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The History of Animal Testing and Buying Cruelty-Free

Trigger Warning: Animal cruelty and animal testing methods are briefly described in this post. I have avoided excessive detail and have not included any images of the testing. I have included a warning before the portion describing the testing. Please feel free to skip it.

Anyone that has purchased cosmetics – either skincare or makeup – has seen the label “cruelty-free.” Indeed it is a phrase that has become more popular in the last two decades thanks to consumer advocacy groups and growing concern over animal cruelty and mistreatment. Due to this, many companies have adopted cruelty free stances, unless hamstrung by laws (such as China, which requires animal testing before a product can go to market, though this has gotten less stringent since 2014), or have adopted alternative methods of testing, such as in vitro testing, which allows many products to be tested on grown cells in a controlled environment.

The history of animal testing begins in the 30s, at a time when the FDA was creating stricter laws around cosmetics, drugs, and health concoctions. There were several public health disasters and deaths that lead to the passing of the 1938 law in the US, specifically snake oil medicine that was quite popular at this time, with “radioactive quackery” being perhaps the most obscene.

Radithor, a “cure for the living dead” as well as “perpetual sunshine,” developed by Bailey Radium Laboratories, claimed to cure impotence and other ills. It contained triple distilled water as well as 1 microcurie each of the radium 226 and 228 isotopes. Eben Byers, an American socialite who died from radium poisoning from Radithor in 1932, was buried in a lead coffin and later exhumed in 1965 for testing, only for his remains to still be highly radioactive.

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Elixir Sulfanilamide

Sulfanilamide was another popular drug in the 30s, and in 1937, an improperly prepared medicine called Elixir Sulfanilamide caused the deaths of over 100 people in the United States. This liquid formulation of sulfanilamide – a popular drug for strep infections – had never been tested for toxicity, and contained diethylene glycol – a chemical used as an antifreeze that is a deadly poison. It was only confiscated from the public due to it’s labeling as an “Elixir,” which was covered in the original 1906 Pure Food and Drugs Act. According to the FDA’s description of the incident:

 

A few simple tests on experimental animals would have demonstrated the lethal properties of the elixir. Even a review of the current existing scientific literature would have shown that other studies–such as those reported in several medical journals–had indicated that diethylene glycol was toxic and could cause kidney damage or failure. But in 1937 the law did not prohibit the sale of dangerous, untested, or poisonous drugs. Dr. Samual Evans Massengill, the firm’s owner, said: “My chemists and I deeply regret the fatal results, but there was no error in the manufacture of the product. We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part.” The firm’s chemist apparently did not share this feeling; Harold Watkins committed suicide after learning of the effects of his latest concoction.

Of 240 gallons manufactured and distributed, 234 gallons and 1 pint was retrieved; the remainder was consumed and caused the deaths of the victims. (Source)

The Smithsonian also details pre-FDA cosmetics – from mercury in face creams to coal tar in mascara. Three such cosmetics were Koremlu, Lash Lure, and Gouraud’s Oriental Cream.

Koremlu, a hair-removal cream, contained thallium acetate – an ingredient that was used as rat poison (now banned in the US due to how toxic it is). Women who used the cream suffered hair loss all over their bodies as well as paralysis and permanent eye damage. The Journal of the American Medical Association described it in 1932 as a “viciously dangerous depilatory.”

4901257463_2df8c35932_b-wrLash Lure was another product that prompted movement by the FDA. It contained a chemical known as p-phenylenediamine, which, according to the authors of Science, Medicine, and Animals, “caused horrific blisters, abscesses and ulcers on the face, eyelids and eyes of Lash Lure users, and it led to blindness for some. In one case, the ulcers were so severe that a woman developed a bacterial infection and died.” (Source)

Gouraud’s Oriental Cream was advertised as a “cleansing cream that puts new life into sluggish complexions and brings a Natural ‘Healthy Glow’ to the Cheeks,” but unfortunately, it contained a mercury compound, calomel, which caused mercury poisoning in it’s users. One woman “developed dark rings around her eyes and neck, followed by bluish black gums and loose teeth.” Many acne products at the time contained these poisonous compounds.

Following these events, the 1938 US Congress approved the Food, Drug, and Cosmetics Act, which mandated that products be tested before they went to market, lest they bear a warning label. While the FDA did (and still does) not mandate animal testing specifically, it does advise manufacturers of “appropriate and effective” testing “for substantiating the safety of their products.” A year after the 1938 law, John Henry Draize joined the FDA, where he was soon promoted to the head of the Dermal and Ocular Toxicity Branch.

