Calcium D glucarate
Calcium D-glucarate is a naturally occurring chemical compound that can be found in the human body or foods like orange, apple, broccoli, etc. It is a calcium salt in combination with glucaric acid. It is similar to glutaric acid. Instead of converting into sugar, it gets converted into D-glucaro-1,4-lactone that further blocks the enzyme beta-glucuronidase. It is very useful for preventing certain types of cancers. While playing its role, it reduces the level of estrogen, so specifically, works against hormone-dependent cancer like breast cancer and prostate cancer. Additionally, it works by removing toxins from the body, detoxifying the cancer-causing agents and steroid hormones.
Functions:
Calcium D-glucarate built-up the immune system to defend against other toxic substances in the body along with the steroid hormones. Because of the presence of metabolite D-glucaro-1,4-lactone, it works in the favor of glucuronidation, which is a mechanism of eliminating toxin and steroid hormones. In this process, various toxic compounds are neutralized such as polycyclic aromatic hydrocarbons and nitrosamines, and excess steroid hormones. This process occurs by the addition of carcinogenic compounds to glucuronic acid resulting in the formation of glucuronide-bound toxins with the help of glucoronysyl transferase, which can be eliminated by the body through urine and bile.
Role of beta-glucuronidase:
It interrupts the detoxifying ability of the liver, as a result of which toxins enter into the blood again. This further results in inflammation in the body.
Highlighted role:
Improves detoxification: It improves the removal of toxic substances.
Hormonal balance: in the case of the extra undesired hormone, it removes the unwanted hormones from the body.
Reduce cholesterol: It reduces LDL cholesterol and triglyceride level
Act as an antioxidant: protecting free-radical damage.
Role of Calcium D-glucarate:
Glucuronide bounded products get deconjugated, If there is no need for removal of glucuronide substances then beta-glucuronidase acts for the re-release of these harmful toxins inside the body. Here comes the role of Calcium D-glucarate, it acts upon beta-glucuronidase, and inhibits this conjugating enzyme. This results in increased glucuronidation, hence the detoxifying mechanism.
Some animal studies also stated that oral administration of calcium glucarate resulted in a decrease in beta-glucuronidase activity in the patient suffering from breast cancer, liver cancer. Prostate cancer, and skin cancer. After ingestion, it gets converted into D- glucaric acid aided by gastric HCL. It is metabolized slowly, approx. 5 hrs.’ or more, hence maintaining the level of D-glucaro-1,4-lactone for a longer time, as it is a precursor of D-glucaro-1,4-lactone.
Food Resources:
The citric acid (21% elemental calcium) and calcium carbonate( 40% elemental calcium) leafy vegetables are the major resources for Glucaric acid.
Examples are grapefruit, oranges, lemons, apples, peaches, plums, cabbage, Brussels sprouts, spinach, broccoli, cauliflower, alfalfa sprouts, potatoes, corn, cucumber, lettuce, celery, green pepper, and tomato.
Studies reveal that in lettuce, glutaric content is 0.1 grams per kilogram (2.2 lbs.), and an apple and grapefruits 3.5 grams per kilogram.
In Pregnancy, it should be avoided due to lack of clinical evidence.
Applications:
There is not much evidence for clinical trials for calcium-glucarate but there are many animal-based studies that resulted in healthcare outcomes of calcium-glucarate.
- Level of estrogen:
Playing its role, the liver eradicates excess hormones like estrogen and estradiol, with the consumption of Calcium D-glucarate. Studies showed that it lowered the level of blood estradiol by 28%. Another study stated that a combination of supplements containing DIM (diindolylmethane) and Calcium D-glucarate resulted in improved estrogen metabolism within 28 days (Matsugo et al., 2011) (Laidlaw et al., 2010).
In the case of fibroids, and polycystic ovary syndrome, some healthcare professionals recommend a 1000 mg – 3000 mg dose of Calcium D-glucarate.
2. Lowering the cholesterol level:
Some studies reveal that it reduces LDL level in the blood, which was observed in a study of rats in which consumption of Calcium D-glucarate prevented the development of high cholesterol levels.
3. Role in preventing cancer.:
Because of the tendency of Calcium D-glucarate of detoxifying the liver and other benefits on liver functioning, it suits beneficial in cancer treatment or lowering the risk of cancer, which is also explained by some of the studies.
Lung cancer: Beta-glucuronidase retards the removal of Cancer-causing toxins so increases the lung cancer risk, Calcium D-glucarate degrades Beta-glucuronidase, hence increasing the prevention of lung cancer-causing chemicals. This was observed while increasing doses from 1.5 g to 9g per day for 6 weeks.
- Estrogen and Breast Cancer: In the rat study, it was observed with lowering the tumor in hormone-dependent cancers like cervical and breast cancer, estrogen got cleared out from the body.
- Others: Calcium D-glucuronidase prevents wasting of muscles, hence reducing inflammation and enhance the natural death of cancerous cells.
Shrinking was observed in colon and liver cancer, or if calcium D-glucuronidase is present in diet it will reduce the formation of skin cancer.
