Speed-Dating Your Liver To Get Ready For Summer

By George Gillson MD PhD CCFP

Many Canadians have fond memories of summer days and nights spent on the shore of a lake, beside a river or creek, on a houseboat or maybe even on the shore of an ocean. (If you own a wetsuit!) Many of these same Canadians might also have not-so-fond memories of waking up the next morning with a hangover and as most of us know, the liver and alcohol have had a long and somewhat tempestuous relationship.  In this post I want to get you better acquainted with your liver so that you can get the most out of your summer and well, the rest of your life, really, when we get right down to it.

The liver is busy pretty much 24-7. (It’s like the Leatherman Multitool of organs, if you’re into similes.) In fact it took me weeks to schedule an interview with the liver. One of the key things it asked me to convey to alert readers is an explanation of exactly what “detox” means. Seems like every magazine at the supermarket checkout has “detox” on its cover: e.g. “I lost 286 pounds with this new detox diet cleanse. Oddly enough, I only weighed 138 pounds before I started it.”

Before I get into detox and hangovers, here is a brief overview of the many functions of the liver, gleaned from various sources. Because of its many roles, the liver is basically indispensable and has the unique ability to regenerate itself after injury, unlike other organs.

• Energy regulation: The liver removes excess glucose (sugar) from the bloodstream and stores it as glycogen. As needed, it can convert glycogen back into glucose. The liver can convert certain amino acids into fats and convert other amino acids into glucose. It can also convert dietary sugars into fats including cholesterol. The liver is regarded as the powerplant of the body as it is able to manage the various fuels which power our cells.
• Bile Production: Bile is made in the liver and stored in the gall bladder. It is critical to the digestion and absorption of fats and fat soluble vitamins in the small intestine. Bile also has an indirect role in regulating blood sugar through interaction with the colonic bacteria.
• Biochemical transformation: The liver is constantly operating on molecules and changing their structures. These include foreign molecules not normally found in the body and molecules naturally present in the body arising from all the biochemical reactions that characterize living things. Some of the modifications involve making things more water-soluble so that they may be removed from the body; some modifications prepare molecules for storage; some modifications liberate energy. The liver does all this by manipulating the chemical structures via a wide variety of enzymatic reactions. The liver is basically a vast, versatile biochemical processing factory.
• Synthesis of carrier proteins: These proteins include albumin, sex hormone binding globulin, cortisol binding globulin, and thyroid binding globulin. Albumin can carry loosely-bound hormones, vitamins, and enzymes throughout the body via blood. The other binding proteins are much more specific and bind their “cargo” more tightly. Albumin also helps keep water in the blood, preventing it from leaking into extracellular tissues and causing swelling.
• Regulation of Blood Clotting: Various blood clotting factors are made in the liver
• Infection fighting: The liver can remove harmful bacteria from the bloodstream.
• Storage of Vitamins and trace elements: The liver stores significant amounts of vitamins A, D, E, K, and B12, as well as iron and copper.
• Protein recycling Proteins including antibodies are scavenged in the liver and broken down for recycling. Red cells are also broken down to recycle the iron-containing proteins such as hemoglobin

With that brief overview under our belts let’s move on so I can fulfill the livers request for me to explain detoxification in more detail. I’m going to stick to the detoxification of organic molecules/toxins and steer away from removal of toxic elements such as mercury. (Toxic elements need to be chelated or bound via specialized supplements in order to permit them to be flushed out.)

In simple terms, detoxification of organic toxins involves the conversion of toxic fat-loving molecules into forms that can be excreted in watery body fluids and waste (think sweat, urine and feces). Enzymes are the complex proteins that carry out the conversions and there are many, many different enzymes in the liver.

Toxic molecules include alcohol (ethanol to be specific), pesticides, herbicides and components of plastics, personal care products and so forth. Fungi produce potent organic toxins and this can be an issue that is often overlooked in people living in water-damaged homes, old homes, and generally damp environments.

Enzymes usually require cofactors to function and these can include various vitamins, quite often, B-vitamins. Metal ions such as selenium, iron, cobalt, manganese, magnesium and copper can also act as cofactors to the enzymes. Energy in the form of ATP is often necessary as well. In the diagram below, the pink blob (technical term) represents a molecule that will be operated on by the enzyme.

Source: Source: https://www.abc.net.au/science/articles/2010/10/13/3037285.htm

In case you already forgot, organic detoxification reactions usually convert fat-soluble toxin molecules into water-soluble forms that can be excreted. The more-soluble molecule that is created is called a conjugate.  Conjugates can be made by adding various electrically-polarized things such as sugars, amino acids, sulfate ions (sulfur-oxygen molecules) or specialized molecules such as glutathione or dimethyl sulfone (from MSM!). Note that an adequate supply of “donors” i.e. other molecules willing to give up a sugar, a sulfate, etc is necessary. Note also, that good urine flow, good lymphatic flow, regular bowel movements and regular sweating all play a role in eliminating the water-soluble conjugates of toxic molecules, once the liver has made them.

Parent molecule (at left) and two different water-soluble conjugates

Any enzyme works best if the two gene copies directing its synthesis are “good”. If one of the gene copies is “bad”, the resulting enzyme may still work but won’t be as fast or effective. If BOTH gene copies are bad, the enzyme won’t work at all. Therefore, Genetics plays a role in the ability to detoxify.

There are inhibitor molecules that can poison enzymes by binding to them, often irreversibly, altering their structure and deactivating them temporarily or permanently. These inhibitors can be found in plants, fruits and vegetables; inhibitors can also include toxic pesticides, herbicides and metal ions such as cadmium or mercury.

