Your skin: 40's, 50's and beyond:
At any age, good skincare starts with protecting your skin from avoidable damage, particularly sun damage, and establishing a sensible basic daily routine matching your skin type. However, in the fourth and fifth decades of life your physiology (especially if you are a woman) changes dramatically. If you are to retain as youthful a look as possible, your skin care will have to change as well.
After 40 skin faces more challenges with fewer resources The fourth and fifth decades of life are characterized by a marked decline in the levels of various hormones and growth factors. Cell damage has accumulated in many tissues; the skin is one of the most affected. As a result, the rate at which the skin renews and repairs itself becomes much slower.
Women in their 40s and 50s, 60s experience particularly dramatic hormonal changes because they either approach or undergo the menopause, which causes a dramatic decline in the hormones produce by the ovaries: estrogens and progesterone. The loss of these hormones causes a decline in the synthesis of collagen, elastin and other components of skin matrix, reduces the production of sebum (skin oil) and thus leads to skin thinning, dryness and other negative changes. Notably, the effects of declining testosterone in men are somewhat similar but not as marked or abrupt.
Another problems of older skin is excessive inflammation. While usually not visible to the naked eye, age-related skin inflammation manifests in higher levels inflammatory mediators (cytokines, prostaglandins and others) and abnormal activity of certain immune system cells. Inflammation increases the production of harmful free radicals and leads to increased cell damage, degradation of skin matrix and other problems.
All of the above results in a number of visible changes:
While aging remains inevitable, you don't have to passively accept all those negative changes in your appearance. Some can be reversed, while others kept under control or slowed down.
Dr. Todorov, smartskincare.com
After 40 skin faces more challenges with fewer resources The fourth and fifth decades of life are characterized by a marked decline in the levels of various hormones and growth factors. Cell damage has accumulated in many tissues; the skin is one of the most affected. As a result, the rate at which the skin renews and repairs itself becomes much slower.
Women in their 40s and 50s, 60s experience particularly dramatic hormonal changes because they either approach or undergo the menopause, which causes a dramatic decline in the hormones produce by the ovaries: estrogens and progesterone. The loss of these hormones causes a decline in the synthesis of collagen, elastin and other components of skin matrix, reduces the production of sebum (skin oil) and thus leads to skin thinning, dryness and other negative changes. Notably, the effects of declining testosterone in men are somewhat similar but not as marked or abrupt.
Another problems of older skin is excessive inflammation. While usually not visible to the naked eye, age-related skin inflammation manifests in higher levels inflammatory mediators (cytokines, prostaglandins and others) and abnormal activity of certain immune system cells. Inflammation increases the production of harmful free radicals and leads to increased cell damage, degradation of skin matrix and other problems.
All of the above results in a number of visible changes:
- Thickening and drying up of the outer layer of the epidermis (stratum corneum) leading to the dull, parched appearance.
- Thinning and weakening of the skin's middle layer (dermis), which is the layer responsible for the skin's strength, firmness and resilience. This leads to the accelerated development of fine lines and wrinkles.
- Progression and deepening of motion wrinkles and creases. Motion wrinkles are those developing in the area where facial movements result in skin folding. Weakened dermis cannot cope with continuous folding of the skin, which leads to a rapid deepening of motion wrinkles.
- Development of uneven pigmentation, discolorations, broken capillaries, redness and other blemishes associated with skin aging.
- Loss of subcutaneous fat and slackening of facial muscles, both of which contribute to tired, haggard look and facial sag
While aging remains inevitable, you don't have to passively accept all those negative changes in your appearance. Some can be reversed, while others kept under control or slowed down.
Dr. Todorov, smartskincare.com
There are hundreds if not thousands topical skin rejuvenation treatments on the market, from wrinkle creams to eye serums to lifting gels. If all of them worked as advertised, anyone with a bit of extra cash could have a skin of a fifteen year old. In reality, relatively few topical agents are clinically proven to improve wrinkles and other signs of skin aging. Others are supported by some positive evidence but not enough to confidently say that they work. Numerous others aren't backed by any reliable science at all and can even be harmful. As you may know, cosmetics is not regulated by the FDA. Hence it is largely up to the manufacturer's conscience not only to ensure effectiveness but safety as well. Conversely, it is up to the consumer to buy wisely.
