Frequently Asked Questions on Nicomenthyl 20

General characteristics

Yes. What was previously called “Nicomenthyl” is now named “Nicomenthyl 20”.

Nicomenthyl 20 is the same substance (menthyl nicotinate: purity >99%), same CAS number (40594-65-8), same INCI name, same chemical & physical properties, same technical characteristics as the previous substance named Nicomenthyl.

The trademark Nicomenthyl® at first represented a single product; however, during the years, it has evolved into a range comprising 2 other cosmetic products, both of them based on menthyl nicotinate (i.e. Nicomenthyl Cool & Nicomenthyl Hot). To better differentiate the original Nicomenthyl from these new products, it was chosen to give the original pure molecule (menthyl nicotinate) the name Nicomenthyl “20”, with reference to the date 2020, January 20, that’s to say when Multichem R&D had implemented a more advanced and innovative proprietary procedure to manufacture a more purified and fully deodorized menthyl nicotinate.

Nicomenthyl 20 IS NOT a mixture.
It is a “substance”, per definition of substance according to art. 2 (b) of Reg. EC 1223/2009: “substance’ means a chemical element and its compounds in the natural state or obtained by any manufacturing process, including any additive necessary to preserve its stability and any impurity deriving from the process used but excluding any solvent which may be separated without affecting the stability of the substance or changing its composition”.

Being a substance, Nicomenthyl 20 has only one INCI denomination: “Menthyl nicotinate”.

Nicomenthyl 20 is obtained through a new patented proprietary industrial synthesis which guarantees a purity higher than 99%.

Yes, it is. Nicomenthyl 20 is characterized by an exceptional oxidative stability; it is thermostable, can be processed either hot or cold in any cosmetic formulation, does not have any incompatibility with other ingredients. However, like any ester, it is stable at moderately acid pH, while it has a tendency to hydrolyze at alkaline pH (> 8.0) particularly if warmed up.

Nicomenthyl 20 is a “derived natural ingredient” as per definition in section 3.1 of ISO 16128-1 Definition for ingredients. Natural Origin Index (NOI) = 0.59

No. It is obtained through synthesis from Menthol and Niacin, both of them existing in nature.

No. No added preservatives or antioxidants are required for its storage.

Since Nicomenthyl 20 is completely thermostable, it does not require any special condition for storage. Its shelf life is well over 36 months.

Nicomenthyl 20 is not (directly or indirectly) derived or manufactured from GMO (genetically modified organisms) and their derivatives, as per Regulation EC 834/2007.

No. Nicomenthyl 20 is not of animal origin and does not contain animal derived ingredients, nor has it come into contact with animal origin derivatives in any phase of its production.

Nicomenthyl 20 is white transparent (colorless), almost as water.

Nicomenthyl 20, unlike other more volatile nicotinates (as for example methyl nicotinate, ethyl nicotinate, etc.) is odorless.

Relationships with Niacin and Menthol

NO, there is no functional relationship between Menthyl nicotinate and Nicotine. Niacin or Vitamin B3 was originally given the name of nicotinic acid by Austrian chemist Hugo Weidel in 1873. Having obtained it by oxidizing Nicotine he called it “Nicotinic acid”.
The discovery that Niacin was a vitamin was made in 1937 by the American chemist Conrad Elvehjem. A few years later, in 1942, the American Medical Association gave this substance a more popular name less misleading than Nicotinic acid, to prevent illogical, unfounded associations between the harmful effects of Nicotine and the therapeutic ones of vitamins. Its new name became NI AC IN, from the first two letters of NIcotinic ACid, and the last two letters of vitamIN.

In 1873 the Austrian chemist Hugo Weidel managed to synthetize it by oxidizing nicotine with nitric acid. This has been the only reason this substance was then called “Nicotinic” acid, even though it was not biochemically or toxicologically related to the well-known tobacco alkaloid.

None. Nicotinic acid and Niacin are synonyms, both terms indicating the same molecule. Nicotinic acid = Niacin = Vitamin B3 = Vitamin PP (Pellagra Preventing). Deficiency of Vitamin B3 is the cause of Pellagra, a dreadful desease, characterized by the famous 4 “D”s:  dermatitis, diarrhea, dementia and death.

