NA-PCA (the sodium salt of pyrrolidone carboxylic acid. NaPCA holds water molecules. Skin contains NaPCA and it decreases with age. But when applied to the outer skin, it cannot penetrate the skin barrier. The problem is that when NaPCA is applied to the outer skin it keeps the outer skin proteins wet and hydrated. This stops the upward migration of new replacement keratinocytes to the skin's surface.

The signal to send new keratinocytes to the skin's surface is the dryness of the skin's outer proteins. Because NaPCA, when it is applied to the skin, keeps the outer skin proteins wet, this slows skin renewal and results in an older skin surface.

I want to avoid all the inredients you say are not healthy for the skin. Can you make a chart here that lists these ingredients. Also can you list additional names for the same ingredient so that I can recognize them on a label?
Thank you,
Julie Burgo

quote:

Originally posted by juliebb:
I want to avoid all the inredients you say are not healthy for the skin. Can you make a chart here that lists these ingredients. Also can you list additional names for the same ingredient so that I can recognize them on a label?
Thank you,
Julie Burgo

We are planning to build such a page on the website. But for now, we are focused on turning all of our websites into one website and this is taking much effort by our staff.

quote:

Originally posted by Dr. Pickart:
The problem is that when NaPCA is applied to the outer skin it keeps the outer skin proteins wet and hydrated. This stops the upward migration of new replacement keratinocytes to the skin's surface.

The signal to send new keratinocytes to the skin's surface is the dryness of the skin's outer proteins. Because NaPCA, when it is applied to the skin, keeps the outer skin proteins wet, this slows skin renewal and results in an older skin surface.

Dear Dr. Pickart,

I was going to figure out the answer to this old question of mine, but perhaps you have the answers and can expedite the process.

Do biological healing oils and natural oils not moisturize and hydrate the outer skin the same way as NaPCA and Hyaluronic Acid, and does the biochemistry of the oils work differently than these wetting agents and do not prevent and slow the upward movement of keratinocytes?

My guess here is that Na PCA and hyaluronic acid attract water to the skins outer surface, slowing the keratinization rate as Dr. Pickart explained. Whereas, the BHOs act as water repellents, thereby working as a sealant to hold the skins own water content in. We all know the old saying that "oil and water dont mix", and we know that sodium attracts water, thats why eating too much of it can cause edema/hypertension/puffiness, so this all makes sense to me.

Now if the keratinocytes can tell when to move up and not move up and the cells can differentiate between an humectant and oil, it'd be interesting to decode such cellular "intelligence".

From Dr. Anna Margolina...

Here are some references on how skin barrier repair is influenced by water loss through the stratum corneum and dry environment. As you will see, they all say basically the same: acute barrier disruption leads to increased water loss through the stratum corneum and gives a signal for barrier repair. Dryness of upper level leads to increase of DNA synthesis in keratynocytes, cell proliferation, lipid synthesis. Water impermeable membrane preventing water loss impairs barrier recovery, blocks DNA synthesis, impedes lipid synthesis.

Arch Dermatol Res. 1998 Mar;290(3):145-51.
The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane.

Jiang S, Koo SW, Lee SH.

Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO4) or ruthenium tetroxide (RuO4). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction.

J Invest Dermatol. 1998 Nov;111(5):873-8.
Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses.

Denda M, Sato J, Tsuchiya T, Elias PM, Feingold KR.

Shiseido Research Center, Skin Biology Research Laboratories, Yokohama, Japan.