Draize has obtained a BSc in Chemistry and then a PhD in Pharmacology. He had worked with the University of Wyoming to study plants that were poisonous to cattle, livestock, and people, and in 1935, worked with the US Army to investigate the effects of mustard gas. At the FDA, he was charged with testing developing methods of testing, and established the techniques that were later used by the FDA to evaluate the safety of insecticides, sunscreens, and many other compounds.

One such test was the Draize test, which can be distinguished by the target organs, namely the Draize eye and Draize skin test.

Trigger Warning: Testing description ahead. Please feel free to skip this section.

 


To test the products, the animal’s eyes are held open with clips, and solutions of the product are applied directly into the eyes. This lasts the entire duration of the testing period, which can be several days, during which the animals are also placed in restraining stocks and cages. For skin tests, the hair is shaved, layers of skin is removed with tape, the product is applied, and then covered with plastic sheeting to occlude the area, enhancing penetration and exaggerating the effect. After, the animal is frequently euthanized and autopsied for any additional reactions, particularly cancerous or reproductive.

Albino rabbits are the most common choice for this testing, but dogs can also be used.

Some groups, such as the British Research Defence Society, say the Draize eye test is now a “very mild” test due to improvements and changes to the test, which include washing the product out of the eye at the first sign of irritation. In an article that appeared in Nature in 2006 entitled “Testing is necessary on animals as well as in vitro,” Andrew Huxley defended the practice, saying

A substance expected from its chemical nature to be seriously painful must not be tested in this way; the test is permissible only if the substance has already been shown not to cause pain when applied to skin, and in vitro pre-screening tests are recommended, such as a test on an isolated and perfused eye. Permission to carry out the test on several animals is given only if the test has been performed on a single animal and a period of 24 hours has been allowed for injury to become evident. (Source.)


 

Groups against animal testing have argued that the differences between the eyes of rabbits and humans should be considered, specifically that rabbit eyes are much more prone to irritation than human eyes. In 2001, Kirk Wilhelmus, a professor in the Department of Ophthalmology at Baylor College of Medicine noted, “the Draize eye test … has surely prevented harm,” but predicts that it will be supplanted by other tests in the future.

Since then, many alternatives have been developed that have evaluated potential replacements, such as in vitro tests that use human corneal cells or human skin equivalent models. Other progress has been made as well. In 2004, animal testing for complete products was banned in the EU, and by 2009, ingredients were no longer allowed to be tested on animals. Furthermore, 2013 and 2016 saw the banning of imported goods into the EU that had been tested on animals.

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Leaping Bunny Logo

Consumers have also weighed in with their wallets, and “cruelty-free” labels have popped up everywhere. Unfortunately, “cruelty-free,” while it carries the weight of the assumption that no animal has been harmed or killed in the testing of the whole product or the ingredients within the product, this is not always the case. As a term, “cruelty-free” has no strict definition, nor is it a legal definition, which means that while the product you are purchasing may not have been tested on animals, the ingredients within the product may have been tested on animals in the past.

Some groups have tried to make this less muddy for consumers, such as the Leaping Bunny Program, which was established in 1996, which dictates that companies that want to participate comply by “The Standard,” such as:

  1. The Company does not and shall not conduct, Commission, or be a party to Animal Testing of any Cosmetic and/or Household Products including, without limitation, formulations and Ingredients of such products.
  2. The Company does not and shall not purchase any Ingredient, formulation, or product from any Third Party Manufacturer or Supplier that conducted, Commissioned, or had been party to Animal Testing on said Ingredient, formulation, or product after the Company’s Fixed Cut-off Date. If a formulation, Ingredient, or product is found not to comply with the Standard, the Company will replace it with an alternative that complies with the Standard’s criteria or remove it from the product range.

They have also strictly defined animal testing as:

All testing of finished Cosmetics and/or Household Products, or any one or more Ingredients or formulations used in manufacturing or production of such products in which whole non-human animals are the test subjects, including without limitation, fish, amphibians, reptiles, birds, and non-human mammals. Animal Testing excludes in vitro tests or tests conducted completely with human volunteers.

The prohibition against Animal Testing contained in the Standard does not apply to the purchase of animal-tested Ingredients if: (a) the ingredient was tested to meet explicit statutory or regulatory requirements for animal testing; AND (b) the testing was not conducted to assess safety, efficacy, or environmental effects of Cosmetics and/or Household Products.

