Article at a Glance
- Glutathione is an “endogenous antioxidant,” meaning it is made by our bodies, but stress, toxins and periods of illness can all deplete glutathione levels.
- Oral glutathione supplements are poorly absorbed, however, N-acetyl-cysteine, or NAC, can help restore glutathione after a life event has depleted glutathione. NAC is only effective at restoring depleted glutathione, not at building or maintaining normal levels.
- Because glutathione supplements aren’t well absorbed, many people turn to IV therapy. Glutathione IV therapy can cause bad reactions, sometimes called Herxheimer reactions, in people with chronic illness, genetic polymorphisms that alter sulfur metabolism, or when doses are just too high.
- If you’re considering glutathione IVs, start out at a small dose of below 500 mg, and know the status of your CBS genes before starting the protocol.
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 my notes, I wrote “glutathione, turns off inflammation,” right next to my notes on Omega 3 vs. Omega 6 ratios.
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?
- What is glutathione?
- Can glutathione supplements be absorbed?
- Choosing a glutathione supplement
- Glutathione supplement comparison
- IV glutathione – Mixed reactions
- My experience with glutathione IV therapy
- Months later – experiment #2 – Lower glutathione dosage and Vitamin C IV
- Are certain genotypes sensitive to glutathione?
- Alcohol and Tylenol deplete glutathione – N-acetyl-cysteine rebuilds
- The bottom line
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. Normally glutathione is recycled in the body — except when the toxic load becomes too great…
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. (R) 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.
See also: Why I removed my dental amalgams for a discussion on mercury, genetics, and toxicity.
Can glutathione supplements be absorbed?
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 a type of fat. (R) As a general rule, I am not a big fan of liposomal supplements because the phospholipids used to encase the desired nutrient can have negative health consequences independent of the focus of the supplement. I’ve written about this 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. So, although phospholipid encased glutathione supplements increase absorption of glutathione, they may also be bad for your heart at the same time.
Choosing a glutathione supplement
In light of the poor bioavailability of glutathione supplements, the trick is navigating the additives supplement manufacturers add to products to make their formulas more readily absorbable. In almost every case, the oral glutathione supplements available to consumers use some form of lecithin, either sunflower or soy derived.
Glutathione supplement comparison
|Nordic Naturals Omega Curcumin||Fish||150 mg L-glutathione||60/ct|
|Seeking Health Optimal Liposomal Glutathione||Sunflower||500 mg L-glutathione||30/ct|
|Pure Encapsulations Liposomal Glutathione||Soy/extra-virgin olive oil||250 mg Setria glutathione||60/ct|
|ReadiSorb Liposomal Glutathione||Soy||422.7 mg reduced glutathione||4 fl oz|
Optimal Liposomal Glutathione by Seeking Health (Not recommended)
For example, Optimal Liposomal Glutathione by Seeking Health contains 400mg of phosphatidylcholine in addition to 500mg of glutathione. That is a big dose of sunflower-derived phospholipids. Some in the functional health community advocate for phosphatidylcholine supplementation, especially in the presence of mutations in the PEMT genes, but I am skeptical.
As I mention above, there is good data suggesting that phosphatidylcholine is metabolized in the gut into TMAO. The only way I would take a supplement so heavy in phospholipids on a regular basis is if I knew my serum TMAO levels, and I don’t. We know the body’s ability to clear TMAO varies by genotype, but I also don’t know of a single person who is regularly testing for TMAO. Furthermore, one of the primary reasons for taking glutathione is to quell inflammation, but the sunflower derived phosphatidylcholine blend used by Seeking Health is loaded with inflammatory omega-6 fats, and we know that one of the drivers of inflammation is more omega 6 fatty acids than omega 3 fatty acids. (R) In summary, I like the bioavailability of the glutathione, I just don’t like all the other gunk you have to ingest to get it in your system.
Omega Curcumin with Glutathione by Nordic Naturals (Recommended)
I added Omega Curcumin by Nordic Naturals to my Omega 3 Fish Oil guide as well, and even gave it an A- rating, which will likely confuse some people. After all, this is a post about glutathione, not curcumin. However, in addition to 400mg of curcumin, the Omega Curcumin product contains 150mg of glutathione for every two capsules, and the best part is that the glutathione is encased in a high quality, omega-3 fish oil rather than a sunflower lecithin. Nordic Naturals adds N-acetyl-cysteine (NAC) to the formula to complete, what is in my view, a very high quality product.
I will get into glutathione dosing later in this post, but although some people will view it as too small, I think 150mg of glutathione is a nice starter dosage for people getting started with glutathione. It’s unlikely most people will have major detox reactions at 150mg.
IV glutathione – Mixed reactions
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. (R) (R)
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.
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. This is why I think the Omega Curcumin product by Nordic Naturals is such a good option.
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 (recently 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. I felt a cessation of my normal workplace concerns, and felt generally at ease, but not as though I’d taken some type of sedative — just less concerned than usual, perhaps more centered. I would compare the feeling with how I’ve felt after finishing a month-long liver detox.
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.
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
It’s now been 4 days since my shot, and I’ve napped every day since taking the IV. Each day I wake up feeling better and more energetic, but still feel lower energy than usual in the afternoons. Workouts seem to snap me back to my normal energy levels, which are usually high. Even fours 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.
I’m finishing up this portion of the blog one week after taking the glutathione IV. As I write this, I feel good, back to my normal self.
However, I have had more fatigue this week than I normally would. I haven’t felt sick, just more prone to an afternoon nap than most days. Toward the end of the week, I traveled to the east coast and have some jet lag. I also arrived in a state where everything is in bloom and my allergies are going a bit haywire, so both of those changes could be a factor.
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.
Months later – experiment #2 – Lower glutathione dosage and Vitamin C IV
Again, after researching SOD A16V mutations, I was making a conscious effort to include glutathione in my supplement regimen. However, after having labs done and finding that my serum glutathione levels were normal, I don’t go for glutathione IVs as often as I used to. Instead, if I’ve had a big night out, I will supplement with N-acteyl-cysteine, which is a glutathione precursor.
For more, see: Supplements to use for avoiding a hangover
Are certain genotypes sensitive to glutathione?
The primary glutathione producing gene is GSTP1.
Variants of this gene (rs1695 G and rs1138272 T), which result in greater glutathione activity, have been associated with lower mercury levels.
However, it’s not the GSTP1 gene that is our focus at present, but instead genes related to sulfur metabolism.
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 genes.
Lower levels of CBS – not 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. (R) This is the first step in a metabolic process called the transsulfuration pathway. Mutations in the CBS genes which lower levels of the enzyme, have been linked to conditions like hyperhomocysteinemia and homocystinuria. (R) 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 promise. (R)
Up-regulated CBS potentially sensitive to glutathione – not conclusive
However, some mutations can go in the opposite direction, and cause an “up-regulation” of sulfur activity. These are the mutations that can supposedly 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
The two most common substances that deplete glutathione are alcohol and acetaminophen. (R) (R) 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. (R) (R) (R) (R)
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.
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.
Feel free to leave your experiences in the comments.