If calcium D-glucuronidase is applied to the skin it reduces the chances of skin cancer.
- As an antioxidant: In another study, it was observed to reduce the chances of organ failure in diabetic rats.
Side effects:
There is no clinical evidence stating the safety of calcium D-glucuronidase so there might be side effects also and one should contact the health professional immediately if he or she observes a side effect.
There is no side effect observed in the clinical trial, even with high doses of 27 grams per kilogram of body weight and excess amounts of acid are removed through urine.
Drug interaction:
While taking Calcium D-glucarate the person should be in contact with a doctor because the drug interaction may cause some unfamiliar responses. It may induce the removal of some pharmaceuticals from the body. Some of the drugs that need to be carefully taken along with Calcium D-glucarate include acetaminophen, digoxin, statins, benzodiazepines, opioids anticonvulsants, and some antibiotics.
Dosage:
Usually, 1.5-3grm of the daily dose is preferred for Calcium D-glucarate uptake, while in cancer patients 1.5 to 9 grams of the dose is generally recommended.
Supplementation:
It is found naturally and the supplements are available in the form of 200mg, 300mg, and 500mgcapsule. Oral consumption is generally preferred as the detoxification action occurs in the gut.
Firstly DIM is used to neutralize toxic substances in the liver known as phase one detoxification, while the calcium D-glucarate is the 2nd phase detoxifying agent. In addition to DIM, it acts synergistically. In a study, 200mg, 300mg, and 500mg, improved the level of estrogen in 28 days. DIM and Calcium D-glycerate, both are available as separate supplements and also in combination. They act as a detoxifying agent and balance hormonal levels. DIM 100-200mg daily can be taken alone.
KEYWORDS: Breast cancer, Prostate cancer, Skin cancer, Lung cancer, liver cancer, Calcium salts, Glucuronidation, cancer risks, estrogen, cholesterol level.
REFERENCES:
(No Title). (n.d.-a). Retrieved June 24, 2021, from http://www.c4oh.org/monographs/pdr_dhea.pdf
(No Title). (n.d.-b). https://doi.org/10.1177/1947603516686146
(No Title). (n.d.-c). Retrieved June 24, 2021, from http://orthomolecular.org/library/jom/2001/pdf/2001-v16n02-p083.pdf
[Anticarcinogenic effect of potassium salts of glucaric and glucuronic acid in induced models of cervical and esophageal tumors] – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/23607211/
[The biological role of D-glucaric acid and its derivatives: potential use in medicine] – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/18772850/
Abou-Issa, H., Koolemans-Beynen, A., Minton, J. P., & Webb, T. E. (1989). Synergistic interaction between 13-cis-retinoic acid and glucarate: Activity against rat mammary tumor induction and MCF-7 cells. Biochemical and Biophysical Research Communications, 163(3), 1364–1369. https://doi.org/10.1016/0006-291X(89)91129-7
Barash, U., Spyrou, A., Liu, P., Vlodavsky, E., Zhu, C., Luo, J., Su, D., Ilan, N., Forsberg-Nilsson, K., Vlodavsky, I., & Yang, X. (2019). Heparanase promotes glioma progression via enhancing CD24 expression. International Journal of Cancer, 145(6), 1596–1608. https://doi.org/10.1002/ijc.32375
basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/8517653/
Bhattacharya, S., Manna, P., Gachhui, R., & Sil, P. C. (2011). D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway. Toxicology and Applied Pharmacology, 257(2), 272–283. https://doi.org/10.1016/j.taap.2011.09.013
Calcium-D-glucarate – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/12197785/
Calcium glucarate prevents tumor formation in mouse skin – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/12747003/
Cremer, D. R., Rabeler, R., Roberts, A., & Lynch, B. (2006). Safety evaluation of α-lipoic acid (ALA). Regulatory Toxicology and Pharmacology, 46(1), 29–41. https://doi.org/10.1016/j.yrtph.2006.06.004
Dwivedi, C., Heck, W. J., Downie, A. A., Larroya, S., & Webb, T. E. (1990). Effect of calcium glucarate on β-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochemical Medicine and Metabolic Biology, 43(2), 83–92. https://doi.org/10.1016/0885-4505(90)90012-P
Gasbarrini, G., & Mangiola, F. (2014). Wheat-related disorders: A broad spectrum of “evolving” diseases. United European Gastroenterology Journal, 2(4), 254–262. https://doi.org/10.1177/2050640614535929
Hadzik, B., Grass, H., Mayatepek, E., Daldrup, T., & Hoehn, T. (2014). Fatal non-accidental alpha-lipoic acid intoxication in an adolescent girl. Klinische Padiatrie, 226(5), 292–294. https://doi.org/10.1055/s-0034-1372622
