Calcium-D-Glucarate's Effectiveness in Estrogen Balance: An Integrative Endocrine View

More than 50 hormones facilitate the orchestration of physiological processes within the human body. Even minor fluctuations in hormone levels can trigger significant alterations in function, potentially resulting in conditions that necessitate medical intervention. It’s also important to recognize that hormones interact intricately with each other. Changes in one hormone can impact the levels and functions of others. Maintaining a delicate hormonal balance, particularly in the context of estrogen, is pivotal for overall health in both men and women. Estrogen plays a multifaceted role in various physiological functions, ranging from reproductive to cardiovascular health. Calcium-D-Glucarate (CDG) has emerged as a promising natural supplement to support hormone balance by supporting the detoxification process and aiding in managing estrogen levels. 

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Understanding Estrogen Balance 

Estrogen is a steroid hormone associated with the female reproductive system and the development of female sexual characteristics. Still, it is also involved in male reproduction, as well as numerous other body systems including the neuroendocrine, vascular, skeletal, and immune systems. There are three major forms of estrogen, including estrone (E1), estradiol (E2), and estriol (E3). Estrogen levels rise during puberty, leading to the development of secondary sex characteristics in women. It also plays a role in regulating the menstrual cycle and ovulation. Estrogen peaks in the days leading up to ovulation, thins cervical mucus, and thickens the uterine lining to prepare for possible pregnancy. Estrogen also affects the reproductive health of men. Too little estrogen can diminish sex drive, while too much can cause erectile dysfunction and infertility. Estrogen regulates important processes outside of the reproductive system, including cholesterol levels, blood sugar, bone and muscle development, vascular circulation, collagen production in the skin, and brain function.

An imbalance in estrogen can manifest in various forms, including estrogen deficiency, estrogen excess, or estrogen dominance. These imbalances may arise from issues with estrogen production, metabolism, or a combination of both. Estrogen deficiency occurs when there is an insufficient amount of estrogen. This can arise from the natural aging process, autoimmune conditions, eating disorders, pituitary insufficiency, primary ovarian insufficiency, genetic conditions, and stress. On the other hand, excess estrogen involves higher-than-normal levels and can be due to liver problems, alcohol consumption, excess body fat, stress, certain medications, and exposure to xenoestrogens. Estrogen dominance occurs when estrogen levels are elevated relative to progesterone. Conditions associated with estrogen imbalance include:

• Menstrual irregularities
• Premenstrual syndrome (PMS)
• Polycystic ovarian syndrome (PCOS)
• Endometriosis
• Tender or fibrocystic breasts
• Fibroids
• Breast cancer
• Ovarian cancer
• Menopausal symptoms such as hot flashes and night sweats
• Osteoporosis
• Cardiovascular disease
• Mood disorders
• Cognitive changes
• Low libido
• Breast development in men (gynecomastia)

What is Calcium-D-glucate? 

Calcium-D-glucarate (CDG) is a form of D-glucaric acid, which naturally occurs in various fruits and vegetables and is produced in small amounts by humans. It is a calcium salt of D-glucaric acid found in certain plant foods like broccoli, Brussels sprouts, cabbage, and oranges. Calcium D-glucarate is also available as a dietary supplement. 

Glucuronidation is a phase II detoxification process in the liver, where various substances, including drugs, toxins, and hormones, are conjugated with glucuronic acid. This conjugation forms water-soluble glucuronides, which are more easily excreted from the body. Glucuronic acid improves liver detoxification by reducing liver cell apoptosis or cell death, reducing the production of reactive oxygen species (ROS) and supporting glucuronidation. When taken orally, CDG becomes D-glucaric acid, from which D-glucaro-1,4-lactone is derived. 

Beta-glucuronidase is an enzyme that can hydrolyze or cleave glucuronides. This enzyme is found in various tissues, including the liver, intestines, and certain bacteria in the gut. When glucuronides are deconjugated by beta-glucuronidase, the original substances are released and may be reabsorbed into the bloodstream. This recycling can extend the duration of certain substances in the body before final elimination. CDG’s derivative D-glucaro-1,4-lactone inhibits beta-glucuronidase, reducing the chances of the deconjugation process and promoting the effective elimination of glucuronides.

Using Functional Medicine Testing to Evaluate the Need for Calcium-D-Glucarate 

When considering CDG supplementation, functional medicine tests can help guide decisions by providing information on various aspects related to detoxification, hormone metabolism, and overall health.

Hormone Panels

There are various testing methods available to measure hormones, including blood, saliva, and urine. Although blood tests are the traditional choice for diagnosing endocrine conditions, there are advantages to saliva and urine tests, including providing non-invasive collection methods and revealing information about free or bioavailable hormone levels and hormone metabolism.

The Male Hormone Panel or Female Hormone Panel by Precision Point measures the levels of important hormones in the blood, including estrogen, for male and female health. The DUTCH Complete is a dried urine test that includes information on hormone metabolites and the daily rhythm of cortisol.

Comprehensive Stool Analysis

The GI Effects test by Genova Diagnostics analyzes microbiome composition, gastrointestinal inflammation, and digestive capacity. Certain bacteria in the gut can produce the beta-glucuronidase enzyme. High levels or overgrowth of these bacteria can contribute to high levels of the beta-glucuronidase enzyme. The GI Effects identify both intestinal dysbiosis and elevated levels of beta-glucuronidase that can contribute to poor estrogen elimination. 

