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Functional Medicine

Managing gamma-GT

gammaGT

Just this week a friend of mine was concerned, because his bloodwork returned with an isolated elevated gamma-GT. We worked out a strategy to optimise detoxification function, which results in reduced gamma-GT. I want to share this strategy with you.

In this article we will answer these questions :

  • What is gamma-GT?
  • Why can gamma-GT become elevated?
  • Why does it matter for health and longevity?
  • What can we do to reduce gamma-GT?

 

What is gamma-GT?

Gamma-GT is short for gamma-Glutamyltransferase. Traditionally it has been used as a marker liver function. It was used to diagnose alcoholic liver damage and to track success rates in alcohol abstinence programs. That is because gamma-GT is an enzyme that is home inside of liver cells. And when liver cells get damaged, the gamma-GT will be released into the bloodstream and will be measured in the blood serum. Elevated gamma-GT values are a very sensitive marker for liver issues like gall obstruction, liver inflammation, (non-)alcoholic fatty liver disease or liver cancer.

But gamma-GT is not only present in liver cells. It can be found in the kidneys, the lungs, the spleen, the pancreas, the heart, and the brain. And that is why elevated gamma-GT are NOT a direct sign of liver damage. There are many other markers of liver damage, and if gamma-GT is the only suspicious liver marker, then an isolated liver issue is highly unlikely. When gamma-GT is elevated in isolation there is something systemic going on. To understand what it might be we have to look at the role and function of gamma-GT in our metabolism.

 

Glutathione Transporter

The main function of gamma-GT lies in shuttling parts of Glutathione into the cell. Glutathione is one of the most important anti-oxidants (anti-rust solution) of our body. Because of its biochemical structure it cannot pass through the cell wall. That is where gamma-GT comes in. gamma-GT lives inside the cell wall, disassembles Glutathione, and then re-assembles it inside the cell.  You know similar to you trying to move your bedroom closet into your new apartment. You cannot fit it through the door, so you disassemble it, and re-assemble it on the inside. Good on you, you are just like gamma-GT.

So without gamma-GT we probably wouldn’t be able to shuttle Glutathione in and out of our cells. But there is rust (reactive oxygen species) inside and outside of our cells, so we need Glutathione both inside and outside of the cells. These reactive oxygen species are what we could call “toxins”. That makes Glutathione the “detoxifier”. I put “toxins” in quotation marks, because reactive oxygen species (ROS) are an important stimulus for growth and adaptation, when we are able to get rid of them. For example in training a high amount ROS are being created. Optimally our body is able to neutralise these during the recovery period (with the help of glutathione). ROS only become a problem when we are confronted with more than we can handle, or when we are constantly confronted with them. ROS are something we want to spike hard for some hours, and then stay away from them for a day or so. Like training. But if we are confronted with ROS all the time, our bodies ability to neutralise them will get fatigued.

A shortlist of substances/habits that lead to high amounts of reactive oxygen species :

  • ionising radiation (sunlight, X-Rays)
  • exhaust smoke from cars
  • cigarette smoke
  • xenobiotics (industrial chemicals found in food, cosmetics, water, air)
  • dioxins and PCBs from low quality drinking water or food
  • constant immune activation (inflammation) / constant adrenal stress system activation (no relaxation)
  • medication (for example anti-epileptic medication )
  • low vegetable diet
  • food allergies
  • Glucose & Fructose consumption
  • constant eating (no longer fasting periods)

 

Why does gamma-GT become elevated?

As we discussed earlier, all forms of liver damage can lead to increased gamma-GT levels. This is mostly associated with elevated levels of AST and ALT. But as an isolated elevated marker gamma-GT is more a sign of chronic oxidative damage and inflammation.

First, there seems to be a feedback loop between glutathione and gamma-GT. When we have enough glutathione, gamma-GT is in the normal range. But when our glutathione levels become depleted, then gamma-GT gene expression becomes upregulated, resulting in more gamma-GT. This is a panic reaction to bring as much glutathione as possible into the cell. So the first goal is to manage oxidative stress, and to support glutathione function.

When our glutathione levels become depleted, then gamma-GT gene expression becomes upregulated, resulting in more gamma-GT Click To Tweet

Secondly, gamma-GT is necessary to break down xenobiotics (industrial chemicals in the body) after they have been modified by glutathione. So another reason that gamma-GT can become upregulated is a high burden with toxic industrial chemicals from food, cosmetics, water, and/or air. A reduction of chemical burden and/or optimisation of detoxification pathways to deal with these toxins is necessary.

Third, gamma-GT will become upregulated when heavy metals are present in the blood. This is mostly iron in the form of serum ferritin. Aside from some genetic disorders, the most common reason for elevated serum ferritin is iron leakage from Red Blood Cells. This is caused by instable cell membranes in the red blood cells. The best way to stabilise these cell membranes is with Omega-3 fatty acids, mostly found in fish, and C15:0 and C17:0 saturated fatty acids, found in butter and the meat of cattle, goats and deer. To ameliorate the iron load and excrete the iron, curcumin will do the trick. It is a great chelator (excreter) of iron.