Hanausek, M., Walaszek, Z., & Slaga, T. J. (2003a). Detoxifying Cancer Causing Agents to Prevent Cancer. In Integrative Cancer Therapies (Vol. 2, Issue 2, pp. 139–144). https://doi.org/10.1177/1534735403002002005
Hanausek, M., Walaszek, Z., & Slaga, T. J. (2003b). Detoxifying Cancer Causing Agents to Prevent Cancer. In Integrative Cancer Therapies (Vol. 2, Issue 2, pp. 139–144). Sage PublicationsThousand Oaks, CA. https://doi.org/10.1177/1534735403002002005
Kolodziejczyk, J., Saluk-Juszczak, J., & Wachowicz, B. (2011). In vitro study of the antioxidative properties of the glucose derivatives against oxidation of plasma components. Journal of Physiology and Biochemistry, 67(2), 175–183. https://doi.org/10.1007/s13105-010-0061-3
Laidlaw, M., Cockerline, C. A., & Sepkovic, D. W. (2010). Effects of a breast-health herbal formula supplement on estrogen metabolism in pre- and post-menopausal women not taking hormonal contraceptives or supplements: A randomized controlled trial. Breast Cancer: Basic and Clinical Research, 4(1), 85–95. https://doi.org/10.4137/BCBCR.S6505
Macfadyen, A., & Ho, K. ‐J. (1989). D‐Glucaro‐1,4‐lactone: Its excretion in the bile and urine and effect on the biliary secretion of β‐glucuronidase after oral administration in rats. Hepatology, 9(4), 552–556. https://doi.org/10.1002/hep.1840090408
Matsugo, S., Bito, T., & Konishi, T. (2011). Photochemical stability of lipoic acid and its impact on skin ageing. Free Radical Research, 45(8), 918–924. https://doi.org/10.3109/10715762.2011.587420
Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate: retinoid combination – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/8297119/
Ohbuchi, K., Nishiumi, S., Fujitsuka, N., Hattori, T., Yamamoto, M., Inui, A., Azuma, T., & Yoshida, M. (2015). Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma. Evidence-Based Complementary and Alternative Medicine, 2015. https://doi.org/10.1155/2015/871832
Oredipe, O. A., Barth, R. F., Dwivedi, C., & Webb, T. E. (1992). Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis. Toxicology, 74(2–3), 209–222. https://doi.org/10.1016/0300-483X(92)90140-A
Reddy, B. S., Weisburger, J. H., & Wynder, E. L. (1974). Fecal bacterial β-glucuronidase: Control by diet. Science, 183(4123), 416–417. https://doi.org/10.1126/science.183.4123.416
Role of urinary beta-glucuronidase in human bladder cancer – PubMed. (n.d.). Retrieved June 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/6331654/
Saluk-Juszczak, J. (2010). A comparative study of antioxidative activity of calcium-D-glucarate, sodium-D-gluconate and D-glucono-1,4-lactone in a human blood platelet model. Platelets, 21(8), 632–640. https://doi.org/10.3109/09537104.2010.512210
Schmittgen, T. D., Koolemans-Beynen, A., Webb, T. E., Rosol, T. J., & Au, J. L. S. (1992). Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants. Cancer Chemotherapy and Pharmacology, 30(1), 25–30. https://doi.org/10.1007/BF00686481
Verma, A. K., Tiwari, A., Lionetti, E., Srivastava, A., Monachesi, C., Naspi Catassi, G., Gatti, S., Galeazzi, T., & Catassi, C. (2020). Status and contribution of CRISPR/Cas9 based gene-editing system in the development of a low-immunogenic wheat variety. https://doi.org/10.20944/preprints202002.0296.v1
Walaszek, Z., Hanausek-walaszek, M., Minton, J. P., & Webb, T. E. (1986). Dietary glucarate as anti-promoter of 7, 12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Carcinogenesis, 7(9), 1463–1466. https://doi.org/10.1093/carcin/7.9.1463
Walaszek, Z., Hanausek, M., Narog, M., Raich, P. C., & Slaga, T. J. (2004). Mechanisms of lung cancer chemoprevention by D-glucarate. Chest, 125(5 SUPPL.), 149S-150S. https://doi.org/10.1378/chest.125.5_suppl.149S
Waszkiewicz, N., Szajda, S. D., Konarzewska-Duchnowska, E., Zalewska-Szajda, B., Gałazkowski, R., Sawko, A., Nammous, H., Buko, V., Szulc, A., Zwierz, K., & Ładny, J. R. (2015). Serum β-glucuronidase as a potential colon cancer marker: A preliminary study. Postepy Higieny i Medycyny Doswiadczalnej, 69, 436–439. https://doi.org/10.5604/17322693.1148704
Xie, B., Liu, A., Zhan, X., Ye, X., & Wei, J. (2014). Alteration of gut bacteria and metabolomes after glucaro-1,4-lactone treatment contributes to the prevention of hypercholesterolemia. Journal of Agricultural and Food Chemistry, 62(30), 7444–7451. https://doi.org/10.1021/jf501744d
Zoltaszek, R., Kowalczyk, P., Kowalczyk, M. C., Hanausek, M., Kilianska, Z. M., Slaga, T. J., & Walaszek, Z. (2011). 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. Oncology Letters, 2(1), 145–154. https://doi.org/10.3892/ol.2010.221
