Lipophilic Vitamin B3 Derivative with NAD-Boosting Effect
Nicomenthyl 20 is a multifunctional sensorial cosmetic active, derived from vitamin B3 (niacin or nicotinic acid), manufactured in Italy by Multichem R&D, through a patented synthesis process.
Nicomenthyl 20 significantly enhances skin microcirculation, without causing hyperemia or irritation. At the contrary, it produces a localized pleasant tingling sensation.
Vitamin B3 is a precursor of the coenzyme NAD (Nicotinamide Adenine Dinucleotide), one of the most important and interesting molecules in human energetic metabolism. Defined by some researchers as “the molecule of life”, NAD is required for over 500 enzymatic reactions and plays key roles in the regulation of almost all major biological processes, including those concerning immune response and DNA repair against damages caused by aggressive chemicals or radiations.
Niacin deficiency and consequent lack of NAD in skin cells causes intracellular incidents which can lead to lipid peroxidation, oxidative stress of the cell membranes, premature skin ageing, erythema and skin irritation, and eventually more serious consequences, including unrepaired DNA damage, disruption of epidermal barrier integrity, mutagenesis, immune suppression, actinic keratosis and skin cancers.
A recent study, published in the prestigious journal Nature, has also evidenced that vitamin B3 is highly effective even in preventing lung tissue inflammation damages of COVID-19 patients. In-vivo testing carried out by researchers of the Chinese Academy of Sciences have shown that “…NAD+ supplementation can protect the lung from infiammatory injury, including cell death, caused by SARS-Cov-2 infection in both old and young mice...".
Composition and Technical Specifications
Nicomenthyl 20 (INCI Name: Menthyl nicotinate; CAS 40594-65-8) is the product resulting from the esterification reaction of nicotinic acid (vitamin B3 or niacin) with natural menthol (Fig. 1).
It is in a liquid state (easier to incorporate in any formulations), and remains liquid even at very low temperatures (less than -20°C).
Completely thermostable, can be processed either hot or cold, stable between pH 4 - 8. No incompatibility known.
It has a remarkable carrier and booster effect over other liposoluble substances, such as: Tocopheryl acetate, Retinyl palmitate, Vitamin F, EPA, DHA, essential oils, etc.
Figure 1 – Molecular Composition of Nicomenthyl 20 (Mentil nicotinato).
Technical characteristics of Nicomenthyl 20 are reported in Table 1.
|Colour||White transparent, colourless|
|Smell||Odourless or slight characteristic odour|
|Specific gravity (at 20°C)||1.031|
|Solubility||Insoluble in water; soluble in alcohol, polar oils, esters|
|Boiling point at atmospheric pressure||292.23°C|
|Heavy metals (ppm)||< 10|
|Arsenic (ppm)||< 0.02|
|MICROBIOLOGICAL PROPERTIES (UFC/g)|
|Total bacterial load||< 10|
Stability and Storage:
Table 1 – Technical characteristics of Nicomenthyl 20.
Mechanism of Action
Once through the horny layer (stratum corneum), Nicomenthyl 20 undergoes hydrolysis and splits into its two original components: niacin and menthol.
The latter, thanks to its vasoconstricting activity, causes the pleasant cooling sensation that may be experienced already a few minutes after application, and acts as a kind of controlling/ modulating role toward the vasoactive activity of niacin released from the hydrolysis of Menthyl nicotinate.
The freed niacin triggers a complex cascade of biochemical reactions that lead to the synthesis of NAD, that’s to say the molecule that provides temporary storage of the energy produced by the cellular respiration, and thus considered as the “energy currency molecule” of the organism (Fig. 2).
As already demonstrated in previous studies, thanks to its rapid penetration through the skin barrier, its time-released delivery of niacin and consequent significant increase of NAD’s levels in skin cells (NAD-booster effect), Nicomenthyl 20 shows an extraordinary protective efficacy against oxidative stress caused by external agents.
Fig. 2 Nicomenthyl 20 mechanism of action in skin.
In vitro Studies
In vitro studies have shown the kinetics profile of the rapid skin penetration of menthyl nicotinate and, meanwhile, its slow, time-released delivery of niacin.
Its protective, antioxidant and detoxifying efficacy against UV radiation, oxidant chemicals, pollutants and cigarette smoke has been evaluated as well. Results have clearly confirmed Nicomenthyl 20 as effectively enhancing the defense mechanisms of skin cells against all tested damaging agents. Similar studies on keratinocytes cultures (HaCaT), in a complete medium (Dulbecco's Modified Eagle Medium enriched with 10% fetal bovine serum), have been done to assess the detoxifying power of Nicomenthyl 20 against skin damages caused by Blue Light and WIFI radiations, through monitoring the activity of Glutathione S-transferase (GST), an enzyme which plays a pivotal role in the detoxication of skin tissues and elimination of xenobiotic toxicants.
