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All of the things that livers do

Herbalists love livers. Liver lovers, you might call us. And there’s a good reason for this: The liver regulates many of the body’s chemical and nutrient levels. It’s a metabolic powerhouse of detoxification, chemical organization, and regeneration. So herbalists, who like to support the body systemically, find a wonderful leverage point in this one single but not simple organ.

To give you an idea of what a human liver looks like: it’s a 3lb organ that sits in the right upper abdomen, under your diaphragm. The organ consists of liver cells called hepatocytes, which are grouped into lobules, who are then grouped into lobes. When you look at it, it may appear as large but unassuming.  Until you realize that it performs a staggering 500+ known functions in the body. Its large size makes sense when you consider all the work it does.

First, consider that all of the blood leaving the stomach and intestines pass through the liver. In fact, at any given moment, your liver is holding 13% of your body’s blood supply. Oxygenated blood enters through the hepatic artery, and nutrient-rich blood leaves the liver through the portal vein.

Deeper into detoxification

Many people associate the liver with filtration/detoxification activities. This is true- the liver is responsible for breaking down old and damaged blood cells. Specifically, it clears bilirubin (a by-product of the breakdown of hemoglobin. Its accumulation will turn the skin and eyes yellow, which is recognized as jaundice and indicative of liver failure.) It also converts ammonia- an end product of protein metabolism, toxic in the bloodstream- to urea. Urea is less toxic and carried by blood to the kidneys where it leaves the body in the form of urine. The liver metabolizes drugs and other exogenous substances. For this, it specifically employs the CYP450 enzyme system.

Exploring the CYP450 system

This (admittedly awkwardly-titled) group of enzymes system metabolizes thousands of endogenous (from within) and exogenous (from outside) chemicals. Some seem to play more of a role in drug metabolism than others, and therefore get more scrutiny. 6 of these 50 enzymes metabolize 90 percent of drugs, with the two most significant enzymes being CYP3A4 and CYP2D6. (If you’ve ever punished yourself by reading herb-drug interaction research papers, these may look familiar.) These enzymes are located in many cells of the body, but are especially concentrated in the liver. (For cell physiology enthusiasts, they are located either in the inner membrane of mitochondria, or in the endoplasmic reticulum of cells.)

How do these enzymes work? CYP450 enzymes essentially make compounds more soluble so they can be excreted by the body. This enzyme system is a component of Phase 1 detoxification. You might be familiar with Phase 1, 2, and 3 metabolism in the liver. You can think of phase 1 as modification. In this first pass, substances are prepared for metabolism and excretion. (For the chemically adept, this occurs by oxidation, reduction, and hydrolysis reactions. The CYP450 system carries the weight of oxidation.) There is a step that follows called conjugation, also known as Phase 2. This is not CYP450-mediated. During this step, substances are paired (“conjugated”) with something like glutathione, glycine, or another charged species to make it water soluble. This is important in order to make the compound safer, and to get it out of the body. There is a phase 3, which provides further chemical rendition and escorts the molecules for excretion from the body.

You might be tempted to think of these enzymes as confined to the liver and its detoxification activities. Not so! While the CYP enzyme system is located mostly in liver cells, but are also abundantly concentrated in small intestine epithelial (tissue) cells. In fact, recent research has revealed these enzymes are found in cells in most tissues of the body. We know now that these enzymes play a varied role in the body and goes far beyond xenobiotic metabolism. CYP is vital to vitamin D metabolism, hormone synthesis, the formation of cholesterol, steroids as well as arachidonic acid metabolites.