Out of all of the advocacy groups I researched while writing this piece, the Leaping Bunny program is by far the most thorough, concise, and easy to follow.

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Caring Consumer – PETA

Two other commonly seen and trustworthy  programs are the Caring Consumer from PETA as well as the CCF Rabbit from Choose Cruelty-Free, which is an Australian-based organization.

Any other logo is not accredited by a reputable cruelty-free program or organization.

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CCF Rabbit

Many consumer advocacy groups also recommend that you check for authenticity by checking the appropriate database to verify that the product is indeed listed by the organization. In addition, only about 50% of products that are cruelty-free use the logos of the organizations that they are associated with, so you may be pleasantly surprised by checking the databases.

 


Sources

 

 

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Molecular Weights, Hyaluronic Acid, and Product Penetration

In the world of skincare, very few companies actually test the penetration of their products. The reason for this is usually very simple: cost. It’s extremely expensive to test your products, just as it is needlessly expensive to have products pushed through the FDA (example: we only have 16 FDA-approved sunscreen filters, with 8 being actively used, despite many countries having many more).  Because of this, there are very few products on the market today that have been truly tested for their ability to penetrate the skin, and if so, how deeply they penetrate the skin. Brands owned by pharmaceutical companies tend to be the most well-tested for their absorption, distribution, metabolism, and excretion (ADME).

This is fine for some products, such as sunscreen, which you do not want to penetrate the skin anyway (sunscreen must form a barrier on top of the skin to effectively protect you from UV, for instance). However, it can be a bit trickier when you are considering products that claim to be active or anti-aging ingredients, such as retinol, or ones that advertise various molecular weights to their products (such as hyaluronic acid).

There are several factors that can change or inhibit penetration of a product. The first, and perhaps the most obvious, is the molecular weight. The 500 Dalton Rule gets the most attention regarding this, and perhaps for good reason. In 2000, an article was published in “Experimental Dermatology” titled “The 500 Dalton Rule for the skin penetration of chemical compounds and drugs.” The abstract is as follows:

Human skin has unique properties of which functioning as a physicochemical barrier is one of the most apparent. The human integument is able to resist the penetration of many molecules. However, especially smaller molecules can surpass transcutaneously. They are able to go by the corneal layer, which is thought to form the main deterrent. We argue that the molecular weight (MW) of a compound must be under 500 Dalton to allow skin absorption. Larger molecules cannot pass the corneal layer. Arguments for this “500 Dalton rule” are; 1) virtually all common contact allergens are under 500 Dalton, larger molecules are not known as contact sensitizers. They cannot penetrate and thus cannot act as allergens in man; 2) the most commonly used pharmacological agents applied in topical dermatotherapy are all under 500 Dalton; 3) all known topical drugs used in transdermal drug-delivery systems are under 500 Dalton. In addition, clinical experience with topical agents such as cyclosporine, tacrolimus and ascomycins gives further arguments for the reality of the 500 Dalton rule. For pharmaceutical development purposes, it seems logical to restrict the development of new innovative compounds to a MW of under 500 Dalton, when topical dermatological therapy or percutaneous systemic therapy or vaccination is the objective. (Source)

500 Daltons is essentially a measurement of molecular weight. For perspective, water is 18 Daltons, while hyaluronic acid can vary from 5,000 to 20,000 Daltons. Here are others:

Molecular Weight of Common Skincare Ingredients (Source)
INGREDIENT DALTONS
Water 18
Glycerin 92.09
Matrixyl 578
Ethanol (Alcohol) 46
Caprylic/Capric Triglyceride 408
Lactic Acid 90
l-Ascorbic Acid 176
Retinol 286
Retinol Palmitate 524

Ingredients that are smaller than 1000 Daltons can penetrate the skin, with 500 Daltons being the golden rule for products that can penetrate through the lipids between corneocytes and into the deeper layers of skin. Molecules around 400 Daltons can enter cells, while those less than 100 can enter the blood stream.

However, it is important to keep in mind that the penetration of your products does not occur in a vacuum. Just because caprylic/capric triglycerides have a molecular weight of 408 does not mean that they are penetrating your skin cells. In fact, many ingredients only remain on top of the skin, among the very top layers of the stratum corneum. This is because there are a variety of factors that can effect penetration, namely other ingredients.

The cosmetic chemist and author of “The 500 Dalton Rule of Dermal Penetration and Cosmetic Science,” Amanda Foxon-Hill, explains this by using testosterone patches as an example:

Testosterone patches are a good example of an active that is less than 500 Daltons (testosterone is 288 Daltons) and that is able to penetrate the skin this way. Here is some information I found online about a Testosterone patch called Androderm. 

