Health Effects of Glucuronolactone
Even if you have never heard of it before, chances are you drank it. Glucuronolactone is a naturally-occurring substance and a lesser-known ingredient in energy drinks like Red Bull. It is also added to pre-workout supplements touted to increase physical performance, stamina, endurance, and detox. Find out if the popular claims about its benefits are substantiated.
What Is Glucuronolactone?
Glucuronolactone is a normal product of glucose breakdown in the liver. All connective tissues contain it, as well as many plant gums. The amounts found in food and those produced in the body, though, are negligible compared to the dosage in energy drinks and supplements [R].
Glucuronolactone is believed to aid in liver detoxification from hormones and chemicals. Unlike animals, though, humans can’t use this compound (or any other) to synthesize vitamin C. That’s why we need to obtain enough vitamin C from our diet [R+].
Glucuronolactone is an ingredient in certain sports and energy drinks, such as Red Bull. It is advertised as a supplement to enhance athletic performance, detoxify the liver, and reduce mental fatigue.
Glucuronolactone is considered safe by the Food and Drug Administration. It is readily available as a supplement in either functional energy drinks or in powder/capsule form. Surprisingly, though, research about the specific effects of this compound is very limited.
- Naturally occurring substance
- No reported side effects and toxicity
- Might have heart- and liver-protecting benefits
- May improve cholesterol levels
- Might aid in cancer prevention
- Combined with potentially harmful ingredients into energy drinks
- Lack of clinical trials
- Very few animal studies
- Animal studies only examined its breakdown products
What Does Glucuronolactone Do?
Glucuronolactone converts to glucuronic acid in the body. This conversion occurs back and forth; there are equal amounts of each molecule in the body [R+].
Glucuronic acid is involved in detox and the breakdown of glucose, as part of a specific pathway crucial for creating fatty acids, amino acids, and DNA components (known as the Pentose Phosphate Pathway) [R].
When you take in glucuronolactone, your glucuronic acid levels (in both blood and urine) will rapidly increase [R+].
Glucuronic acid plays a key role in the body’s detoxification through glucuronidation. During glucuronidation, glucuronic acid binds to chemical and environmental toxins, pharmaceutical drugs, and cancer-causing molecules. By joining with glucuronic acid, these toxins become [R, R, R]:
- More soluble
- Transported faster in the body
- Less toxic
- Eliminated through urine or feces
Another product of glucuronolactone breakdown is called D-glucaro-1,4-lactone. About 25% of glucuronolactone is quickly converted to it. This compound is a potent inhibitor of beta-glucuronidase, an enzyme dominantly produced by your gut bacteria. Various tissues can also make it in lower amounts (the liver, spleen, kidney, gut, endocrine glands and sexual organs) [R, R+].
Gut bacteria that make beta-glucuronidase can break down complex carbohydrates. However, this enzyme reverses the glucuronidation process, which slows down detox. Its levels rise with exposure to chemical and environmental pollutants, such as tobacco smoke and heavy metals [R, R].
High levels of beta-glucuronidase may point to [R]:
- Liver inflammation and cirrhosis
- Liver inflammation
- Cancers: brain, colon, pancreatic, breast and prostate
1) Protecting The Heart
In a study on human plasma, a product of glucuronolactone breakdown (D-glucaro 1,4-lactone) decreased damage to the blood proteins caused by free radicals. It reduced the excessive clumping of platelets that can lead to heart disease and stroke. This effect is amplified in combination with the antioxidant resveratrol, found in red wine [R, R, R].
2) Liver Health
Glucuronolactone might protect the liver by enhancing the glucuronidation detoxification pathway.
In rats with liver disease, D-glucuronolactone lowered liver inflammation (IL-6, NF-κB) and tissue injury markers. In addition, it increased antioxidant liver enzyme activity (SOD, glutathione, and the free-radical-scavenging glutathione peroxidase) [R].
3) Enhancing Exercise Performance
In a rat study, high doses of glucuronolactone enhanced physical performance and increased stamina given shortly before swimming exercises [R].
The effects of glucuronolactone on exercise performance and endurance have been widely studied, but only as an ingredient in functional energy drinks. Energy drinks contain numerous ingredients aside from glucuronolactone, including caffeine, taurine, glucose, and B-vitamins. Therefore, the observed benefits cannot be attributed to glucuronolactone alone.
Taking a pre-workout energy supplement (mix of caffeine, taurine, glucuronolactone, beta-alanine, creatine, and amino acids) 10 minutes before resistance exercises significantly increased workout performance in eight resistance-trained men [R].
In a clinical trial of 12 trained cyclists, consumption of Red Bull energy drink 40 minutes prior to exercise increased endurance and overall physical performance [R].
4) Cancer Prevention
Supplementation with a glucuronolactone breakdown product (D-glucaro 1,4-lactone) inhibited breast tumor growth in rats. It lowering sex hormones progesterone and estradiol, which contribute to the growth of breast cancer [R+].