Environmental Toxins

The Environmental Pollutants Profile by Us Biotek measures specific metabolites in the urine that can identify exposure to environmental toxins, including endocrine-disrupting chemicals (EDCs) and xenoestrogens like parabens and phthalates. Xenoestrogens are compounds that are structurally or functionally related to estrogen and can bind to estrogen receptors. EDCs can interfere with the body's production, transport, binding, action, and/or elimination of hormones. EDC exposure is associated with altered reproductive function and increased incidence of breast cancer.

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Clinical Applications of Calcium-D-Glucarate in Hormone-Related Conditions 

Estrogen dominance is associated with common hormone-related conditions such as PMS, PCOS, and endometriosis. Hormone fluctuations throughout the monthly menstrual cycle and higher estrogen levels can contribute to the severity of PMS symptoms. In PCOS, elevated estrogen levels are associated with insulin resistance. Estrogen stimulates the growth of endometrial tissue outside the uterus, leading to inflammation and pain in endometriosis. Hormones, including estrogen, can also stimulate the growth of some breast cancers. Due to estrogen’s role in all these conditions, optimizing estrogen metabolism has become an area of interest to help manage estrogen dominance and promote healthier hormonal balance.

Due to CDG’s promotion of glucuronidation, it has become a popular supplement for supporting estrogen metabolism. Studies have shown that CDG can help to manage breast cancer development and support estrogen levels in rats, but high-quality evidence from human studies is still lacking. 

Integrating CDG with Other Endocrine Therapies 

CDG can be considered part of a comprehensive and holistic approach to hormone balance, including other recommendations such as dietary changes, lifestyle modifications, and stress management. In some cases, medications and hormone therapies might also be recommended. Each person's hormonal profile and health condition are unique. Consulting with healthcare professionals, such as endocrinologists and integrative medicine practitioners, ensures an individualized approach that considers specific needs and goals. 

Diets higher in fiber, monounsaturated omega-3 polyunsaturated fatty acids, and phytoestrogens and lower in animal fats and refined carbohydrates are associated with reduced circulating estrogen levels (2, 31). Mediterranean-style diets emphasize fresh fruits, vegetables, legumes, whole grains, and healthy fats. The high proportion of fibers, unsaturated fatty acids, antioxidants, and polyphenols in this diet also helps support a healthy microbiome composition, which is important for optimal estrogen metabolism. This type of diet has been shown to not only support a host of chronic conditions but also help manage estrogen levels.

Reducing exposure to xenoestrogens is also important, as these compounds can interact with estrogenic pathways and impact estrogen metabolism. Avoid plastic exposure by using metal or glass water bottles and food storage containers. Also, try to use natural household and personal care products when possible. The EWG Skin Deep database is an excellent tool to help swap out current products for natural alternatives.

Under higher amounts of stress, the hypothalamic-pituitary-adrenal (HPA) axis produces more cortisol. Higher amounts of cortisol can negatively impact the body’s ability to produce progesterone, increasing the risk of developing estrogen dominance. Incorporating mind-body practices into our daily routines helps support balance in the neuroendocrine system and manage stress. Many types of mind-body practices exist, but some options include meditation, yoga, and breathing exercises.

In cases where hormonal imbalances are significant, hormonal therapies may be prescribed. CDG may complement hormone replacement therapy (HRT) or oral contraceptive pill (OCP) use by supporting the detoxification and elimination of hormones and their metabolites.

Dosage, Safety, and Side Effects 

CDG is taken orally, and dosage recommendations range from 1500 mg to 3000 mg daily. No side effects have been observed in animal studies, even at high concentrations, but more human studies are needed. Because some medications may be metabolized through glucuronidation in the liver, there is a hypothetical risk that CDG could affect their rate of elimination or effectiveness. Always check with your doctor before starting CDG in combination with other prescribed medications. 

Challenges and Limitations in CDG Research 

Research on CDG faces several limitations that hinder a comprehensive understanding of its potential health benefits. There are a limited number of human studies investigating the effects of CDG. While some preclinical studies and animal models suggest potential benefits, the extrapolation of these findings to humans is uncertain due to species differences and varying metabolic pathways. There is also a lack of standardized dosages and treatment regimens, making it challenging to establish optimal therapeutic strategies. Finally, comprehensive information about potential interactions with medications and long-term safety is limited. One challenge to consider in future CDG research is that individual response may vary due to factors such as genetics and diet (19). Research exploring the factors that influence individual responses is necessary.

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Calcium-D-Glucarate for Estrogen Balance: Final Thoughts

Calcium-D-glucarate has emerged as a potential therapy to support estrogen balance in hormone-related conditions. Preliminary studies suggest CDG's ability to support the detoxification of excess estrogen. However, ongoing research is necessary to understand CDG's mechanisms and efficacy more completely. While promising, individuals seeking to integrate CDG into their health regimen should seek professional guidance. Collaborating with healthcare professionals ensures a tailored approach, considering the nuances of individuals’ health histories.