Detox & Digestion

 

Posted: January 2023
Author: Katie Donnelly, Adv Dip HSc Naturopathy

Detoxification is a crucial function of the liver that is directly impacted by the gastrointestinal (GI) system and food utilisation. Phytomedicine can help to regulate and support this process to re-balance and repair the body, prevent illness and support optimal health. This can provide clients with improved energy and mental clarity, reduce hunger and cravings, minimise aches and pain, rebalance hormones, restore sleep cycles, support digestion, and strengthen the immune system.

Phase I Detoxification

Phase I liver detoxification involves compound breakdown through oxidation, reduction, and hydrolysis, primarily involving cytochrome P450 (CYP450) enzymes. This biotransformation can make metabolites temporarily more harmful, with electron loss reducing stability and increasing reactivity. Dysfunction of phase I detoxification can cause an accumulation of toxins and subsequently oxidative stress and cellular damage. ¹

Rosmarinus Officinalis (rosemary) has displayed significant hepatoprotective actions in phase I through potent antioxidant constituents including rosmarinic acid, caffeic acid, and carnosic acid. Sufficient antioxidant presence has shown to reduce alterations to cell structure and lipid and DNA damage, crucial in preventing disease development.²

Recent animal studies identified R. officinalis as protective on liver and kidney cells post-heavy metal exposure, an important consideration in toxin elimination. Animal models pre-treated with rosemary showed notably less cellular damage when exposed to lead, measured by cellular membrane damage, reactive oxygen species (ROS), and reduced movement of lymphocytes into the liver, compared to those who were not treated.³

Reduced enzyme presence and variation can be the result of genetics, chronic illness, diet, and gender, and impacts efficient breakdown of xenobiotics and endobiotics. Changes in CYP450 enzymes also occurs across the lifespan.⁴ In cases of insufficiency, rosemary supports phase I through increasing enzyme activation.

Similarly, Taraxacum officinale (dandelion) displays protective and replenishing actions on the liver, throughout phase I and in acute liver damage. Dandelion acts as an antioxidant and anti-inflammatory through caffeic acid and chicoric acid polyphenols. Animal models with induced liver failure were treated with dandelion hydroethanolic and displayed reduction in liver markers including aminotransferase, alanine aminotransferase, and total bilirubin. The results were dose-related, with higher dosing associated with increased antioxidant actions and relative cellular protection. Dandelion also stimulates bile flow and phase II conjugation. ⁵

 

The Gut Factor

For enzymatic metabolism to occur adequately, sufficient nutrients are also required. This includes B vitamins, branch-chain amino acids leucine, isoleucine, and valine, along with flavonoids, glutathione, and phospholipids.⁶ Access to these nutrients depends on sufficient GI breakdown and absorption.

Poor digestive function impairs liver signalling. This can occur from microbiome alterations, GI junction permeation, and systemic inflammation. Bile flow is a crucial factor in food breakdown and waste removal, that relies on intricate signalling from Farnesoid X receptor (FXR) binding on the intestinal lining. CYP450 enzyme regulation is also linked to FXR. ⁷

Mahona aquifolium (Oregon grape) is a bitter tonic commonly utilised for bile formation and GI function. A primary constituent in M. aquifolium, berberine, has shown to regulate GI microbiome, lower inflammatory markers, and aid in renewing damaged intestinal junctions.⁸ It also reduces accumulation of lipids in the liver, preventing the development of fatty liver disease. Recent studies on berberine displayed interaction with nuclear factor erythroid 2–related factor 2 (Nrf₂), important in inflammatory regulation.⁹ Cynara scolymus (globe artichoke) also improves bile formation and reduces symptoms of nausea, GI pain and poor appetite.

Phase II Conjugation

The phase II pathways increase water solubility of the newly activated metabolite from phase I. Each pathway is relative to the xenobiotic being processed and the chemical structure that needs altering to remove it from the body.⁶ Each pathway has its own specific nutrient and enzymatic needs, and targets specific wastes. The nutrient requirements in this phase highlight the importance of adequate dietary intake and digestion.

Glutathione pathway uses glutathione-s-transferase on toxins including alcohol, heavy metals, and pesticides. Rosemary and dandelion support glucuronidation pathways, particularly relative to heavy metal processing. ¹¹ Smilax ornate (sarsaparilla) can support this pathway by reducing the requirements of glutathione in phase I, displaying antioxidant actions in rodent studies that protected hepatocytes.¹²

Amino Acid conjugation requires glycine, glutamine, arginine, taurine, and ornithine and facilitates salicylate removal. Low dietary protein and chronic toxin exposure can inhibit this pathway.¹²

Methylation involves methyl transferases and the synthesis of S-adenosylmethionine (SAM) from methionine. This process requires pyridoxine, cobalamin, folate, and choline.¹³

Glucuronidation is a primary pathway involving UDP-glucuronosyltransferases facilitating glucuronic acid binding to endobiotics, including bilirubin, and xenobiotics. Glucuronic conjugates are then removed via bile. Genetic factors can interfere with this pathway.¹⁴ Bile-stimulating herbs are beneficial for this pathway, including Rumex crispus (yellow dock), which supports the gallbladder and sluggish digestion.

Acetylation joins benzidine and amine xenobiotics with acetyl-CoA via N-alpha-acetyltransferase. This reaction requires thiamine, pantothenic acid, and vitamin C. Individuals with liver damage may have reduced acetylation detoxification.¹⁵ Arctium lappa (burdock) increases free radical scavenging actions, which may benefit this pathway through hepatocellular protection as demonstrated in vivo.

Sulfation involves a sulfonate group conjugating with endogenous wastes for water solubility. Cysteine, methionine, and molybdenum are needed. This pathway can compensate for other pathways under-functioning.¹⁶

Phase III Elimination

This phase involves waste transportation out of the body, largely by Adenine Triphosphate Binding Cassette (ABC) protein transporter, P-glycoprotein (PGP). These transporters move wastes into the bile duct for removal via the bowel, or into urine-conducting ducts for removal through the kidneys. PGP are present throughout the small intestine, on villi. This identifies another detoxication pathway, whereby xenobiotics are moved out of cells prior to moving into the liver.¹

GI inflammation can cause dysfunction of this phase. Associated factors include dysbiosis and low fibre and nutrient intake. Food intolerances also impact stool formation and movement. Toxin recirculation is a precursor in hormonal imbalance, fatigue, brain fog, increased sensitivities, arthritis, and systemic inflammation.

Microbiome renewal is crucial for GI and liver health, which can be facilitated with prebiotics and probiotics. Sufficient protein intake and facilitation is also important. Anthraquinone and stilbene glycosides in Rheum officinale (rhubarb) contribute to GI and liver function, with anti-inflammatory and laxative actions.¹²

C. scolymus has also demonstrated in vivo reduction of inflammatory markers through luteolin and chlorogenic acid actions. This included reduced presence of Interleukin-1-beta, nitric oxide, Tumour-necrosis factor-alpha, and Interleukin-6, demonstrated in animal model studies.¹⁷

 

Reference List

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