N-acetylcysteine and Glycine for Endometriosis: Pain Relief, Fertility Outcomes, and Oxidative Stress Reduction
NAC and Glycine for Endometriosis: Powerful Antioxidants for Pain, Fertility, and Healing
As a nutritional therapist, I’m a food-first kind of gal! Our dynamic bodies need a dynamic set of minerals, vitamins, amino acids, fatty acids, fibers, sugars, antioxidants, and more to thrive. After dietary strategies are employed as a foundation, though, there are some great supplemental considerations for those with endometriosis, since many of us have an incredibly high amount of free radicals that need “subduing.”
Too many free radicals create stress and damage to surrounding tissues, which is why it’s referred to as oxidative stress (OS). If you have endometriosis, chances are high you too have high levels of OS, both surrounding endometriotic cellsas well as throughout the body.
NAC increased pregnancy success rates while simultaneously reducing period pain, endo pain, pain with sex, chronic pain, size of endometriomas, and CA-125 levels (which is indicative of the severity of endo). Wow!
OS is, well, gnarly. And the gnarly environment forces endometriotic cells to adapt in order to survive the horrendous conditions, transforming into worse forms of disease. The chronic OS additionally results in tissue damage, culminating in scar tissue, adhesions, and worsening endometriosis symptoms. This is why treating oxidative stress is an absolute must when dealing with endometriosis [1,2].
One powerful punch against OS comes from the side-kick effects of N-acetylcysteine (NAC) and glycine. Today we’ll dive into how these nutrients support the body alone, and how they may be even more helpful when they work together.
N-acetylcysteine Endometriosis Research
N-acetylcysteine (NAC) is an antioxidant derived from the amino acid cysteine. Cysteine is necessary to manufacture glutathione, an incredible antioxidant your body makes. Without cysteine, you won’t be able to make enough glutathione to meet your needs. This may be why supplementation with NAC has been shown to increase glutathione levels and reduce oxidative stress in various clinical trials. Reducing oxidative stress and increasing glutathione additionally supports egg health, which is why NAC can be so helpful in infertility cases. All part of the reason why research shows supplementing with NAC is beneficial to endometriosis patients [2].
In vitro, NAC has been found to reduce endometriotic cell growth, movement, and the expression of inflammation-related genes. It even helps limit the lifespan of these abnormal cells, which is a form of controlled cell death (very useful in this disease context). In animal models, NAC treatment has demonstrated promising results in reducing the size of induced endometriomas — suggesting that NAC contributes to size reduction of ovarian cysts [3,4,5].
Pelvic Pain and Endometriosis Related Pain
Even more, NAC has been shown to work wonders on actual humans with endo — not just Petri dishes or rats.
The first time I heard about the potent effects of NAC and endometriosis was at the beginning of my real healing journey (i.e. when I stopped spinning my wheels with juice cleanses and intense yoga), many years ago. I read a 2013 observational cohort study out of Italy detailing NAC as an alternative treatment option for endometriosis. It was the first study that made me realize endometriosis could regress, rather than just progress.
NAC not only improved fertility outcomes, as I describe below, it also significantly reduced chronic pelvic pain, pelvic pain during sex, and period pain. It even improved markers like CA-125 levels (associated with disease severity) and supported natural pregnancy rates. For women living with chronic pain every month, this was groundbreaking.
Fertility Outcomes and NAC Treatment
The Italian researchers recruited women with ovarian endometriomas who also were dealing with infertility. All of these women were scheduled for surgical removal of the endometriomas, so in the meantime, half were given NAC, and half a placebo.
Well, after three months of treatment, the average size of the endometriomas within the NAC group had shrunk slightly, while the placebo group’s had increased significantly. Moreover, one-third of the women on NAC canceled their surgery due to either cyst decrease or disappearance, pain reduction, or pregnancy. The NAC group had eight pregnancies versus six in the placebo group. Finally, the researchers concluded that this type of therapy may actually be more effective than hormonal therapy, without the negative side effects [6].
As an additional consideration, the participants had this success even without an accompanying shift in diet and lifestyle (sleep, stress, movement, nutrients, anyone?).
A more recent clinical trial also demonstrated NAC’s potential benefits:
Researchers recruited a group of 120 patients with ovarian endometriomas. They tracked the level of chronic pelvic pain, painful sex, and period pain, as well as the size of endometriomas and CA-125 levels. After three months of NAC treatment, the intensity of endometriosis related pain significantly decreased, while there was a simultaneous decrease in NSAID use. The size of ovarian endometriomas significantly reduced, CA125 levels dropped, and 39 of the 52 women trying for pregnancy successfully conceived within six months of NAC therapy [7].