In rats with liver cancer, the same compound increased survival rates from 45% to 70%. It also reduced the levels of a liver cancer marker (alpha-fetoprotein) [R].
This suggests that glucuronolactone might reduce cancer progression by relying on the effects of its breakdown products. It may help detoxify the body from cancer-promoting chemicals, hormones, and pollutants. However, clinical trials are much needed to substantiate these claims.
5) Cholesterol Levels
The mentioned glucuronolactone breakdown product (D-glucaro 1,4-lactone) prevented high cholesterol levels in rats eating a typical unhealthy Western diet, high in fat and cholesterol [R].
6) Attention and Memory
In a study of 36 participants, drinking Red Bull (composed of taurine, glucuronolactone, and caffeine) led to significant improvements in attention, concentration, and memory [R].
Drinking Red Bull resulted in improved driving quality, reduced variation in speed, and lowered mental strain from prolonged driving in 24 healthy volunteers [R].
In an observational study of 10 graduate students, drinking Red Bull led to faster motor reaction time, improved attention and decision making when compared to the control group [R].
Supplementation, Dosage & Side Effects
Glucuronolactone is most widely available as an ingredient of various energy drinks. One 250 ml can of Red Bull contains about 600 mg glucuronolactone [R].
Wine is the richest natural source of this compound with concentrations around 20 mg/L [R].
Glucuronolactone is also available as a supplement, including the following formulations:
- Powder (in bulk or smaller boxes)
- Capsules (500 mg/capsule)
In an average diet, glucuronolactone intake through food sources is estimated to be very low (1.2 mg/day) [R].
Drinking one 250 ml can of a glucuronolactone-containing energy drink will give you between 500-600 mg of glucuronolactone, depending on the brand. However, most manufacturers don’t specify the exact glucuronolactone content.
In supplement form, glucuronolactone is usually taken at 500-1000 mg/day. Such dosage recommendations can’t be scientifically verified, due to the lack of clinical studies on glucuronolactone alone.
In six healthy people, 1 g of glucuronolactone did not cause negative health effects [R+].
As mentioned previously, the effects of glucuronolactone in humans have otherwise only be evaluated using functional energy drinks. Any adverse effects mentioned here are due to energy drink consumption as a whole.
- Aggressive behavior: fighting, bullying
- Stress, anxiety, insomnia, depressive symptoms, suicidal ideation
- Negative cardiovascular impact: increase in blood pressure and heart rate
- Metabolic effects: obesity, increased risk of developing type 2 diabetes
- Dental decay
- Progression of chronic kidney disease
- Lack of sleep quality, fatigue/tiredness
- Stomach cramps/irritation
We can assume that a great deal of these effects could be due to caffeine, sugars, and other detrimental compounds in energy drinks that worsen HPA activation and may disrupt the circadian rhythm. This is especially dangerous for people prone to anxiety, insomnia, or for those with an existing heart condition. However, the exact contribution of glucuronolactone the risks is unknown.
The following ingredients are found in Red Bull, which was used in most of the cited studies:
|Ingredient||Dose (per 500 ml)|
|Niacin (Vitamin B3)||40 mg|
|Pantothenic Acid (Vitamin B5)||10 mg|
|Vitamin B6||10 mg|
|Vitamin B12||10 µg|
*The sugar-free version only contains Aspartame and Acesulfame K
The ingredients may vary in different countries.
There is no research on glucuronolactone interactions with prescribed medications or supplements.
Most glucuronolactone-containing drinks and supplements contain a wide array of stimulants and ergogenic aids. Consult your physicians before consuming them, especially if you take prescription medication, have heart or mental health problems.
Users taking glucuronolactone supplements generally report an increase in physical performance, stamina, improved mood, and reduced mental fatigue. However, it is important to mention that many users took this compound in combination with other performance-enhancing ingredients, such as caffeine, vitamin b12 and taurine.
Limitations and Caveats
Only energy drinks have been evaluated in clinical trials, while additional trials are required to evaluate the effectiveness and side effects of glucuronolactone supplementation alone.
Most animal and cell studies tested the effects of glucuronolactone metabolites, such as D-glucaro 1,4-lactone and D-glucaric acid, but not the direct effects of this compound.
While glucuronolactone shows some promise as a performance and energy enhancer, its clear benefits remain unknown. Most clinical studies used energy drinks, which contain many additional ingredients, some of which can have detrimental health effects. Used by athletes, however, such functional drinks do increase endurance, energy, and overall workout performance.
On the other hand, glucuronolactone may play a role in helping the body detox. It activates pathways that bind and flush drugs, pollutants, and toxins. While this may sound very appealing, the extent to which this compound affects detox remains to be determined.
People with anxiety and heart conditions should not consume energy drinks. If you’re considering glucuronolactone supplements, stay on the cautious side as information is lacking on its dosage and side effects.