No doubt you ask, why the name CYP450? For this, I’ll present an anethesiologist’s view:

Why cytochrome P 450? There’s a story attached to this. Initially, when researchers realised how important cytochromes were in metabolism, they needed a way of identifying them unequivocally. We know that most CYP is anchored to membranes of the microsomal portion of the cell. This attachment is unfortunate for investigators, as grinding up cells and extracting the microsomal portion results in a rather opaque suspension. Special tricks are needed to identify the CYP component – the microsome-containing solution is divided into two (after adding an agent that reduces any haem that might be present), and one part is exposed to carbon monoxide. If the solution exposed to CO strongly absorbs light at a wavelength of 450nm compared with the original solution, it must contain CYP. This is called “difference spectroscopy”, and we are finding the “reduced CO difference spectrum”. (The P in P450 stands for “pigment”). 

As you might guess, there are many genetic variations that can affect an individual’s CYP makeup and detoxification pathways. Recent research in genomics and personalized medicine has revealed myriad SNPs that affect CYP function, methylation, and other aspects of detoxification. Phase 1 activity tends to decline in age (most likely due to reduced blood flow to the liver).

Herb-drug interactions and the liver

Here is where herb-drug interactions enter the picture. Interactions fall into one of two categories: pharmacodynamic and pharmacokinetic interactions. Pharmacodynamics can be interpreted as the effects of the drug on the body. If you take a stimulant and sedative together, their effects will cancel out. Or if you take 2 stimulants, they will have a combined additive effect. These are what I call “no duh” interactions. They’re common sense. Pharmacokinetics are a little different. These interactions concern the ADME aspects of herb or drug metabolism: absorption, distribution, metabolism, and excretion. Most pharmacokinetic herb-drug interactions concern metabolism and excretion, chiefly through the CYP enzyme system. This is how it works: a substance may increase or decrease the activity of various CYP enzymes either by inducing the biosynthesis of it (enzyme induction) or by directly inhibiting its activity (enzyme inhibition). Once the makeup of the liver’s CYP enzymes are altered, a substance (say, a drug) traveling through it is going to be treated a little bit differently. We’ve changed the biochemical landscape a bit.

Much more than detoxification!

Detoxification is not the whole story when it comes to liver function. The liver also produces many vital compounds for our physiology: blood plasma proteins, cholesterol, glucose, and bile, to name a few. Bile is especially important. It helps carry away waste product from the liver and is critical for the digestion of fats and lipids.

The liver also processes proteins into amino acids (creating ammonia as a by-product) and regulates these levels in the bloodstream as needed. It’s also responsible for processing hemoglobin and distributing iron content. It also regulates a laundry list of substances in our body: clotting factors, immune factors, nutrient levels, and so on. One way the liver regulates these substances is by acting as a reservoir for substances like glycogen, iron, copper, and vitamins A, D, B12, K storage.

The liver also our partner in endocrinology. It metabolizes and convert many of our bodie’s hormones. It produces estrogen and testosterone, creates serum proteins that act as hormone carriers, converting thyroid hormones, and regulating sex hormone levels and eliminating their excess. In my practice, when we work with hormone imbalances, we work with the liver too.

Historical perspectives

I want to pause here and marvel at the miracle that is the liver. Is this not an impressive array of activities? It’s no wonder that Roman anatomist Galen (200AD) considered the liver to be THE principle organ in the body. In fact, historical understandings of the liver as as colorful as the Ancient Greek humors of the body (blood (liver), yellow bile (gallbladder), phlegm and black bile (spleen)). The gallbladder and spleen were considered to be crucial subsidiary organs of the liver. These humors were the color palette with which individual consistutions were mixed. As a result, emotional composition was understood to be rooted in humoral constitution.

We think of blood as associated with the heart and cardiovascular system. But this was not always the case. Physicians of times past understood the liver as the seat of the blood. This was a component of Galenic or humoral medicine, which dominated Western medical thinking until the 14th century when the work of French anatomists challenged its tenets. (Humoral medicine emerged from the observations of the fluids from ill patients. Hippocratic and Greek physicians were firmly against dissection.)

The liver was a central organ for most of medical history. These might be antiquated ideas. Or, perhaps, some truth remains.

