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Let’s begin by clarifying the numerous terms that are seen when discussing vitamin B3, which is a water-soluble essential nutrient.
- Vitamin B3 is known as niacin or nicotinic acid (NTA).
- Niacinamide (NCA) or nicotinamide is the “amide” form of vitamin B3. What that means is that outside of the pyridine ring, the carboxyl group (COOH) of nicotinic acid has been replaced by a (carbox)amide group (CONH2). It is debatable whether or not the two forms interconvert between one another in vivo. It is known that when taken orally, NTA does convert to NCA in order to exhibit the known vitamin effects. However, it is unknown whether or not NCA converts to NTA. It seems likely that a small amount of NCA is metabolized to NTA. The amount appears to be negligible however, as NCA does not exhibit many of the same pharmacological effects (skin flushing, lowering of cholesterol) as does NTA.
Therefore, for the purposes of this skin care post, the two terms (niacinamide and nicotinic acid) will not be used interchangeably and will be discussed separately.
***Note that both NTA and NCA can however, prevent development of pellagra, or vitamin B3-deficiency when taken orally.
SO THE OBVIOUS QUESTION IS, “WHEN IT COMES TO THE SKIN, IS NTA BETTER THAN NCA?”
Unfortunately, the answer is unclear.
Background Information on NTA and NCA
Both NTA and NCA are important precursors of the cofactors niacinamide adenosine dinucleotide (NAD) and its phosphate derivative, niacinamide adenosine dinucleotide phosphate (NADP). These cofactors and their reduced forms (NADH and NADPH) function as redox (reduction-oxidation) coenzymes in a myriad of cellular biochemical reactions. I’m not sure if you remember high school biology, but perhaps you’ll recall using these abbreviations while studying the basic processes of cellular respiration and photosynthesis. Because they are precursors, both NTA and NCA have the potential to exhibit multiple effects on the skin, and they affect so many non-enzymatic and enzymatic biochemical reactions. In this aspect, they are on potentially equal footing. The main advantage of NTA is that, while it exerts vitamin effects on the skin (increasing levels of NAD and NADH), it may also have drug-like effects by interacting with NTA (G protein-coupled) receptors present in the skin. While that sounds impressive, even then the effects aren’t that different from those of NCA or are that “amazing.” NTA has been shown to enhance epidermal differentiation and act as an anticarcinogen, in addition to stimulating wound healing (by increasing skin levels of leptin). As you will see later in this article, NCA can also function as a mild exfoliant and be anticarcinogenic, albeit via sometimes diverging pathways. And wound healing has little to do with the average skin care routine, though of course it can help conditions that involve open lesions such as inflammatory acne. However, NCA also helps inflammatory acne, albeit again via a different pathway.
Now, the main disadvantage of NTA is that when applied topically, it has an unpleasant and undesirable side effect of intense vasodilation or skin flushing, which is mediated by the release of prostaglandin D2. Furthermore, because NTA has even more side effects when administered orally (including alterations in blood pressure, pulse, and/or body temperature), there are significantly fewer studies that document topical NTA as compared to NCA. So how good is NCA then?
There is a wealth of evidence supporting the benefits of topical NCA use. While some of the mechanisms by which NCA provides these skin benefits have yet to be elucidated, several clinical studies have demonstrated its capacity to exact these positive changes.
ANTIOXIDANT CAPACITY: NCA acts as an antioxidant mainly by increasing the levels of the reduced form of NADP, NADPH. While most of its beneficial properties can be attributed to this ability, in terms of antioxidant capacity, NCA can prevent NAD depletion during DNA repair of keratinocytes by inhibiting poly (ADP-ribose) polymerase (PARP), which may similarly help repair UV-induced DNA damage. Note that this is different than the antioxidant capabilities of compounds such as L-ascorbic acid (vitamin C) and polyphenols (such as green tea and pomegranate).
EPIDERMAL BARRIER FUNCTION: The stratum corneum (SC) or the top layer of the skin has the crucial responsibility to inhibit transepidermal water loss (TEWL). It does this in-part by synthesizing ceramides and other SC lipids, as well as stimulating keratinocyte differentiation in order to obtain adequate impermeability. However, various factors such as UV exposure, aggressive cleansing, and dermatological conditions can negatively affect the SC’s function. Fortunately, NCA has been shown to not only increase ceramide synthesis (by upregulating serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid synthesis), which has been demonstrated in clinical studies such as this one utilizing 2% NCA; but to also stimulate keratinocyte differentiation by influencing keratin (K1), which increases “epidermal turnover,” and of course by raising levels of NADP!
IRRITATION AND ACNE: An improved epidermal barrier, as described above, will naturally lessen the amount of irritation from negative environmental exposure. In terms of acne and other inflammatory conditions, NCA has the ability to inhibit neutrophil chemotaxis or the movement of inflammatory aspects of the skin’s immune system. At 4%, it was even shown to be comparable to 1% of the antibiotic clindamycin.
