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My Experience With Glutathione Supplements: Benefits vs. Side Effects

glutathione dosage

A couple years ago now, I attended the Institute for Functional Medicine annual conference in San Diego, close to where I used to live in La Jolla. One of the things that struck me about the conference was how often glutathione was mentioned, both in the lectures, as well as among exhibitors. 

In fact, there was an IV station right in the exhibitor hall that offered IV therapy, glutathione being one option.

Glutathione is all the rage in the supplement world, but what is it? Does flooding the system with IV glutathione alleviate inflammation?

Let’s dig in, shall we?

What is glutathione?

Glutathione has been called the “mother of all antioxidants,” and is lauded for its detoxification abilities.

According to Dr. Mark Hyman:

Glutathione is a very simple molecule that is produced naturally all the time in your body. It is a combination of three simple building blocks of protein or amino acids — cysteine, glycine and glutamine. The secret of its power is the sulfur (SH) chemical groups it contains. Sulfur is a sticky, smelly molecule. It acts like fly paper and all the bad things in the body stick onto it, including free radicals and toxins like mercury and other heavy metals.

Glutathione is an endogenous antioxidant, which means our bodies produce it naturally, but like many other processes, our ability to utilize glutathione is impacted by environment.1 Stress, toxicity, NSAID use, or illness can lower our glutathione levels, and ultimately, degrade our health.

One of the reasons I am interested in glutathione is because of research I’ve done on the SOD2 A16V gene, and how certain variants of the gene carry lower levels of superoxide dismutase (SOD2), another endogenous antioxidant responsible for clearing free radicals. If levels of SOD2 are reduced, antioxidant activity from other sources becomes that much more important.

Can glutathione supplements be absorbed?

In a word, no, which is why the IV glutathione industry has exploded. Delivering glutathione via IV gets the product into your blood stream where it can do its job.

Studies that looked at oral glutathione’s effect on oxidative stress have shown no benefits.2

Oral glutathione supplementation has traditionally been viewed as less effective because it was not able to be absorbed as readily into the blood, however, recent studies demonstrate that human subjects can absorb, and benefit from, glutathione in what is known as liposomal form, meaning it’s encased in fat.3

As a general rule, I am not a big fan of liposomal supplements because the phospholipids used to encase nutrients can have negative health consequences in some people with less than healthy microbiomes. I’ve written about this previously in the context of curcumin supplements.

Curcumin is often paired with fats, like phosphatidylcholine, in order to improve bioavailability. However, what most people don’t know is that phosphatidylcholine, lecithins, and other phospholipids increase levels of a gut metabolite known as TMAO, which has been linked to heart disease.4 They are also high in pro-inflammatory omega-6 fats.

So, although phospholipid encased glutathione supplements increase absorption of glutathione, they may also be bad for your heart at the same time. 

IV glutathione

It’s no coincidence that glutathione IVs are often administered to people who are suffering from serious illness, such as lyme, cancer and HIV patients.

In fact, among other illnesses, such as cancer, cardiovascular disease, and even cystic fibrosis, glutathione deficiency is linked to poor survival rates in HIV patients, showing the link between healthy glutathione levels and immune function.56

When I began researching glutathione online, I came across a number of Lyme disease forums discussing different experiences with IV therapy, but not many from healthy people who have experimented with glutathione as a means to bolster antioxidant activity. 

Herxheimer reaction and glutathione IV

For example, this Lyme disease forum thread discusses glutathione induced “Herx” after taking an IV. Herx is short for what is known as a Herxheimer reaction, the process of bacteria dying off after treating Lyme disease with antibiotics. Many Lyme disease patients describe Herx like symptoms after taking glutathione intravenously. I’ve included a snippet from one of the threads below:

Not the orals, that I’ve noticed, but the IVs cause me to herx (at least I believe it’s a herx), usually lasts a day or two and I feel extremely tired and usually very emotional. Then I usually feel much better by the 2nd or 3rd day. My integrative doctor told me that these could definitely cause a herx because it’s boosting the immune system and removing toxins.

Since the internet is lacking information on this topic, and since glutathione therapy is likely to continue growing in popularity, I am sharing my experience with a 1,200mg IV dose I took a couple days ago. Note: 1,200 mg is a very high glutathione dosage — I would recommend starting much smaller, with a 200mg dose to see how your body reacts. 

My experience with glutathione IV therapy

When I take a B vitamin shot, I feel an energy surge, sometimes for days after, but glutathione produced the opposite result for me. Again, I do not have Lyme disease (tested negative in a comprehensive blood panel), but I did feel similar symptoms to the Herx reaction described in the Lyme forums at the 1,200mg mega glutathione dose.

The doctor who administered the IV told me I could expect to feel euphoric after taking glutathione, but that wasn’t my experience, except for maybe 10 minutes of mild euphoria toward the end of the IV. Instead, I felt very calm.

Two hours after the IV

About two hours after the IV, I felt fatigue, so much so that I took a long afternoon nap. When I woke up, I still felt groggy and just generally “off.” I took my dog for a walk and although the walk wasn’t strenuous, I didn’t feel like my normal energetic self. Slightly light headed. When I came home, I still felt withdrawn, with low energy, and the best I can do to describe my mental state would be to say I was “out of it,” but not in an extreme way — it was subtle. A low-level malaise had set in.

It is very possible I had a Herx like reaction at the 1,200mg mega dose.