Clinically Proven Effective * if formulated correctly: correct concentration, correct molecule formation, correct base, and applied correctly.
Niacinamide, Tretinoin (Retin A, Renova), Retinoids, Alpha-hydroxy Acids, Estrogens, Vitamin C + E + ferulic acid, Vitamin C & Vitamin C derivatives, Anhydrous vitamin C combo, Oat beta-glucan
Possibly Effective but Need More Research *same note as above
Retinaldehyde Retinol / retinyl palmitate Retinyl retinoate
Copper peptides (don't use concurrently with vitamin c-they cancel each other out), Alpha lipoic acid, Coenzyme Q10 (Idebenone), Lycopene, Astaxanthin, DMAE, Green tea & White tea, MMP inhibitors, Furfuryladenine (Kinetin), Progesterone (many cautions with it), Hyaluronic acid (although it can dry the skin out more in dry weather), Palmitoyl pentapeptide-4 (Matrixyl), Palmitoyl oligopeptide / tetrapeptide-7 (Matrixyl 3000).
Popular but Unproven
Acetyl hexapeptide-3 (Argireline), Ethocyn, Resveratol, Sirtuins, Beta-hydroxy acids
Quite a few of these cosmeceutical ingredients are useful for the treatment of other skin conditions
Copyright © 1999-2012 by Dr. G. Todorov / SmartSkinCare.com
Vitamin C-Link to article
Niacinamide
Excerpted from the medical journal “:The Journal of Clinical & Aesthetic Dermatology” article:
How Much Do We Really Know About Our Favorite Cosmeceutical Ingredients? Jacquelyn Levin, DO and Saira B. Momin, DO
James Q. Del Rosso, DO, FAOCD, Section Editor
James Q. Del Rosso, Dr. Del Rosso is Dermatology Residency Director, Valley Hospital Medical Center, Las Vegas, Nevada;
...
What background information is available on niacinamide and nicotinic acid?
While the nutritional value of niacin (vitamin B3) may be well recognized, the skin care benefit of topically applied niacin is a recent discovery based on recently published studies. Niacin (vitamin B3) has two potential forms that can be used in cosmeceuticals: niacinamide (nicotinamide) and nicotinic acid. It is debatable as to whether these two forms of niacin are interchangeable as topical cosmeceuticals. Some studies claim that niacinamide and nicotinic acid are readily converted into each other in vivo40 while other studies speculate that niacinamide and nicotinic acid may have very different pharmaceutical activities despite having identical vitamin activities.41 In other words, nicotinic acid may have more benefits than topical niacinamide on the skin due to the fact that in addition to having the vitamin effects on skin (increasing levels of niacinamide adenosine dinucleotide [NAD]), it may also have drug-mediated effects on skin via interacting with nicotinic acid receptors present in the skin.41–44 Yet, the disadvantage of using nicotinic acid as a topical cosmeceutical is its unpleasant side effect of vasodilation that results in skin flushing. This is an effect that is not harmful but intensely disliked by most patients.45,46 In contrast to nicotinic acid, niacinamide does not cause skin flushing nor does it cause changes in blood pressure, pulse, or body temperature.47 Due to the decreased number of side effects of topical niacinamide compared to nicotinic acid, the effects of niacinamide as a topical cosmeceutical agent have been studied more to date.
Niacinamide, also known as nicotinamide, is the precursor of important cofactors niacinamide adenosine dinucleotide (NAD) and its phosphate derivative, niacinamide adenosine dinucleotide phosphate (NADP). These cofactors and their reduced forms (NADH and NADPH) serve as reduction-oxidation (redox) coenzymes in more than 40 cellular biochemical reactions. Thus, niacinamide has the potential to exert multiple effects on skin and is a promising anti-aging cosmeceutical ingredient.
What data is available on the percutaneous absorption of niacinamide?
Feldmann et al48 highlighted the possibilities for the topical application of niacinamide because they were able to prove sufficient percutaneous penetration into human skin.48,49 In addition, several other studies have used increased levels of NAD in skin cells after the topical application of niacinamide as evidence of percutaneous penetration.50
What are the potential mechanisms of action of niacinamide?
