Meeting Kligman's standards for active ingredients in Cosmeceuticals, Niacinamide is gaining widespread attention and application in Dermatology. The active ingredient impresses with its gentle action on the skin and effectiveness across most skin concerns. Let's explore how this versatile active ingredient works, as well as the all-in-one serum oh!oh! Skin Health Serum.

1. Overview of Niacinamide Structure

Niacinamide is one of the members of the Vitamin B3 family, a pyridine with a hydrogen atom at the 3rd position replaced by a carboxamide group. This structure participates in the synthesis of NAD+, which is then used to synthesize the coenzymes NADH and NADPH, involved in the reaction chains that generate energy for cellular activities.

In recent decades, Niacinamide has gradually gained attention and demonstrated its role in dermatology. This active ingredient is widely known and applied in skincare products by meeting "Kligman's standards" for active ingredients in Cosmeceuticals:
(1) Penetrates the stratum corneum, achieving the desired target with the necessary concentration;
(2) Biochemical mechanism of action on human cells, tissues, and skin is described corresponding to specific effects;
(3) Clinical, double-blind, controlled trials record statistically significant efficacy proving the claims of the active ingredient's effectiveness.

2. Unraveling the Versatility of Niacinamide on Skin

2.1 Regulating enzyme activity through NAD+

This is also the mechanism that makes Niacinamide a "versatile" active ingredient because, through NAD+, this vitamin B3 family member participates in almost all physiological activities of skin cells, comprehensively influencing and demonstrating its effects on the skin.

In cells, Niacinamide undergoes several metabolic steps to be synthesized into the nicotinamide adenine dinucleotide (NAD+) structure. Subsequently, this structure is converted into NADP+ under the catalysis of NAD+ kinase, and then into NAD(H) and NADP(H). These two coenzymes play a role in countless redox reactions, performing biochemical functions and providing vital energy for skin cells.

2.2 Antioxidant capacity

Reactive oxygen species and free radicals can be inactivated by Niacinamide in two ways: (1) Through NADP/NAPH reducing the activity and expression of NADPH oxidase, and (2) Increasing the expression level of the endogenous antioxidant superoxide dismutase. Recently, another antioxidant mechanism of Niacinamide has also been discussed, where some studies indicate that Niacinamide can inhibit NOS mRNA production in cells, thereby reducing enzyme activity and NO formation.

2.3 Anti-inflammatory properties

This effect is widely known and applied to improve inflammatory symptoms in acne. The anti-inflammatory properties of Niacinamide not only come from combating the influence of free radicals on inflammatory reactions, but this active ingredient also has the ability to inhibit the secretion of pro-inflammatory cytokines, reduce PGE2 secretion by macrophages, thereby inhibiting COX-2 in the inflammatory mechanism.

2.4 Antibacterial activity

Niacinamide is thought to have antibacterial activity against Cutibacterium acnes, a bacterium that causes acne. This is the second mechanism by which Niacinamide is effective in treating acne conditions. Clinical trials have shown that Niacinamide at a concentration of 4% is as effective as Clindamycin in the treatment regimen for mild to moderate acne.

2.5 Sebum regulation

The third mechanism by which Niacinamide treats acne is by reducing sebum production. This is also one of the highlights of Niacinamide, as very few active ingredients can target 3 out of 4 factors related to acne, including: (1) excessive sebum production; (2) colonization by Cutibacterium acnes; (3) inflammation, and the remaining factor is (4) abnormal keratinization.

The mechanism of Niacinamide in reducing sebum production is suggested to be an indirect effect, through its metabolism into Niacin, which activates the HCA2 receptor - the receptor responsible for regulating sebum production in human sebocytes.

2.6 Skin brightening

Niacinamide effectively reduces the manifestation of hyperpigmentation in the epidermis. Although compared to other classic active ingredients for treating hyperpigmentation like Hydroquinone or retinoids, the effect of reducing dark spots from Niacinamide takes longer, this active ingredient shows superior advantages in terms of safety and fewer side effects.

Research on the skin-brightening mechanism of Niacinamide has found that Niacinamide hardly affects melanin synthesis but can prevent the transfer of these dark pigments from melanocytes to keratinocytes.

2.7 Anti-aging

2.7.1 Strengthening skin barrier function

The gradual accumulation of skin damage can lead to premature aging. Therefore, building a strong skin barrier and minimizing damage that can be encountered on the skin due to external factors is also an effective way to prevent aging. Niacinamide can increase the expression of mRNA encoding ceramide synthase, a part of the skin's natural protective barrier that helps maintain moisture and transmits cell signals to ensure the activity of this protective system.

