Biotransformation is an intricate biochemical process, and is a cornerstone of human health. It is the body’s remarkable ability to convert a wide array of substances, including drugs, toxins; both endogenous and exogenous, and dietary compounds, into different chemical forms.
While the liver serves as the primary hub for biotransformation, the kidneys and intestines also play vital roles in this complex process[1]. More recently the importance of the human microbiome as a key community that affect our health through the products of biochemical reactions catalysed by microbial enzymes (microbial biotransformation’s) has been studied, and is better understood[2].
The major purpose of biotransformation is to chemically modify (metabolise) poorly excretable lipophilic (lipid loving) compounds to more hydrophilic (water loving) chemicals that are readily excreted in urine and/or bile. Without this metabolism, lipophilic xenobiotics accumulate in tissues, increasing the potential for toxicity. Examples of such compounds are highly halogenated polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (tetrachlorodibenzodioxin (TCDD) and dioxins), which occur as tissue residues in humans.
Biotransformation is normally not required for xenobiotics with high water solubility because of rapid excretion in urine. R.T. Williams, a Welsh pioneer in biotransformation studies, classified these pathways as phase I mainly catalysed by the cytochrome P450 system (oxidation, reduction, and hydrolysis reactions) and phase II (conjugation reactions).
After a toxin undergoes phase I detoxification through cytochrome P450 enzymes, it is deemed an “intermediate metabolite” that must be further metabolised by phase II detoxification. Intermediate metabolites are often more toxic than their parent compound. If phase II detoxification pathways
are inefficient, the intermediate metabolites may cause cellular damage by binding with various proteins, lipids, or nucleic acids in the cell. Phase II detoxification increases the water-solubility of the toxic metabolites, leading to enhanced and successful excretion in stool and urine.
Biotransformation is continuously affected by age, sex, nutritional status, dysbiotic status, disease state, medications, environmental exposures, and genetics of a patient. There is variance in expression and activity level of the CYP450 system throughout prenatal development and from the neonatal period to adulthood depending on many internal and external variables.
The significance of efficient biotransformation cannot be overstated, as it serves several essential functions within the body:
Detoxification: A primary role of biotransformation is the detoxification of potentially harmful substances. This process involves neutralising and converting toxins, drugs, and metabolic waste products into forms that are more easily excreted from the body and is influenced by the presence and availability of nutrients. By doing so, it helps safeguard the body from the damaging effects of these harmful agents[3].
Activation/Inactivation of Compounds: Biotransformation plays a pivotal role in converting inactive compounds into active ones, particularly with certain drugs. Conversely, it can also deactivate active substances, allowing the body to regulate their effects. This fine-tuning mechanism ensures that the body can efficiently manage the presence of various compounds. The processes are highly influenced by the presence and absence of micro and macro nutrients extracted from the diet or supplements[4].
Metabolism of Nutrients: Beyond its role in detoxification, biotransformation processes are integral to nutrient metabolism. These processes facilitate the breakdown of nutrients such as carbohydrates, fats, and proteins into forms that the body can utilize. Additionally, they contribute to the synthesis of essential molecules required for various bodily functions[5].
Various food sources have been studied in vivo and clinically to support phase I detoxification[6]. The most well-known foods that directly induce P450 enzymes with antioxidant properties and help with the successful removal of toxins through their fibre content are cruciferous vegetables, such as broccoli, kale, Bok choy, watercress, and cauliflower[7]. Certain foods may upregulate or inhibit P450 enzyme activity, working to favourably balance phase I to phase II metabolic pathways[8]. For instance, grapefruit is a well-known P450 enzyme inhibitor8. Depending on the serving size, many foods may both upregulate or inhibit phase I enzymes and are commonly referred to as bifunctional modulators8.
Nutrients: The Guardians of Biotransformation
The optimisation of biotransformation for human health hinges on the availability of specific nutrients:
Antioxidants: Nutrients like vitamins C and E, along with minerals such as selenium, act as powerful antioxidants. They shield cells from oxidative damage—a critical function, as oxidative stress can compromise biotransformation and give rise to harmful reactive molecules.
B Vitamins: B vitamins, including B2 (riboflavin), B3 (niacin), B6 (pyridoxine), B12 (cobalamin), and folic acid (folate), function as indispensable cofactors in various biotransformation reactions. They participate in processes like methylation and the conversion of homocysteine to methionine.
Amino Acids: Amino acids, particularly cysteine and glycine, are fundamental in the synthesis of glutathione—a pivotal antioxidant and detoxifying molecule in the body.
