Nutritional interventions to support endometriosis

Endometriosis is a condition that affects 10% of women of reproductive age. It is a condition that is painful, inconvenient and which can affect fertility, therefore it may have a significant effect on quality of life. The actual cause of endometriosis is unknown but there are specific risk factors and, like many conditions, there may be multiple contributory factors. In this blog we investigate the pathogenesis of endometriosis and discuss nutritional and supplemental interventions which may be beneficial to clients suffering the debilitating symptoms associated with endometriosis.^1,2

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What is it?

Endometriosis is the presence of endometrial tissue, which should reside solely in the uterus, in other parts of the body; these are mainly within the peritoneal cavity but have also been found, although rarely, in tissues including the brain, liver and lungs. Symptoms include pelvic pain that usually occurs just before menstruation and lessens afterwards, painful sexual intercourse, cramping or pain during bowel movements or urination, infertility and pain with pelvic examinations. However it is often only diagnosed by visual identification of lesions via surgery.²

Pathogenesis

There are a few hypotheses as to the pathogenesis of endometriosis and it is likely that it is due to a combination of these mechanisms.

Retrograde menstruation – this is the occurrence of a backflow of menstrual fluid from the uterus back through the fallopian tube and into the peritoneal cavity. However the flaw in this hypothesis is that it is thought that 90% of menstruating women experience some form of retrograde menstruation and it also does not account for endometrial tissue being found outside of the peritoneal cavity. Therefore other processes must be involved.^2,3

Metaplasia – it has been proposed that endometriosis originates from extra-uterine cells that abnormally differentiate into endometrial cells, this is known as coalomic metaplasia. Hormonal or immunological factors are thought to stimulate the transformation of normal peritoneal tissue or cells into endometrium-like tissue. This theory may explain the occurrence of endometriosis in pre-pubertal girls, as the usual driving force for endometrial growth, oestrogen, is not present. Therefore this condition in pre-pubertal girls may be a different form of endometriosis to that found in women of reproductive age.^2,3

Angiogenesis – The peritoneal fluid of patients with endometriosis is a complex suspension carrying inflammatory cytokines, growth factors, steroid hormones, proangiogenic factors, macrophages (immune cells), and endometrial and red blood cells. These cells and their signalling products together promote the spreading of new blood vessels at the endometriotic lesions and surroundings, which contributes to the ability of endometrial tissue to remain outside of the uterus.

Drivers

Oestrogen Dominance – Oestrogen is a growth promoting hormone, particularly stimulating the growth of endometrial tissue. Oestrogen dominance refers to an excess of oestrogen relative to progesterone, however oestrogen levels can be low, normal or high. Oestrogen is the driving force of endometrial proliferation and ectopic lesions may have an increased responsiveness to oestrogen, thus enhancing the development of endometriosis. Environmental toxins, such as dioxin, are implicated in the aetiology of endometriosis, which may mimic oestrogen via interacting with oestrogen receptors. There is also some evidence that there is a higher bioavailability of the most potent form of oestrogen, oestradiol, in endometriotic tissue. This is due to circulating androgens being converted to oestradiol via aromatisation by endometriotic stromal cells.^2,3

Inflammation and oxidative stress

Endometriosis is considered to be a chronic inflammatory condition, and therefore inflammation is a major contributor to the pathogenesis of the disease. Increased numbers of peritoneal macrophages (immune cells) and their secreted inflammatory products characterises the condition. Inflammation plays a major role in the pain and infertility associated with endometriosis, but is also extensively involved in the molecular processes that lead to the development of lesions within the peritoneum.

In addition, peritoneal oxidative stress is currently thought to be a major part of the endometriosis-associated inflammatory response. Excessive production of reactive oxygen species due to an influx of pro-oxidants such as haem and iron into the peritoneum during retrograde menstruation, may induce cellular damage and increased pro-inflammatory gene expression. Increased pro-inflammatory prostaglandin concentrations have been demonstrated within the peritoneum of patients with endometriosis.^3,5

Iron

In patients with endometriosis, iron overload has been observed within the peritoneal cavity. Peritoneal immune cells have been shown to degrade red blood cells and subsequently have effects on peritoneal iron metabolism, leading to an overload of iron. Iron overload could affect a wide range of mechanisms involved in endometriosis development, such as oxidative stress or lesion proliferation and can result in toxicity. It appears that iron overload does not affect lesion establishment but may contribute to the further growth of endometriosis by promoting cell proliferation of lesions.⁶

Nutritional Interventions

Therapeutic interventions focus on supporting a healthy balance of hormones, particularly oestrogen, by supporting oestrogen metabolism and excretion pathways in the liver and gut; as well as stabilising blood sugar levels, supporting a healthy inflammatory response, reducing oxidative stress and maintaining healthy iron levels (considering iron chelation methods if appropriate).

Supporting liver and gut

Oestrogen that has been used by the body is transported to the liver where it undergoes detoxification and is conjugated via phase II enzyme pathways. Following this, it is excreted via the bile into the gut where, when working effectively, it will be removed from the body in faeces. If the liver is under stress, detoxification of oestrogen may be slow.

