Ingredient Incompatibilities

We’re starting a series about ingredient incompatibility that we usually see circulating on social media pages, and we want to dig deeper into the science behind them. The first pair we want to dive into is the Vitamin C and Niacinamide combo. We’ve seen quite a bit of posts saying not to mix both, but is there any scientific evidence to back this up?

One of the most popular one is the Vitamin C and Niacinamide combination. We get asked this all the time. Other experts have already weighed in to debunk this, but there is an interesting development in the last few years. Tune in to find out whether or not you can actually mix these two together.

Niacinamide conversion to Niacin

The hypothesis here is that Niacinamide can convert to Niacin which can cause flushing an irritation. KindofStephen did an awesome explanation on why this is unlikely, as it happens quite quite slowly and would require heat. Niacinamide is pretty stable even at 120C, so it hydrolyzing to Niacin isn’t a huge concert. We won’t be exploring this further as the explanation is complete.

Niacinamide-Ascorbic acid complex

In the video, we show that mixing aqueous solutions of Niacinamide and Ascorbic acid produced a yellow-colored substance. People were concerned that the formation of this complex may cause lesser penetration of the two molecules. Is it actually something to be concerned about?

This was first seen in 1945, when a yellow color was formed upon mixing the two compounds. The resulting complex was characterized to be reversible, a 1:1 complex with a maximum interaction at a pH of 3.8. As KindofStephen also explained in his blog, this interaction is a weak interaction where 50% of the molecules exist in a complex at pH 3.8, and 50% of them exist as individual molecules.

The concern is that when they are in a complex, they would not have the same ability as their individual counterparts. However, when the complex penetrates the skin, it becomes weaker and weaker as the pH becomes closer to neutral. Essentially the Niacinamide-Ascorbate complex penetrates the skin and dissociates once they reach the Stratum Granulosum.

Ascorbic acid is a charged molecule depending on the pH, so it has a bit of a hard time penetrating the skin. The mechanism mentioned above isn’t entirely new to Ascorbic acid penetration. Ion Pairing is when two oppositely charged molecules transiently bind together (ionic pairing), resulting in a “less” charged complex, making its penetration easier. So, in essence, it’s not much of a concern that Ascorbic acid forms a complex when penetrating the skin.

Should they be formulated together?

Interestingly, there are some papers that characterized the use of this complex to stabilize Ascorbic acid. One paper even found that the complex can reduce melanin production upon UV exposure. However, one interesting paper that was recently published showed that the rate of photodegradation of Ascorbic acid is faster (2-fold) in the presence of Niacinamide compared to without Niacinamide. Without Niacinamide, the values of the rate constants as measured by UV spectroscopy and HPLC range from 0.50 (pH 2.0) to 1.75 × 10−3 min−1 (pH 12.0). When Niacinamide is present with Ascorbic acid, the values double, 1.17 (pH 2.0) to 3.61 × 10−3 min−1 (pH 12.0). Even at lower pH, the photodegradation was still doubled compared to Ascorbic acid being alone in the solution. Not surprisingly, the rate increases with increasing pH. Thus, Niacinamide acts as a promoter of the photodegradation of Ascorbic acid.

Source: Ahmad, I., Mobeen, M. F., Sheraz, M. A., Ahmed, S., Anwar, Z., Shaikh, R. S., Hussain, I., & Ali, S. M. (2018). Photochemical interaction of ascorbic acid and nicotinamide in aqueous solution: A kinetic study. Journal of photochemistry and photobiology. B, Biology, 182, 115–121. https://doi.org/10.1016/j.jphotobiol.2018.04.011

The proposed mechanism of this photodegradation shows that Niacinamide (NA) absorbs a photon of light and is promoted to an excited state [1Na]. It is then converted to an excited triple state [3Na], which then reacts with Ascorbic acid (AH2) to form the reduced form of NA (NAH) and an ascorbyl radical (AH). NAH then gets oxidized by O2 to give NA and H202. The two AH. radicals combine to form one molecule of AH2 and one molecule of DHA. NA acts as an electron acceptor from AH2 to promote its degradation.Essentially, they shouldn’t be formulated together as, in the long run, Niacinamide promotes the photodegradation of Ascorbic acid.

References

Ahmad, I., Sheraz, M. A., Ahmed, S., Bano, R., & Vaid, F. H. (2011). Photochemical interaction of ascorbic acid with riboflavin, nicotinamide and alpha-tocopherol in cream formulations. International Journal of Cosmetic Science, 34(2), 123–131. doi:10.1111/j.1468-2494.2011.00690.x

Ahmad, I., Mobeen, M. F., Sheraz, M. A., Ahmed, S., Anwar, Z., Shaikh, R. S., … Ali, S. M. (2018). Photochemical interaction of ascorbic acid and nicotinamide in aqueous solution: A kinetic study. Journal of Photochemistry and Photobiology B: Biology, 182, 115–121. doi:10.1016/j.jphotobiol.2018.04.011

Bailey, C. W., Bright, J. R., & Jasper, J. J. (1945). A study of the binary system nicotinamide—ascorbic acid1,la. Journal of the American Chemical Society, 67(7), 1184–1186. doi:10.1021/ja01223a047

Guttman, D. E., & Brooke, D. (1963). Solution phase interaction of nicotinamide with ascorbic acid. Journal of Pharmaceutical Sciences, 52(10), 941–945. doi:10.1002/jps.2600521006

Milhorat, T. H. (1944). A color reaction of ascorbic acid with nicotinamide and nicotinic acid. Experimental Biology and Medicine, 55(1), 52–52. doi:10.3181/00379727-55-14453