Each Androderm® 2.5 mg/day Transdermal Patch contains 12.2 milligrams of testosterone and delivers 2.5 milligrams of testosterone over 24 hours.

Looking at this we see that only around 20% of the available Testosterone is absorbed in the 24 hours. It is available in packs of 60 patches.

Each Androderm® 5 mg/day Transdermal Patch contains 24.3 milligrams of testosterone and delivers approximately 5 milligrams of testosterone over 24 hours.

It is available in packs of 30 patches. Other ingredients in the gel reservoir include:

  • ethanol,
  • purified water,
  • glycerol,
  • glycerol monoleate,
  • methyl laurate,
  • carbomer copolymer (type B)
  • sodium hydroxide.

The adhesive substance is laminate AR-7584.

So this is a gel type base with the Testosterone suspended or emulsified into it (I’m not entirely sure exactly where it sits as I haven’t thought about it for long enough but anyway…). The base would be designed to facilitate the release of the Testosterone through the skin.  Often an excess of active on the outside of the cell helps to force some of it through the cell, this may be why only 20% of the available testosterone gets through.  If you think of it as like a crowd situation where the momentum of the crowd behind you pushes you along, it’s the same scenario here.

While the author admits that testosterone patches are not a perfect analog to cosmetics – the target destination for testosterone in Androderm is the blood stream, which is not the target location for cosmetics – it demonstrates the effects of the solvents on how the active ingredient (testosterone) is taken in by the skin. In cosmetics, for instance, alcohol is frequently used to remove or break down the barrier of the stratum corneum so that products may penetrate deeper. This can occassionally lead to more irritation in some products, as other ingredients penetrate slightly deeper than intended. Tape stripping, dermabrasion, and chemical peels are all used to the same effect.

Many other things can effect penetration of products into the skin. Those things include:

  • Absorption channels (follicles, pores, glands)
  • Solubility (lipophilic or hydrophilic)
  • Polarity (negatively or positively charged molecules)
  • Sound waves (ultrasound)
  • Mild electric currents (iontophoresis)
  • Occlusion

That last one brings me to hyaluronic acid (HA), which is frequently marketed based on it’s molecular weights. My beloved HadaLabo products, for instance, advertise five different molecular weights of hyaluronic acid. As I said before, hyaluronic acid is usually a pretty large weight – somewhere between 5,000 and 20,000 Daltons. This puts the lowest weight HA close to elastin (collagen is heavier than low weight HA) that is in our dermis, but it does not end up in our dermis. Instead, it frequently acts as a delivery system for other ingredients. According to Ms. Foxon-Hill:

Hyaluronic acid works as an osmotic delivery system that can push water-soluble actives deeper into the skin by forming a highly hydrated reservoir on the surface of the skin. The main difference between the low and regular weight HA is in how thick it can get when you hydrate it and how it feels on the skin. Both work well as osmotic pumps. This situation would be quite different if we were looking at injecting HA as a dermal filler.

In short, it frequently does not matter the size of your hyaluronic acid because both are achieving the same goal due to their equal inability to penetrate the skin. Exceptions are some skin conditions, such as sebhorrheic dermatitis, which may do better with smaller sizes of HA. (Source)

This is important, however, when you are choosing active ingredients. For instance, I mentioned above that collagen is heavier than the lowest weight HA, which is roughly 5,000 Daltons. This explains why topical collagen only serves to form a smooth, emollient base on the skin, but is not an effective anti-aging ingredient for topical products. On the flip side, it explains why tretinoin is such an effective anti-aging ingredient and not recommended for pregnant women (roughly 5-8% of topical tretinoin ends up in the bloodstream [Source]).

Peptides are perhaps another ingredient that comes up frequently when discussing what products can truly penetrate the skin, with argirelene (889 Daltons) and matrixyl (578 Daltons) being the two chief synthetics designed to improve the look of the skin by inciting a cell to produce collagen and other proteins. However, there is not a large body of evidence around these ingredients yet, and it is important to look at the vehicle of the finished product rather than simply the peptide itself.

To sum up, when you’re considering a product, especially one that is designed for anti-aging or cell-communication, it is imperative to consider not only the weight of the product, but also the vehicle of delivery.

 

 

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An Overview of Product and Claims  Regulation in the United States

Edited 6/7/2018 for clarity, typos.

