The liver weighs around 1.5kgs and comprises on average around 2% of an adult’s body weight.[1] It’s fair to say that the liver’s role is potentially as undervalued as it is misunderstood.
It might seem strange to hear that I think the liver is misunderstood but depending on how many coffees I’ve had, my patients will note my mini-rants around the notion of how often detox seems a little close to original sin.
“Everyone’s toxic, your liver is congested, and you must detox for life.”
Don’t get me wrong; the liver deconstructs toxins both of environmental and endogenous (from within the body) origin. Still, this article aims to reframe what many people call detoxification into the reality of the liver’s role, which is metabolism.
From there, you can better understand just exactly how much more than toxins it deals with on your behalf every day.
You’ll be surprised at just how many different molecules encounter the liver on the way around the body.
And that’s just the tip of the iceberg.
The liver deals with digestive and immune function, vitamin storage, and detoxification that it’s so well known.[2]
In contrast to the other organs in the body, the liver is involved in nearly every body system.
For example, it stores your fat-soluble vitamins A, D, E, and K, creates important immune cells like Kupffer cells for the immune system and breaks down red blood cells. Another important example is the liver’s critical role in the breakdown of all the sex hormones, oestrogen, progesterone and testosterone.
Let’s look a little closer at some of these functions to understand the liver’s role better.
When looking at the central metabolic organ, it’s an excellent start to revisit metabolism.
Metabolism is the sum of biochemical processes that either produce or consume energy.[3]
Metabolism can be broken down into three different pathways to simplify this further.
Pathways that build simple molecules into more complex ones; a process known as anabolism, commonly associated with the term “anabolic.” Pathways that deconstruct molecules to release energy are called catabolic and, finally, pathways that help the body eliminate the toxic waste produced by the pathways, as mentioned earlier.[4]
It’s not understated when I say that these processes are exactly why you can sit, stand, lie down and read this article. They are the essence of how your body works, and your liver is the centre of many of them.
The liver manages the metabolism of proteins, carbohydrates, and fats, making it essential to regulate the energy released to your cells.
When it comes to fat, the liver produces a vital substance for the digestion of fats called bile. While bile plays a critical role in excreting material not eliminated by the kidneys, bile salts and bile acids secreted into the small intestine help absorb and digest dietary fats.[5]
One of the functions bile facilitates that you might be familiar with is catalysing the liver to create energy from dietary fats in the form of ketones. The form of energy the body uses for fat in fasted or ketogenic states where consumption of carbohydrates is at its lowest.[6]
This ability to handle fats makes the liver such an essential organ for absorbing all of the fat-soluble vitamins we mentioned earlier, vitamin A, D, E and vitamin K.
It’s fair to say that most people think of protein and carbohydrates when thinking about metabolism in the context of weight loss.
But did you know that the building and breaking down of proteins is vital for all cellular and organ level functions?[7]
More importantly, did you know that the liver deals with up to 90% of circulating protein volume in the body?
What does circulating protein volume even mean?
Let’s look at one of the most abundant proteins the liver is in charge of, for instance, albumin. In your blood-based pathology reports, you may recognise albumin from the liver function test. This protein is vital for keeping your blood volume at the right level along with the transport of fats and hormones. Interestingly, low levels of albumin can be a sign of malabsorption.[8]
So let’s get this clear. Without the liver, your body would have trouble creating the buses your fats and hormones board to travel around the body.
One of the other vital roles that the liver plays with protein is called “gluconeogenesis.” A process that can often interfere with a lot of the low carbohydrate, high protein diets internet connoisseurs have been engaging in over the last decade.
Let me explain.
Gluconeogenesis is when the liver turns non-carbohydrate molecules, such as lactate and amino acids, from protein into glucose.[9] The process of gluconeogenesis exists to protect the body from a situation of extreme starvation where glucose isn’t readily available.