2.7.2 Reinforcing the extracellular matrix

The connective tissue between the dermis and epidermis contains fibroblasts, protein structures like Collagen and Elastin, and other components such as Proteoglycans and Hyaluronic acid, forming a cushion called the extracellular matrix. The decline of these components with age leads to the degradation of this structure, causing the skin to lose its elasticity, become loose, and form folds or wrinkles. Accordingly, Niacinamide can delay the appearance of wrinkles by stimulating the production of collagen and elastin, thereby significantly improving the structure of the extracellular matrix and maintaining skin firmness.

More broadly, skin aging is a complex process involving many factors and manifesting in a series of signs such as wrinkles, dryness, and hyperpigmentation. With the mechanisms of action of Niacinamide described above, the anti-aging effect of Niacinamide may not come from a specific property but rather is the overall result of this active ingredient's multifaceted actions.

3. Practical applications

3.1 Usage concentrations

One notable aspect when studying and conducting experiments on the effects of Niacinamide is that these effects tend to depend on the concentration of the active ingredient in the formulation. For this reason, depending on the purpose and need for use, the concentration levels of Niacinamide on the market are quite diverse, including common concentrations such as: 2%, 4-5%, 10%, and the highest recorded threshold to date is 20%:

• Niacinamide 2-5%: At concentrations of 2-5%, Niacinamide shows effects such as sebum control and pore reduction, as well as demonstrating its antibacterial properties. Therefore, this is a common concentration level found in formulations and routines for oily and acne-prone skin.
• Niacinamide 10%: Improves skin texture and reduces hyperpigmentation when using a serum containing 10% Niacinamide twice daily for 8-12 weeks. Survey studies also indicate that at higher concentrations (within the permissible range), the brightening and anti-aging effects of Niacinamide are more pronounced.
• Niacinamide 15- 20%: This concentration allows the active ingredient to maximize its versatility. Not only are there improvements in hyperpigmentation and inflammatory acne conditions, but formulations using this concentration also report positive results such as: reduced redness, reduced transepidermal water loss, improved rough skin, and reduced wrinkles.

3.2 oh!oh! Skin Health Serum (with 20% Niacinamide & 2% Acetyl Glucosamine)

3.3.1 High concentration levels

To maximize the benefits of Niacinamide, oh!oh! Skin Health Serum uses Niacinamide at a concentration of 20%, the highest concentration of the active ingredient currently available on the market. Maximizing the versatility of the active ingredient is one of the foundations for the product's "versatility":

• Acts on acne conditions through all 3 mechanisms: (1) soothes inflammatory reactions; (2) regulates sebum; (3) supports antibacterial properties;
• Minimizes pores, improves rough and uneven skin texture;
• Reduces the formation of hyperpigmentation and improves existing dark spots, leading to brighter, more even skin tone;
• Strengthens the skin's natural barrier function;
• Stimulates collagen synthesis, reversing signs of aging.

3.3.2 Excellent combined formula

Although high concentrations of Niacinamide show promising benefits, in reality, very few brands offer products containing Niacinamide at 15-20% due to concerns about flushing or skin irritation. This is a significant challenge, and the solution to this problem is: Optimizing the combined formula. A scientifically formulated ingredient blend can not only minimize the risks of irritation but also enhance efficacy and accelerate the improvement of skin imperfections, as demonstrated by oh!oh! Skin Health Serum:

• Niacinamide 20%: A concentration at which the active ingredient can address most skin concerns.
• Acetyl Glucosamine 2%: An active ingredient that helps maintain essential water levels for skin cell activity, keeping the skin hydrated, smooth, and firm. It also inhibits melanin synthesis in the skin, reduces genes related to melanosome transport, and effectively complements Niacinamide's ability to prevent dark spots and brighten the skin.
• Arginine: Repairs wounds and enhances antioxidant activity on the skin.
• Pro Anti-Irritant Complex containing:

REFERENCES

1. Marques, C.; Hadjab, F.; Porcello, A.; Lourenço, K.; Scaletta, C.; Abdel-Sayed, P.; Hirt-Burri, N.; Applegate, L.A.; Laurent, A. Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products. Antioxidants 2024, 13, 425

2. Ong, R., Goh, C. Niacinamide: a review on dermal delivery strategies and clinical evidence. Drug Deliv. and Transl. Res. (2024).

3. Zhen AX, Piao MJ, Kang KA, et al. Niacinamide Protects Skin Cells from Oxidative Stress Induced by Particulate Matter. Biomolecules & Therapeutics. 2019 Nov;27(6):562-569.