Frequently on skincare communities, people will ask “Does this product work?” This is especially true of products like La Mer, which is a whopping $175 per oz (or $325 for 2oz! – a whopping $25 cheaper than buying two one ounce tubs).

It’s important to not be wooed by marketing jargon when buying your products, and it’s important to know how they work, how they’re tested, and if they’re safe.

Consider this an introduction into the overview of products and claims regulation in the US, which will be part of a longer series on product efficacy.


The Chemical Abstracts Service, a division of the American Chemical Society, tracks more than 130 million organic and inorganic substances used today. Roughly 15,000 new chemicals are submitted every day, but only about 1% of all chemicals have been tested for safety – a worrisome statistic.

According to the Personal Care Product Council, there are about ~20,000 different ingredients that can be used in cosmetics. Many of those ingredients are multi-functional and can work synergistically with each other. For example, BHA is a common acne treatment but can also be used as a preservative, pH buffer, or anti-aging ingredient. Additionally, vitamin A is frequently paired with AHAs such as glycolic or lactic acid due to their ability to slough away dead skin, leading to better absorption and efficacy of the vitamin A.

Also of important note is the original FDA definitions of cosmetics and drugs:

Cosmetics: “Any product, except soap, intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering appearances.”

Drugs: “A substance that altered the structure or function of the body.”

These definitions were part of the 1938 Food, Drug, and Cosmetic Act and are still the definitions used by the FDA today to regulate the cosmetics industry. In 1938, skin was considered virtually impermeable dead tissue, so the description of cosmetics as “altering appearances” was perfectly acceptable. However, by the 1980s, doctors Van Scott and Yu patented modern AHA technology and demonstrated that AHAs could not only plump skin, but minimize lines and wrinkles by stimulating the production of collagen in the skin. This would seem to meet the definition of “a substance that alter[s] the structure or function of the body,” and yet AHAs are not considered a drug (though high percentage AHAs and BHAs are frequently restricted to professional-only sale and use).

In the 1970s, a group of estheticians were given a jar of 100% petrolatum (now called Vaseline) and several pairs of cotton gloves. They were instructed to apply petrolatum to their hands each night, put on a pair of gloves, go to sleep, and remove it in the morning with gentle soap or cleanser. This “altering of skin structure and function” is another example of a product that meets the FDA’s standards for drugs, and indeed, Vaseline is now sold as an over-the-counter drug (OTC) with a “drug facts label” emblazoned on the back.91VcIrKAdmL._SL1500_

Many products that are now available contain biologically active ingredients and can interact with the body’s biochemistry, going far beyond the FDA’s 1938 definitions. These products are now defined as cosmecueticals and are often considered the “active” ingredients in most skincare circles online.

Another thing to consider when reading ingredients is the Fair Packaging and Label Act of 1967, which issued regulations requiring that all “consumer commodities” be labeled to list their ingredients in order of concentration, starting with the highest and ending with the lowest, up to 1%. The specific wording:

“The Fair Packaging and Labeling Act (FPLA or Act), enacted in 1967, directs the Federal Trade Commission and the Food and Drug Administration to issue regulations requiring that all “consumer commodities” be labeled to disclose net contents, identity of commodity, and name and place of business of the product’s manufacturer, packer, or distributor. The Act authorizes additional regulations where necessary to prevent consumer deception (or to facilitate value comparisons) with respect to descriptions of ingredients, slack fill of packages, use of “cents-off” or lower price labeling, or characterization of package sizes. The Office of Weights and Measures of the National Institute of Standards and Technology, U.S. Department of Commerce, is authorized to promote to the greatest practicable extent uniformity in State and Federal regulation of the labeling of consumer commodities.” (Source)

Since this only affects “consumer commodities,” products packaged for professional use as exempt from this requirement. Additionally, ingredients that are in concentrations lower than 1% may be listed in any order. Unfortunately, this does not mean that manufacturers cannot advertise that their product contains such ingredients, even if they are in infinitesimally small concentrations. For example, a product may contain less than 1% vitamin C, but can advertise their product as containing vitamin C, which is misleading but legal. According to Milady’s Skin Care and Cosmetic Ingredient Dictionary (2014 edition):

“When looking at an ingredient label and the first ingredient is not water, but perhaps ‘aloe gel,’ the manufacturer is not indicating that the ingredient is in a water-based solution. While the product label may claim it contains 80% ‘aloe gel’ it is highly probable that it contains approximately 0.5% (or less) of Aloe and 79.5% (or more) water.”

When possible, ask the manufacturer for clinical data or look to the company’s website for testing results to check efficacy of the product before making a purchase.