Studies have shown that niacinamide has the potential to act as an antioxidant, can improve epidermal barrier function, decrease skin hyperpigmentation, reduce fine lines and wrinkles, decrease redness/blotchiness, decrease skin yellowness (sallowness), and improve skin elasticity.51,52 The mechanisms by which niacinamide provides this array of skin benefits is not completely understood, but the role of niacinamide as a precursor to the NADP family of coenzymes may play a significant role in all of these improvements.50
Antioxidant capacity. Niacinamide increases the antioxidant capacity of skin after topical application by increasing the reduced forms (NADPH), which have potent antioxidant properties.53–55 This is probably the most well-studied anti-aging effect of niacinamide.
Epidermal barrier function. Niacinamide may improve the skin barrier function in two ways: first, by its ability to upregulate the synthesis of ceramides as well as other SC intercellular lipids, and second, by stimulating keratinocyte differentiation.56,57 Ceramides and other intercellular SC lipids are known to play a central role in the structural and functional integrity of the epidermal barrier function. The responsible mechanism for the increase of ceramide synthesis in niacinamide-treated, cultured keratinocytes was found to be based on the upregulation of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid synthesis. The increase in ceramide synthesis has been confirmed in an in-vivo trial after topical application of 2% niacinamide emulsion for four weeks applied twice daily.56 The elevation of ceramides after treatment with niacinamide is associated with an improved barrier function as evidenced by a reduced TEWL and an increase in the cutaneous resistance to potential harmful topical agents.56 The second mechanism likely responsible for improved barrier function is a stimulation of keratinocyte differentiation seen both in cell cultures in vitro and in-vivo studies conducted by Tanno et al.56,57 In cell cultures, more rapid keratinocyte differentiation following treatment with niacinamide was established.56 In particular, it was possible to determine an influence on keratin, K1. K1 is a basic keratin synthesized mainly in the lowest layers of the stratum spinosum. The functional limitations of aging skin include reduced “turnover of the epidermis” (i.e., a slower epidermal cell cycle) due to a deficiency of NADP in aging cells.58,59 Tanno et al also demonstrated an in-vivo improvement in epidermal barrier function with improved keratinocyte differentiation after the application of topical niacinamide. Once again, the improved barrier function was evident by a decrease in TEWL and increase in SC moisture content. Similar results were also obtained by Ertel et al.57 In conclusion, it seems that topical application of niacinamide increases NADP levels, which in turn stimulates keratinocyte differentiation. This results in a thicker SC, which is not only associated with an improved barrier, but is also associated with greater hydration retention capacity in the SC.59
Erythema and blotchiness. The mechanism by which redness/blotchiness is improved may be related to the improved skin barrier function for reasons discussed above.50,60,61 Increased barrier function may mean less irritation and redness when the skin encounters environmental insults, such as detergents and soaps, and hence less reddening of the skin. However, this theory has not been substantiated.
Yellowing of skin. The yellowing of skin that comes with aging may be a result of glycation of proteins in the skin called the Maillard reaction. The Maillard reaction is a spontaneous oxidative reaction between protein and sugar that results in cross-linked proteins (Amadori products) that are yellowish-brown in color and are fluorescent.62–64 These proteins can accumulate in the skin matrix components, similar to collagen, in response to oxidative stress as we age. Published data show a fivefold increase in collagen oxidation products in human skin from age 20 to 80.65 Since NADH and NADPH are antioxidants and their levels can be increased with niacinamide, a possible effect of topical niacinamide is inhibition of oxidative processes, such as protein oxidation, glycation, and the Maillard reaction, and hence the inhibition of skin yellowing.66–68
Fine lines and wrinkles. Multiple mechanisms may be involved in the ability of niacinamide to reduce the appearance of fine lines and wrinkles. The first to consider is that niacinamide may have the ability to increase dermal collagen and protein production. The development of wrinkles is a result of the decrease in epidermal cell layers and dermal components from a reduction in protein and collagen synthesis. Reduced protein synthesis is reflected in the levels of keratin, fillagrin, and involucrin in the skin. Keratin deficiency has an effect on the epidermal cell structure and its water-binding capacity. Fillagrin is an antecedent of natural moisturizing factor (NMF) and hence affects skin hydration. Involucrin is seen as significant for the cell envelope and structure of the SC. In summary, the effects of reduced collagen and protein synthesis are poor skin structure and reduced skin elasticity as well as a decrease in epidermal barrier function with a reduction in SC hydration. In studies on cell cultures, Oblong et al58 found that in aging cells it was possible to prove that niacinamide, as a precursor of NAD/NADP, stimulated collagen synthesis and the epidermal proteins keratin, fillagrin, and involucrin.51,58 In addition, another study was able to show niacinamide's ability to increase dermal matrix collagen production.66
The second mechanism that may be relevant to decreasing the appearance of wrinkles is the ability of niacinamide to reduce excess dermal glycosaminoglycans (GAGs). This is a controversial theory because both the elevation and depletion of dermal GAGs are associated with photodamaged or wrinkled skin.52,69 What is known is that the presence of GAGs is required for normal structure and function of the dermal matrix and increasing the levels of GAGs can increase the moisture content of skin. Testing has indicated that niacinamide reduces excess production of GAGs in old human dermal fibroblasts, thus supporting the potential involvement of this mechanism in reducing the appearance of fine lines and wrinkles.51,70 Given the above analysis and scientific data, it seems more likely that an increase in dermal proteins (including collagen) may play a bigger role in reducing fine lines and wrinkles than decreasing the level of GAGs.
