Hompes Method - Amazon S3 · •Glucoronidation is the detoxification “workhorse”, adding...

Hompes MethodPractitioner Training Level II

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Lesson Seventeen

General Detoxification Principles

Detoxification - Introduction

• You learned in lesson eleven that your clients and patients are exposed to thousands of toxins over a lifetime. These toxins stockpile in the body – in some folk more than others – and ultimately lead to the development of common symptoms and even debilitating diseases.

Detoxification - Introduction

• In lesson twelve, you’ll learn the basic principles of detoxification. We’ll then move on to assessing detoxification function and designing detoxification protocols.

Detoxification – The Problem

Introducing Biotransformation

“Detoxification is the process of transforming and removing potentially harmful products from the body. The detoxification process has its own energy, nutrient

and regulatory requirements. The process of transforming toxins into a form suitable for excretion is called biotransformation. Biotransformation is the sum

of all chemical processes of the body that modify endogenous or exogenous chemicals.”

Functional Medicine University – Physiology & Biochemistry of Biotransformation & Detoxification. Page 3.

Introducing Biotransformation

• Biotransformation is influenced by many factors:– Age

– Sex

– Body composition

– Existing disease / pathology

– Diet

– Nutritional status

– Stress burden

– Genetics

– Exposure levels

Biotransformation and Genetics

• Genetic variation can create significant differences in people’s ability to detoxify – e.g. the methylation pathways. We’ll cover this topic in a separate lesson, though genetic testing is not (yet) a core part of Hompes Method.

Biotransformation Organs and Glands

• As you’ll see, detoxification is not limited to the liver and kidneys – it’s a whole body process involving many glands and organs, including the skin, lungs and gut. However the liver and kidneys are major players in the detoxification process.

Biotransformation Interactions


Biotransformation and Toxin Classes

• Remember that toxins are not just entering the body as xenobiotics. The body’s own metabolic waste products (e.g. ammonia, hormones), toxins from food and water that are not xenobiotic in nature, viruses and other systemic infections, as well as toxins from the gut, all need to be processed.

Biotransformation Interactions


Biotransformation – Main Concept

• Most toxins are fat-soluble, meaning they readily hang around in fat. Unfortunately this means the body can’t get rid of them. In order to eliminate fat soluble (lipophilic) substances, the body must transform them into water soluble (hydrophilic) compounds.

Biotransformation - Simple Explanation

• Toxins enter liver in fat soluble form (which is why they get stored in fat cells!)

• They cannot be excreted from the body.

• The role of Phase I is to begin the process of converting to water soluble molecules.

• Intermediate compounds can be equally toxic and even more so.

• Phase II is required to complete the conversion to water soluble molecules, be “adding bits on” (e.g. sulfation).

Biotransformation Diagrams

Biotransformation – Phase I

• Phase I reactions consist of:

– Oxidation

– Reduction

– Dehalogenation

– Hydrolysis

• These reactions convert molecules into substrates for the Phase II enzymes.


• Phase I adds or uncovers a reactive group on the toxin making it more “polar”. However it may not be fully water soluble, and therefore ready for elimination. In fact the toxin may be more chemically reactive (reactive intermediate metabolites and/or reactive oxygen species), and therefore more toxic.


• The end result of Phase I reactions can be that the metabolites are:

– Inactive

– Equally active

– More active

– Toxic

– Activated (pro-drug)

Biotransformation - Cytochromes

• The phase I enzyme system is mainly composed of cytochrome P450 (CYP or CYP450) supergene family. (The P stands for pigment and the 450nm is the wavelength of light absorption). CYP450 is also known as NADPH CYP450 system because it uses oxygen and the co-factor NADPH. CYP contains an iron protoporphyrin prosthetic group (heme).


• The cytochromes catalyze a variety of reactions including epoxidation, N-dealkylation, O-dealkylation, S-oxidation and hydroxylation. In addition to detoxification, the cytochromes are important in steroid, cholesterol, and vitamin D synthesis.


• Cytochromes are primarily located in the smooth endoplasmic reticulum (microsomal fraction) and some are located in the inner mitochondrial membrane.


• There are different isoforms of CYP450 (sn isoform is a cytochrome enzyme variant that derives from a particular gene). Some cytochrome metabolize very few toxins, while some metabolize multiple. There are over fifty human genes coding for the various cytochrome P450 enzymes.


