vitamin A

Could Altered Vitamin A Metabolism Be Responsible for Endometriosis and Fibroid Growth?

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Yes, and increased use of environmental toxicants may be partially to blame. Over the last decade researchers have uncovered connections between tissue level vitamin A activity – the retinoic acid pathway – hormone metabolism, and the cell cycle overgrowth noted in fibroid tumor development, breast and ovarian cancer, and endometriotic tissue growth. Moreover, researchers from the environmental side have found that the popular glyphosate-based herbicides alter vitamin A or retinoic acid metabolism which in turn alters androgen and estrogen metabolism. Connecting the dots, we may have a first step to reducing cell growth in these conditions; remove the toxicant exposure and increase nutritional resources. A second step may be to develop locally absorbed vitamin A, applied directly to the aberrant tissues.

What is Vitamin A?

Vitamin A, (retinol, carotene) is a fat-soluble nutrient that we derive solely from dietary sources. It is responsible for a myriad of functions in a vast number of tissues from the eye, to the ovary, to the heart. Historically, nutrition from diet, coupled with the old wives’ tales of good health, carrots for eyesight, and cod liver oil for all that ails you, were all that were needed to maintain healthy levels of Vitamin A in most individuals. However, with the increase in processed foods, modern farming, intense use of herbicides and pesticides, and the general replacement of the old wives’ nutritional wisdom with pharmaceuticals, many men, women, and children are vitamin A deficient and likely do not even know it. The WHO estimates vitamin A deficiency in 19 million pregnant women and 150 million children worldwide. When Vitamin A deficiency reaches its nadir night blindness, maternal mortality, and difficulty fighting infections are common. In women, the first signs of vitamin A deficiency may be unrecognized and include fibroids or endometriosis. Earlier signs of vitamin A deficiency in women could also be menorrhagia (heavy menstrual bleeding) that often precedes fibroid or endometriosis diagnosis, but research is lacking here, or even genital warts of the common HPV strains.

Why Retinoic Acid, Hormones, and Cell Growth

Retinoic acid (RA), is the form of vitamin A stored in the body. RA is what is called a paracrine, perhaps even an intracrine hormone regulator. That means it turns hormone metabolism on or off in the cells within its immediate vicinity (paracrine) or within its own cell (intracrine). This is compared to endocrine control of hormone metabolism – where hormones and the factors that regulate hormone synthesis and metabolism travel vast distances through the blood to reach their targets tissues (the hypothalamus-pituitary – ovarian system is an example of endocrine regulation) or autocrine where the hormone leaves its own cell only to turn around and bind to a receptor on that cell. In contrast, retinoic acid stays close to home and regulates local cell behavior, both internally and proximally. The vitamin A deficiency leading to fibroids or endometriosis represents a cell and tissue level disruption of the retinoic acid pathway that in turn interrupts the normal cell cycle (differentiation, proliferation, and apoptosis -cell death) and elicits all sorts of problems from decreased estrogen metabolism (too much estradiol at the cells), to cell overgrowth, or more specifically, not enough cell death where needed. The results include aberrant cell growth as in fibroids, tumors, and endometriosis.

Retinoic Acid, Progesterone and Estrogen Metabolism

With many women’s health conditions too much estradiol at the tissue level is at the root. Estradiol is an excitatory hormone that tells our cells to go forth and prosper. Progesterone, depending upon the tissue and the relative values of each circulating hormone can work synergistically to enhance estradiol’s actions or it can shut it down entirely via the upregulation of a specific estradiol metabolizing enzyme called 17 beta-hydroxysteroid dehydrogenase type 2  (17B -HSD2).  When these enzyme levels are high, more estradiol is converted to estrone. Since estrone is a less potent estrogen than estradiol, metabolism of estradiol to estrone somewhat inactivates the estrogen and slows cell proliferation. When the enzyme levels are low, more estradiol remains, and cell growth is enhanced.  Vitamin A or retinoic acid mediates the progesterone-dependent activation of this enzyme, effectively regulating estradiol concentrations locally. Too little retinoic acid or a disrupted retinoic acid pathway and estradiol is not converted to estrone – e.g. it is not inactivated. Cell proliferation dominates, while normal cell death or apoptosis is reduced. Fibroids, tumors, or endometriosis ensue.

What Causes Low Retinoic Acid or Reduced Functioning?

Vitamin A is derived entirely from diet. Foods high in vitamin A include brightly colored vegetables, dark leafy greens, carrots, pumpkin, sweet potatoes, bell peppers, and fatty fish oils, like cod liver oil and organ tissues like the liver. Meat and dairy also have high concentrations of vitamin A. Diets high in processed food do not contain sufficient vitamin A to maintain the proper cell cycle balance and so we get too much proliferation and too little apoptosis. Tissues grow and grow and do not die.