Niacin plays an essential metabolic role throughout the animal kingdom. It is the precursor of important cellular coenzymes such as NAD e NADP, essential for energetic metabolism of skin cells and skin barrier integrity; it is needed for red blood cell formation, increased transport of oxygen and nutrients, removal of toxins & cellular waste products through skin microcirculation; it reduces triglycerides and cholesterol levels, prevents cardiovascular diseases, helps maintain healthy nervous system functioning and brain activity (its deficiency may cause serious mental illnesses); it plays a key role in synthesis of sex hormones estrogen, progesterone, and testosterone, etc.

Scientific studies have revealed that, in 24 hours, the quantity of Niacin released in the skin is about 18% of the total niacin contained in the original dose of Nicomenthyl 20.

Menthol exerts an essential balsamic and soothing activity. The simultaneous and equi-molar release of menthol into the skin prevents the niacin-flush effect that is usually observed with other nicotinate-based formulations, without however inhibiting its biochemical and vitaminic functionality.

Thorough in vitro testing has confirmed that Nicomenthyl 20 is not sensitizing.
As a precaution however, considering that Nicomenthyl 20 slowly releases Menthol into the skin, we advise the subject allergic to that substance to test first the cosmetic product containing Nicomenthyl 20 by applying a small quantity of it inside the forearm.

Niacin flushes your system by increasing blood flow. It causes small veins, called capillaries to dilate, allowing blood to flow more freely.

This is considered a natural, helpful and beneficial effect of niacin, because toxins tend to build up in the stored fatty tissue of the body where larger vessels don't get to. The increase of blood flow helps flushing toxins out of the fatty tissue and out of your body. Such activation of the microcirculation causes the skin to warm up and look blushed, and may be accompanied by a  kind of “tingling” sensation. It is only a temporary manifestation, usually lasting about ten minutes or so. This phenomenon, called niacin-flush, is totally harmless and is indicative of an enhancing microcirculation.

No. It just means skin cells are being cleansed by the beneficial enhancement of blood circulation and toxins flushing from your body. It is completely harmless and usually lasting only ten minutes or so.

Absolutely not. Some people misinterpret the Niacin flush (vasodilation) as an allergic reaction. There is a similarity but they are not the same. The flush caused by an allergy may be due to a local release of histamine into the epithelial tissues, triggered by the presence of allergens. The Niacin-flush instead is the result of a complex cascade of chemical reactions which, apart from activating some specific skin thermoreceptors, produce substances known as prostaglandins (PGD2 e PGE2), responsible for a temporary skin vasodilation.
The production of prostaglandins is the very factor that brings about a higher oxygenation and nourishment of tissues as well as a more effective and simultaneous elimination of toxins and cellular metabolic waste in the flushed skin area. There isn’t any allergen-related reaction in this mechanism. On the contrary, it is an oxygenating, nourishing and detox mechanism, activated by Niacin.

The menthylic (from menthol) moiety of the menthyl nicotinate molecule acts as a kind of controller or modulator of the flushing effect caused by the nicotinic (from niacin) moiety. Occasionally however, skin care or hair care products containing Nicomenthyl 20, depending on the concentration and the type of formulation, may cause a light beneficial flush in the application area and a kind of slightly “tingling” subcutaneous sensation, that will disappear in a short time.
The Niacin being released from Nicomenthyl 20 flushes the skin area by increasing blood flow in that area. This is to be considered very HELPFUL and BENEFICIAL. Such blood flow enhancement promotes the flushing of toxins out of the skin fatty tissues. The flush will be minimized by repeating the application of the product, with no reduction of the detox efficacy of the product.

The potential Niacin-flush can be avoided or minimized in two ways:

  • Decreasing the concentration of Nicomenthyl 20 in the formulation, down to 0.5% or even less.
  • Formulating a more “anhydrous” composition, with less glycols and more oily ingredients (such as waxes), to slow down the skin penetration of menthyl nicotinate. This will extend the time-release absorption and prevent the flush effect or make it almost unperceivable, still maintining an optimal detox efficacy.