YELLOWING OF THE SKIN: As skin intrinsically ages, it begins to yellow due to the glycation of proteins known as the Maillard reaction. Glycation is when proteins and sugars (like glycose) cross-link and form complexes that are yellowish-brown in color; you could call them advanced glycation end-products (AGEs). Because NCA increases the levels of NADP, and its reduced form, it seems likely that NCA can inhibit oxidative processes, one of which is protein glycation.
FINE LINES AND WRINKLES: NCA has been shown to stimulate collagen synthesis and the epidermal proteins K1 (keratin), fillagrin, and involucrin, which are responsible for protein synthesis (collagen is a protein) and increasing skin hydration (by altering the natural moisturizing factor (NMF) as well as the structure of the SC). The SC of course, as we discussed above, inhibits TEWL. The cited study also shows clinical evidence of improvement in terms of skin yellowing or sallowness.
HYPERPIGMENTATION: Unlike tyrosinase-inhibiting ingredients like hydroquinone, arbutin, and kojic acid, NCA combats hyperpigmentation by inhibiting melanosomes transfer. As stated in our “The Biology of Skin Color“ post, melanosomes are the vesicles that transport and distribute melanin from melanocytes to the keratinocytes of the epidermis. The exact mechanism of this inhibitory action of NCA is unclear; though several clinical in-vivo studies have shown that NCA is effective against hyperpigmentation. While not as effective as hydroquinone, NCA represents an effective alternative. Of course, they can also be used together as combination therapy.
As stated in the introduction, the topical use of NCA for anti-aging purposes has been proven many times over. It is one of the best studied “cosmeceutical” ingredients available in our armamentarium. And while all of these attributes have been demonstrated in clinical studies, more in-vitro studies need to be done to elucidate the specific mechanisms by which NCA achieves these benefits.
Nicotinic Acid (NTA)
As mentioned earlier, the main disadvantage of NTA is that it causes intense vasodilation or skin flushing. Note that while this effect looks harmful, it actually isn’t. It’s just redness, not irritation. Some potential workarounds have been implemented, one of which is to link the link the NTA with a long fatty chain ester such as myristic acid. This gives birth to myristyl nicotinate (MN), which was designed to prevent the vasodilation side effect. Therefore, because NTA is not applied to the skin nor contained in topical products, the discussion of NTA will be in reference to the MN form.
The cited study demonstrated that MN increased levels of NAD (by 25%) in the skin, which increased SC and epidermal thickness. These, of course, help prevent TEWL and increase barrier function. However, the main problem is that in this MN form, NAT did not demonstrate any of the other positive attributes of NCA such as those dealing with inflammation, sallowness, wrinkles, and hyperpigmentation.
This may be because as NM, the NAT is not in its free acid form. It is unclear whether or not the skin has the capability nor the desire to cleave/hydrolyze the fatty acid chain from the NAT molecule because if it did, there would be that unwanted vasodilation effect. In solution, it was shown that very little MN converts to free NAT (< 0.05%).
THE QUESTION IS THEN, “DOES MN HAVE TO CONVERT TO FREE NTA IN ORDER TO FUNCTION OPTIMALLY?”
The answer is again, unfortunately, unknown. However, given the various similar examples seen in skin care, I’d say that it’s logical for the answer to be, “Yes.” For example, if you take two other essential nutrients: vitamins A and E, ester-linked forms such as retinyl palmitate and tocopheryl acetate, are commonly found in skin care products. Both of these have different functions than their “pure” counterparts, retinol and tocopherol. And I demonstrated in “What is Retinol Metabolism?”, retinyl palmitate would have to go through multiple conversion steps in order to become tretinoin, the only metabolite that has any vitamin A activity in the skin. And since NTA also has receptors like tretinoin, that only further substantiates this hypothesis.
Overall, there are just too many unknowns when considering NTA (and therefore MN) as an effective, multi-faceted topical treatment.
Closing Remarks for Niacinamide and Nicotinic Acid
NTA has definitely been shown to facilitate epidermal barrier function, wound healing, and keratinocyte differentiation. However, NCA has also been shown to do these things (except wound healing), in addition to improving so many other common skin conditions such as sallowness, hyperpigmentation, and irritation. Furthermore, NCA is present in significantly higher amounts of products, indicating a wider choice in selection, and elicits very few if any negative reactions. Finally, NCA is stable, inexpensive, and above all: well-documented.
Therefore, given the numerous question marks about the attributes of NTA, in conjunction with the sheer amount of proven benefits of NCA, it is my personal opinion that for now NCA>NTA in skin care, and my personal recommendation for everyone to introduce and implement an NCA product into your routine!