Aside from some genetic disorders, the most common reason for elevated serum ferritin is iron leakage from Red Blood Cells. This is caused by instable cell membranes in the red blood cells. The best way to stabilise these cell… Click To Tweet

Because gamma-GT is a general marker of inflammation and oxidative stress it is tightly associated to markers of inflammation (hs-CRP) and oxidative stress (anti-oxidant availability). When gamma-GT is found to be high it is not unusual to find elevated CRP and decreased anti-oxidant status.

 

Oxygen (Reactive Oxygen Species), Heat (Inflammation), and Fuel (High Calorie Diet) is a dangerous triad

 

Why does an elevated gamma-GT value matter for health and longevity?

We have learned in the first part of this article, that gamma-GT is a sensitive general marker of oxidative stress, inflammation, and toxic burden. That is why it should be no surprise that gamma-GT serves as a very good early warning sign for disease that are associated with oxidative stress and inflammation.

gamma-GT is a strong independent predictor of the following :

  • cardiovascular disease
  • cancer
  • all-cause mortality
  • type 2 diabetes
  • metabolic syndrome
  • hypertension

In fact it is a REALLY good early marker of cardiovascular disease. People with gGT levels over 28U/L were 28% more likely to die from cardiovascular disease, and people with levels over 56U/L had a 64% increased likelihood of dying from cardiovascular disease.

This does NOT mean that you are dying from heart disease when you have elevated gamma-GT. We always have the opportunity to make life choices that put us on the good side of statistics. We are not a lottery ticket.

We always have the opportunity to make life choices that put us on the good side of statistics. We are not a lottery ticket. Click To Tweet

 

What can we do to reduce gamma-GT?

First off, our goal is NOT to reduce gamma-GT. Our goal is improve the health of our anti-oxidant and detoxification system, of which gamma-GT is an indicator. When you drive in your car and the motor oil sign starts to light up, you do not want to turn off the light of the motor oil sign. You want to fill up the motor oil, so the sign does not light up anymore.

So lets take a look at how we can improve the health of our anti-oxidant and detoxification system.

 

Via negativa – Reducing toxic burden

There is no use in creating an elaborate anti-oxidant and detoxification strategy, when we keep exposing our bodies to reactive oxygen species and xenobiotics.

 

Strategies to reduce reactive oxygen and xenobiotic burden :

  1. Keep your foods as natural as possible. Pesticides are already showing up in the urine of most of us. And peeing them out is a good thing. It is worse when we are not peeing them out, but instead keep them inside of us. This happens when our detoxification pathways are not functioning optimally. Natural foods have higher amounts of vitamins and minerals than industrial foods, and these minerals and vitamins are the main support of our natural detoxification pathways. So thats a double-reason to eat natural foods. We are not only what we eat, but also what our food has eaten. So choose plants from natural and local fields, and choose animal foods from animals that have moved and have eaten grass instead of corn pellets, like they do in industrial meat factories. Also, artificial sweeteners like aspartame, which is being used in most light/diet products, are know to increase gamma-GT.
  2. Reduce xenobiotics in personal hygiene. Most cosmetics rely on chemicals for structure, smell, or color. Many of these chemicals will penetrate the skin. Our body can detoxify some of them and excrete them via the urine or stool, but many of them we cannot detoxify. In 2016 Johnson&Johnson lost a case, where a woman died of ovarian cancer and it was proven that the cause was in the use of Johnson&Johnson baby powder she was using. Not all cosmetic ingredients lead to cancer, but many of them will stress our detoxification pathways. Our body will try hard to detoxify, and that is one reason why gamma-GT can become elevated. The Environmental Working Group created the “SkinDeep Project”. It is a database that will give you accurate information on your personal cosmetics products, what their ingredients are, and the risks of each ingredient. Check them out here. It is best to take some time and evaluate the ingredients of your main personal hygiene products (toothpaste, soap, washing lotion, sunscreen, etc). Then toss out the toxic ones and stack up on non-toxic alternatives.
  3. Minimize Fructose Consumption. It has been found that fructose is very liver toxic.  In fact, fructose has a very similar behaviour to alcohol in the liver biochemistry. That is why both alcohol and fructose damage the liver in very similar ways. They both lead to the formation of reactive oxygen species in the liver. And because both fructose and alcohol get directly converted into fat. They both lead to fatty liver disease and elevated triglycerides. The liver seems to have a daily upper capacity of handling fructose and it is in the area of 20g/day. To get some perspective on that number : One can of coke has 38g of fructose, 100g of applesauce have 10g of fructose, and one small jar of babyhood has 15g of fructose. Damon Gameau of the movie “THAT SUGAR MOVIE” showed on himself that it is possible to induce non-alcoholic fatty liver disease within 18 days by eating 300g of fructose per day.