Phytonutrients: Found in fruits, vegetables, and herbs, phytonutrients like flavonoids, polyphenols, and glucosinolates enhance biotransformation by promoting the activity of enzymes integral to detoxification.
Minerals: Essential minerals such as magnesium and zinc act as cofactors for enzymes involved in diverse biotransformation pathways.
Phospholipids: Nutrients like phosphatidylcholine and choline are crucial components of cell membranes and lipoproteins. They play pivotal roles in the transport and metabolism of lipids and toxins.
Sulfur-Containing Compounds: Sulfur-containing amino acids like cysteine and methionine are indispensable for glutathione synthesis—an antioxidant and detoxifier of paramount importance.
Detoxifying Enzymes: Nutrients like quercetin and curcumin have the potential to bolster the activity of detoxifying enzymes, particularly in the liver.
Fibre: Dietary fibres, or nondigestible carbohydrates, may support the body’s main detoxification organs, the liver and kidneys. The concept has given rise to terms such as the gut-liver axis and the gut-kidney axis. First, dietary fibre promotes healthy bowel movements and intestinal motility, thereby aiding in eliminating toxins from the body. Second, fibre may support detoxification through its systemic benefits in supporting healthy microbial environments, gut barrier function, healthy inflammatory and immune responses, and by potentially activating detoxifying enzymes in the liver, such as cytochrome P450 enzymes in phase I detoxification
In conclusion, biotransformation stands as a fundamental process essential for human health. It empowers the body to metabolise a wide range of compounds and efficiently eliminate toxins. The presence of specific nutrients in the diet is pivotal in optimising these biotransformation pathways, bolstering detoxification, and mitigating the risk of health issues stemming from toxin exposure and oxidative stress. Thus, a well-rounded, nutrient-rich diet plays an indispensable role in ensuring overall well-being and vitality[9].
Our bodies have natural intelligence, and can handle the occasional xenobiotic entering the body. However, when much of what we eat, drink and breathe is laced with non-nutritive substances, our bodies need additional nutritional support to bolster our natural detoxification pathways, phase I and phase II.
To further support these nutritional requirements, medical foods enriched with these essential nutrients can be a valuable addition to one’s nutritional regimen. These specialized foods are designed to meet specific dietary needs, often in cases where conventional dietary sources may not provide adequate levels of these vital nutrients. When used under the guidance of healthcare professionals, medical foods can be a targeted and effective way to support biotransformation and overall health.
While the liver serves as the primary hub for biotransformation, the kidneys and intestines also play vital roles in this complex process[1]. More recently the importance of the human microbiome as a key community that affect our health through the products of biochemical reactions catalysed by microbial enzymes (microbial biotransformation’s) has been studied, and is better understood[2].
The major purpose of biotransformation is to chemically modify (metabolise) poorly excretable lipophilic (lipid loving) compounds to more hydrophilic (water loving) chemicals that are readily excreted in urine and/or bile. Without this metabolism, lipophilic xenobiotics accumulate in tissues, increasing the potential for toxicity. Examples of such compounds are highly halogenated polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (tetrachlorodibenzodioxin (TCDD) and dioxins), which occur as tissue residues in humans.
Biotransformation is normally not required for xenobiotics with high water solubility because of rapid excretion in urine. R.T. Williams, a Welsh pioneer in biotransformation studies, classified these pathways as phase I mainly catalysed by the cytochrome P450 system (oxidation, reduction, and hydrolysis reactions) and phase II (conjugation reactions).
After a toxin undergoes phase I detoxification through cytochrome P450 enzymes, it is deemed an “intermediate metabolite” that must be further metabolised by phase II detoxification. Intermediate metabolites are often more toxic than their parent compound. If phase II detoxification pathways
are inefficient, the intermediate metabolites may cause cellular damage by binding with various proteins, lipids, or nucleic acids in the cell. Phase II detoxification increases the water-solubility of the toxic metabolites, leading to enhanced and successful excretion in stool and urine.
Biotransformation is continuously affected by age, sex, nutritional status, dysbiotic status, disease state, medications, environmental exposures, and genetics of a patient. There is variance in expression and activity level of the CYP450 system throughout prenatal development and from the neonatal period to adulthood depending on many internal and external variables.
The significance of efficient biotransformation cannot be overstated, as it serves several essential functions within the body:
Detoxification: A primary role of biotransformation is the detoxification of potentially harmful substances. This process involves neutralising and converting toxins, drugs, and metabolic waste products into forms that are more easily excreted from the body and is influenced by the presence and availability of nutrients. By doing so, it helps safeguard the body from the damaging effects of these harmful agents[3].