Although seasonal changes in humidity are thought to exacerbate various skin diseases, whether these flares can be attributed to prolonged exposure to extremes in environmental humidities has not been studied systematically. We recently showed that prolonged exposure to high versus low humidities induced profound changes in epidermal structure and permeability barrier homeostasis. Therefore, we asked here whether comparable extremes in humidity could initiate not only homeostatic, but also potentially pathophysiologic alterations. We showed first that exposure to low humidity increases epidermal DNA synthesis in normal murine epidermis. Moreover, exposure to a low humidity for 48 h further amplifies the DNA synthetic response to barrier disruption, resulting in marked epidermal hyperplasia. Additionally, exposure to a dry environment for 48 h prior to barrier disruption results in dermal mast cell hypertrophy, degranulation, as well as histologic evidence of inflammation. To demonstrate the role of changes in external moisture on these phenomena, we applied either an occlusive, water-impermeable plastic membrane, Petrolatum, or a nonocclusive humectant, both to nonperturbated and to perturbed skin. All three forms of treatment prevented the epidermal hyperplasia and dermal mast cell hypertrophy and degranulation induced by exposure to low humidity. These studies indicate that (i) exposure to changes in environmental humidity alone induces increased keratinocyte proliferation and markers of inflammation, and (ii) that these changes are attributable to changes in stratum corneum moisture content. Finally, these studies provide evidence that changes in environmental humidity contribute to the seasonal exacerbations/amelioration of cutaneous disorders, such as atopic dermatitis and psoriasis, diseases which are characterized by a defective barrier, epidermal hyperplasia, and inflammation.

J Lipid Res. 1989 Mar;30(3):323-33.
Grubauer G, Elias PM, Feingold KR.

Dermatology Service, Veterans Administration Medical Center, San Francisco, CA.

Previous studies have demonstrated that perturbations in barrier function stimulate epidermal lipid synthesis and that this increase can be prevented by occlusive membranes. These observations suggest that epidermal lipid synthesis might be related to barrier function and raised the question whether transcutaneous water flux might regulate epidermal lipogenesis. In the present study we first abrogated the barrier with acetone, and then compared the rate of repletion of stainable lipids, barrier recovery, and epidermal lipogenesis in animals covered with occlusive membranes or vapor-permeable membranes versus uncovered animals. Acetone treatment of hairless mice removed stainable neutral lipids from the stratum corneum, with repletion evident both biochemically and histochemically within 48 hr in uncovered animals. In contrast, when the animals were covered with an occlusive membrane, the usual return of stratum corneum lipids was aborted. Since application of vapor-permeable membranes allowed normal lipid repletion, occlusion alone is not responsible for the inhibition of lipid repletion. Acetone treatment also perturbed epidermal barrier function, which returned to normal in uncovered animals in parallel with the reappearance of stratum corneum lipid. However, when animals were covered with an occlusive membrane, barrier function did not recover normally. In contrast, occlusion with vapor-permeable membranes allowed barrier function to recover normally. Finally, whereas occlusive membranes prevented the characteristic increase in epidermal lipid synthesis that follows barrier perturbation, epidermal lipid synthesis was increased in animals covered with a vapor-permeable membrane. These results point to transepidermal water flux itself as the signal that regulates epidermal lipid synthesis, which is associated first with the redeposition of stratum corneum lipids and then the normalization of stratum corneum barrier function.

Arch Dermatol Res. 1998 Nov;290(11):634-7.
Loss of water from the stratum corneum induces epidermal DNA synthesis in hairless mice.

Sato J, Denda M, Ashida Y, Koyama J.

Shiseido Research Center, Yokohama, Japan.

Many clinical studies have shown that low humidity has a deleterious effect on skin, but the mechanisms involved are poorly understood. To clarify the changes that occur in skin, we examined epidermal cell proliferation in mice kept in a dry (relative humidity < 10%) or a moist (relative humidity > 90%) environment. In animals exposed to low humidity, epidermal DNA synthesis started to increase within 12 h, reaching twice the original level, and the increased level was maintained for up to 5 days. The transepidermal water loss (TEWL) of mice kept for 12 h in the dry environment was the same as that of mice kept in the moist environment, but the skin conductance was lower. The increase in epidermal DNA synthesis following exposure to the dry environment was inhibited by topical application of petrolatum. It is concluded that loss of water from the stratum corneum induces epidermal cell proliferation within 12 h, and this change occurs in the absence of apparent cutaneous barrier dysfunction.