• There are several isoforms that are important due to their involvement in metabolism of drugs and other exogenous substances. These include:– CYP3A4 – CYP3A5 – CYP2D6– CYP2C9– CYP2C19– CYP2C8– CYP1A2– CYP2E1– CYP2A6


• The activity of the cytochrome enzymes may differ due to genetic polymorphisms. From a clinical perspective, the differences can have profound clinical consequences when prescribing pharmaceutical, botanical and supplements. A genetic polymorphism can cause reduction in the ability to detoxify a certain chemical or chemicals.

Biotransformation - Adrenal Glands

“The enzymes that are responsible for biosynthetic hydroxylations in the adrenal cortex are from the same family of cytochrome P450 enzymes found in the liver.”

Remember that CYP450 enzymes are also involved in steroid synthesis, which may explain their high activity in the adrenals (i.e. not necessarily just detoxification).

Biotransformation - Adrenal Glands

“Adrenocortical cells contain high concentrations of biological antioxidants including superoxide dismutase (SOD), catalase, alpha tocopherol, glutathione and, in particular, ascorbic acid. It has been suggested that

these high levels of antioxidants serve to protect cytochrome P450 enzymes from toxic effects of oxygen

radicals generated during steroid biosynthesis.”

Biotransformation – Mucosal System

“The mucosal surfaces of the GI tract, the nasal passages and lungs are major portals of entry for

xenobiotics into the body. Mounting evidence shows that many of the clinically relevant aspects of CYP450

may in fact occur at the level of the intestinal mucosa…The highest concentration of CYP450s occur in the duodenum with a gradual tapering into the ileum.”

Biotransformation – Mucosal System

“Both phase I (CYP450) and phase II activities are found in the skin, placenta, breast, GI and nasal mucosa, lung

and kidney. These extra-hepatic organs play a major role in overall body detoxification ability.”

Biotransformation – Skin

“Although it is the largest organ of the human body, skin is often not considered in discussions of drug

metabolism. However, there is growing evidence that most common drug-metabolizing enzymes are

expressed in the skin.”

Biotransformation – Skin

“Evidence for expression of cytochromes P450, flavinmonooxygenases, glutathione-S transferases, N-

acetyltransferases, and sulfotransferases in human skin and skin cells are presented. Additional discussion is

focused on the evidence of actual metabolism of drugs.”

Biotransformation – Phase II

• Phase II reactions involve the process of conjugation of the Phase I molecules making them water soluble, and therefore amenable for elimination. It’s like sticking a molecule onto another molecule –conjugating them. These products are then excreted into the bile and urine for elimination via urination and defecation.


• Phase II conjugation reactions include:

– Glucuronidation

– Glutathione transferases

– S-Methylation

– N-Methylation

– Acetylation

– Sulfotransferases (sulfation)

– Thioltransferases

– Glycination

Glutathione Conjugation

• Glutathione is the most abundant antioxidant in cells:

– It is made from glycine, cysteine and glucarate.

– There is an age-related decline in glutathione levels (more toxins = more degradation).

– Glutathione conjugates many toxins in the liver.

Sulfate Conjugation

• Sulfate conjugation is a high affinity, low-capacity conjugation system. In other words it’s very effective but can’t process high volumes. The sulfationpathway is used for detoxification and for synthesis of neurotransmitters, steroids and connective tissue.

Glucuronide Conjugation

• Glucoronidation is the detoxification “workhorse”, adding glucuronic acid to toxins/xenobiotics, bilirubin, various hormones and bile acids:

– It’s calorically expensive (think “fatigue” in the toxic client/patient).

– It kicks in when other pathways are diminished or saturated.

– It’s slower than sulfation or glycination.

– Its capacity correlates linearly to bodyweight.

Biotransformation Nutrients


• Nutrients that Support Phase I:– Thiamine (B1)– Riboflavin (B2)– Niacin (B3)– Folic acid – Pyridoxine (B6)– Cobalamin (B12)– Vitamin C– Flavonoids – Phospholipids– Indoles– Iron, zinc, selenium, magnesium


• Nutrients that support the intermediate pathways, between phases I and II:

– Antioxidants (A, C, E)

– Flavonoids

– CoQ10


• Nutrients that support the proper function of phase II:

– Flavonoids

– Indole-3 carbinol

– Carnosinic acid

– Isoflavones

– Ellagic acid

– Garlic

Biotransformation Induction & Inhibition

• The activity of the enzymes involved in detoxification are either induced or inhibited by a number of factors which include genetics, diet, environment toxins, medication and nutritional status.


• There are some excellent tables listing the inducers and inhibitors of the cytochrome enzymes. See:

– http://www.biology-online.org/kb/print.php?aid=2340

– Cutler, Amalgam Illness: Diagnosis & Treatment -page 41.

