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 endo, chances are high you too have high levels of OS, both surrounding endometriosis lesions as well as throughout the body.

OS is, well, gnarly. And the gnarly environment forces endometriosis to adapt in order to survive the now horrendous conditions, genetically and epigenetically transforming endo into worse forms of disease. The chronic OS additionally results in tissue damage, culminating in scar tissue and adhesions. This is why treating OS is an absolute MUST when dealing with endo. [1,2]

One powerful punch against OS comes from the side-kick effects of 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.

NAC Supplementation for Endometriosis Treatment

NAC stands for N-acetyl cysteine, 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 contexts. 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 sufferers. [2]

In vitro, NAC has been found to reduce endometriosis by targeting abnormal cell growth, cell movement, and the expression of certain inflammation-related genes. Additionally, helps limit the lifespan of endometriotic cells (which is great). In animal models, NAC treatment shows promising results in reducing the size of induced endometriomas. Looks promising. [3,4,5]

Even more, NAC has been shown to work wonders on actual humans with endo (i.e. not 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 study out of Italy detailing NAC as an alternative treatment option for endo, and it was the first study I came across that had me realize endometriosis could shrink! Before that, I thought it was only progressive; little did I know it was possible for endo to regress.

The study goes like this: Researchers recruit women with ovarian endometriomas who also are dealing with infertility. All of these women are scheduled for surgical removal of the endometriomas, so in the meantime, half are given NAC, and half are given a placebo. Well, after 3 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, 1/3 of the women on NAC canceled their surgery due to either a cyst decrease or disappearance, pain reduction, or pregnancy. The NAC group had 8 pregnancies versus 6 in the placebo group. Finally, the researchers conclude this type of therapy is actually more effective than hormonal treatments, without 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?).

This year another study that came out on NAC analyzing its effect on endometriosis-related pain and lesion size with a similar success story:

Researchers recruited a group of 120 patients with ovarian endometriomas. They track the level of chronic pelvic pain, period pain, and painful sex, as well as the size of endometriomas and CA125 levels (which is an excellent insight into the stage of endo, with higher levels of CA125 associated with worse stages of endometriosis). After 3 months of NAC treatment, the intensity of endo pain (chronic, with sex, or with periods) significantly improved, while there was a simultaneous decrease in the use of NSAIDs. The size of endometriomas significantly reduced, and the serum levels of Ca125 significantly decreased. Even more, 39 of the 52 women trying for pregnancy successfully conceived within 6 months of starting the 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, and is an immunomodulator. So yes, it’s incredibly important on numerous fronts for those of us with endometriosis. [8]

Like, NAC, glycine is also necessary for the body to make glutathione. If you’re deficient, you won’t be making much of this superhero of the antioxidant world.

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 inflammation). This means that if you have an inflammatory condition like endometriosis, you must make sure you’re directly consuming abundant amounts in your diet, or you won’t have enough to meet your needs.[9]

And meeting your needs is important. While there are no studies on endometriosis and glycine to date, we know from studies of glycine on other diseases of chronic inflammation and immune dysfunction that increasing glycine consumption can significantly decrease inflammatory markers. [10,11]

GlyNAC: An Endometriosis 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 study 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 dysfunction, chronic inflammation, endothelial dysfunction, multiple aging hallmarks, impaired physical function, and insulin resistance. Nine functional issues also shared by those with endometriosis, as discussed in published literature. No wonder I felt like a 90-year-old curmudgeon when I was at my endo-worst.

And, in the case of these older adults, GlyNAC supplementation either improved or totally corrected these problems! [12]

I was intrigued. So, naturally, I decided to destroy more of my eyesight by waking up grotesquely early to stare way-too-close to my computer while stalking PubMed. The similarities I found were pretty remarkable and definitely worth sharing. Some of it include:

• Oxidative stress reduced by 73%: GlyNAC supplementation in this study 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]

• 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]

• 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]

Wow, this is pretty significant! And I hope some researcher out there with the powers of getting grant money scoops some up to try this combo on endometriosis patients.