J Invest Dermatol. 1998 Nov;111(5):858-63.
Exposure to a dry environment enhances epidermal permeability barrier function.

Denda M, Sato J, Masuda Y, Tsuchiya T, Koyama J, Kuramoto M, Elias PM, Feingold KR.

Shiseido Research Center, Yokohama, Japan.

Previous studies have suggested that transepidermal water movement may play an important role in epidermal homeostasis and barrier repair. Here we analyzed cutaneous barrier function, epidermal morphology, and lipid content of the stratum corneum in hairless mice maintained in a high relative humidity (RH > 80%) versus low humidity (RH < 10%) environment for 2 wk. Basal transepidermal water loss was reduced by 31% in animals maintained in a dry versus humid environment. Moreover, the number of lamellar bodies in stratum granulosum cells, the extent of lamellar body exocytosis, and the number of layers of stratum corneum increased in animals kept in a dry environment. Furthermore, the dry weight of the stratum corneum and the thickness of the epidermis also increased in a dry environment. In addition, total stratum corneum lipids increased but lipid analysis revealed no significant differences in lipid distribution. Lastly, barrier recovery following either acetone treatment or tape stripping was accelerated after prolonged prior exposure to a dry environment, while conversely, it was delayed by prior exposure to a humid environment. These studies demonstrate that environmental conditions markedly influence epidermal structure and function, and suggest mechanisms by which the environment could induce or exacerbate various cutaneous disorders.

J Invest Dermatol. 1992 Mar;98(3):279-89.
Lamellar body secretory response to barrier disruption.

Menon GK, Feingold KR, Elias PM.

Dermatology Service, Veterans Administration Medical Center, San Francisco, California 94121.

Abundant evidence points to an important role for epidermal lamellar body secretion in permeability-barrier maintenance. However, the response of the lamellar body secretory system to barrier disruption has not been examined. Hence, we examined the lamellar body secretory response at various points after acetone-induced barrier abrogation in hairless mice in air-exposed animals and those occluded with impermeable versus vapor-permeable membranes. Tape-stripped animals served as a control for chemical toxicity. Barrier perturbation with either acetone or tape stripping was followed by rapid secretion of lamellar body contents from the uppermost granular cell layer, leaving the cytosol largely devoid of lamellar bodies. The newly secreted lamellar body contents comprised pleated sheets (not "discs," as previously thought), which unfurled in the intercellular spaces at the granular-cornified cell interface. At this time (15-30 min), the basic unit structure of the lamellar bilayers in the mid-to-upper stratum corneum appeared disorganized and interspersed with large lacunae, reflecting solvent extraction. Nascent lamellar bodies began to reappear in the granular cell cytosol by 30 min and by 360 min the cells displayed a full complement of normal-appearing lamellar bodies. Between 60 and 360 min, the density of lamellar body sheets at the granular-cornified cell interface increased, whereas the membrane bilayers of the outer stratum corneum remained disorganized. New lamellar bilayer units first appeared in the lower stratum corneum between 60 and 180 min, as a result of the transformation of secreted lamellar body sheets and over time these lamellae appeared at more apical locations. Occlusion with a water vapor-impermeable but not a vapor-permeable membrane resulted in a) decreased quantities of lamellar bodies and lamellar body-derived intercellular products; b) formation of lamellar bodies with abnormal internal contents; c) inhibition of lamellar body secretion; and d) inhibition of transformation of lamellar body-derived sheets into lamellar bilayer units. These results demonstrate the central role of the lamellar body-secretory system in barrier repair and homeostasis.

Br J Dermatol. 1993 May;128(5):473-82.
Barrier function regulates epidermal lipid and DNA synthesis.

Proksch E, Holleran WM, Menon GK, Elias PM, Feingold KR.

Dermatology Service, Veterans Administration Medical Center, San Francisco, CA.