Hyperpigmentation. Topical niacinamide may be effective in decreasing epidermal hyperpigmentation and reducing pigmented spots as we age.71 Hakozaki et al71 showed that the reduction of cutaneous pigmentation, surprisingly, was not due to the direct influence of niacinamide on melanin synthesis by melanocytes. Instead, they showed that niacinamide reduced melanosome transfer from melanocytes to surrounding keratinocytes in a co-culture system, although the specific mechanism remains unknown.71 This was supported by a study using 5% niacinamide moisturizer, which provided 35 to 68 percent inhibition of melanosome transfer from melanocytes to keratinocytes.71
What clinical studies are available on niacinamide?
Tanno et al56 showed a reduction in pigmentation as a result of niacinamide. Eighteen Japanese women with hyperpigmentation were treated on one side of the face with 5% niacinamide and on the other side with vehicle only. The pigmentation change was evaluated qualitatively and quantitatively using high-resolution digital images and subjective judgments. In both forms of evaluation, it was found that after eight weeks of treatment there was significant lightening of hyperpigmentation on the side treated with niacinamide when compared with the effect of the vehicle (p<0.05).56
In a separate study also reported by Tanno et al performed with 120 Japanese women, comparisons were made among a sun protection factor (SPF) 15 cream with and without 2% niacinamide and the relevant vehicle. As a result of niacinamide treatment, there was a lightening of the skin after four and six weeks, which was noted to be markedly better than the formula without niacinamide.56
It is theoreticized that niacinamide may improve the texture of skin by speeding up epidermal turnover hence functioning as a mild exfoliant.72 Using a multiple angle reflectance spectrophotometer in an in-vivo test of the back of the hand, Matts and Solenick73 established a beneficial effect for the topical application of niacinamide in smoothing the skin surface structure. This study demonstrates that the long-term application of 2.5% niacinamide can correct the skin surface damage that results from aging. These results were statistically significant compared with the influence of the vehicle alone (p<0.05).59 In agreement with the above, another clinical trial using 3.5% niacinamide cream was compared with placebo for four weeks and demonstrated a 14.8-percent reduction in skin roughness (p=0.05).56,74,75
One of the best randomized, double-blind, split-face, placebo-controlled, clinical trials published on the anti-aging effects of topical niacinamide was done by Bissett et al.51 In this study, 50 white females with clinical signs of photodamage applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks. Analyses of the data revealed a variety of effects related to improvements in skin appearance for topical niacinamide including reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and improvement in skin elasticity.51 Matts and Solenick later confirmed the results of Bissett et al with 5% and 2% niacinamide.59 The results also demonstrated that the anti-aging effects of niacinamide were dose dependent.
What conclusions can be drawn from data on niacinamide?
The topical use of niacinamide for anti-aging has proven to be effective not only when there are signs of a niacin deficiency. Despite the recent discovery of the cosmetic benefit of niacin for the skin, there have been sufficient studies completed to answer all three “Kligman questions.” It is the opinion of the authors that niacinamide is one of the best studied cosmeceutical ingredients for anti-aging. However, further research is required to uncover the specific mechanisms of niacinamide in the skin and to optimize the concentration of niacinamide in cosmeceutical formulations.
Is there additional information on nicotinic acid?
