Prototype Nutrition Ur Spray

Hot on the heels of their “anti-aging” pregnenolone and DHEA sprays, Prototype Nutrition have released another new topical product; an ursolic acid spray. Ursolic acid is a naturally-occurring compound found in small doses in things like the peel of apples, and in herbs such as rosemary and lavender, that has been linked to a whole host of health benefits.

Figure 1. Structure of Ursolic Acid

Ursolic acid has been found in animal models to reduce fat storage and increase fat burning through several mechanisms, [1][2] enhance glycogen storage, [3] improve cholesterol levels, [4] and perhaps most importantly, increase muscle mass. [5]

In June 2011 researchers at the University of Iowa published a study in a prestigious journal that found ursolic acid to be a promising candidate in the fight against both obesity and muscle-wasting. [5] They searched a computer database of over 1300 small bioactive molecules for one that would elicit the genetic responses necessary to reduce muscle-wasting during fasting and after nerve damage, using the mRNAs that are common to both mice and humans, hoping to find a substance that they would be able to test on mice, but for which the effects could be reasonably expected to translate to humans. The only compound that matched both search terms was ursolic acid, so that’s what their research concentrated on.

The results of their experiments were surprising – even to them. Ursolic acid increased muscle weight in fasted mice by 7%. This led them to test it on mice that were allowed to eat ad libitum (an unrestricted diet) with added ursolic acid. This resulted an increase in (anabolic) IFG1 mRNA expression and a decrease in (catabolic) atrogin-1 and MuRF1 expression in muscle tissue, and enhanced insulin/IGF-1 signaling, leading to muscle hypertrophy with simultaneous loss of body fat as shown in the graphs below.

Figure 2. Ursolic Acid Induces Skeletal Muscle Hypertrophy In Mice

This research was extremely promising, but some problems dogged the first wave of ursolic acid dietary supplements:

  • Ursolic acid (and related triterpene compounds) are poorly bioavailable by oral administration (probably less than 1% bioavailable), [6] meaning large doses are required to elicit the desired effects.
  • High-grade (90%+) extracts are prohibitively expensive, making lower-grade (~25%) extracts the only commercially viable basis for supplements.
  • Ursolic acid is extremely hydrophobic and does not dissolve in water, and only very poorly in traditional solvents, [7] making transdermal application unfeasible.

Figure 3. Structure of Sodium Ursolic Acetate

The new “Ur-Spray” from Prototype Nutrition aims to solve all of these problems by using a novel form of ursolic acid: the sodium salt of ursolic acid acetate.

  • By changing ursolic acid into its acetic acid ester, and then into the sodium salt of that ester, they have transformed an essentially nonpolar and insoluble compound to one with favourable solubility characteristics suitable for use in an isopropanol-based transdermal solution.
  • Transdermal application bypasses intestinal uptake and first-pass hepatic metabolism to get a greater amount of ursolic acid into circulation.
  • By significantly increasing bioavailability, higher quality extracts become more commercially viable, and lower doses are required. Ur-Spray uses an ursolic acid extract of around 95% purity.

References:
[1] Arch Pharm Res. 2009 Jul;32(7):983-7.
[2] Bioorg Med Chem. 2010 Feb 15;18(4):1507-15.
[3] Faktorov Regul. Sist. Org. (1976), 101-2.
[4] Bioorg Med Chem Lett. 2011 Oct 1;21(19):5876-80.
[5] Cell Metab. 2011 Jun 8;13(6):627–38.
[6] Biopharm Drug Dispos. 2007 Mar;28(2):51–7.
[7] Phytochemistry Letters. 2009 Apr 29;2(2):85–7.