Oestrogen can be detoxified by one of three pathways resulting in the metabolites 2-hydroxy oestrone, 4-hydroxy oestrone or the potent 16-hydroxy oestrone. Therefore, it is important to support the detoxification pathways that produce the less potent 2 and 4-hydroxy oestrone forms which are far less potent and proliferative.

In addition, if the gut is under stress and the bowel is not emptying regularly i.e. constipation, conjugated oestrogen can remain in the gut for a longer period giving more time for dysbiotic bacteria to deconjugate it. Certain gut bacteria produce the enzyme beta-glucuronidase, which cleaves oestrogen from its conjugated amino acid and allows it to be reabsorbed and therefore recirculate in the body (thus contributing to higher levels of oestrogen). Therefore gut and liver function, as well as the microbiome, should be considered in cases of endometriosis.^{1, 7}

Dietary interventions that support the gut and liver include:

• Drinking lemon in hot water first thing in the morning – to stimulate bile production
• Maintaining adequate zinc levels, zinc is very important for the production of stomach acid as well as for maintenance of epithelial tissue lining the digestive system
• Eating prebiotic foods such as baked apples, chicory and artichoke and fermented foods such as kefir, sauerkraut and kimchi to support gut flora
• Increasing foods that support the liver such as brassicas, onions, garlic, rocket and watercress. Broccoli, rocket and watercress are natural sources of sulphurophane and diinolylmethane, which upregulates the detoxification pathways that produce 2-hydroxy oestrone
• Eating a wide variety of colours of fruits and vegetables, particularly greens, yellows and oranges which are high in flavonoids and carotenoids which acts as antioxidants but also support phase II liver detoxification
• Drinking green tea which is a liver antioxidant
• Supplementing, as appropriate, with a live bacteria supplement, digestive enzymes, nutrients which support gut integrity (e.g. vitamin A and D) as well as nutrients which support liver function (flavonoids, carotenoids, curcumin, B vitamins, B6, folate and B12)

In addition, support blood sugar regulation by avoiding refined carbohydrates and sugar and including fibre from wholegrain carbohydrates and vegetables with healthy fat and protein.

Reducing inflammation and oxidative stress

As mentioned before, in order to support clients with endometriosis attenuating oxidative stress and inflammation is essential as these have been shown to be major drivers of the condition. Therefore an anti-inflammatory diet which is high in antioxidants is useful.⁶

Reduce inflammation by:

• Optimising gut health
• Reducing omega-6 fatty acids from meat, dairy and vegetable oils
• Increasing omega-3 fatty acids from oily fish, chia and flax seeds and dark leafy green vegetables and if necessary take an omega-3 supplement
• Using anti-inflammatory foods such as turmeric (curcumin) and ginger. Consider a curcumin supplement
• Increasing vitamin E containing foods such as avocado

Reduce oxidative stress by:

• Reducing exposure to pro-oxidative toxins such as heavy metals, pesticides and persistent organic pollutants
• Increasing antioxidants such as vitamin A, vitamin C, CoQ10, selenium, zinc, N-acetyl-cysteine and alpha-lipoic acid. Vitamin C and NAC will also support the synthesis of glutathione, an antioxidant made in the body. Glutathione can also be supplemented directly

Iron homeostasis

Although iron is obviously an essential mineral, as mentioned, in excess it can become pro-oxidative and can increase endometriosis symptoms. Therefore maintaining iron homeostasis is an important intervention:⁶

• Avoid supplementing iron (unless prescribed by a G.P. for iron-deficiency anaemia)
• Ensure zinc and copper intake is adequate (consider a supplement) as they compete with iron for absorption
• Ensure intake of antioxidants from a range of colours of vegetables and fruits.
• Include iron chelating nutrients such as alpha lipoic acid, curcumin, quercetin

Specific Nutrients

Nutrient	Research
Vitamin C	Besides playing a role in preventing invasion and metastasis (relevant for endometriosis), it is an antioxidant having anti-inflammatory and anti-angiogenic effects. In vivo studies have shown that vitamin C might have a suppressive effect and prevent endometriotic implant induction and reduce endometriotic implant volumes.1,8
Beta carotene and Vitamin A	Women with endometriosis have a lower intake of pro-vitamin A (eg. beta carotene) nutrients than women without the condition. Vitamin A can moderate effects of IL-6 (an inflammatory mediator) and is protective against tumour growth, which also has relevance for endometrial growth.1,9
Vitamin E	Vitamin E helps to correct abnormal progesterone : oestradiol ratios, and is also an important antioxidant as well as possessing anti-inflammatory properties. One study showed that vitamin E levels were significantly lower in the peritoneal fluid of women with endometriosis, attributing this finding to a local decrease of antioxidants caused by excessive oxidative stress.1,8,10
Selenium	Aids the synthesis of detoxification enzymes in the liver. Individuals with reduced selenium have sub-optimal cell-mediated immunity, decreased T cells and associated inflammation.1
Lipotrophic factors	These aid in supporting liver function by promoting the flow of bile and fat from the liver and out through the large intestine, these include products such as choline, methionine and betaine.1