The liver in 5-element medicine

Today, herbalists consider biomedical physiology, but incorporate even more language and concepts to describe liver function. For example, in Chinese 5-element medicine, the liver official is associated with the Spring season and that rapid period of growth, vision, and organization. This is correlated with the Wood element, which represents rapid growth and strategic planning. Wood is able to lay the foundation for the Fire element, which is associated with the season of summer, love, and fierce presence. In this particular medical system, the small intestine is associated with the fire element. The wood-fire elemental connection seen in Chinese 5 element medicine mirrors the physical processes between the liver and digestive system. In this system, the liver is vital to the digestive fire. This paralells biomedical perspectives: the liver’s bile production directly supports digestion.

The liver’s capacity for chemical organization and order-making in our bodies make it possible for our cells (and their mitochondria) to function. Without it, we would have derranged hormones, blood sugar, and nutrient levels. Our cells would not be able to produce energy and reproduce, and we wouldn’t be able to maintain homeostasis.

This is how herbalists like to think: zoom in on the details, zoom out to see the patterns. And we might have different language for each of these layers. It’s good to learn different languages.

Western herbal perspectives

Western herbalists often describe liver patterns in terms of constitution. The revered herbalist Michael Moore was influential to contemporary perspectives on constitution. Moore taught that there were 2 essential types of stress that people experience. Anabolic people are builders- they get physically bigger with stress. Catabolic people (ahem, me) do the opposite- they break down and get thinner with stress. The former tend to have “hotter” livers because it makes mostly building materials (and little fuel). The liver of the catabolic types, tends to be “cool” and even a little sluggish, preferring to process easy things like glucose over harder things like fat and protein digestion.

An herbalist might look for dry eyes/skin, excess fat in stool, headaches, jaundice, coating on tongue, postprandial fatigue when assessing liver function. I also consider hormone imbalances and chronic fatigue. When presented with imbalances, Western herbalists might engage some differentials: Is the liver hot, or too agitated? This could be a result of inflammation (viral infection), solvent exposure (including alcohol), or improper diet. In that case, there’s a class of liver cooling herbs that might bring balance, like our simple dandelion (Taraxacum off.) and burdock (Arctium lappa) leaf and root.

Or is it too cool, stagnant, and needs a little push to get going? There’s an another class of liver herbs that are warming and stimulating, such as Oregon grape root (Mahonia nervosa and other species), and Berberis species. Milk thistle is considered to be neutral and regenerative to liver tissue.

Liver, evolution, and bitters

Alone and left to their own devices (for example, in a petri dish), liver cells don’t really do any work. But when you add chemicals to the mix and give them some stimuli, they become alive again. I’ve described anti-fragility as it relates to our immune systems before, and it’s applicable here too. This comes as no surprise when we consider that our livers co-evolved with the xenobiome (or, less poetically, all the things outside of us). Plants have always provided our livers with abundant chemical diversity. And the bitter flavor really stirs the pot. In the plant world, the bitter flavor is your signal to watch out, as it is what potentially toxic alkaloids taste like. Throughout most of our history, we would get frequent little bitter blasts that act like an alarm clock to our livers, waking them up periodically. Like many things in life, these goodnatured challenges may help increase our resiliency. This is vcertainly the case with livers and bitters.

The bitter flavor, however, is conspicuously absent from our present day diets. The decrease in bitter consumption and inverse rise in liver diseases (particularly fatty liver disease) may be connected.

How to support your liver

Through bitters! Bitter herbs can be used daily or as needed to support the liver and its myriad functions. They do so because they provide stimulus to the liver.

To better understand how this works, let’s look at the bitter receptors. The bitter taste receptor (T2R) is one of several types of taste receptors. When engaged, this receptor increases enzyme/bile secretion through hormones (cholecystokinin) and nerves (vagus nerve). Surely I’m enlightening you by saying that these receptors are found on the tongue. However, T2R found in other body tissues – throat, stomach, small intestine, pancreatic duct- reinforcing these biochemical signals there. Even the lungs and brain have T2R receptors. (In the brain, these receptors play a role in the apetite regulation pathway. After a “bitter warning signal” is received, the body wants to reduce food intake. This might be one reason that people report feeling more full after eating vegetables.)