– Neil B. Sandson, MD: http://www.psychiatrictimes.com/articles/exploring-drug-interactions-psychiatry

http://www.biology-online.org/kb/print.php?aid=2340

http://www.psychiatrictimes.com/articles/exploring-drug-interactions-psychiatry


“Substrates are those agents that are metabolized by particular P450 enzymes. Inhibitors impair the ability of

specific P450 enzymes to metabolize their target substrates, thus producing increased blood levels of

those substrates. Conversely, Inducers cause an increase in the production of particular P450 enzymes, leading to increased metabolism of the substrates of

that P450 enzyme.”

Neil B. Sandson, MD: http://www.psychiatrictimes.com/articles/exploring-drug-interactions-psychiatry

http://www.psychiatrictimes.com/articles/exploring-drug-interactions-psychiatry

Biotransformation Induction

• Certain substances can cause the upregulation of Phase I enzymes without the corresponding upregulation of the Phase II enzymes. If Phase I enzymes are upregulated or induced without an increase in Phase II activity, the result will be an increase in oxidative stress due to the fact that the intermediate metabolite can be more toxic that the original compound that activated the Phase I enzymes.


• Substances that induce Phase I include:

– Drugs; nicotine, alcohol, phenobarbital, steroids, sulfonamides.

– Foods; cabbage, broccoli, high protein diet, niacin, oranges, tangerines, B2, saturated fats, sassafras, grilled foods (black), schizandra, ginseng, licorice.

– Environmental toxins; exhaust fumes, paint fumes, dioxin, pesticides, charbroiled meats.

– Nutrients

Biotransformation Inhibition

Biotransformation Inhibition

• The enzyme systems of phase I and II can be inhibited by several mechanisms, including medications, food, botanicals and nutritional deficiencies. Substances that inhibit phase I include:

• Drugs (see list)

• Foods (e.g. grapefruit)

• Gut dysbiosis

* Stress, through hormonal and physiological adaptation, can also inhibit detoxification.

Biotransformation - Inhibition

• Please note that it’s not just drugs that inhibit phase I. According to Cutler, the following can all inhibit phase I:

– Endotoxin

– Iron deficiency

– Excess sugar

– Niacinamide

– Partially hydrogenated fats

– Tyrosine (in large amounts)

Biotransformation Phase II

• Specific Phase II nutrients can be both inducers of phase II activity when present in adequate amounts, or inhibitors when they are depleted / deficient.


• Glutathione conjugation:

– Glutathione, B6, N-acetyl cysteine

• Inducers - Brassica family, dill, caraway

• Inhibitors –deficiencies of selenium, B12, zinc and glutathione itself


• Amino Acid conjugation:

– Glycine

• Inducers – glycine, taurine

• Inhibitors - low protein diet


• Methylation:

– S-adenosyl-methionine

• Inducers - Lipotropic nutrients – choline, methionine, betaine, folic acid, and B12

• Inhibitors – deficiency of B12 or folic acid


• Sulfation:

– Cysteine, methionine*, molybdenum:

• Inducers - cysteine, methionine, taurine)

• Inhibitors – NSAIDS, molybdenum deficiency, tartrazine(yellow food dye)

• * careful with methionine as it can convert into homocysteine.


• Acetylation:

– Acetyl-CoA, B5:

• Inhibitors – deficiency of B2, B5, or C

• Genetic/epigenetic control

Biotransformation Induction & Inhibitions

• Glucuronidation:

– Glucuronic acid:

• Inducers - fish oils

• Inhibitors probenicid, aspirin, inflammation, low thyroid, insulin resistance

Biotransformation – Energy Requirements

• All of these reactions require energy (ATP) and cofactors to proceed. Detoxification/biotransformation is an energy demanding process. Thus, anything that interferes with cellular energy production will also inevitably down regulate the body’s ability to detoxify (food selection, gut function, thyroid & adrenal status, nutrient deficiency, etc.)

Biotransformation - Summary

• The biotransformation process is extremely complex. Interactions between Phases I and II plus the biochemical/genetic uniqueness of your client/patient are important factors to address when evaluating your patient’s detox status/capacity. Optimal health requires a balance between exposure avoidance, all detox phases, as well as good digestive function.

Thank you!

• As always, thanks a million for tuning in. In Lesson twelve, part two, we’ll look at how to test detoxification function/capacity to facilitate the design of an effective detoxification programme.

Hompes Method - Amazon S3 · •Glucoronidation is the detoxification “workhorse”, adding...

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