Calcium D-Glucarate: A Closer Look at Hormone Regulation

Calcium D-Glucarate: A Closer Look at Hormone Regulation

Calcium D-glucarate is a popular supplement with some buzz these days. It is used for cancer prevention, liver detoxification, and hormone regulation, but few know why exactly it’s recommended. This article will discuss why it’s used and whether it’s a band-aid or a root-cause approach to chronic disease.

What is Calcium D-Glucarate?

First, let’s take a closer look at the compound itself. Calcium D-glucarate is a calcium salt of D-glucaric acid, a non-toxic compound found in many fruits and vegetables, especially grapefruits, apples, oranges, and even cruciferous vegetables, such as broccolini and Collard greens, but in trace amounts. (1)

Red and blue illustration of a nerve cell

Calcium D-Glurate and Liver Detoxification

The liver works 24/7 to help carry waste products out of your body. The liver has three phases of detoxification, and the middle or second phase, or Phase II, uses a process called glucuronidation, which involves processing end-metabolite hormones such as estrogen so that as end-metabolites, they can safely move out of the body. (2, 3) All steroid hormones, for example, are detoxified in the liver via glucuronidation.

Calcium D-Glucarate and Beta-Glucuronidase

Oral supplementation of Calcium D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microbiota heavily involved in liver detoxification. (4) This inhibitory enzyme can be produced excessively when our microbiome is compromised by a pathogenic bacterial foothold.

Beta-Glucuronidase Run Amuck

When our gut microbiota are thrown off, a state otherwise called dysbiosis generates a host of byproducts, which can lead to dysbiosis-associated changes. (5) Some common agents that can wreak havoc on our microbiome include antibiotics, such as clindamycin, and NSAIDs, such as ibuprofen. (6, 7) One of these dysbiosis-associated changes include overproduction of the beta-glucuronidase. (8)

But the danger here is that if there is excessive beta-glucuronidase in the body due to pathogenic bacteria having taken ahold in the gut, then these end-metabolites of estrogen can be cleaved at the junction of (soon-to-be-excreted) toxin, and glucuronic acid. The toxin can then stay in the body and lead to the formation of carcinogens in the bowel, increasing the risk of cancer. This whole process can lead to the promotion of enterohepatic recirculation, wherein a toxic soup of toxins, hormones, and even drugs circulates freely throughout the body. (9)

Black and orange human liver illustration

A deeper discussion of enterohepatic recirculation can be saved for a future article, but it has been shown to lead, for example, to higher estrogen levels, which in turn increases the risk for breast cancer. In other words, elevated beta-glucuronidase activity is associated with hormone-dependent cancers.

Calcium D-Glucarate Benefits

 

Enter the supplement, calcium D-glucarate, supposedly to the rescue. Studies indicate that calcium D-glucarate will prevent the excess beta-glucuronidase from cleaving the end-products of estrogen, allowing them to remain glucuronidated and excreted properly.

Beta-glucuronidase actively conjugates estrogens into their active forms, a process which is impaired by dysbiosis and results in less circulating estrogen, which may contribute to conditions such as obesity, metabolic syndrome, PCOS, cardiovascular disease, and cancer. (10)

Calcium D-glucarate is thought to confer protective properties against breast cancer via estrogen clearance.

In mice models, D-glucarates appear to suppress cell proliferation and inflammation and induce cell apoptosis. They can potentially support proper cell death to keep malignancy in check. (11)

Other compounds thought to inhibit breast cancer include diindolylmethane (DIM) and isothiocyanates (sulforaphane) found in cruciferous vegetables. (12) Hence, eat adequate amounts of these sulfur-rich foods.

In other words, it is thought that oral supplementation of calcium D-glucarate is a way of favoring the body’s natural defense mechanism by upregulating the clearance of carcinogens.

Is Excessive Beta-Glucuronidase a Calcium D-Glucarate Deficiency?