Can you then work out why having high protein at the same time as low carbohydrates may be an issue? Once the body senses that the glucose levels have diminished, it will use the extra protein to create glucose instead.
I’m hoping that your liver’s hard work beyond detoxification is now becoming a little more apparent.
Let’s finish off the liver involvement with micronutrients by looking at its role in glucose metabolism.
As mentioned above, the liver plays a vital role in maintaining your blood sugar. If your glucose levels elevate too high, then the liver will remove it from the blood and convert it for storage in a different form called glycogen. If your blood sugar gets too low, the liver will convert the glycogen back into glucose and release it back into the blood to restore things to their optimal levels.[10]
This crucial role in macronutrient management makes the liver now a critical site of focus for all metabolic illnesses from diabetes type 2, metabolic syndrome and, of course, non-alcoholic fatty liver disease (NAFLD).
NAFLD affects an estimated twenty-five per cent of the global population. Whilst, its development is largely down to dietary choices, NALFD is connected with environmental toxin exposure to pesticides used to spray our food.[11]
This connection is because the liver is exposed to nearly every toxin that enters your body via its intrinsic relationship to blood flow around your body. This exposure, of course, means that the liver is often responsible for dealing with these toxins and sending them out of the body.
Now we can talk about how the liver plays a role in detoxification.
The liver’s role in detoxification came about more due to the high exposure to toxins mentioned earlier. It has two phases when it comes to this defence.
Phase one liver detoxification comprises enzymes that break down pharmaceutical drugs, steroid hormones and carcinogenic substances.[12] The enzyme systems in phase one also play a role in preparing the toxin or molecule for further treatment in phase two, where it gets changed further, ready to be eliminated by the kidneys or the bowel.
There are six different phase two channels that don’t just deal with toxins from our environment but hormones, neurotransmitters, and everything in between.
For this reason, I wanted this article to focus away from the role that the liver plays in detoxification. It is not to undervalue this critical role but more because it is a component of the more significant metabolic role the liver plays.
For example, let’s look at the methylation channel of the liver.
This channel is particularly famous via functional medicine’s focus on MTHFR gene mutations and doesn’t just deal with classic toxins such as heavy metals, such as mercury and lead.[13] It also deals with neurotransmitters such as dopamine and norepinephrine[14] (think your brain’s version of adrenaline), as well as histamine[15] and oestrogen.[16]
Just looking at this one channel of “detoxification” shows the majority of the molecules going through this channel aren’t toxins at all. They are, instead, molecules that have played their role in the body and simply need to be turned over so that the body can create new versions in their place.
Let’s revisit the definition of metabolism as the total of building things up, breaking things down and eliminating them out of the body. Based on this, It sounds more appropriate to label the function of the liver as metabolically driven as opposed to anything else.
There I go ranting again. Let’s keep our focus on detoxification.
Over the past five years, the third phase in this pathway has been revealed. The journey these toxins or molecules take to their primary organs of elimination like the kidneys or bowel.
An excellent example of this third phase is when we look at oestrogen metabolism. There are times when the initial two phases within the liver do an adequate job and wrapping oestrogen up into the state it needs to be in to leave the body through the bowel.
Sometimes though, an enzyme in the bowel called beta-glucuronidase can stop the oestrogen from leaving the body by unwrapping this parcel in the bowel and recirculating the oestrogen back into the body.[17]
The analogy I use to explain this to patients is to imagine for just one moment that your name was oestrogen and you were due to catch a flight out of the body.
You’ve been through customs and got your passport stamped (think the liver), and you’re sitting in your seat reading the inflight magazine, ready to go.
It’s at this precise point that beta-glucuronidase gets on the plane, walks straight up to your seat and says, “Maam, I’m going to have to escort you off this flight.”
When these phases of liver metabolism become less effective over time, we can see problems begin.
Furthermore, we can see the liver become a sustaining factor in conditions such as irritable bowel syndrome and small intestinal bacterial overgrowth (SIBO) for example. Therefore, treating the function of the liver can be hugely beneficial.