Pretty cool, huh?
Glycine Supplementation for Endometriosis Symptoms
Glycine is an amino acid vital for fighting inflammation, protecting against LPS, hypoxia, free-radical damage, and inflammatory cytokines. It also has anti-inflammatory properties and supports immune system modulation. So yes, it’s incredibly important on numerous fronts for those of us with endometriosis [8].
Like NAC, glycine is necessary for the body to make glutathione. If you’re deficient, you won’t be making much of this potent antioxidant.
While the human body alone can make up to 3 g glycine per day, a healthy 150-pound person needs around 10 g/day (although you need more when faced with an inflammatory disease). This means that if you have endometriosis, you must consume abundant amounts in your diet or via supplementation, or you won’t have enough to meet your needs [9].
And meeting your needs is important. While there are no direct clinical trials on endometriosis and glycine yet, we know from studies of glycine on other inflammatory diseases that increasing glycine consumption can significantly decrease inflammatory markers [10,11].
GlyNAC: A New Supplement Combination to Consider
When put together, glycine and NAC (GlyNAC) pack a powerful punch. I read about the two successfully used together in a recent systematic review on aging adults and was — first of all — blown away by how similar aging adults sounded to the endometriosis population.
These older adults had glutathione deficiency, oxidative stress, mitochondrial damage, chronic inflammation, endothelial dysfunction, impaired physical function, and insulin resistance. Sound familiar? All of these issues are also previously reported in women with endometriosis.
In the case of these older adults, GlyNAC supplementation either improved or totally corrected these problems [12].
Oxidative stress reduced by 73%: GlyNAC lowered plasma 8-OHdG by 73% after 16 weeks. Women with endometriosis have higher 8-OHdG (a measure of oxidative stress) concentrations in the follicular fluid and peritoneal cavity. Additionally, women with severe PMS had significantly higher plasma levels of 8-OHdG before menstruation than those without PMS. [13,14,15]
Insulin resistance reduced to same levels as controls: After 16 weeks, GlyNAC supplementation totally reversed the insulin resistance associated with inflammation and oxidative stress within the older adults (to the same level as controls, reducing HOMA-IR levels by 64% and fasting insulin levels by 65%). Endometriosis, too, is associated with inflammatory-based insulin resistance (women with endo had 2x more insulin secretion, signaling insulin resistance).[16]
IL-6 is higher in the peritoneal fluid and serum of endometriosis patients. GlyNAC supplementation lowered IL-6 by 78% after 16 weeks. [19,20]
TNF-α (tumor necrosis factor-alpha) may have a contributive role in the genesis and establishment of endometriosis. Serum levels of TNF-a are elevated in endometriosis patients, particularly in the early stages of the disease, and may serve as a diagnostic biomarker. After 16 weeks, GlyNAC supplementation reduced TNFα by 54%. [21,22]
Cell adhesion molecules reduced up to 57%: Higher serum levels of cell surface adhesion molecules ICAM-1 and VCAM-1 are associated with endometriosis. 16 weeks of GlyNAC supplementation substantially improved these markers (sICAM1 57% lower; sVCAM1 44% lower). [17,18
Clearly, GlyNAC demonstrates potential benefits not only for aging but possibly also for those struggling with endometriosis related pain, infertility, and inflammation.
Supplementing With NAC and Glycine
First, check with your doc before changing your diet, lifestyle, or supplement routine (#disclaimer). Now, if you’re interested in supplementing, here are the dosing strategies used in clinical trials:
NAC treatment in endometriosis-specific studies: 600 mg taken 3 times/day, for 3 consecutive days of the week, for three months.
GlyNAC studies: 100 mg/kg body weight per day each of glycine and NAC, with no breaks, for three months.
If you do choose to supplement, make sure you only use high-quality brands that are third-party tested for purity (you don’t want heavy metals as a side dish). Brands I like include Integrative Therapeutics, Thorne, Biotics Research, and Pure Encapsulations. Pure Encapsulations also has a product called NAC + Glycine, offering 1,800 mg of each per scoop.
If you’d like 15% off quality supplements you can trust, click here to create a FREE account with Fullscript, a company I fully trust for high-quality supplementation. All of the following supplements listed are available in their catalog, and items will be shipped directly to you and everything is 15% off.
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