Everyone is Talking About Mevalonic Acid

Mevalonic acid is the hot new cosmetic ingredient in the block. But what is it and what does it do?

The Chemistry

Mevalonic acid, also known as (3R)-3,5-dihydroxy-3-methylpentanoic acid, is a key precursor in the mevalonate pathway, a fundamental biosynthetic pathway that, in humans, produces vital molecules such as cholesterol, as well as steroid-based hormones such as testosterone, estrogen and progesterone, Figure 1. In the body, mevalonic acid can exist in two forms: the open-chain carboxylic acid or the closed lactone, with interconversion between the two being facile under physiological conditions. 

Figure 1: (a) (R)-Mevalonic acid, which can exist as either the open form (acid) or closed form (lactone) under physiological conditions; (b) Chemical structures of cholesterol, estradiol (estrogen), testosterone and progesterone. 

Biosynthetically, mevalonic acid is prepared from acetyl-coA through a cascade of reactions in the mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway. In the first step, two acetyl-CoA molecules condense to form acetoacetyl-CoA, Figure 2. HMG-CoA synthase mediates addition of another acetyl-CoA molecule, resulting in preparation of HMG-CoA, which then undergoes reduction via an aldehdye to give mevalonic acid. Mevalonic acid can then undergo further functionalization to give materials such as sterols (including cholesterol), heme, prenylated proteins and ubiquinone (coenzyme Q10). 

Figure 2: The first steps in the mevalonate biosynthetic pathway, where mevalonic acid can be further converted into biologically useful materials. 

The Cosmetic uses

Mevalonic acid and the corresponding lactone have been of interest to the cosmetic community for several decades. For example, a patent filed by Asahi Denka Kogyo KK in 1990 (JPH0499707A) included (R)-mevalonic acid in a cosmetic formulation to provide “a moist window and softness to the skin”. Later patents, for example from Beiersdorf AG, moved to use mevalonic acid (or the corresponding lactone) as a treatment for “treatment of the symptoms of intrinsic or extrinsic skin-ageing or in treatment of UV skin damage” (DE10148266A1).  The Beiersdorf AG patent from 2001 states that the inclusion of mevalonic acid (or lactone) can “promote formation of coenzyme Q10 in the skin”, which is a natural antioxidant produced by the body that protects the skin against free radicals that can cause aging, and also aids production of collagen and elastin. 

The Future

The inclusion of mevalonic acid within cosmetic items is starting to gain traction again. It’s being billed as a material that can deliver hydration – likely due to its ability to form hydrogen bonds with water molecules, locking water in the skin – and as an ingredient that can calm irritation and promote cell renewal. And there may be something to this. A study on mice from Japan has shown that application of topical mevalonic acid to areas where skin barrier function was compromised enhanced the skin’s recovery and resistance to damage in aged mice. This may have been due to the observed increase in HMG-CoA reductase activity and stimulation of cholesterol synthesis, where cholesterol is known to play a leading role in maintaining the skins barrier function with production declining as skin ages.  

How TRI can help

TRI can help with claim substantiation when using existing, or developing new, cosmetic ingredients. In particular, our penetration studies can show whether an active truly crosses the epidermis, delivering benefits within the skin itself. Contact us today to find out more!