One of the first things most new students coming out of school do in their shiny new natural medicine practice is put the finishing touches to their “liver cleansing” program.
Would you believe mine is now in its fifth incarnation after years of refining it?
These programs have come under criticism due to their extreme methods. Still, one of the benefits of undertaking a process to improve the functionality of the pathways we have mentioned above is the reversal of some of the most widespread chronic illnesses we see in our modern health landscape.
Illnesses such as NAFLD and diabetes, but indirectly, menstrual irregularities, drug-induced toxicity, such as long-term non-steroidal anti-inflammatory use[18] and irritable bowel syndrome are all influenced by this amazing organ.
Do you think your liver needs some love?
Ultimately this was the title of the article. When writing these articles, I take the words from one of my recent patients and give my community a head start on whether your intuition is pointing you in the right direction.
At the same time as introducing the liver and how it helps you daily, I also wanted to expand awareness beyond the detox reputation and hopefully move your mind into a broader, metabolically-oriented mindset when thinking about your liver.
Managing your hormones, toxins, macronutrient levels, storing vitamins and minerals and activating the pharmacy you take is all in a day’s work for the liver; indeed, there’s some time to send it some love?!
Hope this helps x
References
[1] Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 9, 2021.
[2] Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 9, 2021.
[3] DeBerardinis RJ, Thompson CB. Cellular metabolism and disease: what do metabolic outliers teach us?. Cell. 2012;148(6):1132-1144. doi:10.1016/j.cell.2012.02.032
[4] DeBerardinis RJ, Thompson CB. Cellular metabolism and disease: what do metabolic outliers teach us?. Cell. 2012;148(6):1132-1144. doi:10.1016/j.cell.2012.02.032
[5] Kalra A, Yetiskul E, Wehrle CJ, et al. Physiology, Liver. [Updated 2021 May 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535438/
[6] Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147-R1151. doi:10.1016/j.cub.2017.09.019
[7] Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147-R1151. doi:10.1016/j.cub.2017.09.019
[8] Moman RN, Gupta N, Varacallo M. Physiology, Albumin. [Updated 2022 Jan 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459198/
[9] Zhang X, Yang S, Chen J, Su Z. Unraveling the Regulation of Hepatic Gluconeogenesis. Front Endocrinol (Lausanne). 2019;9:802. Published 2019 Jan 24. doi:10.3389/fendo.2018.00802
[10] InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. How does the liver work? 2009 Sep 17 [Updated 2016 Aug 22].Available from: https://www.ncbi.nlm.nih.gov/books/NBK279393/
[11] Rives C, Fougerat A, Ellero-Simatos S, Loiseau N, Guillou H, Gamet-Payrastre L, Wahli W. Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants. Biomolecules. 2020; 10(12):1702. https://doi.org/10.3390/biom10121702
[12] Hodges RE, Minich DM. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab. 2015;2015:760689. doi:10.1155/2015/760689
[13] Jan AT, Azam M, Siddiqui K, Ali A, Choi I, Haq QM. Heavy Metals and Human Health: Mechanistic Insight into Toxicity and Counter Defense System of Antioxidants. Int J Mol Sci. 2015;16(12):29592-29630. Published 2015 Dec 10. doi:10.3390/ijms161226183
[14] Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008;13(3):216-226.
[15] Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020;10(8):1181. Published 2020 Aug 14. doi:10.3390/biom10081181
[16] Chagay NB, Mkrtumyan AM. Probl Endokrinol (Mosk). 2019;65(3):161-173. Published 2019 Sep 12. doi:10.14341/probl10070
[17] Ervin SM, Li H, Lim L, et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem. 2019;294(49):18586-18599. doi:10.1074/jbc.RA119.010950
[18] Saad J, Mathew D. Nonsteroidal Anti-Inflammatory Drugs Toxicity. [Updated 2021 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526006/