The day after

The next day, I still felt off. I’d say it was like I was in the mood for a form of hibernation, but not a happy one, an unsettled hibernation, like as if I had been separated from my bear wife and was kind of down about it. Add to that feeling unusually emotional, which is consistent with the Herx reactions described on the Lyme forums. I felt sad, down, and still tired. I took another nap in the afternoon, for a good hour and a half. Did a cardio workout to snap out of it, and that seemed to help, but it didn’t bring me all the way back.

Two days later

Woke up feeling clear, feeling great. Much improved and alert, the lingering melancholy/hibernation feeling largely gone; however, toward the end of the second day I still had some unusual fatigue. 

Three days after and beyond

Four days out from the IV, I’d napped every day. Each day I woke up feeling better and more energetic, but still felt lower energy than usual in the afternoons. Workouts seemed to snap me back to my normal energy levels, which are usually high. Even four days after, I still felt the lingering effects of being slightly more down than I’m used to, but to be fair, the feeling is subtle, not overwhelming.

After one week, I was back to normal.

In sum, as a healthy person taking glutathione, I did not experience euphoria at the 1200mg glutathione dosage; instead, I felt tired and emotional immediately after taking the IV. That quickly faded, and left in its wake a low-level fatigue that decreased in intensity each day until it went away completely.

Was this a Herx?

Was this simply too much glutathione?

Tough to say, but I would bet on the mega-dose mobilizing toxins from my system faster than I could clear them which caused a Herx like reaction.

What happened at lower doses?

Lower IV glutathione dose and Vitamin C IV

After having labs done and finding that my serum glutathione levels were normal, I don’t go for glutathione IVs very often. However, I was curious to try another glutathione IV, this time at a lower dose.

I found that a glutathione push of 500mg plus Vitamin C gave me the euphoric feeling described by some when they get a glutathione surge. None of the moodiness or lethargy.

Concerns about regular glutathione IVs

The body makes its own glutathione. The same is true for testosterone, but when men receive testosterone replacement therapy, their bodies stop making their own testosterone.7 That’s my concern with glutathione.

If we continually flood the body with IV glutathione will the body stop making its own?

Genetics of glutathione production

One of the primary glutathione producing genes is GSTP1.

Some variants of this gene (rs1695 G and rs1138272 T) result in greater glutathione activity, and have been associated with lower mercury levels. For a deeper dive into mercury metabolism, see my post on removing dental amalgams.

Glutathione Side Effects

As I mentioned above, some people will have a Herx like reaction when taking large doses of glutathione via IV. Whether this is indeed a Herx or simply a bad reaction is up for debate.

However, there are certain genetic polymorphisms that could also have a tough time with glutathione and supplements like it.

Let’s focus again on the quote from Dr. Mark Hyman at the beginning of this post: “the secret of glutathione’s power is in the sulfur chemical groups it contains.”

When you take glutathione, you also take the sulfur compounds it binds to, and emerging research is showing us that people metabolize sulfur differently based on their genetic predispositions.

Lower levels of CBS – less likely sensitive to glutathione

The bottom line is that an enzyme called cystathionine beta synthase (CBS) is responsible for breaking down homocysteine (an amino acid linked to heart disease) and converting it to cystathionine.8

This is the first step in a metabolic process called the transsulfuration pathway. “Mutations” in the CBS genes which result in lower levels of the enzyme, have been linked to conditions like hyperhomocysteinemia and homocystinuria.9

CBS deficiency causes poor metabolism of sulfur groups, causing them to “pool,” and homocysteine levels to rise. In these situations, supplementing with N-acetyl-cysteine (a precursor to glutathione) has shown some promise.10

See also: 7 genes linked to high homocysteine

Up-regulated CBS  – potentially sensitive to glutathione

However, some mutations can go in the opposite direction, and cause an “up-regulation” of sulfur metabolism activity.

These are the mutations that may cause sensitivity to sulfur donor supplements like glutathione. The research seems to show that the most critical gene determining this type of sulfur sensitivity is CBS C699T, with A as the risk allele.

What happens here is the opposite of the low CBS situation where homocysteine is converted too slowly to cystathionine, instead, homocysteine is converted too quickly. The resulting issues can be excess ammonia and sulfites, both of which are toxic to the body and can create symptoms such as anxiety, lethargy, high cortisol, and ADHD.

Alcohol and Tylenol deplete glutathione – N-acetyl-cysteine rebuilds

In an ideal world, those supplementing with glutathione would first confirm their levels were low with a blood test.

However, even if glutathione depletion were confirmed, the best course might not be to take a glutathione supplement.

The two most common substances that deplete glutathione are alcohol and acetaminophen.1112 So, you’ve had a night our drinking, or maybe a few nights, is there a supplement you can take to restore glutathione levels?

The beginning of the post describes glutathione as an “endogenous antioxidant,” which means it’s made by our bodies without supplements. However, there are available supplements like N-acetyl-cysteine, which are direct precursors to glutathione, and can he helpful in restoring glutathione levels after they’ve been depleted.1314 

This study in the European Journal of Clinical Pharmacology had this to say about N-acetyl-cysteine:

N-acetyl-cysteine had no effect on plasma glutathione in the absence of increased stress on the glutathione pools. However, NAC supports glutathione synthesis when the demand for glutathione is increased, as during the metabolism of paracetamol.

The bottom line

Whether you have a good experience with glutathione supplements depends on a number of factors, such as the state of your overall health, dosage, whether you have a build of toxins in your system, and the state of your genetics.

It is possible to “Herx” from a large dose of glutathione, but if you have a bad reaction, it could also be that you don’t tolerate sulfur donor supplements well.

The biggest thing I learned is to take it slow. I don’t recommend jumping right in with a 1,20mg IV dosage.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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