The stratum corneum, the permeability barrier between the internal milieu and the environment, is composed of fibrous protein-enriched corneocytes and a lipid-enriched intercellular matrix. The lipids are a mixture of sphingolipids, cholesterol and free fatty acids, which form intercellular membrane bilayers. Lipid synthesis occurs in the keratinocytes in all nucleated layers of the epidermis, and the newly synthesized lipids are delivered by lamellar bodies to the interstices of the stratum corneum during epidermal differentiation. Disruption of barrier function by topical acetone treatment results in an increase in the synthesis of free fatty acids, sphingolipids and cholesterol in the living layers of the epidermis, leading to barrier repair. Cholesterol and sphingolipid synthesis are regulated by the rate-limiting enzymes HMG CoA reductase and serine palmitoyl transferase (SPT), respectively. Acute barrier disruption leads to an increase in both enzymes, but with a different time curve: increase in HMG CoA reductase activity begins at 1.5 h, whereas the increase in SPT activity occurs 6 h after barrier impairment. Topical application of HMG CoA reductase or SPT inhibitors after acetone treatment delays barrier repair, providing further evidence for a role of cholesterol and sphingolipids in epidermal barrier function. Repeated application of lovastatin to untreated skin results in disturbed barrier function accompanied by increased DNA synthesis and epidermal hyperplasia. Therefore, we have examined the specific relationship between barrier function and epidermal DNA synthesis. After acute and chronic disturbances not only lipid, but also DNA synthesis, is stimulated. Thus, stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis repairs defects in barrier function. The link between barrier function and both lipid and DNA synthesis is supported further by occlusion studies. Artificial barrier repair by latex occlusion prevents an increase in both lipid and DNA synthesis. In addition, increased epidermal lipid and DNA synthesis in essential fatty-acid deficiency can be reversed by topical applications of the n-6 unsaturated fatty acids, linoleic or columbinic acid. These studies may be of relevance in understanding the pathogenesis of hyperproliferative skin diseases, such as ichthyosis, psoriasis, atopic dermatitis, and irritant contact dermatitis.

Crit Rev Ther Drug Carrier Syst. 1991;8(3):193-210
The regulation of epidermal lipid synthesis by permeability barrier requirements.

Feingold KR.

Metabolism Section (111F), VA Medical Center, San Francisco, CA 94121.

A major function of the skin is to prevent the loss of fluids. The barrier to fluid loss resides in the intercellular lipids (primarily sterols, fatty acids, and sphingolipids) of the stratum corneum. The epidermis is a very active site of lipid synthesis and when the permeability barrier is disrupted by topical solvents or detergents a marked stimulation of sterol, fatty acid, and sphingolipid synthesis occurs. Essential fatty acid deficient mice, with a chronic disturbance in barrier function, also have an increase in epidermal lipid synthesis. When the defect in barrier function is artificially corrected by occlusion with a water vapor impermeable membrane the increase in epidermal lipid synthesis is prevented, suggesting that water flux may be a regulatory factor. The activity of the key rate limiting enzyme in cholesterol synthesis, HMG CoA reductase is increased following barrier disruption due to both an increased quantity of enzyme and an increase in activation state. Similarly, the activity of serine palmitoyl transferase, the rate limiting enzyme in sphingolipid synthesis is also increased following barrier disruption. Occlusion prevents the increase in HMG CoA reductase and serine palmitoyl transferase activity. When the increase in epidermal lipid synthesis is inhibited by occlusion the characteristic rapid return of stratum corneum lipids and recovery of barrier function is prevented. Moreover, when epidermal cholesterol synthesis is inhibited by lovastatin, an inhibitor of HMG CoA reductase, the rate of recovery of barrier structure and function is delayed. Similarly, B chloroalanine, an inhibitor of serine palmitoyl transferase and sphingolipid synthesis, also impairs barrier recovery. Thus, disruption of the barrier stimulates epidermal lipid synthesis which provides the lipids necessary for the repair of the barrier. The signals that initiate and coordinate this response are yet to be defined, but the understanding of this process may allow for pharmacological interventions that will specifically disrupt the barrier and allow for the transcutaneous delivery of drugs.