Lifestyle

It is important to reduce contact with environmental oestrogens (xeno-oestrogens) which can mimic our own natural oestrogen by binding to oestrogen receptors. Xeno-oestrogens are commonly found in many man-made products including skin care products. Although it is impossible to avoid xeno-oestrogens here are a few ways in which exposure can be reduced.⁴

• Avoid skincare products, cosmetics, soaps etc. which contain parabens
• Don’t cover food in cling film and avoid microwaving food with cling film or in plastic
• Avoid storing fatty foods/oils in plastic containers
• Use glass water bottles
• Most till receipts are a source of BPA, so avoid handling
• Filter drinking water through a reverse osmosis filter with post and pre-activated carbon filters (these can be fitted under the sink) [NB: these can waste large amounts of water but it is possible to fit them in a way to avoid this]
• Choose organic vegetables and fruit to reduce pesticides etc., which may contain xeno-oestrogens
• Opt for organic, preferably grass-fed or wild meat, game, poultry and fish

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If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.

helen@cytoplan.co.uk, 01684 310099

Helen Drake and the Cytoplan Editorial Team

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Relevant Cytoplan Products

CytoProtect Liver – a botanical formula comprising milk thistle, dandelion, turmeric, schisandra, burdock and artichoke.

Acidophilus Plus – Live bacteria supplement containing 9 strains of bacteria and 35mg of FOS.
Alternative products: Fos-A-Dophilus, Cytobiotic Active or CytoProtect GI Tract.

Phytoshield – Flavonoid and carotenoid complex, containing green tea, quercetin, curcumin, broccoli and beta-carotene

Cell-Active Curcumin Plus – Longvida® liposomal curcumin with gingerols.

Milk Thistle – Contains 400mg milk thistle. Certified organic by the Soil Association and suitable for vegans. Legislation prohibits us from talk in detail about herbs and their applications. Certified organic by the Soil Association.

Cyto-Renew – Complex containing N-acetyl cysteine, alpha lipoic acid, l-carnitine, CoQ10, gingko biloba and rosemary. Cyto-Renew helps to support healthy cell metabolic activity.

Krill Oil – A rich source of omega-3 essential fatty acids EPA and DHA, with high levels of astaxanthin, an antioxidant; choline, which is a prescursor to acetylchooline, an essential neurotransmitter; and phospholipds.
Alternative products: Vegan Omega 3, High Strength Fish Oil or Lem-O-3

Cherry C – The fruit of the acerola cherry tree is rich in vitamin C, flavonoids and carotenoids, with the cherry-like fruits being one of the richest-known natural sources of vitamin C. Our Cherry C contains 200mg of vitamin C from acerola cherry.

Mixed Tocopherols/ Tocotrienol – Containing the full spectrum of vitamin E as it occurs in nature; alpha,  beta, delta, gamma tocopherol and alpha, beta, delta, gamma tocotrienol.

Vitamin A Retinol Palmitate – 5000IU vitamin A. This product is not suitable for pregnant or lactating women. If you smoke or have every smoked heavily consult your doctor before taking.

Food State Selenium – 100ug of elemental selenium. Food State Selenium yeast has been documented by the European Food Standards Agency as being the safest and most bio-effective form of Selenium. Food State Selenium is far better absorbed and used (by the body) than inorganic selenium.

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References

1. Murray JPM. Textbook of Natural Medicine. 4th Ed.; 2013.
2. Greene AD, Lang SA, Kendziorski JA, Sroga-Rios JM, Herzog TJ, Burns KA. Endometriosis: where are we and where are we going? Reproduction. 2016;152(3):R63-78. doi:10.1530/REP-16-0052
3. Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014;2014:179515. doi:10.1155/2014/179515
4. Roy D, Morgan M, Yoo C, et al. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer. Int J Mol Sci. 2015;16(10):25285-25322. doi:10.3390/ijms161025285
5. Greene AD, Lang SA, Kendziorski JA, Sroga-Rios JM, Herzog TJ, Burns KA. Endometriosis: where are we and where are we going? Reproduction. 2016;152(3):R63-78. doi:10.1530/REP-16-0052
6. Defrere S, Lousse JC, Gonzalez-Ramos R, Colette S, Donnez J, Van Langendonckt A. Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod. 2008;14(7):377-385. doi:10.1093/molehr/gan033
7. Bland J et al. Textbook of Functional Medicine.; 2008.
8. Erten OU, Ensari TA, Dilbaz B, et al. Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis. Taiwan J Obstet Gynecol. 2016;55(2):251-257. doi:10.1016/J.TJOG.2015.07.004
9. Harris HR, Eke AC, Chavarro JE, Missmer SA. Fruit and vegetable consumption and risk of endometriosis. Hum Reprod. 2018;33(4):715-727. doi:10.1093/humrep/dey014
10. Seeber BE, Czech T, Buchner H, et al. The vitamin E-binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis. Fertil Steril. 2010;94(7):2923-2926.

Last updated on 3rd November 2022 by cytoffice