As mentioned earlier, a major obstacle in the topical delivery of therapeutic amounts of nicotinic acid to any tissue is its ability to cause a peripheral vasodilation that leads to a skin flushing response. While this effect is not harmful, it is intensely disliked by most patients.45,46 This issue may be avoided by using the long chain ester derivative of nicotinic acid, myristyl nicotinate (MN), which is able to deliver large amounts (in concentrations near 5%) of nicotinic acid without flushing.76,77
The advantage of using nicotinic acid over niacinamide is its drug-mediated effect on skin as a result of its ability to interact with nicotinic acid receptors present in the skin.42–44 Nicotinic acid receptors are G protein coupled receptors that when stimulated lead to an increase in skin leptin, which in turn activates several signaling pathways to enhance epidermal differentiation and stimulate wound healing.78,82
In a clinical study by Jacobson et al,76 MN increased skin cell NAD by 25 percent (p=0.0001) demonstrating effective delivery. Relative to placebo, MN treatment of photodamaged facial skin increased SC thickness by approximately 70 percent (p=0.0001) and increased epidermal thickness by approximately 20 percent (p=0.001). In two separate studies, MN treatment increased rates of epidermal renewal by six (p=0.003) to 11 percent (p=0.001) and increased the minimal erythemal dose by 8.9 (p=0.07) and 10 percent (p=0.05) relative to placebo. MN treatment also resulted in reductions in the rates of TEWL of approximately 20 percent relative to placebo on cheeks and arms of study subjects.
The above data demonstrates that topical nicotinic acid preparations can enhance epidermal differentiation and barrier function, suggesting that it may be effective in the treatment of photodamaged skin and other conditions (such as atopic dermatitis) with skin barrier impairments. However, it is hard to compare these results with the results presented above on niacinamide since not all of the same attributes were monitored (such as redness, yellowing, wrinkling, etc). Further investigation is needed to compare the efficacy of MN to niacinamide. Both niacinamide and nicotinic acid have significant numbers of published studies to answer all three major questions to date. However, there is more data available on the anti-aging effects and mechanisms of topical niacinamide.
Clinically Proven Effective * if formulated correctly: correct concentration, correct molecule formation, correct base, and applied correctly.
Niacinamide, Tretinoin (Retin A, Renova), Retinoids, Alpha-hydroxy Acids, Estrogens, Vitamin C + E + ferulic acid, Vitamin C & Vitamin C derivatives, Anhydrous vitamin C combo, Oat beta-glucan
Possibly Effective but Need More Research *same note as above
Retinaldehyde Retinol / retinyl palmitate Retinyl retinoate
Copper peptides (don't use concurrently with vitamin c-they cancel each other out), Alpha lipoic acid, Coenzyme Q10 (Idebenone), Lycopene, Astaxanthin, DMAE, Green tea & White tea, MMP inhibitors, Furfuryladenine (Kinetin), Progesterone (many cautions with it), Hyaluronic acid (although it can dry the skin out more in dry weather), Palmitoyl pentapeptide-4 (Matrixyl), Palmitoyl oligopeptide / tetrapeptide-7 (Matrixyl 3000).
Popular but Unproven
Acetyl hexapeptide-3 (Argireline), Ethocyn, Resveratol, Sirtuins, Beta-hydroxy acids
Quite a few of these cosmeceutical ingredients are useful for the treatment of other skin conditions
Copyright © 1999-2012 by Dr. G. Todorov / SmartSkinCare.com
Vitamin C-Link to article
Niacinamide
Excerpted from the medical journal “:The Journal of Clinical & Aesthetic Dermatology” article:
How Much Do We Really Know About Our Favorite Cosmeceutical Ingredients? Jacquelyn Levin, DO and Saira B. Momin, DO
James Q. Del Rosso, DO, FAOCD, Section Editor
James Q. Del Rosso, Dr. Del Rosso is Dermatology Residency Director, Valley Hospital Medical Center, Las Vegas, Nevada;
...
What background information is available on niacinamide and nicotinic acid?