Mechanism of action and properties

Once absorbed through the skin barrier, Menthyl nicotinate is slowly hydrolyzed into its original components: Niacin and Menthol.
Menthol has a refreshing effect, while Niacin generates a sensation of warmth and enhances skin microcirculation (mild modulated vasodilation). With no irritation or sensitization.
Furthermore, Niacin triggers a complex cascade of biochemical reactions that produce one of the most important cellular coenzymes, NAD (nicotinamide adenine dinucleotide). NAD plays a pivotal role in hundreds of enzymatic reactions, including those related to energy (ATP) production, many reduction-oxidation metabolic reactions, the Krebs cycle, as well as many others involved in cell signaling within the immune system, DNA repair, epithelial cell renewal, the synthesis of particular lipids (ceramides) essential to skin barrier functionality and integrity.

A Doppler Laser Blood-flow Velocity Test has been carried out on twenty volunteers of both sexes, using a topical preparation containing 3% of Nicomenthyl 20, compared to a negative control (placebo). Increases in microcirculatory flow values reached remarkable levels, up to nearly 150% at 30 minutes and 90% at 60 minutes after application, without any irritating or sensitizing effects.

The main benefits of enhanced blood flow are: a) increased supply of oxygen, nutrients and glucose b) removal of cellular waste products c) enhanced skin barrier integrity.

Skin Barrier Integrity is an extremely important concept in skin care. It mainly refers to the stratum corneum (outermost layer of the epidermis) and describes the strength and resilience of the skin and how well it protects the internal tissues and organs from external aggressions. Desquamation (shedding) of skin barrier helps remove bacteria and other infectious agents that have adhered to the epithelial surfaces. The skin barrier is highly impermeable, a characteristic designed to prevent the loss of water out of the skin and to keep out damaging agents such as bacteria, viruses, chemicals, oxidants, pollutants, smoke particles, UV radiations, etc. It is the front shield of the innate immune system, acting as the first line of defense against invading microorganisms.

Keeping the skin barrier function in good condition fits entirely into the general definition of “cosmetic product”: “… any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odours” (Regulation (EC) no 1223/2009 of 30 November 2009 on cosmetics products, art. 2).

Because, once absorbed through skin barrier, Nicomenthyl 20 slowly releases niacin (Vitamin B3) into the skin. Niacin is the precursor of coenzyme NAD (Nicotinamide Adenine Dinucleotide), that is the most important biochemical factor responsible for skin barrier integrity. NAD is used in over 450 biochemical reactions, most of which are involved with crucial anabolic and catabolic functions, such as: cell energy production (ATP), chromosome stability, DNA repair, immune cell signaling, redox reactions, epidermal renewal, cell longevity mechanisms, etc.

Recent studies have confirmed that a very high rate of penetration occurs, reaching 53.8% of the applied dose in only 30 minutes. The whole process of skin absorption gets practically completed in a period of 24 hours after application.

Nicomenthyl 20, being a powerful skin microcirculation enhancer (thanks to its time-release transcutaneous delivery of Vitamin B3), has deep beneficial effects on hair follicle cycling.
The increased blood flow generated by Nicomenthyl 20 in the hairbulb zone is essential for oxygenating, transporting nutrients and glucose, removing cellular waste products.
Such functions are instrumental in preventing excessive hair loss and promoting hair fullness.

Yes, it is. The time-release high transcutaneous delivery of Vitamin B3 and the enhancement of skin microcirculation produced by Nicomenthyl 20 are key factors for oxygenating, transporting nutrients and glucose, removing cellular waste products in all types of skin.

In some cases it can even improve it. As a matter of fact, Nicomenthyl 20, because of its high boiling point, may act as a fixative of the more volatile fractions, thus reducing their vanishing rate and bettering the whole fragrance longevity.

Because such high concentrations are useless and needless. For concentrations higher than those recommended, the amount of niacin released into the skin by the hydrolyzation of menthyl nicotinate could produce a vasodilation (niacin-flush) much stronger than necessary, and that result could be bothersome though still not dangerous.

