You all know by now how much I love talking about the powerful effects too much estrogen has on the body. Estrogen dominance, for women, causes so many symptoms including PMS symptoms, anxiety, depression, weight gain, heavy bleeding and fibroids, and really rough peri and menopause phases. Indeed you need estrogen. In the first half of the cycle, that is what is helping all those luscious eggs that could, one day, become beautiful babies. It is one of the hormones that make us women. (Though let me make it clear that men CAN and DO suffer from estrogen dominance!)
Recently, we have been addressing the most important and first line of defense detoxification organ in the body; the liver. The liver is responsible for many functions in the body so it’s not surprising that when the liver is dysfunctional many other illnesses surface. The estrogens we manufacture in our body as well as those we ingest and are exposed to daily have a massive effect on health. When estrogens become so great, or the pathways that are responsible for disposing of hormones becomes dysfunctional, chaos ensues. I know I sound melodramatic but, really, think about the fact that when one hormone, like estrogen, in the body is unbalanced, it sets off a cascade of imbalances from hormones such as progesterone, testosterone, thyroid hormone, cortisol, leptin, insulin, and even ghrelin. (Those last three are the lead singers of a band called ‘Weight Gain’ with all of the rest of them really off-key backup singers.)
I can’t think of one bodily function where having balanced hormones is not imperative.
The liver, essentially, takes every single thing we eat or drink, inhale, or absorb and processes it so it can be utilized or disposed of. This filtration system is so intelligent that it filters out all of the nutrients we need for energy metabolism and every other function from what the does not serve a purpose in the body such as toxins, metabolic waste and anything left over that the body cannot or does not need to store.
Let’s take a closer look at all the things the liver really does in the body.
- Converts fats, proteins and carbohydrates to energy and nutrients (which is why you want your liver on your side when maintaining weight!)
- Creates bile to break down fats and eliminate fat-soluble toxins and excess substances, including excess hormones
- Removes harmful chemicals, bacteria, and excesses
- Metabolizes drugs and breaks down alcohol
- Stores vitamins and minerals, such as iron
- Stores sugars as fuel (glycogen) for future use
- Aids in maintaining fluid and electrolyte balance
- Creates serum proteins that act as hormone carriers
- Creates immune substances, such as gamma globulin
- Filters blood, regulates blood clotting, and stores extra blood for quick release
- Manufactures testosterone and the estrogen hormones
- Regulates sex hormone levels and eliminates excess hormones. (which explains why I preach about the liver with estrogen dominance.)
Do you love your liver yet?
What can possibly go wrong?
That’s the million dollar question. I argue with doctors all the time when they say it really doesn’t matter what we put into our bodies or absorb. I usually end up pointing out that Non-Alcoholic Fatty Liver Disorder is at epidemic proportion and hormonal imbalances and hormone dependent cancers are ever on the rise.
Processed foods covered in industrial oils and toxic chemicals like solvents, dyes, and “flavorings” (for those who don’t understand how toxic processed foods can be, check out this FACEBOOK UPDATE and never eat Cheetos again!), exposure to man-made chemicals such as preservatives and pesticides (along with the countless ones we willing put on our face and body in the name of beauty) , lead from paint, exposure to petroleum (we pump our own gas these days, ladies), alcohol, drugs (both pharmaceutical and recreational), and exposure to an inordinate amount of hormones either due to our body’s imbalances caused by exposure to many of the things listed above or the many xenoestrogens that are everywhere these days, all of these affect the ability of the liver to process and dispose of these toxins properly.
Couple all that with the fact that intestinal permeability (Leaky Gut) is commonplace and, in many cases, we are not eating a nutrient dense diet so the liver does not have the nutrients it needs to process quickly enough and toxins and used hormones get “backed up” which can cause them to be released back into the body to wreak havoc on health and wellness.
The liver plays a vital role in how the body uses hormones, both those that are produced naturally in our bodies as well hormones such as those “introduced” via hormone therapies, foreign hormones such as xenoestrogens, phytoestrogens and other hormone disruptors. The liver processes hormones, regulates some hormone levels (even manufactures a few) and directs various hormones to where they need to go to perform their proper function in the body. All this becomes impaired or even grinds to a halt when the body experiences a hormone excess (whether produced by the body or introduced by hormone therapy). As a result of this excess the liver may not be able to process the hormone or hormones as quickly or efficiently, causing an often tremendous hormone imbalance.