While the nutritional value of niacin (vitamin B3) may be well recognized, the skin care benefit of topically applied niacin is a recent discovery based on recently published studies. Niacin (vitamin B3) has two potential forms that can be used in cosmeceuticals: niacinamide (nicotinamide) and nicotinic acid. It is debatable as to whether these two forms of niacin are interchangeable as topical cosmeceuticals. Some studies claim that niacinamide and nicotinic acid are readily converted into each other in vivo40 while other studies speculate that niacinamide and nicotinic acid may have very different pharmaceutical activities despite having identical vitamin activities.41 In other words, nicotinic acid may have more benefits than topical niacinamide on the skin due to the fact that in addition to having the vitamin effects on skin (increasing levels of niacinamide adenosine dinucleotide [NAD]), it may also have drug-mediated effects on skin via interacting with nicotinic acid receptors present in the skin.41–44 Yet, the disadvantage of using nicotinic acid as a topical cosmeceutical is its unpleasant side effect of vasodilation that results in skin flushing. This is an effect that is not harmful but intensely disliked by most patients.45,46 In contrast to nicotinic acid, niacinamide does not cause skin flushing nor does it cause changes in blood pressure, pulse, or body temperature.47 Due to the decreased number of side effects of topical niacinamide compared to nicotinic acid, the effects of niacinamide as a topical cosmeceutical agent have been studied more to date.
Niacinamide, also known as nicotinamide, is the precursor of important cofactors niacinamide adenosine dinucleotide (NAD) and its phosphate derivative, niacinamide adenosine dinucleotide phosphate (NADP). These cofactors and their reduced forms (NADH and NADPH) serve as reduction-oxidation (redox) coenzymes in more than 40 cellular biochemical reactions. Thus, niacinamide has the potential to exert multiple effects on skin and is a promising anti-aging cosmeceutical ingredient.
What data is available on the percutaneous absorption of niacinamide?
Feldmann et al48 highlighted the possibilities for the topical application of niacinamide because they were able to prove sufficient percutaneous penetration into human skin.48,49 In addition, several other studies have used increased levels of NAD in skin cells after the topical application of niacinamide as evidence of percutaneous penetration.50
What are the potential mechanisms of action of niacinamide?
Studies have shown that niacinamide has the potential to act as an antioxidant, can improve epidermal barrier function, decrease skin hyperpigmentation, reduce fine lines and wrinkles, decrease redness/blotchiness, decrease skin yellowness (sallowness), and improve skin elasticity.51,52 The mechanisms by which niacinamide provides this array of skin benefits is not completely understood, but the role of niacinamide as a precursor to the NADP family of coenzymes may play a significant role in all of these improvements.50
Antioxidant capacity. Niacinamide increases the antioxidant capacity of skin after topical application by increasing the reduced forms (NADPH), which have potent antioxidant properties.53–55 This is probably the most well-studied anti-aging effect of niacinamide.
Epidermal barrier function. Niacinamide may improve the skin barrier function in two ways: first, by its ability to upregulate the synthesis of ceramides as well as other SC intercellular lipids, and second, by stimulating keratinocyte differentiation.56,57 Ceramides and other intercellular SC lipids are known to play a central role in the structural and functional integrity of the epidermal barrier function. The responsible mechanism for the increase of ceramide synthesis in niacinamide-treated, cultured keratinocytes was found to be based on the upregulation of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid synthesis. The increase in ceramide synthesis has been confirmed in an in-vivo trial after topical application of 2% niacinamide emulsion for four weeks applied twice daily.56 The elevation of ceramides after treatment with niacinamide is associated with an improved barrier function as evidenced by a reduced TEWL and an increase in the cutaneous resistance to potential harmful topical agents.56 The second mechanism likely responsible for improved barrier function is a stimulation of keratinocyte differentiation seen both in cell cultures in vitro and in-vivo studies conducted by Tanno et al.56,57 In cell cultures, more rapid keratinocyte differentiation following treatment with niacinamide was established.56 In particular, it was possible to determine an influence on keratin, K1. K1 is a basic keratin synthesized mainly in the lowest layers of the stratum spinosum. The functional limitations of aging skin include reduced “turnover of the epidermis” (i.e., a slower epidermal cell cycle) due to a deficiency of NADP in aging cells.58,59 Tanno et al also demonstrated an in-vivo improvement in epidermal barrier function with improved keratinocyte differentiation after the application of topical niacinamide. Once again, the improved barrier function was evident by a decrease in TEWL and increase in SC moisture content. Similar results were also obtained by Ertel et al.57 In conclusion, it seems that topical application of niacinamide increases NADP levels, which in turn stimulates keratinocyte differentiation. This results in a thicker SC, which is not only associated with an improved barrier, but is also associated with greater hydration retention capacity in the SC.59
Erythema and blotchiness. The mechanism by which redness/blotchiness is improved may be related to the improved skin barrier function for reasons discussed above.50,60,61 Increased barrier function may mean less irritation and redness when the skin encounters environmental insults, such as detergents and soaps, and hence less reddening of the skin. However, this theory has not been substantiated.
