Size Matters When It Comes to Active Ingredients


Bigger is Not Better in Skin Care Products!

Have you ever ordered skin care products that contain “anti-aging” ingredients such as  Collagen, Elastin, or Growth Factors?  The suggestion to the consumer is that collagen and elastin somehow get into the skin to increase the level of these important proteins. In regard to growth factors the marketing “hype” is that growth factors stimulate your skin cells to produce more collagen, elastin and other important components. The result will be a younger looking skin, right? Unfortunately, it is likely that these ingredients will do very little, if anything, to improve your skin. Why? They are simply WAY too big to get into your skin. They will simply sit on top of the skin’s surface and will be washed away when you shower. So if you’ve spent a lot of money on products that contain these miracle “anti-aging” ingredients, the next time you take a shower, look down at the drain because that’s likely where these ingredients are going, along with your money.

How do we know that big molecules can’t get into the skin? Well, that’s where the “500 Dalton Rule” comes in. So what is a Dalton? Simply put it’s just a measure of size (mass) of a molecule but on a very tiny scale. For example the mass of vitamin C is 176 Daltons while the mature form of collagen in the skin has a mass of about 120,000 Daltons. Over 20 years ago two scientists, Drs. Box and Meinardi, conclusively showed that molecules larger than 500 Daltons CANNOT penetrate through the skin’s surface. This “rule” has been proven again and again over the years, and all dermatology drug companies that develop topical formulations know that any topical drug they develop needs to be smaller than 500 Daltons to easily penetrate through the skin’s surface. Examples of topical dermatology drugs on the market that follow this “rule”  include corticosteroids (hydrocortisone, clobetasol-both less than 500 Daltons), retinoic acid (300 Daltons), estrogen (272 Daltons), testosterone (288) and retinol (286 Daltons) to mention just a few.

So given this  “rule” which, for the past 20 years, has been proven to be completely accurate, what is the likelihood that  collagen, elastin, growth factors, hyaluronic acid, or even large peptides that exceed 500 Daltons, will be able to penetrate through the skin’s surface to reach the layers underneath? The answer is; not at all likely. If we look at the table below we can see just how big these popular ingredients are.

For the most part they are just going to sit on the surface of your skin and get washed away. In regard to HA (hyaluronic acid) although HA is way too big to penetrate into the skin, it can sit on the skin, and because it can hold 1000 times its weight in water,  it can provide a layer of water to the skin’s surface. This helps prevent a loss of water from inside the skin. However, in areas of low humidity, the use of HA in skin care products can be problematic. In very dry climates, water will evaporate from the HA sitting on the surface of your skin, and to replace it this molecule will want to attract water from somewhere. As a result of this affinity for water, it can pull water OUT of the skin, thereby dehydrating the skin.

Finally, any “anti-aging peptide” that is larger than 500 Daltons is also going have a difficult time getting into the skin. It should be noted that some scientific data has shown that since small molecules can also enter the blood stream through hair follicles, it is theoretically possible that large molecules like collagen, elastin, and growth factor could get into the skin through this route. However, since the percentage of the skin’s surface represented by hair follicles averages only 0.1-1% , there is little data to suggest molecules larger than the “Rule of 500” enter into the skin in any appreciable amount to exert significant effects on skin function.

The many “anti-aging” peptides that are in anti-aging skin care products will only penetrate through the skin’s “barrier layer” (the stratum corneum) in any appreciable amount if their size is less than 500 Daltons. Typically the peptides in skin care products range in size from 3 amino acids to over 10 amino acids. If one uses 110 Daltons as the average size of a single amino acid, one can predict the ability of any of these peptides to get into the skin by simply looking at the number of amino acids in the peptide. Any peptide with 5 amino acids or less (pentapeptide) has a chance to get into the skin, while peptides larger than 7 amino acids will find it difficult to enter the skin in any significant amount. The cartoon below gives you a visual idea of the challenge large molecules have in getting through the skin. The molecules shown here were drawn to scale to show the relative difference in their size. The molecules shown in green represent the size of the "500 Dalton Rule". Note how much bigger growth factors are than the size of the 500 Dalton molecules.

The best “rule of thumb” to follow when looking for skin care products that contain ingredients that can actually improve the skin, is to look for ingredients that are considered “Small Molecule Actives”. These will have a size less than 500 Daltons and will have credible scientific data to support their effects on skin. Examples that you are familiar include Retinol, Retinoic Acid, Vitamin C (aka Ascorbic Acid), and the small peptide, Matrixyl, to mention just a few. DermaMedics’ SMA, Therosol®, is another example of a very small molecule with significant benefits for the skin. Therosol® was discovered by research scientists at a major university medical school. The molecular weight of of this molecule is 166 Daltons, a size which allows it to move through the skin’s surface barrier very easily. For the reader interested in reviewing some of the science of DermaMedics’ SMA compounds, more information can be found by going to the U.S. patent and trademark website ( and selecting Dr. Fuller’s issued U.S. patents (U.S. patent numbers 9,622,950 and 9,616,006).

               Since  a molecular size under 500 Daltons is critically important for any molecule to be able to penetrate through the skin’s tough barrier layer and offer any benefits for improving skin, it is clear that for topically applied products one should remember that  “BIGGER IS NOT BETTER”.




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