Hepatology & Liver Detoxification - an important parameter in digestive health

Hepatology is the study of accessory organs; a subspecialty of gastroenterology that is concerned with the prevention, diagnosis and management of diseases that affect the liver, gallbladder, biliary tree and pancreas.

The liver is not an organ that is predominant in the minds of those who are concerned about their digestive health per se, and is sometimes the last port of call for individuals suffering from issues of gastrointestinal concern.

The liver is usually what people think about when consuming alcohol. Fairly so, as the liver does metabolise alcohol & aids in the detox of such a substance. Cool fact: alcohol is considered a macronutrient (…ish) because it contains calories, so it is an energy source just like carbs, lipids & proteins that your body may use for energy & so contributes to your total daily energy intake. It isn’t often spoken about when discussing macronutrients because it is nonessential & also is simply an energy source (& doesn’t provide further nutritional value, hence the “ish”). Something you already knew & most likely have personally experienced is that in excess, alcohol is a toxin to the human body.

Around two litres of blood is filtered through the liver each day. This is necessary because of the bacteria and toxins we are exposed to in our environment & what we consume, as well as secondary metabolites from the liver during necessary detoxification processes.

The liver is your major detoxification organ and is where bile is produced. Bile is then transported to the gallbladder for storage, where it waits to be used to break down (catabolise) said metabolites & send them to where they will be utilised or to be excreted in sweat, urine, stool or through our breath. Around one litre of bile is produced via this mechanism each day.

• Bile serves as a carrier of toxic substances. This is one way the products of detoxification are removed from the liver.

• Bile enters the duodenum via the common bile duct. Here, it emulsifies dietary fats to enable their digestion.

• Fibre in diet may bind to bile and enable excretion of fats and fat-soluble vitamins.

Now we have covered the basics, let us get more complex & into the nitty gritty nerdy part (my fav);

There are two main parts to the function of our liver.

PHASE ONE

Phase one metabolism: small chemical changes that make a compound more hydrophilic (water soluble), so that it can be effectively eliminated by the kidneys or allow it to be further acted upon by enzymes of phase two.

Within phase one we find the supergene family of heme dependent enzymes (roughly 100 enzymes) which grouped together are called the Cytochrome P450 family (CYP for short). The CYP family are responsible for detoxifying certain chemicals. The pathway exhibits significant individual variability, and is affected by environment, lifestyle, and genetic influences. Now as we already know CYP is heme dependent, so here is some information about what that means. Heme is an iron-containing molecule that is crucial in several biological processes. Heme combines with globin proteins to form hemoglobin, which carries oxygen in red blood cells from the lungs to the rest of the body. So this molecule is NECESSARY for phase one to OCCUR. If we are low in heme, this process is compromised. There are several reasons for this, and nutrient deficiency is a very common one.
These nutrients are necessary cofactors in the phase one detoxification process of the liver:

• Ascorbic acid (Vitamin C)

• Copper (Cu)

• Magnesium (Mg)

• Zinc (Zn)

• Thiamin (B1)

• Riboflavin (B2)

• Niacin (B3)

• Pyridoxine (B6)

• Folate (B9)

• Cobalamin (B12)

• the branch chain amino acids: leucine, isoleucine & valine

Beyond this, as research & understanding of the human body deepens we find certain phytochemicals that affect the CYP enzymes. Here are a few examples:

• Curcumin at 0.1% of the diet has been shown, in animals, to induce CYP1A1

• Grapefruit juice is perhaps the most well-known food inhibitor of CYP 34A (is contraindicated with specific medications such as blood pressure or heart medications)

• Cruciferous vegetables have been shown, in humans, to act as inducers of CYP1A1 and 1A2

• Clinical studies indicate that resveratrol enhances CYP1A1 activity

• In vivo evidence demonstrates that N-acetyl cysteine, ellagic acid, green tea, black tea, dandelion, chrysin, and medium chain triglycerides (MCTs) may downregulate CYP2E1

  (Hodges & Minich, 2015)

Research demonstrates that dietary components, especially phytochemicals, not only scavenge reactive oxygen species, acting as direct antioxidants, but also regulate Nrf2 activity. Nrf2 is an endogenous protein that’s job is to help regulate the work of antioxidant proteins that can help protect against oxidative damage.

PHASE TWO

The phase two detoxification system involves the conjugation of intermediate metabolites (made in the phase one) with a variety of different enzymes. The conjugation reaction either neutralises the intermediate metabolite making it more soluble or facilitates elimination through bile. There are 6 phase II detoxification pathways:

1. Glutathione conjugation
2. AminoAcid conjugation
3. Methylation
4. Sulfation
5. Acetylation
6. Glucuronidation

(Jancova & Siller, 2011, Murray & Pizzorno, 1998, 2013)

Various nutrients are required for optimal conjugation as they bound to the toxicants to enable chemical transformation, and hence they potentially can become depleted unless appropriate dietary supply exists. Here is a chart simplifying the processes of phase two liver detoxification:

Pathway: Responsible for: May assist: