Glucuronolactone

Last Updated: September 28, 2022

Glucuronolactone is a molecule commonly found as a component of energy drink formulations with surprisingly minimal research on it, given its societal usage.

Glucuronolactone is most often used for



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1.

Sources and Stucture

1.1

Structure

Glucuronolactone is a molecule that is commonly found in energy drinks (at around 10-60mg, with variance depending on brand), although in studies 'disassembling' the constituents of energy drinks suggest no significant contribution towards energy.[1][2]

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1.2

Biological Significance

In vitro, D-glucuronolactone can be metabolized by a dehydrogenase into D-Glucaro-1,4-Lactone (G14L), where D-glucuronolactone appears to metabolize into a dilactone (d-glucaro-1,4-3,6-dilactone) and then spontaneously degrade into G14L.[3]

D-Glucaric acid is the main urinary metabolite of the glucuronic acid pathway,[4][5] which synthesizes Glucuronic Acid for the purposes of conjugation by drug metabolizing enzymes (UGT transferases). Daily urine output of D-Glucaric Acid is approximately 30-100umol.[6][7]

Glucuronolactone is a prodrug for the compound D-Glucaro-1,4-Lactone

In animals (non-primapes) that are capable of synthesizing ascorbic acid (Vitamin C) endogenously, glucuronolactone is used as a pre-requisite for ascorbic acid.[8]

Can be used to synthesize Vitamin C in creatures capable of this conversion, which are not humans

1.3

Enzymatic Interactions

D-Glucaro-1,4-Lactone (G14L) appears to be an inhibitor of the β-Glucuronidase enzyme.[3]

2.

Pharmacology

2.1

Metabolism

Glucuronolactone can be formed when glucuronic acid is degraded in subcritical water interchangeably.[9]

3.

Cardiovascular Health

3.1

Blood Flow

1,4-GL can be seen as protective for blood vessel health by alleviating oxidative/nitrative damage to lipoproteins from reactive species such as hydroperoxide and peroxynitrate, as well as acting as an anti-platelet aggregative compound.[10][11] It may be synergistic with resveratrol in this regard.[12]

When consuming an energy drink (80mg caffeine, 1000mg taurine, 800mg Glucuronolactone; sugar free with B-complex), an overall increase in platelet aggregation appears to occur in otherwise healthy persons with infrequent energy drink consumption.[13] Participants refrained from caffeine for a week prior to testing, and the contribution of Glucuronolactone towards the observed effects was not established.[13]

4.

Skeletal Muscle and Performance

4.1

Aerobic Exercise

One study injecting glucuronolactone (100mg/kg) intraperitoneally in rats immediately prior to a 30 minute swim and subsequent rest (the swim which was repeated three times, each with an injection prior to the swim) noted that glucuronolactone failed to affect time to exhaustion in the first swim but improved performance relative to saline in the second and third swim.[14]

5.

Interactions with Cancer

Via its actions as a beta-glucuronidase inhibitor (of which too much activity is correlated with some forms of cancer), 1,4-GL can be seen as potentially anti-carcinogenic.[15] 1,4-GL and D-Glutarate also have potent anti-proliferative properties.[16]

References
1.^Mets MA, Ketzer S, Blom C, van Gerven MH, van Willigenburg GM, Olivier B, Verster JCPositive effects of Red Bull® Energy Drink on driving performance during prolonged drivingPsychopharmacology (Berl).(2011 Apr)
8.^Smirnoff NL-ascorbic acid biosynthesisVitam Horm.(2001)
9.^Wang R, Neoh TL, Kobayashi T, Miyake Y, Hosoda A, Taniguchi H, Adachi SDegradation kinetics of glucuronic acid in subcritical waterBiosci Biotechnol Biochem.(2010)
10.^Saluk-Juszczak J, Olas B, Nowak P, Staroń A, Wachowicz BProtective effects of D-glucaro-1,4-lactone against oxidative modifications in blood plateletsNutr Metab Cardiovasc Dis.(2008 Jul)
11.^Olas B, Saluk-Juszczak J, Nowak P, Glowacki R, Bald E, Wachowicz BProtective effects of D-glucaro 1,4-lactone against oxidative/nitrative modifications of plasma proteinsNutrition.(2007 Feb)
12.^Olas B, Saluk-Juszczak J, Wachowicz BD-glucaro 1,4-lactone and resveratrol as antioxidants in blood plateletsCell Biol Toxicol.(2008 Apr)
13.^Worthley MI, Prabhu A, De Sciscio P, Schultz C, Sanders P, Willoughby SRDetrimental effects of energy drink consumption on platelet and endothelial functionAm J Med.(2010 Feb)
15.^[No authors listedCalcium-D-glucarateAltern Med Rev.(2002 Aug)