Yellowing of skin. The yellowing of skin that comes with aging may be a result of glycation of proteins in the skin called the Maillard reaction. The Maillard reaction is a spontaneous oxidative reaction between protein and sugar that results in cross-linked proteins (Amadori products) that are yellowish-brown in color and are fluorescent.62–64 These proteins can accumulate in the skin matrix components, similar to collagen, in response to oxidative stress as we age. Published data show a fivefold increase in collagen oxidation products in human skin from age 20 to 80.65 Since NADH and NADPH are antioxidants and their levels can be increased with niacinamide, a possible effect of topical niacinamide is inhibition of oxidative processes, such as protein oxidation, glycation, and the Maillard reaction, and hence the inhibition of skin yellowing.66–68
Fine lines and wrinkles. Multiple mechanisms may be involved in the ability of niacinamide to reduce the appearance of fine lines and wrinkles. The first to consider is that niacinamide may have the ability to increase dermal collagen and protein production. The development of wrinkles is a result of the decrease in epidermal cell layers and dermal components from a reduction in protein and collagen synthesis. Reduced protein synthesis is reflected in the levels of keratin, fillagrin, and involucrin in the skin. Keratin deficiency has an effect on the epidermal cell structure and its water-binding capacity. Fillagrin is an antecedent of natural moisturizing factor (NMF) and hence affects skin hydration. Involucrin is seen as significant for the cell envelope and structure of the SC. In summary, the effects of reduced collagen and protein synthesis are poor skin structure and reduced skin elasticity as well as a decrease in epidermal barrier function with a reduction in SC hydration. In studies on cell cultures, Oblong et al58 found that in aging cells it was possible to prove that niacinamide, as a precursor of NAD/NADP, stimulated collagen synthesis and the epidermal proteins keratin, fillagrin, and involucrin.51,58 In addition, another study was able to show niacinamide's ability to increase dermal matrix collagen production.66
The second mechanism that may be relevant to decreasing the appearance of wrinkles is the ability of niacinamide to reduce excess dermal glycosaminoglycans (GAGs). This is a controversial theory because both the elevation and depletion of dermal GAGs are associated with photodamaged or wrinkled skin.52,69 What is known is that the presence of GAGs is required for normal structure and function of the dermal matrix and increasing the levels of GAGs can increase the moisture content of skin. Testing has indicated that niacinamide reduces excess production of GAGs in old human dermal fibroblasts, thus supporting the potential involvement of this mechanism in reducing the appearance of fine lines and wrinkles.51,70 Given the above analysis and scientific data, it seems more likely that an increase in dermal proteins (including collagen) may play a bigger role in reducing fine lines and wrinkles than decreasing the level of GAGs.
Hyperpigmentation. Topical niacinamide may be effective in decreasing epidermal hyperpigmentation and reducing pigmented spots as we age.71 Hakozaki et al71 showed that the reduction of cutaneous pigmentation, surprisingly, was not due to the direct influence of niacinamide on melanin synthesis by melanocytes. Instead, they showed that niacinamide reduced melanosome transfer from melanocytes to surrounding keratinocytes in a co-culture system, although the specific mechanism remains unknown.71 This was supported by a study using 5% niacinamide moisturizer, which provided 35 to 68 percent inhibition of melanosome transfer from melanocytes to keratinocytes.71
What clinical studies are available on niacinamide?