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, I will give you the low down on these studies to consider (with your doctor) what may be right for you.

NAC used in the endometriosis-specific studies was prescribed at 600 mg taken 3 times/day, for 3 consecutive days of the week, for 3 months. This translates to 600mg at breakfast, lunch, and dinner (1800mg/day), taken on Monday, Tuesday, and Wednesday (or any 3 days in a row), with the following four days not taking NAC. The reason for this schedule is based on the research shown to get the best serum levels of NAC for those taking it over a more extended period of time (because, yeah, 3 months is a long time).

The levels taken for the GlyNAC study were significantly larger, with participants taking 100 mg/kg body weight per day each of glycine and NAC. This translates to about 6800mg/day glycine and NAC each for a 150-pound person, with no breaks on any days, for 3 months.

[For your own calculation fun take your body weight x .45 = __ x 100 = __ (your dose per day)]

If you do choose to supplement, make sure you only supplement with high quality brands that are third party tested for purity (don’t want to be swallowing a bunch of heavy metals as a side-dish). Brands I like include, but are not limited to, Integrative Therapeutics, Thorne, Biotics Research, Pure Encapsulations. Pure Encapsulations also has a product called NAC + Glycine, which offer 1,800mg 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.

1) Kobayashi, H., Shigetomi, H., & Imanaka, S. (2021). Nonhormonal therapy for endometriosis based on energy metabolism regulation. Reproduction & fertility, 2(4), C42–C57. https://doi.org/10.1530/RAF-21-0053

2) Lu, H., Hu, H., Yang, Y., & Li, S. (2020). The inhibition of reactive oxygen species (ROS) by antioxidants inhibits the release of an autophagy marker in ectopic endometrial cells. Taiwanese Journal of Obstetrics & Gynecology, 59(2), 256–261. https://doi.org/10.1016/j.tjog.2020.01.014

3) A. C. Gustafsson, I. Kupershmidt, E. Edlundh-Rose et al., “Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro,” BMC Cancer, vol. 5, article 75, 2005.

4) E. Edlundh-Rose, I. Kupershmidt, A. C. Gustafsson et al., “Gene expression analysis of human epidermal keratinocytes after N-acetyl L-cysteine treatment demonstrates cell cycle arrest and increased differentiation,” Pathobiology, vol. 72, no. 4, pp. 203–212, 2005.

5) E. Pittaluga, G. Costa, E. Krasnowska et al., “More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis,” Fertility and Sterility, vol. 94, no. 7, pp. 2905–2908, 2010.

6) Porpora, M. G., Brunelli, R., Costa, G., Imperiale, L., Krasnowska, E. K., Lundeberg, T., Nofroni, I., Piccioni, M. G., Pittaluga, E., Ticino, A., & Parasassi, T. (2013). A promise in the treatment of endometriosis: An observational cohort study on ovarian endometrioma reduction by N-acetylcysteine. Evidence-Based Complementary and Alternative Medicine: eCAM, 2013, 240702. https://doi.org/10.1155/2013/240702

7) Anastasi, E., Scaramuzzino, S., Viscardi, M. F., Viggiani, V., Piccioni, M. G., Cacciamani, L., Merlino, L., Angeloni, A., Muzii, L., & Porpora, M. G. (2023). Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes. International journal of environmental research and public health, 20(6), 4686. https://doi.org/10.3390/ijerph20064686

8) Zhong, Z., Wheeler, M. D., Li, X., Froh, M., Schemmer, P., Yin, M., Bunzendaul, H., Bradford, B., & Lemasters, J. J. (2003). L-glycine: A novel antiinflammatory, immunomodulatory, and cytoprotective agent. Current Opinion in Clinical Nutrition and Metabolic Care, 6(2), 229–240. https://doi.org/10.1097/00075197-200303000-00013