Alcohol intake reduces the body’s ability to metabolize retinoic acid because alcohol and the retinoic acid pathway use the same enzymes – alcohol dehydrogenase (ADH1) and aldehyde dehydrogenase (ALDH1) for metabolism. Alcohol competes for the enzyme and so vitamin A from diet cannot be converted to the usable retinoic acid.

Can Toxins Disrupt the Vitamin A Pathway?

Yes, but here is where it gets complicated. Environmental toxins like glyphosate used in common weed killers such as Round-up have a complex relationship with the vitamin A pathway and hormone metabolism. These herbicides and many pesticides are endocrine disruptors, meaning they disrupt ‘normal’ hormone metabolism, often towards a hyper-estrogenic state. Similarly, plastics like BPA and a host of industrial chemicals are also endocrine disruptors that move us towards hyper-estrogenism – a key component of fibroid and endometriosis.

Glysophate activates an enzyme called retinaldehyde dehydrogenase which increases retinoic acid synthesis. This is argued to be the mechanism by which environmental exposures during pregnancy cause birth defects. However, glyphosate also inhibits vitamin A metabolism by a similar mechanism as alcohol, by competing for ADH1 availability, thereby having the ability to reduce vitamin A synthesis. Glyphosate also increases aromatase activity (the enzyme that converts testosterone to estradiol), creating a hyper-estrogenic state and depending upon the time course and the exposure concentration, completely wipes out aromatase activity. So like any true hormone system, that uses a complex chain of compensatory reactions to maintain homeostasis, the reactions to environmental toxins are complicated and non-linear. Nevertheless, they warrant attention, particularly when one is suffering from a condition affected by the environmental toxin in question.

Managing Vitamin A Levels

To determine if you are vitamin A deficient, seek out a lab that specializes in micronutrient testing. The recommended daily values of vitamin A can be found in the Dietary Supplement Fact Sheet.

Vitamin A is a fat-soluble vitamin, meaning that it will be stored in fat, and toxicity from too much vitamin A is possible. It is rare, but nevertheless, if supplementing, vitamin A levels should be monitored by micronutrient testing.

My Two Cents

Much of the research presented here linking local vitamin A deficiencies with endometriotic, fibroid, and cancer growth has not crossed over into clinical care. Moreover, it is complex and far from settled. Except for cancer trials, mostly in males and mostly with oral supplementation, the research regarding dietary vitamin A is limited and mixed. However, I think a local application of an absorbable form of vitamin A or retinoic acid should be investigated for the treatment of endometriotic and fibroid growth in women. Similarly, dietary supplementation within acceptable levels and changes combined with environmental ‘cleaning’ may be of use, if only to improve the overall health status of women currently suffering from fibroids or endometriosis.

Postscript: This article was published previously in August 2013. 

Photo by Tamanna Rumee on Unsplash.

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Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.

5 Comments

  1. I’d like to offer another perspective, if anything just leave alternative information for the inquiring mind. I am still only one month into this, but I am seeing some very interesting progress across the board. And so are my friends. Mind you I rejected this information for several years. Until I got really sick this March. And it completely baffled me.
    Now, I already know about the theory that getting sick actually expunging stuff. Not because of some invasive attacker. And that is a theory that is 100% consistent with my own experiences. I’ve only ever gotten sick when I’ve been heavily poisoned. Immune system reacting violently to get rid of stuff… It also coincided with me taking a break from drinking coffee.

    My theory?

    I started dumping a lot of toxic bile as Garrett Smith so extensively talks about. Nausea, sciatic nerve VERY irritated (and prob has been for 15+ years, as I used to have very severe scoliosis, now 90% better) (Kjetil at mskneurology.com describes how irritation of the sciatic nerve is involved in POTS, the plot really thickens).

    So here’s my point:
    Carotenoids and true ‘vitamin’ A are actually poisons. Animals turning it into the storage form retinyl palmitate in order to get it the hell out of the way in the best way possible. Weight gain being a protective mechanism in order to protect the organs from swimming in toxins. PCOS and obesity often going together, yes? Fat stores toxins.
    Acne is another way for the body to eliminate toxins. As well as inflammation. It’s my understanding that depending on your genetic makeup, available nutrients and environment, the body can choose either of these strategies to deal with toxins. Cancer being an option as well, enveloping the toxins.
    The ultimate solution is to stop ingesting as many poisons as possible (you can never get to zero) and optimize elimination through urine and bile, and eventually the poop (which is why constipation is so detrimental on many levels).