Let’s talk estrogen.
The liver plays an integral role in women’s health with its responsibility for regulating the sex hormones, primarily the estrogen hormones. This role should be taken into account by any woman who endeavors to undergo any type hormone therapy, whether it is conventional hormone replacement therapy (HRT), typically consisting of synthetic hormones or a biologically-identical hormone therapy (BHT). For those of you reading this who think I am talking about menopausal women, think again. Anyone on ‘the pill’ is on hormone therapy. I am talking to all women of child birthing years and beyond.
Researchers, every day, are understanding more and more how estrogens are metabolized and the effects of that metabolism. They understand now that estrogens break down into estrogen metabolites that have varying levels of estrogenic activity, and that the stronger the estrogenic effect, the greater the risk of developing estrogen related cancer and other estrogen-related disorders.
Where do the liver pathways I and II come into the picture?
The liver metabolizes hormones, endotoxins and chemicals that are ingested, absorbed or are metabolites of the body using two primary phases known as the Phase I (cytochrome P450) and Phase II pathways.
During Phase I, cytochrome P450 helps metabolize many hormones and toxins, but most are converted, first, into intermediate forms, which are then further metabolized in Phase II.
These two phases, cumulatively and often in synergy, work in a way whereby the liver provides the body with nutrients and supports the excretion of excess or toxic substances in the urine, liver bile, perspiration and when air is exhaled.
There is a lot riding on whether or not the pathways function properly. They depend on a significant number of nutrients, including enzymes and amino acids, and their availability (or deficiencies) dramatically influence the metabolic outcome. The Phase I pathway is the main metabolic pathway for the estrogen hormones. In premenopausal women, the egg follicles in the ovaries produce estrogen, primarily estradiol, (the “active” form of estrogen) most of which the body converts to estrone (a weaker version), and eventually estriol (a metabolic waste product of estradiol metabolism). Other sites where estrogen can be made include the liver, breast, adrenal glands, placenta and the corpus luteum in the ovaries. The liver then metabolizes the remaining estradiol and the converted estrone, breaking it down further, and excreting the excess from the body.
We in the integrative/holistic medicine field now believe that the liver’s ability to metabolize estrone holds key to understanding and calculating estrogen-related cancer risk. Now here’s where it gets interesting. During Phase I metabolism, estrone is converted into various metabolites including 2-hydroxyestrone, a very weak estrogen, and 16-alphahydroxyestrone, a very potent estrogen. In this conversion process if the stronger form(s) rather than the weaker form(s)are favored, then tissue that has an abundance of estrogen receptors, such as the breasts and uterus, may be more vulnerable to the activity caused by excess estrogen potentially leading to the formation of fibroids or the stimulation of estrogen-sensitive cancers. Even if the worst does not happen, by luck, PMS symptoms, PCOS symptoms (though estrogen is only a factor in this disorder), breast tenderness, weight gain and other estrogen related symptoms may ensue.
Phase I processing is affected by a lot of factors, including extreme toxic overload, the effects of alcohol or drugs, nutrient deficiency, or interference from other substances such as xeonoestrogens. For example, grapefruit juice can slow down the enzymes in Phase I, potentially altering hormone balance. (This is why women with estrogen dominance, in my practice, are told that grapefruit is a no-no). Because many prescription drugs are metabolized in Phase I this can also interfere with the liver’s ability to metabolize estrogen hormones. On the other hand, studies show Indole-3-carbinol (I3C), a phytonutrient derived from cruciferous vegetables (e.g., broccoli, cauliflower, cabbage and brussels sprouts), stimulates enzymes that promote the metabolism of estrogens into milder forms, potentially reducing the risk of estrogen-dependent cancers. (AGAIN, before thinking more is better, these vegetables MUST be well cooked and in the presence of healthy fats such as butter, ghee or coconut oil to be appropriate to eat and if you have thyroid issues, even these vegetables must be eaten with care.)
