In Part II of our series exploring the science of detoxification, we look closely at the role of the liver. If you haven’t read Part I, I encourage you to go back and read through it before proceeding with this section.
The science of how nutrition influences detoxification/biotransformation processes in the body is ongoing and while there’s much left to learn, significant evidence exists to conclude that dietary bioactive components and nutrients can regulate these processes (1).
What’s so Special About the Liver?
In terms of function, no part of our body is truly isolated. Each piece informs the other, for better or for worse. The functioning of your liver influences the functioning of many other parts and processes within your body, such as the functioning of the GI tract, adrenals, thyroid, cognition, hormone regulation, and many others (2, 3, 4, 5).
Your liver is truly powerful, filtering 1.4 L of blood per minute. This blood is coming from the digestive tract, gall bladder, pancreas, and spleen via the hepatic portal vein. The liver stores a wide variety of nutrients, synthesizes proteins and hormones, regulates glycogen storage, and manages the breakdown of red blood cells. It concentrates toxic substances and metabolic waste products for detoxification/biotransformation and ultimate removal. The liver also makes bile, which is involved in cholesterol metabolism and needed for the digestion of fat and fat-soluble vitamins.
Testing Liver Function
Being a supreme multi-tasker in the body, the liver's decline in function will contribute to systemic breakdown. But how do we know if our liver is in trouble?
The most common standard tests looking at liver function will assess alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and bilirubin. ALT, AST, and ALP are enzymes produced by the liver in response to its cells being damaged or diseased; they may become elevated in cases of hepatotoxicity or cirrhosis. Albumin, a protein made by the liver, is required for maintenance of fluid balance. Albumin levels can tell us a little bit about nutrition, liver, and kidney function but can often be skewed by inflammatory processes, hydration status, or acute illness (6). Bilirubin is a byproduct of the breakdown of red blood cells and can become elevated in the presence of increased breakdown of blood cells, hepatitis, reaction to certain medications, or some genetic disorders.
While these tests are especially helpful in the setting of acute care, some degree of clinically-significant liver dysfunction may be present and persist in the presence of normal liver function labs (7). Additional imaging or histological techniques may be necessary for diagnosing these subclinical cases (8). Functional liver challenge tests may also be performed to assess the liver’s ability to clear certain drugs and other chemicals. These attempt to evaluate the function of the liver’s clearance, i.e. detoxification, pathways (9, 10, 11).
Biotransformation Pathways
When we talk about detoxification, we sometimes use the term biotransformation. These terms are interchangeable, though the latter is more specific with regard to describing what takes place when our liver eliminates toxins and waste products. Although many body systems are involved, the transformation of toxic metabolites into non-toxic forms readily excreted primarily takes place in the liver. Factors influencing this detoxification capacity include diet and lifestyle, environment, genetic polymorphisms, age and gender, as well as disease state.
Also known as the Phase I and Phase II detoxification systems, respectively, the liver’s biotransformation pathways concentrate and neutralize toxic chemicals and waste products for efficient removal through the bile/feces, and urine. Phase I utilizes specialized Cytochrome P450 enzymes (CYPs), which convert the original waste product or toxin into uniquely reactive metabolites and free radicals that can be readily conjugated in phase II. Conjugation is a process that, in this case, involves coupling a toxic metabolite with a helper molecule in a way that allows the original toxic compound to be safely and easily excreted from the body. This often involves making the toxin more water-soluble. These phases, especially Phase II, rely heavily on nutrients such as vitamins, minerals, amino acids, and fatty acids (12).
Nutrition status impacts how the liver biotransformation pathways perform and ultimately, how well we are able to clear toxins and metabolic waste from the body.
Phase I
CYPs process environmental toxins, prescription drugs, chemical compounds such as caffeine and herbal bioactives, endogenous hormones, fatty acids, and vitamins such as D and A, among many other things. The chemical processes taking place in Phase I include oxidation, reduction, hydrolysis, dehalogenation, and hydration; utilizing vitamins B2, B3, folate, B12, branched chain amino acids (BCAA), and phospholipids. Some herbal compounds, known as non-nutritive bioactives, can influence how CYPs work by encouraging them to be more or less active.
The CYPs handle an estimated 75% of drug metabolism (13). We will be talking more about drug interactions as well as the impact of non-nutritive nutritional bioactives on liver biotransformation in Part III.
Phase II
After Phase I products have been formed, they are handed off to Phase II for conjugation. This is where they will be bound up and neutralized for safe excretion in feces or urine. The chemical processes involved in Phase II include sulfation, glucuronidation, glutathione conjugation, acetylation, methylation, and amino acid conjugation with glycine, taurine, glutamine, ornithine, and arginine. Additionally, selenium, zinc, copper, manganese, vitamin A, vitamin C, vitamin E, coenzyme Q10 are required. Though both phases require nutrient cofactors in order to function optimally, Phase II may be proportionally more dependent upon them (14).
If Phase II is inhibited in some way, or if Phase I speeds up without a simultaneous increase in the efficiency of Phase II, un-conjugated Phase I reactive intermediates can increase risk of oxidative stress and tissue damage (14). One example of this is found in exposure to the carcinogenic polycyclic hydrocarbons from cigarette smoke or aryl amines from charbroiled meats. These compounds will induce Phase I enzyme activity with little to no induction of Phase II enzymes (15).
In Part III of our series, we will speak more directly about the effect of specific drugs and non-nutritive bioactive compounds on the liver detoxification pathways. We will also tie the whole picture together with an enhanced understanding of how to use food to support and optimize our detoxification pathways.
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About the Author
Heather Davis, MS, RDN, LDN, holds a master's degree in nutrition science and is accredited by the Academy of Nutrition and Dietetics as a registered dietitian nutritionist (RDN). She works as a clinical dietitian, educator, and medical writer specializing in neuroendocrine nutrition and advanced chronic disease medical nutrition therapy