You probably don’t eat broccoli just for its high glucaric acid content. But this often-overlooked nutrient plays a key role in liver metabolism and is vital for your ability to remove toxins and excess hormones. Its cousin, calcium-D-glucarate, is used in supplements and promoted to deliver the same benefits, but the clinical evidence is scarce. Read on to learn its potential benefits, safety precautions, and unverified claims.
What is Calcium D-Glucarate?
Calcium-D-glucarate is the salt form of D-glucaric acid, a close chemical relative of glucose. Like sugar, glucaric acid is found naturally in many fruits and vegetables. But unlike sugar, the gut converts glucaric acid into a compound (D-glucaro-1,4-lactone) that blocks an enzyme called beta-glucuronidase [1, 2, 3, 4].
Beta-glucuronidase reduces the liver’s detox ability, allowing toxins to re-enter the blood. Diets rich in fat and protein increase the amount of beta-glucuronidase in the body. High levels of this enzyme have been linked to inflammation and certain forms of cancer [5, 6, 7, 8, 9].
By blocking this enzyme, calcium-d-glucarate may theoretically achieve the following [10, 1, 11, 12]:
- Improve detoxification: helps more effectively remove dietary, environmental, and drug-related toxins from the body
- Hormonal balance: lowers excess steroid hormones, like estrogen
- Reduced cholesterol: reduces LDL cholesterol and triglycerides
- Antioxidant: protects blood proteins and cells from free radical damage
Snapshot
Proponents:
- Helps remove toxins from the body
- Lowers excess estrogens
- May lower cholesterol
- Naturally present in fruits and vegetables
- Safe and well-tolerated
Skeptics:
- Limited research on benefits in humans
- Megadoses might be required for strong detox benefits
- Interacts with prescription drugs
- Long-term safety unknown
Food Sources
Glucaric acid is the naturally-occurring form of calcium-D-glucarate. While it is produced in small amounts within the body, the vast majority comes from your diet. It’s abundant in citrus fruits and leafy vegetables, some of the best sources being [2, 13]:
- Grapefruit, oranges, and lemons
- Apples, peaches, plums, apricots, and sweet cherries
- Cabbage, Brussels sprouts, spinach, broccoli, and cauliflower (cruciferous vegetables)
Other food sources include grapes, carrots, alfalfa sprouts, potatoes, corn, cucumber, lettuce, celery, green pepper, tomato, and mung bean sprouts.
Fruits and vegetables contain variable amounts of glucaric acid, ranging from 0.1 grams per kilogram (2.2 lbs) in lettuce, to 3.5 grams per kilogram in apples and grapefruit. However, studies are conflicted on whether a diet rich in fruits and vegetables provides enough glucaric acid for the detox benefits [14, 15].
Detox Properties
Your gut converts calcium-D-glucarate into glucaric acid, which helps the liver clear toxins. It improves phase II liver detox, allowing the removal of fat-soluble compounds like pesticides and other toxic chemicals [16, 17, 18].
Glucaric acid in the urine indicates how much demand is being placed on the liver, and more of it is lost when the body is under stress from toxins [19, 20, 21, 22].
Potential Health Benefits of Calcium D-Glucarate
Insufficient Evidence
No valid clinical evidence supports the use of calcium-glucarate for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.
1) Estrogen Levels
The liver removes excess hormones from the blood, including estrogen and estradiol, as well as estrogen-like chemicals found in the environment (xenoestrogens). Several weeks of high-dose calcium-D-glucarate lowered blood estradiol by 23% in animals [23].
In one clinical trial with 95 women, a combination supplement containing DIM (diindolylmethane) and calcium-d-glucarate – along with several other plant-based nutrients – improved estrogen metabolism after 28 days [24].
Based on this effect and clinical experience, some health professionals recommend calcium-D-glucarate supplementation at 1000 mg – 3000 mg daily for conditions involving high estrogen levels, such as PMS, fibroids, and polycystic ovary syndrome [25, 1].
However, there’s not enough clinical evidence to support this practice.
Animal and Cellular Research (Lacking Evidence)
No clinical evidence supports the use of calcium-glucarate for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
2) Cholesterol Levels
Animal studies revealed that calcium-D-glucarate lowers total and LDL cholesterol in the blood [26, 27].
One rat study showed that adding the active form of glucaric acid to the rats’ diet prevented them from developing high cholesterol [28].
3) Cancer Prevention
A great deal of research has investigated the role of glucaric acid in preventing and treating cancer, mostly in animals.
Several reviews have identified calcium-D-glucarate as a promising candidate for cancer prevention due to its safety and potential benefits on liver detoxification [11, 29, 30, 31].
Lung Cancer
In one clinical trial, calcium-D-glucarate reduced beta-glucuronidase in a sample of smokers and non-smokers. At high levels, this enzyme hinders the removal of cancer-causing chemicals, possibly increasing lung cancer risk. The dosage was increased from 1.5 grams to 9 grams per day over the 6 weeks [32].
That said, the clinical relevance of reducing beta-glucuronidase was not fully clear.