In Part 4 of Path(ways) to Detox we talked about the various pathways in Pathway II. Of those pathways the following are most relevant to hormone metabolism:
Methylation, or methyl metabolism, works by passing small parts of molecules, called methyl groups, to another methyl group. Estrogens love the methylation pathway. Once estrogens are methylated, they can be easily excreted. Methyl groups must have the right nutrients to build the right methyl groups. Those nutrients are B6, (e.g., liver, tuna, banana, summer squash and blackstrap molasses),B-12 (the best sources are from animals) and folate (green leafies, avocado, tropical fruit, oranges). An over-the-counter dietary supplement known as SAMe (s-adenylmethionine) is also a rich source of methyl groups and sulfur but some people find it can trigger anxiety. Though I recommend having a full DNA Methylation test (of which I can order and assess) before undertaking a supplement regimen, there are supplements that can greatly improve methylation pathway defects. We will be discussing those in a future post.
Sulfation happens when sulfur groups are added to estrogen or other molecules to prepare them for easy elimination. Adequate consumption of foods containing sulfur should be present in the diet, including egg yolks, garlic, onions and brussels sprouts to optimize sulfation. Animal protein is another important source of sulfur.
Glucuronidation is another process by which estrogens can be conjugated but this is not the preferred pathway. This happens when other pathways are defective. The body is very adaptive but some adaptations are not preferred. Even if this adaptation occurs, if the gut is not healthy (like in the case of IBS, leaky gut or especially gut dysbiosis) an enzyme produced by these unhealthy bacteria may cut off the conjugated part from the estrogen as it reaches the colon. Instead of the message to excrete the excess estrogen is lost and the body will reabsorb the estrogen backing up the entire system. Estrogens build up to excessive levels and a lot of those are very strong estrogen metabolites! This is where the supplement calcium D-glucarate (also found in fruits and vegetables) comes in. It can render the enzyme inactive and prevent this buildup. I usually recommend this supplement over any other with estrogen dominance because there is a fair bit of gut dysfunction in most of the Western population.
Gluthathione conjugation is the process in which glutathione, another sulfur-containing molecule, is bound to estrogen for easy excretion. Foods such as avocado, walnuts and asparagus are rich in glutathione, and vitamin C stimulates the body to produce more of it. Glutathione depletion can be due to a lack of the essential nutrients and amino acids (found in fresh fruits, vegetables, fish and meats) that are needed to synthesize it or it can be from a toxic overload that depletes it faster than it can be synthesized.
Glutathione is called the master antioxidant as well as a crucial detoxifier because it also behaves as an antioxidant in Phase I. Glutathione neutralizes the free radicals produced in the Phase I reactions, and combines with them to produce water-soluble compounds that can be excreted.
Glutathione is also needed for the detoxification of alcohol. Studies have shown that even a small amount of alcohol intake can increase estrogen levels in the blood because alcohol competes for the available glutathione, preventing estrogen excretion.
Smoking is also responsible for depleting glutathione levels, as are chronically stressful conditions such as infections or inflammatory disorders.
A note about Liver bile::
Bile is a complex fluid secreted by the liver needed for digestion and absorption of fats and fat-soluble nutrients and other substances. Bile is stored in the gall bladder where it then flows through the bile duct to the small intestine where it is eventually eliminated in stool.
Many fat-soluble toxins, including excess estrogen hormones, are eliminated from the body into the intestines with the help of bile. Many women, such as those on birth control pills or hormone therapy may have difficulty eliminating excess estrogens. This is thought to be because the hormonal processes in these therapies somehow inhibit bile flow. Methionine, found in an over-the-counter dietary supplement called SAMe, has been shown to improve bile flow, thereby helping to reduce excess estrogen levels. I will address SAMe in another post but it should be used with caution therefore I only recommend this supplement to a very select type of client. I will not give my recommendations until I go into more detail about the supplement.
A word about free radicals::
Every reaction in the Phase I pathway produces an intermediate form called a free radical. Free radicals can be very damaging to body tissues if they are
not quickly neutralized by antioxidants. Nutrients such as vitamins C and E, minerals such as selenium, and other substances such as lipoic acid and, of course, glutathione are antioxidants that guard againstf ree radicals. Because the intermediate forms of metabolites produced in Phase I are in a highly reactive state until they are fully converted in Phase II nutrients, preferably from nutrient dense real foods, are crucial for maintaining clear detox pathways.
Do you suffer from estrogen dominance symptoms? Are you curious about your DNA methylation status and how you can help optimize it? Contact me to find out how I can get your liver and your health humming again.