Tanno et al56 showed a reduction in pigmentation as a result of niacinamide. Eighteen Japanese women with hyperpigmentation were treated on one side of the face with 5% niacinamide and on the other side with vehicle only. The pigmentation change was evaluated qualitatively and quantitatively using high-resolution digital images and subjective judgments. In both forms of evaluation, it was found that after eight weeks of treatment there was significant lightening of hyperpigmentation on the side treated with niacinamide when compared with the effect of the vehicle (p<0.05).56
In a separate study also reported by Tanno et al performed with 120 Japanese women, comparisons were made among a sun protection factor (SPF) 15 cream with and without 2% niacinamide and the relevant vehicle. As a result of niacinamide treatment, there was a lightening of the skin after four and six weeks, which was noted to be markedly better than the formula without niacinamide.56
It is theoreticized that niacinamide may improve the texture of skin by speeding up epidermal turnover hence functioning as a mild exfoliant.72 Using a multiple angle reflectance spectrophotometer in an in-vivo test of the back of the hand, Matts and Solenick73 established a beneficial effect for the topical application of niacinamide in smoothing the skin surface structure. This study demonstrates that the long-term application of 2.5% niacinamide can correct the skin surface damage that results from aging. These results were statistically significant compared with the influence of the vehicle alone (p<0.05).59 In agreement with the above, another clinical trial using 3.5% niacinamide cream was compared with placebo for four weeks and demonstrated a 14.8-percent reduction in skin roughness (p=0.05).56,74,75
One of the best randomized, double-blind, split-face, placebo-controlled, clinical trials published on the anti-aging effects of topical niacinamide was done by Bissett et al.51 In this study, 50 white females with clinical signs of photodamage applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks. Analyses of the data revealed a variety of effects related to improvements in skin appearance for topical niacinamide including reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and improvement in skin elasticity.51 Matts and Solenick later confirmed the results of Bissett et al with 5% and 2% niacinamide.59 The results also demonstrated that the anti-aging effects of niacinamide were dose dependent.
What conclusions can be drawn from data on niacinamide?
The topical use of niacinamide for anti-aging has proven to be effective not only when there are signs of a niacin deficiency. Despite the recent discovery of the cosmetic benefit of niacin for the skin, there have been sufficient studies completed to answer all three “Kligman questions.” It is the opinion of the authors that niacinamide is one of the best studied cosmeceutical ingredients for anti-aging. However, further research is required to uncover the specific mechanisms of niacinamide in the skin and to optimize the concentration of niacinamide in cosmeceutical formulations.
Is there additional information on nicotinic acid?
As mentioned earlier, a major obstacle in the topical delivery of therapeutic amounts of nicotinic acid to any tissue is its ability to cause a peripheral vasodilation that leads to a skin flushing response. While this effect is not harmful, it is intensely disliked by most patients.45,46 This issue may be avoided by using the long chain ester derivative of nicotinic acid, myristyl nicotinate (MN), which is able to deliver large amounts (in concentrations near 5%) of nicotinic acid without flushing.76,77
The advantage of using nicotinic acid over niacinamide is its drug-mediated effect on skin as a result of its ability to interact with nicotinic acid receptors present in the skin.42–44 Nicotinic acid receptors are G protein coupled receptors that when stimulated lead to an increase in skin leptin, which in turn activates several signaling pathways to enhance epidermal differentiation and stimulate wound healing.78,82
In a clinical study by Jacobson et al,76 MN increased skin cell NAD by 25 percent (p=0.0001) demonstrating effective delivery. Relative to placebo, MN treatment of photodamaged facial skin increased SC thickness by approximately 70 percent (p=0.0001) and increased epidermal thickness by approximately 20 percent (p=0.001). In two separate studies, MN treatment increased rates of epidermal renewal by six (p=0.003) to 11 percent (p=0.001) and increased the minimal erythemal dose by 8.9 (p=0.07) and 10 percent (p=0.05) relative to placebo. MN treatment also resulted in reductions in the rates of TEWL of approximately 20 percent relative to placebo on cheeks and arms of study subjects.
The above data demonstrates that topical nicotinic acid preparations can enhance epidermal differentiation and barrier function, suggesting that it may be effective in the treatment of photodamaged skin and other conditions (such as atopic dermatitis) with skin barrier impairments. However, it is hard to compare these results with the results presented above on niacinamide since not all of the same attributes were monitored (such as redness, yellowing, wrinkling, etc). Further investigation is needed to compare the efficacy of MN to niacinamide. Both niacinamide and nicotinic acid have significant numbers of published studies to answer all three major questions to date. However, there is more data available on the anti-aging effects and mechanisms of topical niacinamide.
Vitamin C, niacinamide, and Retinols
I carry PCA in all of these formulations and Image for the vitamin C and retinol. These are all in proper formulations to function as intended in your skin.
I carry PCA in all of these formulations and Image for the vitamin C and retinol. These are all in proper formulations to function as intended in your skin.