    Improvements Im seeing so far:
    – Skin is better
    – Circadian rhythm has started adjusting automatically (gradual improvement in sleep, when dumping more bile and not having enough fiber = sleep quality suffers).
    – Problems with my left foot are improving and thus also gait, breathing, responding better to training (even further improvements in my Scoliosis even though I was told I probably should not expect it).
    – PMS symptoms significantly improved, last cycle I barely even noticed except for the increased need for sleep
    – lips are peeling less
    – body recomp, a lot less bloated too
    – improved cognition

    I did stop eating liver and taking vitamin A about a year ago. Stopped taking vitamin D 2 years ago. I am dark skinned and live in Scandinavia. I am coping increasingly better during winters. In fact my mood is more stable and is thrown off a bit with spring time due to histamine. Def tied into these seemingly severe liver issues I’ve acquired over the years, maybe even had since birth.
    Garrett also covers why all this stuff ties into vitamin B deficiencies. I never could wrap my head around why so many people seemingly have deficiencies, do better with a few doses and just never get the same response again. Even with large doses.
    For a while I had figured there was something unspecific (some of them have sulfur in their structure e.g.) about B vitamins rather than it being specific deficiencies being covered when supplementing with Bs. And surely enough Garrett Smith explains how the B vitamins bind to aldehydes, a build up from impaired liver function and being vitamin A toxic.
    I’ve stopped taking Bs and am still seeing improvements.

    I am doing my own version of what Garrett, Matt and Grant have all been doing. That’s the whole point. Figuring out what will work for you. But it’s been valuable to read about their experiences, take them and learned from them. Added up they probably have over a decade’s worth of research on this topic. Plus the very tangible observations to go with it. Garrett works with clients where he gets to see cause and effects faster than people not working with clients. Isolated lab experiments also falling short when it comes to navigating the real world.

    Grant Genereux:
    https://ggenereux.blog/2016/04/22/ending-the-mystery-of-auto-immune/

    Matt Stone:
    https://180degreehealth.com/vitamin-depletion-discussion-dr-garrett-smith/
    https://180degreehealth.com/vitamin-vitamin-villain/

    Garrett Smith (do check out all his YouTube videos if you want a digestible introduction):
    https://nutritiondetective.com/

    Hope this information finds whoever may need it.

    I am not posting it to be disrespectful towards this post and the author. Just sharing something that’s incredibly helpful to not only myself, but also people in my circle who are testing this out with me. The results are honestly baffling.

  2. It’s polyunsaturated fats that are causing it. It takes 4 years to get it out of the body once you stop eating it. Your body needs sugar to break down protein and it needs saturated fat to break down sugar. If the fat your eating is not saturated then you will get every disease in the book. Butter your vegetables. Butter your food and cut out the fish and fish oils and nut butters and nuts and seeds and seafoods and vegetable oils…. anything that is polyunsaturated fat… don’t eat it. Use butter…. and your 4 years from better health.
    http://raypeat.com/articles/articles/unsuitablefats.shtml

  3. This article is of high scientific caliber and an in-depth look at the link between nutrition and women’s hormones and health. Unfortunately, the medical community is decades behind and nutrition is almost completely ignored. in my experience with over 6500 patients (over 90% women), vitamin deficiency or insufficiency is almost exclusively due to malabsoprtion, intestinal bacterial overgrowth with influx of cytokines into the circulation derailing the hormones from adrenal, sex steroids to thyroid and pituitary hormones. There is a silent epidemic of gluten and lactose intolerance. wide-spread use of proton pump inhibitors that kill stomach acid and cause bacterial overgrowth and malabsorption of multiple nutrients including vitamin A. The best clue of vitamin A insufficiency is low vision and low night vision and excessive glare at night- It can also present with dry skin. The best way to measure vitamin A is to measure the 4 components, also called fractionated vitamin A: alpha and beta carotenes, lutein and zeaxanthines. Once these are low, the best strategy is to look for malabsoprtion since deficiency in affluent countries almsot exclusively due to malabsorption. Thank you. Shirwan Mirza, MD/ Endocrinology, Metabolism and nutrition..https://www.facebook.com/MECFSmetabolicapproach/

  4. Yes! This is an incredibly astute analysis. “Estrogen dominance” can be fostered by “xenoestrogens” or environmental estrogens like pesticides and plastics, but also through changes in gut flora where these estrogens are recirculated rather than excreted, and where vitamin A disruption can also have secondary effects on estrogen as well as critical amino acids like tryptophan. Therapeutic vitamin A trials are absolutely warranted. Thanks for this discussion…women are lucky to have this resource!

    • Thank you for the kind words. What I find particularly interesting is how many nutrient deficiencies we are likely to live with. We all know about the major ones and their associated symptoms but very rarely does the research ask whether or how these impact women in particular. In fact, very little research asks how a particular drug/vaccine/toxin impacts women beyond the basic fertile or not.

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