Also known as pyrimidinecarboxylic acid, orotic acid is an intermediate in pyrimidine synthesis, which is required for DNA and RNA synthesis. It is naturally occurring in the diet; particularly in cow, goat, and sheep’s milk. Orotic acid is ultimately converted to betaalanine, which can subsequently be incorporated in anserine and carnosine.

Orotic acid enhances pyrimidine pools.

The body stores pools of pyrimidines and purines (such as ATP, GTP, CTP and UTP) and for use as energy sources, in cell signalling, and to participate in enzymatic reactions, and these pools can be taxed by intense and/or repeated exercise. [1]
Supplemental orotic acid may serve to replenish depleted pyrimidine pools.

Orotic acid may be nootropic

As a precursor of uridine monophosphate, orotic acid represents a source of bioavailable uridine. Although uridine is present in the diet, it is mainly in the form of RNA and not bioavailable. Several studies show nootropic effects of uridine, often in combination with choline and/or DHA

Orotic acid increases glycogen synthesis in muscle.

Orotic acid is also precursor of uridine triphosphate (UTP). UTP is converted by the enzyme UDP–glucose pyrophosphorylase to uridine diphosphate glucose (UDPG). Glycogen synthase then combines the glucose residues from UDPG into long chains of glycogen; the remaining UDP molecules can then be recycled back into the process. Skeletal muscle uses glycogen as a fuel source during strenuous and prolonged exercise. Experiments from the 1970s demonstrated that additional uridine increased the rate of glycogen synthesis (and thus that glycogen synthase was not the only rate-limiting step in the process). [2]

Orotic acid converts to beta-alanine, and may thus increase carnosine stores

Beta alanine is a product of the catabolism of uracil, a metabolite of uridine, of which orotic acid is a precursor. This process isn’t instant, but begins within minutes of absorption. [3] Orotic acid administration may therefore be viable alternative to beta-alanine, to avoid the paresthesia (‘pins-and-needles’) side effect associated with large doses (>750mg) of betaalanine. [4]

“Supplementation with mineral orotates or orotic acid may represent a practical strategy for boosting the level of carnosine and carnosine derivatives within the body.” [4]

Carnosine acts as a buffer to lactic acid, boosting muscle performance and reducing fatigue.

References:

[1] Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Yamakita J, Higashino K. Effect of muscular exercise on the concentration of uridine and purine bases in plasma–adenosine triphosphate consumption-induced pyrimidine degradation. Metab Clin Exp. 1997 Nov;46(11):1339–42.

[2] Haugaard ES, Frantz KB, Haugaard N. Effect of uridine on cellular UTP and glycogen synthesis in skeletal muscle: stimulation of UTP formation by insulin. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2339–42.

[3] Aonuma S, Hama T, Tamaki N, Okumura H. Orotate as a β-Alanine Donor for Anserine and Carnosine Biosynthesis, and Effects of Actinomycin D and Azauracil on Their Pathway. The Journal of Biochemistry. 1969;66(2):123–32.

[4] McCarty MF, DiNicolantonio JJ. β-Alanine and orotate as supplements for cardiac protection. Open Heart. 2014 Jan 8;1(1):e000119.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Although little-known in the USA, arecoline is the fourth most common self-administered psychoactive substance in the world — only behind after alcohol, caffeine, and nicotine.  No surprise, then, that it’s a potent stimulant that operates via multiple mechanisms of action:

-Arecoline is a non-selective agonist of muscarinic acetylcholine receptors.  The M1 receptor subtype, in particular, underlies Arecoline’s CNS stimulant and nootropic effects.  It is highly expressed in the central nervous system, regulates dopamine and adrenaline secretion in the brain, and is important to the processes of learning and memory.

-Arecoline is a weaker agonist at nicotinic acetylcholine receptors.  This also contributes to its stimulant effect, and may additionally impart anti-inflammatory activity.

-Arecoline has lipolytic effects and inhibits the growth of adipocytes.  Although the molecular mechanisms behind this are not well understood, it has been shown that arecoline inhibits GLUT4, an enzyme which shuttles glucose into fat cells.  Regardless of the mechanism, what is certain is that in addition to arecoline’s effects as a stimulant, it has a separate, and noteworthy, fat-burning effect.

Arecoline HBr is non-toxic at reasonable dosage levels — in most respects it is significantly less dangerous than caffeine.  With chronic oral use in a mouse model, no adverse effects were seen at doses lower than 100mg/kg/day — close to caffeine’s LD50.

Arecoline is a potent stimulant alkaloid, and is ideal for use in fat burner and pre-workout products.  Put the world’s third most popular stimulant to work for you.