Is the above a leading question? Somewhat. Is it a rhetorical question? Well, kind of. But the short answer is no.

Taking calcium D-glucarate, though it may be highly indicated, especially as part of a naturopathic or functional treatment plan, is more a band-aid treatment than a root cause approach. In other words, the right question is, “What exactly is mediating or causing the excessive beta-glucuronidase-producing dysbiosis?”

In other words, the root cause isn’t even the dysbiosis. Dysbiosis is a symptom of an imbalance that likely has a multifactorial etiology that requires the assistance of a naturopathic physician or other integrative medicine practitioner.

The imbalance is occurring in the gut, and correcting whatever is causing the dysbiosis will improve symptomatology and potentially resolve the problem. Hence, taking calcium D-glucarate is a potential first step that should be part of a root cause-oriented approach to mitigate the effects of high estrogen, but it is only a band-aid.

Restoring Your Gut Microbiome

However, it’s best to start with restoring your gut microbiome by way of eliminating the instigators and mediators of dysbiosis, such as multiple rounds of antibiotics or a daily non-steroidal anti-inflammatory (NSAID) such as ibuprofen, regularly eating your food intolerances, eating a Standard American Diet (S.A.D.), being in constant fight-or-flight, or any other number potential culprits known to compromise gut function.

In other words, because the microbiome is one of the primary regulators of estrogen circulation, our hormones are more likely to remain in balance by taking care of our microbiome.

However, remember to consult your naturopathic doctor or your integrative medicine practitioner before considering introducing calcium D-glucarate into your supplement regimen.

Resources

  1. Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44. doi: 10.1177/1534735403002002005. PMID: 15035900.
  2. Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92. doi: 10.1016/0885-4505(90)90012-p. PMID: 2346674.
  3. Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9. PMID: 12197785.
  4. Gillis CC, Hughes ER, Spiga L, Winter MG, Zhu W, Furtado de Carvalho T, Chanin RB, Behrendt CL, Hooper LV, Santos RL, Winter SE. Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth. Cell Host Microbe. 2018 Jan 10;23(1):54-64.e6. doi: 10.1016/j.chom.2017.11.006. Epub 2017 Dec 21. Erratum in: Cell Host Microbe. 2018 Apr 11;23 (4):570. PMID: 29276172; PMCID: PMC5764812.
  5. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016 Apr 13;8(1):39. doi: 10.1186/s13073-016-0294-z. PMID: 27074706; PMCID: PMC4831151.
  6. Rogers MAM, Aronoff DM. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clin Microbiol Infect. 2016 Feb;22(2):178.e1-178.e9. doi: 10.1016/j.cmi.2015.10.003. Epub 2015 Oct 16. PMID: 26482265; PMCID: PMC4754147.
  7. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017 Sep;103:45-53. doi: 10.1016/j.maturitas.2017.06.025. Epub 2017 Jun 23. PMID: 28778332.
  8. Court MH. Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system. Drug Metab Rev. 2010 Feb;42(1):209-24. doi: 10.3109/03602530903209288. PMID: 19821798; PMCID: PMC6174030.
  9. Roberts MS, Magnusson BM, Burczynski FJ, Weiss M. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet. 2002;41(10):751-90. doi: 10.2165/00003088-200241100-00005. PMID: 12162761.
  10. Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. Biologiczna rola kwasu D-glukarowego i jego pochodnych; potencjalne zastosowanie w medycynie [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62. Polish. PMID: 18772850.
  11. Zoltaszek R, Kowalczyk P, Kowalczyk MC, et al. Dietary D-glucarate effects on the biomarkers of inflammation during early post-initiation stages of benzo[a]pyrene-induced lung tumorigenesis in A/J mice. Oncol Lett. 2011;2(1):145-154. doi:10.3892/ol.2010.221
  12. Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016;74(7):432-443. doi:10.1093/nutrit/nuw010
At-Home Hydrotherapy Treatments in Thirty Minutes or Less

At-Home Hydrotherapy Treatments in Thirty Minutes or Less

Used across cultures over millennia to reduce pain and encourage healing, hydrotherapy is one of the oldest forms of natural medicine. Dating back to Ancient Greece, Hippocrates, the father of modern medicine, believed hydrotherapy was a key healing resource.

