Glutathione is an essential supplement for detoxification that also improves mitochondrial function.

What is Glutathione?

Glutathione is one of nature’s most essential compounds. It is a peptide (a very short protein) comprised of the amino acids glutamate, cysteine, and glycine. In biology, we refer to this unique pattern as a thiol, a chemical group that carries an extra electron so that it can be donated.

What Are Antioxidants and Free Radicals?

There are many antioxidant compounds, but none are as crucial as glutathione. An antioxidant is a compound with a negative charge that can donate electrons. A free radical is a compound that carries a positive charge. When a compound becomes positively charged, we call this oxidation. It is a little confusing because oxidation sounds like oxygen, but they have no relationship with each other. Opposites attract, and glutathione is perfect for scavenging free radicals, donating a free electron, and neutralizing the radical. The free radical is positively charged because it lacks an electron, and the glutathione molecules give their electrons to the free radicals, making the charge neutral.[1]

What About Toxins and Toxicants That Are Not Positively Charged?

Free radicals are not the only toxins or toxicants within our bodies. There are lipid peroxides, heavy metals, and metabolic waste. Glutathione uses a different mechanism for detoxifying these compounds called conjugation. Conjugation is when glutathione binds to toxins or toxicants at a specific site to be neutralized and excreted. The antioxidant and conjugation methods use glutathione within the body, and the liver must produce more.[2] [3]

What Happens to the Glutathione That is Used Up?

When glutathione is used as an antioxidant, it gives up an electron or is oxidized. It then becomes a positively charged ion. Two glutathione ions find each other and bind together, forming a glutathione disulfide compound (GSSG). If used in a conjugation (binding) reaction, the molecule is usually excreted from the body and lost. In contrast, GSSG can be recycled into reduced (gaining an electron) glutathione, which can be done with other antioxidants, including vitamin C.[4] [5]

How Does the Body Make Glutathione, and What Can Be Taken to Increase It?

When your body loses enough glutathione, it must produce more to prevent cellular damage. The liver produces gamma-glutamylcysteine synthetase (connecting the glutamate and cysteine amino acids) and glutathione synthetase (finalizing the chain with glycine) enzymes. Your body uses amino acids from the food that you ingest. Glycine and glutamate are abundant within our body and food, but cysteine is rarer and is one of the determining factors in how much glutathione our body can make.[6] [7]

What Can You Do to Make Your Body Produce More Glutathione?

N-Acetylcysteine

N-acetylcysteine (NAC) is the supplement form of the amino acid cysteine, which is one of the rate-limiting factors in synthesizing glutathione within the liver. When you take N-acetylcysteine, the body makes glutathione with the supplemented semi-essential amino acid cysteine. NAC is a double-edged sword because excess cysteine is toxic due to its highly reactive thiol group and can have the opposite effect of what you are trying to achieve. We recommend Thorne (https://amzn.to/3TjtcDk) NAC if you want to try it.[8]

Pros:

• It does an excellent job of raising glutathione levels within the body on a limited scale.
• It dissolves systemic opportunistic biofilms.

Cons:

• It has increased oxidative stress in doses over 1,200 milligrams.[9]
• It can dissolve systemic probiotic biofilms.
• If you are dealing with a heavy toxic load, it may not be enough.

Standard Glutathione Supplements

Some companies sell glutathione powders, capsules, or tablets. The problem with taking standard glutathione supplements is that it is broken down into glutamate, cysteine, and glycine by enzymes within the digestive system. However, it will increase blood glutathione levels to some degree. The body will use the supplemented cysteine to make glutathione. However, it is inefficient to raise glutathione, so we at Fix Your Gut do not recommend taking standard glutathione supplements.[10]

Pros:

• It is sometimes cheaper than some of the other options.

Cons:

• It does not raise glutathione in the body effectively.

Intravenous Glutathione

Intravenous (IV) glutathione is the most effective way to increase glutathione levels in the body. It bypasses the digestive system, so it is 100% absorbed. If I were in the hospital and my liver was failing, I would do everything to get myself hooked up to an IV bag containing a glutathione solution.

Pros:

• It is the most effective way to raise glutathione within the body.

Cons:

• It is invasive.
• It requires special equipment and should be done by a healthcare professional.
• It is the most expensive method.
• It is not very practical.