There is no use in creating an elaborate anti-oxidant and detoxification strategy, when we keep exposing our bodies to reactive oxygen species and xenobiotics. Click To Tweet

Pesticides are a real threat to our detoxification pathways

 

Via positiva – Improving detoxification and anti-oxidative pathways

Managing Glutathione Activity

When Glutathione becomes depleted, then gamma-GT becomes upregulated. Glutathione gets synthesised in our body and it is not really possible to take it in from the outside. But we can give our body the resources to increase Glutathione synthesis and activity. The main rate limiting substances in the production of Glutathione are the sulfur-containing amino acids Methionine and Cysteine. Cysteine is an amino acid mostly found in poultry, eggs, whey protein, oats, and barley. The supplementation of N-Acetyl-Cysteine is also a valuable tool in increasing glutathione synthesis, and thereby improved anti-oxidant activity.

Consuming sulfur-rich vegetables like brokkoli, cauliflower, cabbage, and Brussel sprouts will thereby also increase Glutathione synthesis.

 

Anti-Oxidant foods

To keep Glutathione levels high, Glutathione needs some sidekicks. If Glutathione is Batman, then the other anti-oxidants  are Robin. They are needed to protect Batman and also replenish his life-energy when he is wounded. Other important anti-oxidants are Vitamin E & Vitamin C. Vitamin C is high in Peppers, Kale, Brokkoli and Oranges. Vitamin E is found in Almonds, Spinach, Sweet Potato, Avocado, and Butternut Squash.

Supplementation with Alpha Lipoic Acid (ALA) in a dose of 600mg daily is valuable here. ALA is the master replenisher of all anti-oxidants. It is like the fire hydrant for the firemen.

 

Sleep 

Darkness triggers the production of melatonin. This is released during darkness and induces sleep, but is also secreted during quality sleep. Melatonin is the most powerful intrinsic anti-oxidant of the human body. This is Super-Robin. The Super-Sidekick of Batman Glutathione.

 

Improving Glucuronidation

The liver has 6 main pathways of excreting toxins. One of them is glucuronidation, which is important in lowering gamma-GT. Glucuronidation is responsible for detoxifying us from xenobiotics like polycyclic aromatic hydrocarbons from smoke, bisphenol A from plastic, heterocyclic amines from processed meat, and other industrial chemicals. It also helps to detoxify us from our own overloads like oestrogen, thyroid hormones, fat-soluble vitamins, and the bile acids. The best inducers of glucuronidation are brokkoli, Brussel sprouts, cauliflower, and green tea.

 

Reducing ß-Glucuronidase Activity

Some people just want to watch the world burn and mess up all your valuable work. Bad gut bacteria are one of them. “Bad” gut bacteria produce ß-Glucuronidase, an enzyme that REVERSES the Glucuronidation of the toxins and thereby RE-activates the toxins that have previously been inactivated by Glucuronidation. I do not know WHY they are so evil. But here is what we can do to take them out. We need to eat a lot of PRE-biotics, which will feed our “good” gut bacteria. When we strengthen our good bacteria, they have a chance of winning the epic war against the bad bacteria. The best PRE-biotics (good bacteria food) are fiber-rich vegetables like green leafy vegetables, parsley, and zucchini. The bad Bactria love sugar! It is usually the army that gets fed more regularly, that will win the war.

In the short-term Calcium-D-glucurate in a dose of 1000mg daily, as well as PRO-biotics can be used to lower ß-glucuronidase, but the PRE-biotic route will be the more effective one in the long run.

Some people just want to watch the world burn and mess up all your valuable work. Bad gut bacteria are one of them. Click To Tweet
When I think of our gut microbiome, this is what I imagine

 

Summary

You should have taken away that gamma-GT is NOT a measure of liver function. It is a systemic measure of detoxification function. All strategies I presented are general, valuable strategies effective for 90% of people with elevated gamma-GT. Try these strategies for 3 months and then re-evaluate gamma-GT. If gamma-GT is still elevated, then more serious toxicity from heavy metals, fungi, or bacteria/parasites has to be suspected.

The low down on lowering gamma-GT is :

  • rule out high ferritin as the cause of elevated gamma-GT. If high, go for strategies to lower ferritin.
  • reduce fructose intake. This is one of the biggest causes of elevated gamma-GT. Watch for “hidden” fructose in soft drinks, ketchup, crackers, steak sauce, cold cuts, peanut butter, flavoured yoghurt, salad dressing, and even some nut mixes contain high fructose corn syrup
  • evaluate your cosmetics and personal hygiene products for unnecessary industrial chemicals. Toss them and exchange for better options. Check ewg.org/skindeep for more information.
  • evaluate your food choices for possible pesticide residues in plants, heavy metal residues in fish, and anti-biotic residues in meat. Go for the good stuff and remember that we are what our food has eaten.
  • daily, eat two fists of sulfur-rich vegetables like brokkoli, cauliflower, cabbage and/or Brussel sprouts 
  • Supplement Alpha Lipoic Acid (ALA) at 600mg daily to replenish anti-oxidants, and N-Acetyl-Cystein (NAC) 400-1000mg daily to provide cysteine for glutathione production.

 

 

May the FLOW be with you!

 

 

 

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Gerrit Keferstein, MD

Gerrit Keferstein is a Medical Doctor specialised in Performance & Functional Medicine. He is most known for his work on the optimisation of recovery and adaptation in elite athletes.

Tags : inflammationdetoxgamma-GTglutamyltransferaseß-glucuronidaseglucuronidaseoxidative stressfructosedetoxification

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