This message has been edited. Last edited by: Dr. Pickart,

I would like to pose a question to Dr. Pickart. Why does Vit. C and Copper cancel each other out. and if you use the Vit. C in the morning, and use the Copper at night time is that a problem? also i've been on the obagi nuderm program, and instead of using their Vit. C serum at 15% if i wanted to incorporate the copper peptide serum instead, is that a problem? thank you.

quote:

I would like to pose a question to Dr. Pickart. Why does Vit. C and Copper cancel each other out. and if you use the Vit. C in the morning, and use the Copper at night time is that a problem? also i've been on the obagi nuderm program, and instead of using their Vit. C serum at 15% if i wanted to incorporate the copper peptide serum instead, is that a problem? thank you.

Vitamin C and Copper do not cancel each other out. Biochemically, the Copper cancels out the Vitamin C. However, it is not clear whether this holds true during practical application. Dr. Pickart and Skin Biology now state that it is safe to use both products together if desired, but that you are probably better off raising your Vitamin C levels through oral supplementation, while applying the Copper products topically.
So no, it would not be a problem to apply the Vitamin C product in the morning, and the Copper product at night; and no, it would not be a problem to replace the Vitamin C product with the Copper product.

Thank you very much! i realize that obagi nuderm may or may not be recommended as a skin product care line. But i've been using it, and felt that the copper peptide are a much better antioxidant to use, as opposed to the Vit. C serum. What are your thoughts on this, do you think that it would be affect with this line of products. Thanks you.

I believe that Dr. Pickart has said that Obagi can work well, as long as you have a skilled dermatoligist to walk you through it. That doesnt necessarily mean that it is a recommended product, just that it has the potential to work.

I have question for Dr. Pickart. If CPs cancel out Vit C topically, should one assume that the same thing happens when copper and Vit C are taken orally? Should one take them at opposite ends of the day like topical CPs and Vit C out of an abundance of caution?

Kathy

ok thanks so much for the reply..

quote:

Originally posted by KathyC:
I have question for Dr. Pickart. If CPs cancel out Vit C topically, should one assume that the same thing happens when copper and Vit C are taken orally? Should one take them at opposite ends of the day like topical CPs and Vit C out of an abundance of caution?

Kathy

It is rather easy to raise vitamin C levels in the body since it is water soluble. But copper is tightly bound by proteins and peptides in the body. So I doubt if the internal vitamin C ever really "sees" the copper.

Dear Dr Pickart,

Can you help to clarify a question bring forward by JW:

Do biological healing oils and natural oils not moisturize and hydrate the outer skin the same way as NaPCA and Hyaluronic Acid, and does the biochemistry of the oils work differently than these wetting agents and do not prevent and slow the upward movement of keratinocytes?

I would like to know your answer to the above and whether you would confirm what Blueyes view on this.

How biological oil can moisturise the skin if the skin is dry i.e. not enough water content. Maybe humectant do provide a short term solution at least, while the skin barier is being repair. What do you think?

I am confuse........

I'm confused myself after reading the studies. The conclusions from the studies would seem to contradict what Brett is saying, some usual post cosmetic surgerical procedures, enhanced wound healing for burns and deep skin trauma, and the good results I'm getting from using BHOs and anti-oxidant natural oils with SRCPs, unless by definition BHOs and antibiotic ointment and bandaging are not classified as occlusives but haylurnoic acid and Na PCA are. The abstracts didn't define occlusives.

Yeah, Im kinda' scratching my head here, too.

quote:

Originally posted by FC1233:
Dear Dr Pickart,

Can you help to clarify a question bring forward by JW:

Do biological healing oils and natural oils not moisturize and hydrate the outer skin the same way as NaPCA and Hyaluronic Acid, and does the biochemistry of the oils work differently than these wetting agents and do not prevent and slow the upward movement of keratinocytes?