9) Meléndez-Hevia, E., De Paz-Lugo, P., Cornish-Bowden, A., & Cárdenas, M. L. (2009). A weak link in metabolism: The metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. Journal of Biosciences, 34(6), 853–872. https://doi.org/10.1007/s12038-009-0100-9

10) Vargas, M. H., Del-Razo-Rodríguez, R., López-García, A., Lezana-Fernández, J. L., Chávez, J., Furuya, M. E. Y., & Marín-Santana, J. C. (2017). Effect of oral glycine on the clinical, spirometric and inflammatory status in subjects with cystic fibrosis: a pilot randomized trial. BMC pulmonary medicine, 17(1), 206. https://doi.org/10.1186/s12890-017-0528-x

11) Razak, M. A., Begum, P. S., Viswanath, B., & Rajagopal, S. (2017). Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxidative medicine and cellular longevity, 2017, 1716701. https://doi.org/10.1155/2017/1716701

12) Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., Minard, C. G., Taffet, G. E., & Sekhar, R. V. (2023). Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. The journals of gerontology. Series A, Biological sciences and medical sciences, 78(1), 75–89. https://doi.org/10.1093/gerona/glac135

13) Da Broi, M. G., de Albuquerque, F. O., de Andrade, A. Z., Cardoso, R. L., Jordão Junior, A. A., & Navarro, P. A. (2016). Increased concentration of 8-hydroxy-2'-deoxyguanosine in follicular fluid of infertile women with endometriosis. Cell and tissue research, 366(1), 231–242. https://doi.org/10.1007/s00441-016-2428-4

14) Polak, G., Wertel, I., Barczyński, B., Kwaśniewski, W., Bednarek, W., & Kotarski, J. (2013). Increased levels of oxidative stress markers in the peritoneal fluid of women with endometriosis. European journal of obstetrics, gynecology, and reproductive biology, 168(2), 187–190. https://doi.org/10.1016/j.ejogrb.2012.12.043

15) Yama, K., Shinbo, H., Fujikane, Y., Mikami, C., Machida, M., & Miura, J. (2022). The Concentration of 8-Hydroxy-2'-Deoxyguanosine in Plasma During the Menstrual Cycle in Young Japanese Women. Women's health reports (New Rochelle, N.Y.), 3(1), 267–273. https://doi.org/10.1089/whr.2021.0067

16) Florova M.S., Yarmolinskaya M.I., Tkachenko N.N., Tolibova G.K., Tral T.G. Role of insulin and insulin-like growth factor I receptor expression in the pathogenesis of genital endometriosis // Journal of obstetrics and women's diseases. - 2021. - Vol. 70. - N. 3. - P. 65-74. doi: 10.17816/JOWD58194

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18) Kuessel L, Wenzl R, Proestling K, Balendran S, Pateisky P, Yotova S, Yerlikaya G, Streubel B, Husslein H. Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis. Hum Reprod. 2017;32(4):770–9. https://doi.org/10.1093/humrep/dex028

19) Li, S., Fu, X., Wu, T., Yang, L., Hu, C., & Wu, R. (2017). Role of Interleukin-6 and Its Receptor in Endometriosis. Medical science monitor : international medical journal of experimental and clinical research, 23, 3801–3807. https://doi.org/10.12659/msm.905226

20) Malvezzi, H., Hernandes, C., Piccinato, C. A., & Podgaec, S. (2019). Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis. Reproduction (Cambridge, England), 158(1), 1–12. https://doi.org/10.1530/REP-18-0618

21) Wu MY, Ho HN. The role of cytokines in endometriosis. Am J Reprod Immunol. 2003;49(5):285–296

22) Othman, E. R., Hornung, D., Hussein, M., Abdelaal, I. I., Sayed, A. A., Fetih, A. N., & Al-Hendy, A. (2016). Soluble tumor necrosis factor-alpha receptors in the serum of endometriosis patients. European journal of obstetrics, gynecology, and reproductive biology, 200, 1–5. https://doi.org/10.1016/j.ejogrb.2016.02.025