Liposomal Glutathione

Liposomal technology is an innovation from the pharmaceutical world that allows compounds to enter human cells taken orally, yet bypasses the digestive system. Engineers have found a way to wrap the compound in a liposome or a spherical bilayer sheet.[11]

Pros:

• It is the most practical way to raise glutathione levels within the body.
• It can boost glutathione levels higher than natural levels for extra support.
• Liposomal ingestion also improves cell membrane health.

Cons:

• Liposomal glutathione is challenging to produce.
• Production is unregulated, and there are a lot of counterfeits on the market.
• It is hard for the consumer to find a quality product.

Producing liposomal glutathione is expensive, and it is difficult to achieve the specific phase state to allow the fats to surround the precious glutathione molecule. Let it get too hot or cold, and you have some expensive sludge. Use the wrong pH, and the liposomes break apart. Fail to stabilize the electric charge, and the glutathione leaks out. Some manufacturers of liposomal glutathione do not have the scientific background to know what they are doing. Others know they are ripping off the public and think they can escape it.

We used to recommend a brand of glutathione that we thought would help people, but the company that sold it changed its formula. We contacted them for comment and followed up with them several times. They keep responding, “I have forwarded your email to our product team and will let you know once they send me a response. Thanks!” After a few months of this, we decided to do our independent testing of this product, and it turned out to be another inferior glutathione supplement. We had to look for a new product to recommend and ran across many other ineffective formulations like it. Some of the common problems that we see in just about every glutathione supplement are:

Phosphatidylcholine

There is a loophole in the marketplace. You can advertise that your product contains phosphatidylcholine as long as it contains 30% phosphatidylcholine. Most manufacturers substitute sunflower lecithin instead. The ingredients look right on paper, but lecithin will not form liposomes. Almost every product we tested used lecithin rather than phosphatidylcholine, which is the wrong phospholipid for the job. Only pure phosphatidylcholine will work.

Storage

Many companies store their products in warehouses without climate control. They make large batches, some sitting on the shelf for a year or more. Liposomes do not have a very long shelf life, and excessive exposure to heat will destroy them.

Uncontrolled Phase State

Manufacturing Liposomes is a Mathematical Process:[12]

Ntot = [4π(d/2)² + 4π[(d/2) – h]² / a

Where 4π(d/2)²

Companies Mess This Formula Up Because They:

1. Use supporting lipids that are too short.
2. Are not sufficiently hydrating the liposomes.
3. Fail to use a sufficient amount of phospholipids.

We have even seen products that look as if they were blended instead of using sonic or high-pressure techniques.

“Pre-liposomal”

If you see a “liposomal” product that is not liquid, it is not liposomal. I have asked some companies selling powdered or encapsulated “liposomal” products about their rationale, and they tell me that their product is “pre-liposomal” and say that once you drink the solution, it will form the liposomes in your stomach. If you could read and understand half of the information above, you would know it is impossible. Do not waste your money on this. It is the least effective way to increase glutathione in any of the mentioned areas.

What Glutathione Does Fix Your Gut Recommend?

Designs For Health liposomal glutathione

Dosage Recommendation: Follow supplement dosage recommendations.

When and How to Take Glutathione

If you are stressed out, ill, were on an airplane, or spent time in a toxic environment, your body may not produce enough glutathione to meet your needs, and you might want to supplement with it when needed. If you are chronically ill, live in a toxic environment, or are taking numerous medications, you might benefit from daily supplementation with glutathione. For anyone else, supplementing with glutathione daily will reduce endogenously produced glutathione.

Author’s Note: I have two caveats for glutathione supplementation. First, read the work of Dr. Andrew Hall Cutler. You will find anecdotal evidence of people with mercury amalgams, or otherwise mercury-burdened, having issues with glutathione supplementation and NAC use. I cannot recommend both for them (I greatly caution the use of IV glutathione, especially). Second, individuals suffering from Th1 dominance[13] (https://selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/) might not feel better when supplementing with glutathione.[14]

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422610/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549305/

[3] https://www.ncbi.nlm.nih.gov/pubmed/2251674

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696075/

[5] https://www.ncbi.nlm.nih.gov/pubmed/11687303

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704241/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549305/

[8] https://openheart.bmj.com/content/4/2/e000599

[9] https://www.ncbi.nlm.nih.gov/pubmed/22134636

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536296/

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599573/

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599573/

[13] https://selfhacked.com/blog/supplements-foods-exercise-right-type-th1-vs-th2-dominance/

[14] Lee, Rebecca, Cutler, Andrew. The Mercury Detoxification Manual: A Guide to Mercury Chelation, Perfect Paperback, 2019.