I would like to know your answer to the above and whether you would confirm what Blueyes view on this.

How biological oil can moisturise the skin if the skin is dry i.e. not enough water content. Maybe humectant do provide a short term solution at least, while the skin barier is being repair. What do you think?

I am confuse........

The hyaluronic acid and PCA wet the outer skin layers which hydrates (wets) the outer, protective proteins. This weakens the skin barrier and lets more bacteriam viruses, and allergens into the skin.

Real biological Skin Moisturization depends on only three items.

1. The outer skin oils that help water-proof the skin. This is the Acid Mantle of natural skin oils and acids.
2. The tightness of the skin barrier. This is the outer skin proteins that must remain hard to block water loss through the skin.
3. Within the skin, a high internal level of water holding proteins and sugars such as the proteoglycans and glycosaminoglycans.

Our Skin Biology water/oil creams have no detergents and are always close to breaking up into a water phase and oil phase. They cannot open the skin. Four published studies found they increase the skin barrier strength. The SRCPs also increase the production of the water-holding proteins and sugars within the skin.

You can also use for skin oil either Emu Oil for Skin or Squalane from olives.

Daily supplements of 1 gram vitamin C and 1 gram MSM (glucosamine and chrondroitin sulfate does much the same) will help the production of the skin's water holding proteins.

Skin Damaging Cosmetic Moisturizers are designed to push water into the skin and wet the outer skin proteins. Various detergents (but they may not be called detergents) and water-holding molecules such as collagen fragments or hyaluronic acid often used to loosen the outer skin proteins so water can interact with them. But this weakens the skin barrier and lets in viruses, bacteria, and allergens.

In about 1997, there were studies from Denmark that found that oil/water skin moisturizers broke down the skin barrier. The concern was that this could increase infection in hospital patients. Since then, it has been found that hydrating (wetting) the outer skin proteins slows or even stops the normal flow of keratinocytes to the skin surface. I posted a number of references about this about a months ago.

This means to skin is more slowly replaced and damage remains longer. We are working on a page about skin products that speed aging. Cosmetic moisturizers are designed to wet the outer skin proteins and push water into the skin to puff it up. Various detergents (but they may not be called detergents) are used to loosen the outer proteins so water can interact with them. The best example is the "cold creams" that women applied every night in the 1930s and 1940s. You may have seen these in old movies. Their skin was kept moist but the women ended with horrible wrinkles.

Dear Dr. Pikart,

Your answer above still has not clarified how is the mechanism difference between biological oil and humectant in helping the skin in maintaining its moisture.

I can understand from your explanation about how humectant wet the outer skin layer and such mechanism tends to delay the skin barier repairing ability. However, how biological oil helps skin in maintaining its moisture if the skin is already in dry condition?

If biological oil is forming a oil film in the outer layer of the skin to prevent further loss, for dry skin people, I will presume this may not be effective. May I know what type of oils are defining as biological oils? Appreciate if you can elaborate a little bit more. Thanks

Humans lost their body hair about 1.1 million years ago. After this the skin was covered by a mixture of skin oils, skin acids, and dust from their surroundings. They never - or extremely rarely - washed off this covering. But the oil/dirt covering provided a good protection for skin. Oils on the skin inhibit water loss since water cannot easily get past an oil barrier.

But we modern human wash and clean constantly. So the protective oil barrier scarely exists. But adding an oil will slow water loss - especially in damaged skin (such as sunburned or windburned).

Emu Oil is very much like human skin oil and works very well to protect skin. An alternative is squalane/squalene from oilve oil. Squalane/squalene are the major skin protective lipids. But they decline from 15% of skin fats in the teenage years to 5% by age 60. This is felt to be a major factor in the dry skin of older people.

It is best to stick to oils that are like the oils and lipids in human skin.