Nicomenthyl 20 may be used in all kinds of cosmetic products at the following recommended concentrations:
Face Products: 0.5 – 1%
Body Products: 0.5 – 3%

Special Products (such as skin barrier enhancing serums, cellulite intensive treatment and prevention, intensive hair loss preventive treatments, legs toning and anti-fatigue treatments, etc.): 5%

The sensorial strenght of Nicomenthyl 20 depends: 1) on its concentration in the finished product 2) on the type of cosmetic formulation (water-based emulsion, hydroalcoholic lotions, fatty or anhydrous compositions, etc. 3) on the presence or absence in formulation of carriers such as: solubilizers, glycols, alcohols, light oils with high spreading values, etc. 4) on the body area where the product is applied.
The best way to evaluate the sensorial strength and longevity of Nicomenthyl 20 is to apply on the lips a cosmetic water-based composition containing it at a concentration of 3%.

Through the two moieties of its molecule (i.e. the niacinic vaso-active warming moiety and the menthyl cooling one), Nicomenthyl 20, duly dosed and solubilized in cosmetic finished products, exerts also a kind of “modulator” and synergistic effect over several other sensorial agents. These, when used in combination with Nicomenthyl 20, extend their efficacy in time with a less aggressive impact on the skin.
An example of this is the result obtained when Nicomenthyl 20 is used in combination with Menthol: the refreshing effect of Menthol becomes sort of softened, modulated and dramatically extended with less unpleasant side effects.
A similar modulating action occurs with the warming sensorial agents (i.e. those which activate the heat-sensitive thermo-receptors), such as Vanillyl butyl ether, Methyl nicotinate, Ginger essential oil, etc.: the menthyl moiety of Nicomenthyl 20 molecule produces a sort of “attenuated”, modulating effect, which results in a more gentle, pleasant and persistent warmth sensation.

The unique and modulated sensory effect which characterizes Nicomenthyl 20 is particularly long-lasting. Its typical fresh tingling sensation can still be perceived even one hour after the application, depending of course on the concentration being used and the type of finished product containing it.

Efficacy and Safety Tests

None. In Europe, since 2009, commercialization of cosmetic products containing ingredients tested on animals is illegal, according to Regulation (EC)  n.1223/2009 of 30 November 2009.

The founders of Multichem R&D have a strong stand point against animal testing and therefore Nicomenthyl 20 has never been and will never be tested on animals. All testing regulations and requirements by European jurisdiction have been met to ensure Nicomenthyl 20 complete safety and efficacy.

The following assessment tests were conducted on Nicomenthyl 20: in vitro cutaneous irritation testing on 3D reconstructed human epidermis (according to OCED 439); in vitro model testing to predict skin sensitization through assessment of the stimulating potential of the investigated substance on the immune cellular response mediated by monocyte/macrophage cells; in vitro test method for the prediction of the vaginal tolerability on reconstructed epithelium by means of the viability assessment of reconstructed tissues after single product application; in vitro assessment of the ocular irritancy potential through cytotoxicity assay Neutral Red Uptake on cell culture and in vitro Het Cam testing on fertilized chicken eggs. All tests have confirmed the absence of irritative and/or sensitizing effects on skin and eyes.
However, adopting a precautionary approach to minimize risk of eye irritation, even though in vitro tests on ocular irritancy have all given negative results, this substance has been classified as Eye Irritant 2 according to Regulation 1272/2008/EC (CLP).

No. The mild temporary redness that may be observed in some subjects after the application of a cosmetic product containing Nicomenthyl 20 is due to the beneficial activation of the skin microcirculation in the concerned area. Any possible light reddening occurring in sensitive skin will considerably lessen or completely disappear in less than one hour.

No. As proven by validated in vitro testing, Nicomenthyl 20 is not sensitizing.

No. As demonstrated by validated in vitro testing, Nicomenthyl 20 is not irritant for the eyes. However, for the precautionary principle (cfr. https://en.wikipedia.org/wiki/Precautionary_principle) , it is classified as Eye Irritant 2 H319 (causes serious eye irritation) according to Regulation 1272/2008/EC (CLP).