Through detailed observation, Hippocrates concluded that our health is governed by a vital force or vis medicatrix naturae, meaning “the healing power of nature,” that is constantly working to maintain normal balance in structure and function within the body when confronted with injuries and disease (1).

Despite conducting his observations and analysis over two-thousand years ago, his theories on hydrotherapy were not off the mark. And though the precise mechanisms are still a mystery, the evidence-based results are astounding.

Hydrotherapy is known to improve our body’s natural vitality by aiding detoxification, relieving inflammation and pain, enhancing relaxation and metabolic processes, lowering blood pressure, and stimulating blood flow to vital muscles and organs, among many other benefits (2,3).

How exactly does it work? Let’s take a closer look: Cold water stimulates the body, causing the constriction of surface blood vessels, directing blood to vital organs. Hot water, on the other hand, relaxes the body, causing the dilation of blood vessels, directing the removal of bodily waste. Thus, by alternating between hot and cold, we’re helping our body stimulate circulation, decrease inflammation, and improve homeostasis — allowing the body to naturally heal itself (3).

In this time of uncertainty atop millions of Americans already struggling with a chronic disease, such as obesity, type 2 diabetes, hypertension, and heart disease, it’s more important than ever to boost our natural vitality (4).

Only by supporting and enhancing the efficacy of the vital force can we truly realign with the laws of nature and prevent (as well as reverse) chronic disease. By folding regular hydrotherapy routines into our daily lives, our health will only reap the benefits.

Many different types of hydrotherapy methods exist, but with less access to health centers and spas, we must get creative. Thankfully, there are a few easy ways to take advantage of its healing effects at home. This can include steam rooms and saunas, hot springs, showers and baths rich in magnesium salts, and foot soaks. If possible, take advantage of any nearby waters, as swimming in cold rivers, lakes, and oceans can significantly decrease tension, pain, and fatigue while increasing memory and mood (3). Generally, it’s best to always end with some form of cold, even if it’s 30–60 seconds in a cold shower.

  1. While lying flat on your back, cover the anterior torso with two hot large hand towels folded in half (four thicknesses or layers of terry cloth) soaked in hot water tolerant to touch, and leave in place for five minutes.
  2. Replace hot towels with one cold large hand towel folded in half (two thicknesses or layers of terry cloth), leaving in place ten minutes or longer, until the towel is warmed.
  3. Cover body with a blanket, preferably wool or Vellux, to retain body heat during the length of treatment.
  4. Repeat the entire procedure on your posterior torso while lying face down.

*This version might require someone assisting you in placing the towels.

  1. Immerse the entire body in a hot bath or shower for five minutes.
  2. Then, dry quickly with a towel and soak another towel in cold water, wring out completely, and wrap around both sides of the torso, or from armpit to groin.
  3. Cover the body with wool or Vellux blanket, leaving the cold towel wrapped for twenty minutes, or longer, until the towel is warmed.
  1. Fioranelli M., Gianfaldoni R., Gianfaldoni S., Grazia Roccia M., Lotti T., Tchernev G., Wollina U. History of the Baths and Thermal Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535692/.
  2. Upendra Nagaich, Dr. Hydrotherapy: Tool for preventing illness. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932807/#:~:text=The%20advantages%20of%20hydrotherapy%20comprise,improving%20skin%20and%20muscle%20tone.
  3. Mooventhan A, Nivethitha L. Scientific Evidence-Based Effects of Hydrotherapy on Various Systems of the Body. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049052/
  4. Tackling the Burden of Chronic Diseases in the USA. The Lancet. Volume 373, Issue 9659, P185, JANUARY 17, 2009. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60048-9/fulltext