Results have shown that both damaging agents cause relevant alterations of the GST’s activity in the exposed keratinocyte cultures (CTR+). On the other hand, the concomitant treatment with Nicomenthyl 20 has shown a significant recovery of the monitored GST activity values, bringing them almost back to their basal levels (CTR-), either in acute (24h) or in repeated exposition (72h) (Fig. 3, 4).
Figure 3 - Keratinocyte GST activity in vitro study, after exposition to Blue Light and treatment with Nicomenthyl 20.
Figure 4 - eratinocyte GST activity in vitro study, after exposition to WIFI and treatment with Nicomenthyl 20.
In vivo Studies
A Doppler Laser Blood-flow Rate Test has been carried out on twenty volunteers, using a topical preparation containing 3% of Nicomenthyl 20, versus placebo. Results have shown a significant increase of the microcirculatory flow: +78% at 15 minutes, +147% at 30 minutes, and still +87% at 60 minutes after application (Fig. 5)
Figure 5 – Doppler Laser Blood-flow Rate In Vivo Study, assessing the effect of a cosmetic product containing 3% Nicomenthyl 20 on skin blood micro-flow rate.
All tests, both on skin and vaginal mucosa, have confirmed the absence of irritative and/or sensitizing effects.
The product is to be considered completely safe at the recommended dosages of use. Test reports available under request.
Applications and Directions for Use
Its protection against damages caused by external factors and its activity on skin microcirculation qualify Nicomenthyl 20 as a safe and effective active, either for leave-on or rinse-off cosmetic formulations.
It is particularly indicated for anti-cellulite, hair loss prevention treatments, intimate hygiene products, detox and anti-pollutant products, tonifying and anti-age treatments, especially for oily, impure, asphyxial skin. Generally suitable for all those cases where enhancing skin microcirculation is particularly needed to promote oxygenation, detoxification and normalization of skin metabolism.
Recommended dosage from 0.5 to 3%.
 ⬆︎ L. Rajman, K. Chwalek, D. A. Sinclair Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence Cell Metabolism 27: 529-547, March 6, 2018, Elsevier Inc. https://doi.org/10.1016/j.cmet.2018.02.011
 ⬆︎ Claudia Benavente, Myron Jacobson e Elaine Jacobson, NAD in Skin: Therapeutic Approaches for Niacin, in Current Pharmaceutical Design, vol. 15, n. 1, 1 January 2009, pp. 29–38, DOI:10.2174/138161209787185760, PMID 19149600.
 ⬆︎ Jacobson E.L., Kim H., Kim M., Wondrak G.T., Jacobson M.K. (2005) Developing Topical Prodrugs for Skin Cancer Prevention. In: Alberts D.S., Hess L.M. (eds) Fundamentals of Cancer Prevention. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26337-3_8
 ⬆︎ Elaine L. Jacobson, Hyuntae Kim, Moonsun Kim, Joshua D. Williams, Donna L. Coyle, W. Russell Coyle, Gary Grove, Ronald L. Rizer, M. Suzanne Stratton e Myron K. Jacobson, A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin, in Experimental Dermatology, vol. 16, n. 6, June 2007, pp. 490–499, DOI:10.1111/j.1600-0625.2007.00553.x.
 ⬆︎ Yisheng Jiang, Yongqiang Deng, Tiantian Ma, Huanhuan Pang, Zeping Hu, Cheng Qin, Zhiheng Xu - Treatment of SARS-CoV-2 induced pneumonia with NAD+ in a mouse model - Research Square – October 2020 https://doi.org/10.21203/rs.3.rs-96999/v1.
 ⬆︎ G Segalla, S Giardina e G Bizzaro, Mentil nicotinato - Alto grado di assorbimento cutaneo e lento rilascio di vitamina B3 (niacina), in Cosmetic Technology, 22(2), Milano, CEC, Marzo-Aprile 2019, pp. 36-40
 ⬆︎ G Segalla, S Giardina e G Bizzaro, Cessione transcutanea di niacina ed efficacia antinquinamento, detox, antiossidante, in Cosmetic Technology, 21(5), Milano, CEC, Settembre-Ottobre 2018, pp. 28-34.