Activation/Inactivation of Compounds: Biotransformation plays a pivotal role in converting inactive compounds into active ones, particularly with certain drugs. Conversely, it can also deactivate active substances, allowing the body to regulate their effects. This fine-tuning mechanism ensures that the body can efficiently manage the presence of various compounds. The processes are highly influenced by the presence and absence of micro and macro nutrients extracted from the diet or supplements[4].
Metabolism of Nutrients: Beyond its role in detoxification, biotransformation processes are integral to nutrient metabolism. These processes facilitate the breakdown of nutrients such as carbohydrates, fats, and proteins into forms that the body can utilize. Additionally, they contribute to the synthesis of essential molecules required for various bodily functions[5].
Various food sources have been studied in vivo and clinically to support phase I detoxification[6]. The most well-known foods that directly induce P450 enzymes with antioxidant properties and help with the successful removal of toxins through their fibre content are cruciferous vegetables, such as broccoli, kale, Bok choy, watercress, and cauliflower[7]. Certain foods may upregulate or inhibit P450 enzyme activity, working to favourably balance phase I to phase II metabolic pathways[8]. For instance, grapefruit is a well-known P450 enzyme inhibitor8. Depending on the serving size, many foods may both upregulate or inhibit phase I enzymes and are commonly referred to as bifunctional modulators8.
Nutrients: The Guardians of Biotransformation
The optimisation of biotransformation for human health hinges on the availability of specific nutrients:
Antioxidants: Nutrients like vitamins C and E, along with minerals such as selenium, act as powerful antioxidants. They shield cells from oxidative damage—a critical function, as oxidative stress can compromise biotransformation and give rise to harmful reactive molecules.
B Vitamins: B vitamins, including B2 (riboflavin), B3 (niacin), B6 (pyridoxine), B12 (cobalamin), and folic acid (folate), function as indispensable cofactors in various biotransformation reactions. They participate in processes like methylation and the conversion of homocysteine to methionine.
Amino Acids: Amino acids, particularly cysteine and glycine, are fundamental in the synthesis of glutathione—a pivotal antioxidant and detoxifying molecule in the body.
Phytonutrients: Found in fruits, vegetables, and herbs, phytonutrients like flavonoids, polyphenols, and glucosinolates enhance biotransformation by promoting the activity of enzymes integral to detoxification.
Minerals: Essential minerals such as magnesium and zinc act as cofactors for enzymes involved in diverse biotransformation pathways.
Phospholipids: Nutrients like phosphatidylcholine and choline are crucial components of cell membranes and lipoproteins. They play pivotal roles in the transport and metabolism of lipids and toxins.
Sulfur-Containing Compounds: Sulfur-containing amino acids like cysteine and methionine are indispensable for glutathione synthesis—an antioxidant and detoxifier of paramount importance.
Detoxifying Enzymes: Nutrients like quercetin and curcumin have the potential to bolster the activity of detoxifying enzymes, particularly in the liver.
Fibre: Dietary fibres, or nondigestible carbohydrates, may support the body’s main detoxification organs, the liver and kidneys. The concept has given rise to terms such as the gut-liver axis and the gut-kidney axis. First, dietary fibre promotes healthy bowel movements and intestinal motility, thereby aiding in eliminating toxins from the body. Second, fibre may support detoxification through its systemic benefits in supporting healthy microbial environments, gut barrier function, healthy inflammatory and immune responses, and by potentially activating detoxifying enzymes in the liver, such as cytochrome P450 enzymes in phase I detoxification
In conclusion, biotransformation stands as a fundamental process essential for human health. It empowers the body to metabolise a wide range of compounds and efficiently eliminate toxins. The presence of specific nutrients in the diet is pivotal in optimising these biotransformation pathways, bolstering detoxification, and mitigating the risk of health issues stemming from toxin exposure and oxidative stress. Thus, a well-rounded, nutrient-rich diet plays an indispensable role in ensuring overall well-being and vitality[9].
Our bodies have natural intelligence, and can handle the occasional xenobiotic entering the body. However, when much of what we eat, drink and breathe is laced with non-nutritive substances, our bodies need additional nutritional support to bolster our natural detoxification pathways, phase I and phase II.
To further support these nutritional requirements, medical foods enriched with these essential nutrients can be a valuable addition to one’s nutritional regimen. These specialized foods are designed to meet specific dietary needs, often in cases where conventional dietary sources may not provide adequate levels of these vital nutrients. When used under the guidance of healthcare professionals, medical foods can be a targeted and effective way to support biotransformation and overall health.