Enzyme systems can go dormant if there are no parent molecules for them to work on. Sometimes, detoxification involves upregulation or increasing the synthesis of a given enzyme. Just as there are inhibitors of enzymes, there are activators or upregulators, both naturally occurring in plants, fruits and vegetables, and also in the form of a huge host of prescription drugs. Eating a rich “palette” of different-colored foods can help ensure that a wide range of detoxification enzymes are on hand and ready for action.

To summarize, these are the important factors involved in detoxification:

1. Might need to determine if both organic toxins and toxic elements are a problem.
2. Genetics: Testing can reveal if you are behind the detox “eight ball” due to an inherited non-functioning enzyme or enzymes
3. Proper nutrient intake: Vitamins, trace elements are needed as cofactors for detoxification enzymes, along with intake of foods to upregulate expression of detoxification enzymes. Avoidance of processed foods devoid of nutrients is also important.
4. Ensure adequate supply of donor molecules: Specific supplements that provide sugars, sulfate, amino acid, etc for conjugation
5. Ensure adequate “flushing out”: Ample water intake, adequate intake of specific dietary fibres, exercise (stimulates the flow of lymph and promotes regular bowel movements), intake of foods and supplements to promote bile synthesis and gall bladder function-all this to promote jettisoning of toxins via watery fluids and feces.
6. Elimination of certain foods: IgG food antibody testing can identify foods you may be sensitive to. This can reduce the amount of work the liver must do to scavenge resultant food antibody-antigen complexes. This has been discussed in previous blog posts.

I’m not going to get any deeper into the biochemistry here. Suffice it to say that you need to work with an Integrative/Functional Medicine practitioner who can help you to determine if a detoxification program is right for you.

Struggling with your weight may actually be a sign of ongoing toxin exposure. Since many toxins are fat-soluble, ongoing toxic exposure may be a driver of fat accumulation as it serves to keep the toxins from causing harm to other tissues. If you are so inclined, this link will allow you to download a paper on the notion of toxins as “obesogens”-compounds that promote fat accumulation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279464/.

Other manifestations of a need for detoxification include fatigue, neurologic problems, skin rashes, mood and cognitive issues.  Since these signs and symptoms may be caused by many other issues, once again, you need help to determine if toxins are an issue for you.

Detoxification should not be done aggressively. Patience is the watchword.  It takes time to gently modify your diet to include more liver/gallbladder supportive foods (e.g. beets, animal liver) and gently introduce specialized supplements containing nutrients and natural products supporting the expression and function of the detoxification enzymes. Lifestyle changes will likely be in order: gentle fasting, sauna, more exercise, and massage. Acupuncture can also be tremendously helpful. EvolveWell practitioners are fully capable of partnering with you to put together a comprehensive detoxification program.

Some people may not have an issue with toxins but find that if they undergo a detoxification program periodically they will feel “lighter”, more clear-headed, more energetic. I call this “giving your liver a holiday.”

At this point you’re saying, “OK. OK. Just cut to the chase. What does all this have to do with hangovers?”

Surprisingly, the literature on hangovers isn’t extensive but I found a recent summary paper (Mackus 2020) from which the following figures are taken.

Basically, ethanol is broken down by two enzymes, ADH and ALDH. Acetaldehyde is an intermediate molecule in the breakdown. In the past, researchers were focusing on acetaldehyde as being responsible for hangover symptoms. Current thinking is that ethanol is directly toxic to the brain, which is where many of the hangover symptoms arise. Much of the toxicity is through free radical generation (oxidative stress) that arises as ethanol is being broken down.

Two points arise from the foregoing: if you can speed up ethanol breakdown, the less the effect on the brain and the milder the hangover: if you can combat oxidative stress that will probably also reduce the severity of the hangover.

Breakdown speed: Drinking ethanol on an empty stomach will hasten absorption. You don’t want that. You want to eat while drinking so that the ethanol is absorbed more slowly, giving your liver more time to clear each drink. Drinking more water along with the ethanol will help you pee out more ethanol, leaving less to break down. There are certain proprietary supplements you can take that spin up the ADH and ALDH enzymes and clear ethanol faster. Nutrients are important as well: nicotinamide aka niacinamide is a cofactor for the ethanol clearance enzymes: so is zinc. Regular supplementation with these nutrients may help keep the enzymes revving.

Dampen Oxidative Stress: Supplements you might take specifically before embarking on a night (or day) of imbibing, to put out the oxidative stress “fire” include n-acetyl cysteine (NAC), methylsulfonylmethane (MSM), betaine HCL and glutathione. Taking a gram or so of immediate-release Vitamin C every hour or so might also be worth a shot (no pun intended). The supplements I just mentioned are also important for long-term health of the liver. They are hepatoprotective and can prevent or ameliorate fatty liver.

You should consult with your Integrative/Functional Medicine practitioner regarding dosing of the various things mentioned, both for an impending episode of alcohol consumption but also just for daily liver support.

If you take care of your liver, your liver will take care of you!

Have a great summer!

References

Mackus M, Loo AJV, Garssen J et al. The Role of Alcohol Metabolism in the Pathology of Alcohol Hangover. J Clin Med. 2020 Oct 25;9(11):3421. doi: 10.3390/jcm9113421. PMID: 33113870; PMCID: PMC7692803.

Wang HJ, Zakhari S, Jung MK. Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development. World J Gastroenterol. 2010 Mar 21;16(11):1304-13. doi: 10.3748/wjg.v16.i11.1304. PMID: 20238396; PMCID: PMC2842521.