptoms with autistic spectrum disorders has long been noted, both empirically and clinically, giving rise to the concept of “autistic enterocolitis”. In a recent cross-sectional study, comparing autistic children with matched neurotypical controls, a huge 70% of children with ASD reported a history of GI complaints, compared with just 28% of neurotypical controls (P<0.001). ^[73]

The type and prevalence of gastrointestinal complaints in ASD children is shown in Table 1, which lists the results of a survey of 412 autistic children aged 6.5 (±3.6) years old compared with 43 age-matched healthy siblings. Overall, 84.1% of the autistic patients had at least one of the listed symptoms, compared to just 31.2% of the healthy siblings (p<0.0001).[74]

This is not an isolated observation: 36 children diagnosed with autism and experiencing abdominal pain, chronic diarrhoea, bloating, night-time awakening, or unexplained irritability, were examined using endoscopic biopsy. Abnormal findings included reflux esophagitis in 25 (69%) of the children, chronic gastritis in 15 (42%), and chronic duodenitis in 24 (67%). ^[75]

Observations on a group of 60 children affected with various developmental disorders (mostly autism) found active inflammation of the ileum (ileitis) in 8% and chronic inflammation of the colon (colitis) in 88% of affected children. ^[76]

High incidence of leaky gut in autistic children. Intestinal permeability, as measured by the lactulose-mannitol test, was significantly increased (i.e., greater permeability to lactulose relative to mannitol) in 9 of 21 high-functioning autistic patients (4-16 years of age) when compared with a group of 40 healthy, age-matched children. ^[77] The change in the urinary mannitol:lactulose ratio in 43% of the autistic children was accounted for solely by an increase in the lactulose permeability, as there was no difference in mannitol recovery between the groups.

This suggests that the elevated lactulose permeability reflects damage to the tight junctions between the intestinal epithelial cells in the affected autistic patients. Another study found the incidence of intestinal permeability to be as high as 75% in ASD children with GI symptoms. ^[78]

The gut microflora has also been targeted as a potential player in autism spectrum disorders. There have been anecdotal reports of the onset of autism following broad-spectrum antibiotics, suggesting that disruption of the indigenous flora may lead to colonisation by neurotoxin-producing bacteria. Autistic children have been shown to have higher counts and more species of dysbiotic organisms than age- and sex-matched controls. For example, in a study of 58 ASD children, 15 normal siblings, and 10 unrelated healthy children, the ASD children, most of whom had a history of multiple antibiotics and significant GI symptoms, were found to have a higher incidence of Clostridium histolyticum. ^[79]

Autism: all in the genes? Polymorphisms in genes linked to detoxification are often seen in children with ASD. ^[80] For example, genes involved in GSH production and detoxification may also be affected in children with ASD. ^[81] This combination of genetic defects dramatically reduces their detoxification capacity and has implications for gut function, immune function and especially for brain function.

Several studies have identified that children with ASD more frequently have the genotype that causes reduced activity of some important detoxification enzymes, including:

• PON1 Aryl Esterase – a protein responsible for inactivating organophosphate compounds. ^[82]
• Metal-Regulatory Transcription Factor 1 (MTF1) – a transcription factor involved in producing the intracellular heavy metal detoxifying protein, metallothionien. ^[83]
• Glutathione Transferases (GSTs) – proteins responsible for attaching glutathione to toxins for removal. ^[84]

The discovery of detoxification enzyme polymorphisms in autism indicates these individuals may require additional and/or ongoing support to assist in promoting efficient detoxification of environmental toxins. This may also explain why some children develop ASDs after exposure to seemingly low or “safe” levels of toxins such as heavy metals.

Heavy metals are often an issue in autism. Many ASD patients are unable to efficiently cleave dietary proteins into the individual amino acids needed for MT synthesis, leaving them prone to heavy metal toxicity. ^[85] Mercury has been repeatedly linked to ASD; this toxic metal is directly neurotoxic and also acts to activate microglia, increase CNS oxidative stress and deplete GSH stores. ^[86],[87] Further, children with autism are considered a high risk category for lead exposure because of their repetitive hand-to-mouth behaviour, and high lead levels have indeed been found in children with autism. ^[88] This emphasises the need for detoxification support for these children.

Pectin shown to bind and remove heavy metals. Five case studies represent the first known documentation of clinical effectiveness for the reduction of toxic heavy metal burden. They show that reduction in toxic heavy metals (74% average decrease) was achieved without side effects, with the use of modified citrus pectin (MCP) alone or with an MCP/alginates combination. The gradual decrease of total body heavy metal burden is believed to have played an important role in each patient’s recovery and health maintenance. ^[89]

Disclaimer: In the interest of supporting health Practitioners, all safety information provided at the time of publishing (Oct 2025) has been checked against authoritative sources. Please note that not all interactions have been listed.

For further information on specific interactions with health conditions and medications, refer to clinical support on 1800 777 648(AU), 0508 227 744(NZ) or via email, anz_clinicalsupport@metagenics.com, or via Live Chat www.metagenics.com.au, www.metagenics.co.nz

Pregnancy and Breastfeeding

• Not recommended for use in pregnancy nor during lactation – detoxification and gut repair must be finished well before conception.

Contraindications

• Hepatic encephalopathy: Theoretically, glutamine, which is metabolised to ammonia, might worsen hepatic encephalopathy.

Cautions

• Anticonvulsants, seizure disorders: Theoretically, glutamine, which is metabolised to the excitatory neurotransmitter glutamate, might antagonise the anticonvulsant effects of medications taken for epilepsy, or lower the seizure threshold. However, this interaction has not yet been reported in humans.
• Antidiabetic drugs: Theoretically, taking L-cysteine and Milk Thistle supplements with antidiabetic drugs might increase the risk of hypoglycaemia.
• Corticosteroids: Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
• Immunosuppressants: Theoretically, larch arabinogalactan might interfere with immunosuppression therapy due to immunostimulant effects.

NOTE: For elderly or seriously ill patients on polypharmacy (multiple medications), considering this combination, refer to Clinical Support on 1800 777 648(AU), 0508 227 744(NZ) or via email, anz_clinicalsupport@metagenics.com, or via Live Chat www.metagenics.com.au, www.metagenics.co.nz

Footnotes

[*] The first feeding of colostrum induces rapid and widespread development of intestinal growth (Commare, 2007). In addition colostrum provides what might be termed “instant immunity” to the infant.

[†] “Demulcent” is an internal action, on the skin it would be “emollient”.

[‡] GPx is actually a family of enzymes. So far, eight different isoforms of glutathione peroxidase have been identified in humans.

[§] GSH represents reduced monomeric glutathione, and GSSG represents glutathione disulfide. H ₂ O ₂ is hydrogen peroxide, a source of damaging reactive oxygen species. NADP is Nicotinamide adenine dinucleotide phosphate, a coenzyme used in many biochemical reactions.

[**] CCl4 is a carbon compound used experimentally to induce liver damage. It is also used in dry-cleaning.

[††] Eosinophilia is indicative of allergic inflammation.