Excess Estrogens & Breast Cancer
Glucaric acid may help clear excess estrogens, and it was shown to reduce tumors in rats with hormone-dependent cancers, such as cervical and breast cancer [33, 34, 35, 36].
Other Cancer Types
Based on rat studies, calcium-d-glucarate might directly reduce inflammation, prevent muscle wasting, promote the natural death of cancer cells [37, 38].
Additionally, it could shrink the tumors of rats with liver and colon cancer [39, 40, 41].
Rats exposed to a liver carcinogen were less likely to develop tumors with calcium-D-glucarate in their diets [39].
Applied directly to the skin, glucaric acid also reduced the progression of skin cancer in rats [42, 43, 44].
4) Antioxidant Effects
In animals and test tubes, calcium-d-glucarate protected blood components (such as platelets) from chemical damage. It may act as an antioxidant, protecting cells from free radicals [45, 46].
In one animal study, the active form of calcium-D-glucarate prevented organ damage in diabetic rats [47].
Purported Benefits With No Evidence
Some people report benefits for:
- Weight control
- Hair loss
- Acne
- Increasing testosterone
- Bodybuilding
These are only anecdotal; research is lacking to support supplementing in such cases.
Limitations and Caveats
Despite promising animal studies, barely a handful of human clinical trials using calcium-D-glucarate exist. This makes it very difficult to discuss dosages or any specific benefits. We know it plays a role in healthy metabolism and is a natural part of our diet, but much less is known about its helpfulness as a supplement.
Calcium D-Glucarate Side Effects & Warnings
Side Effects
Keep in mind that the safety profile of calcium-glucarate is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one, and you should consult your doctor about other potential side effects, based on your health condition and possible drug or supplement interactions.
So far, the few clinical trials performed have shown no side effects or toxicity related to calcium-D-glucarate or glucaric acid. It was safe even at extremely high doses (27 grams per kilogram of body weight), as excess glucaric acid is removed through the urine. There is no known toxic or lethal dose [48, 1].
Pregnancy & Breastfeeding
If you’re pregnant or breastfeeding, avoid calcium-d-glucarate supplements due to the lack of safety data. There is no known risk of eating fruits and vegetables containing glucaric acid.
Drug Interactions
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
One major caveat to keep in mind is that increased liver detox may affect the metabolism of prescription drugs. Your liver could potentially remove pharmaceuticals from the body faster than normal with high calcium-D-glucarate consumption.
Drugs to pay additional caution to include acetaminophen, digoxin, statins, benzodiazepines, opioids, anticonvulsants, and some antibiotics.
“Detox Symptoms”
There is no research supporting the existence of “detox symptoms” with calcium-D-glucarate. Some users have complained of hormone-related problems resulting from supplementation. These include:
- Weight gain
- Bloating
- Acne
- Headaches
- Worsened PMS symptoms
- Emotional disturbances (depression, anxiety, mood swings)
People have reported similar side effects when starting new supplements, making major changes to their diet, and during “juice cleanses”. This has led to the labeling of these side effects as detox symptoms. However, studies of several detox diets did not find any symptoms directly related to improvements in liver detoxification [49, 50, 51].
Calcium D-Glucarate Supplements & Dosage
Calcium-glucarate supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.
Formulations
Glucaric acid is the natural form found in the diet, and calcium-D-glucarate is an ingredient in supplements. The supplements are typically sold as 200mg, 300mg, and 500mg capsules. Since the active form is processed in the gut, it is best taken by mouth.
With DIM
DIM (diindolylmethane) is another nutrient found in cruciferous vegetables. DIM improves Phase I liver detoxification, a crucial step for neutralizing toxins and excess hormones.
Calcium-D-glucarate helps Phase II detoxification, and may work synergistically when combined with DIM.
In one clinical trial with 95 women, a combination supplement containing DIM and calcium-d-glucarate – along with several other plant-based nutrients – improved estrogen metabolism after 28 days [24].
Both are available either as separate supplements or combined into products marketed for liver detox and hormonal balance. DIM is usually dosed at 100-200mg daily alone or in tandem with calcium-D-glucarate [52, 53].
Dosage
The below doses may not apply to you personally. If your doctor suggests using calcium-glucarate, work with them to find the optimal dosage according to your health condition and other factors.
In human trials for cancer prevention, dosages ranged from 1.5 to 9 grams per day, although the generally recommended oral dosage is 1.5 to 3 grams daily [1].
You would need to eat at least 1 kilogram (2.2 lbs) of fruit and vegetables in a day to get the same amount. But because of the lack of research, the optimal dosage and timing are still unknown.
Takeaway
Calcium-D-glucarate is the main ingredient in a number of detox supplements. Its relative, glucaric acid, is naturally found in various fruits and vegetables, such as grapefruit, apples, and broccoli.
The detox action of calcium-d-glucarate might help with many issues arising from the modern, industrialized lifestyle: toxic exposure, pollution, high environmental estrogens, and hormonal disturbances. Still, there’s almost zero clinical evidence to support its purported benefits in humans.
Calcium-glucarate appears to be safe when used in moderation, based on preliminary research. Children and pregnant women should avoid it due to the lack of safety data.