Certainly. Recent tests sponsored by Multichem R&D  have demonstrated a very high effectiveness of Nicomenthyl 20 in maintaining and protecting the vitality of skin cells when exposed to all types of sun radiations.

Nicomenthyl 20 is not a sunscreen (i.e. does not absorb or reflect some of the sun's ultraviolet (UV) radiation) and therefore does not have a sun protection factor.
Its protection against UVA and UVB rays is of purely biochemical and biological nature, i.e. due to its release of Vitamin B3 into the skin. Vitamin B3 is currently considered more effective than sunscreens in protecting against skin cancer caused by excessive exposure to sun rays. (RF: Niacin The Real Story by Abram Hoffer, MD., Ph.D – Andrew W. Saul, Ph.D, and Harold D. Foster, Ph.D. Publisher Basic Health Publications INC)

Certainly. A recent antioxidizing activity assessment has shown that Nicomenthyl 20, when cells were exposed to synthetic smoke, was able to provide full protection and reduce basal lipoperoxide content in skin cell cultures.

Recent tests sponsored by Multichem R&D have evidenced that Nicomenthyl 20 fully protects from oxidant agents by increasing skin cells metabolism and thus their capacity to bring back protein synthesis to basal levels or even better.

Yes, it can. A recent study has proven that Nicomenthyl 20, when urban particulate matter was used as a stress agent, exerts a marked detoxifying effect, bringing cell viability biochemical parameters back to basal levels or even better.

Nicomenthyl compared to other niacin derivates

They are completely different substances, with completely different molecular structures:

metil nicotinato

Methyl nicotinate

mentil nicotinato

Menthyl nicotinate

Methyl nicotinate is a very strong vasodilating agent and can be in some cases highly irritating to the skin even at very low concentrations (0.1% or less). Menthyl nicotinate (Nicomenthyl) effectively enhances skin microcirculation without causing bothersome hyperemia or irritations, on the contrary it generates a pleasant hot-cold sensation in the area of application.

Niacinamide (also called Nicotinamide), although it is considered another form of Vitamin B3, has a different chemical structure than nicotinic acid. It is a derivative of nicotinic acid, chemically named amide of nicotinic acid:

niacina

Niacin or nicotinic acid

niacinamide

Nicotinamide or Niacinamide

No, Niacinamide has no vasodilating activity. It is not a microcirculation enhancer.

No. Since Niacinamide is hydrosoluble, its transcutaneous absorption in 24 hours is only 2.2% of the initially applied dose. Such quantities are very low compared to the amount of Vitamin B3 released by Nicomenthyl (liposoluble) in the same period of time. Such amount reaching a rate of approx. 18% of the Vitamin B3 contained in the applied dose of Nicomenthyl 20. Therefore, Nicomenthyl delivers approx. 8 times more Vitamin B3 than Niacinamide.

No, Nicomenthyl 20 is not a whitening agent. On the contrary, it tends to increase cutaneous pigmentation (melanin), while effectively preventing and protecting the skin against UVA and UVB rays damages.

Yes, certainly. There is no incompatibility between these two substances.

Because it ensures the highest and fastest delivery of Vitamin B3 with no skin irritation or sensitization, as thoroughly documented by several safety and efficacy tests.

Regulatory & Certificates

Yes. REACH registration: 01-2120770053-62-0000. INCI name: Menthyl nicotinate.

Yes. Application No. 4-06-2016-5056. INCI name assigned: Menthyl nicotinate.

The only reason is that, to this date, the Chinese legislation mandatorily requires animal testing for all new cosmetic ingredients. This is totally contrary to legislations of nearly all western countries and, particularly, in violation of European legislation on cosmetics, which clearly forbids such tests (Regulation (EC) n.1223/2009 of 30/11/2009, art. 18, Animal testing).
Multichem R&D believes animal testing to be uselessly and needlessly cruel. Nicomenthyl has never been tested and will never be tested on animals.
All testing regulations and requirements by European jurisdiction have been met to ensure Nicomenthyl 20 complete safety and efficacy.

Yes, it is. Halal certification N°445 dated 16/04/2019 by Halal Italia.

Yes, it is. Kosher certification dated 19/03/2020 by Rabbinical Court of Center and North Italy.