There are dozens of herbs that function as bitters and, luckily, we have ways of differentiating them. Think of these less as firm categories and more like overlapping circles on a Venn diagram.

  • Stimulating liver herbs (like Oregon grape root) are great for larger, sluggish, anabolic (kapha) types. If given for an extended period of time, they can cool and dry a person out. (Ginger and licorice can be added to a bitter formula to correct this.)
  • Warming aromatic bitters (i.e. Angelica)- these are better for the cold/dry vata types.
  • Cholagogues (i.e. Artichoke, Gentian, Taraxum off., Turmeric) stimulate the release of bile from the liver and gall bladder. They increase intestinal digestion of fats.
  • Cooler and gentler bitter herbs include Dandelion and Burdock roots and leaves.
  • When the liver is damaged and requires repair, Milk thistle is reliable and effective. It is a neutral herb. (Stimulating liver herbs would not be appropriate here- opt for nourishment instead.)

(Safety note: when we stimulate the liver, bile production is stimulated as well. While uncommon, be sure that there is no blockage in the gall bladder or biliary ducts! Avoid a gallstone emergency.)

Cleansing and misinformation

Many people arrive at herbal medicine with the hopes of losing weight, gaining energy, improving libido and athletic performance. With such high demand, these can be highly problematic product categories in terms of quality control and ethical marketing.

“Liver detox” fanaticism is not a new development. Purification rituals have been an aspect of our healing traditions for all of human history. And that is understandable. Surely, we must support our body’s natural detoxification pathways. However, we aren’t served by indulging in heroic and sometimes harmful “detoxes”.

Many liver detoxification products and programs consist of an herb named here, like Milk thistle, coupled with a laxative (senna, cascara, etc.). The laxative gives the impression that something’s happening, the detox is working. Then there are programs the liver and gallbladder flush. This consists of a short period of fasting, followed by drinking 1c of olive oil with citrus juice in an attempt to force your liver to fill up with bile and dump it, flushing the gallbladder and ridding your body of gallstones. Some instructions include drinking an epsom salt solution. People unsurprisingly feel ill and experience sweating, nausea, and diarrhea. Some claim they see the gallstones in the toilet, and conclude that the flush is working. These “gallstones” are, in fact, saponified olive oil.

When it comes to the liver, tried and true is best. Incorporate dandelion into your foods and drink, and other bitter greens. Consider a digestive bitter blend if you are experiencing digestive difficulties. A key problem with contemporary liver “cleanse and flush” programs is that they assume 1 physiological type, when there are many! Livers can be stagnant, sluggish, or deficient.

When you’re feeling “off” and looking to regain balance, ask: Do I need to cleanse or do I need to build up? 

Liver support is not a one-size-fits-all scheme. Of course we have many things in common. But you are an individual, and so is your liver. Consider the nuances. While it’s important to be open to new information, in the case of the liver, trust your traditions.

3 Comments Post a comment
  1. Terry #

    Great article, very informative.
    The Liver really IS under appreciated.

    July 28, 2016
  2. Susanne #

    Thank you. Great all encompassing information, so crucial, and so little known. I especially enjoyed the “one size fits all heroics” I hear so often (and not only regarding the liver) without consideration to the different possible needs. Then there is this very real reaction to it, and it is considered “done”….some actually feel a bit better due to the psychological effect, but then get into the “need to do this regularly” kind of thinking, causing all kinds of other problems, which again are addressed by more “heroics”. But I get the impression that heroics are easier to do then sensible daily maintenance. They feel like spring cleaning and a day at the spa…they really did something good for themselves….and I don’t know about others, but I can not convince them that is might not be so good for them…. maybe a topic for another great article somewhere (wink)
    Thank you very much for writing and sharing this information.

    September 7, 2016
  3. thank you so much want to share this information. very helpful at all.

    November 17, 2016

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