 

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Skin Anatomy and Physiology – Layers of the Skin

Hi Patrons, and welcome back to the blog. 🙂

I hope you have something fun or at least restful planned for the weekend. I will be sleeping in and trying to decompress from arguably a long week. I also have a tube of Differin (adapalene, a synthetic retinoid) coming in tomorrow (Saturday) so hurrah! I am excited to try it again. Back when I first used Differin, my skin was hella irritated and did not appreciate it. I do have some texture issues on my forehead and chin I’d like to clear up though (as well as sporadic breakouts, since these are the original and only areas I’ve ever really dealt with acne), so I might chronicle my journey with Differin for you all if you’re interested.

Also I apologize that this wasn’t put out sooner – I had a tomato plant emergency (don’t ask) and the DMV took three hours.

So yesterday, I took you through the glands of the skin, and then last night, I was reading a 2009 study on acne that was really interesting and I wanted to share it with you all!

In parallel, research into the functions of the sebaceous gland has yielded exciting information about the central role these glands play in regulation of skin functions. The sebaceous gland regulates independent endocrine functions of the skin and has a significant role in hormonally induced aging of skin. In addition, the sebaceous gland has both direct and indirect antibacterial activities. Sapienicacid, a lipid in sebum, has innate antimicrobial activity and is up-regulated by activation of TLR-2 by skin bacteria. Further, the sebaceous gland has ubiquitous expression of antibacterial peptides and proinflammatory cytokines/chemokines; these substances are induced in sebocytes by the presence of bacteria. The sebaceous gland acts as an independent endocrine organ in response to changes in androgens and hormones, and is the control center for a complex regulatory neuropep-tide program that acts like the hypothalamus-pituitary-adrenal axis. This aspect of sebaceous gland function is primarily influenced by corticotrophin-releasing hormone, its binding protein, and corticotrophin receptors. Corticotrophin-releasing hormone levels change in response to stress, and its role in regulating sebaceous gland function is likely a link in the brain-skin connection that is thought to explain the relationship between stress and skin disorders with an inflammatory component such as acne. Similarly, substance P, a -melanocyte-stimulating hormone, and corticotrophin-releasing hormone-receptor-1 are involved in regulating sebocyte activity. … The response of skin to stress is a subject of active investigation and may soon suggest new targets for therapeutic interventions. (Source)

So from that:

  • The sebaceous gland is a neuro-endocrine inflammatory organ that likely creates local responses to stress (hence why you break out during periods of extreme stress)
  • Androgens have influence on follicular corneocytes (explaining why women tend to have more issues with acne through life and why birth control or androgen-suppressants like spironolactone helps)
  • Oxidized lipids in sebum can stimulate inflammation in skin (meaning exposure to pollution in the air and/or UV oxidizes sebum and inflames skin)
  • Oxidized sebum combined with inflammation ages skin prematurely

Alright, I’ll get on with it, but I just had to share that because I thought it was really interesting!


The skin is a highly-specialized set of tissues that is divided into three parts, with connective matrixes between. These three parts are the epidermis, dermis, and hypodermis, which is also known as the subcutaneous layer.

There are many different types of cells in the skin, but the most important are keratinocytes, melaninocytes, fibroblasts, and the immune cells such as Langerhans, mononuclear cells, and mast cells.

The connective networks in between are known as the extra cellular matrix or the ECM. These networks contain the cells primarily responsible for skin suppleness, elasticity, and flexibility. A surprisingly complex network, it regulates important functions like hydration, temperature, and permeability and acts as the glue that holds everything together.

8e67d7955f24b23819fe88db245d92a9e203a2a5.pngEach cell also is covered with a membrane with receptors which perform what is called “cell signalling.” These receptors allow cells to bind with various chemical components that pass between cells or communicate with ingredients such as tretinoin (brand name Retin-A), adapalene (Differin), or Taz (tazarotene). That is how and why Retin-A can be credited with increasing cell-turnover and is literally called a “cell-communicating ingredient.”

The epidermis is what is visible to your eyes and what we most commonly think of as our skin. It is only 25 to 30 cells deep, which amounts to roughly 1.6mm on the thickest parts (feet) and .04mm on the thinnest parts (eyelids). It is surprisingly complex despite being so thin, composed of keratinocytes, which are constantly reproducing in the deepest layer of the epidermis (stratum basale); Langerhans cells which remove antigens from the skin to the lymphatic system; melanocytes which provide the color of the skin; and Merkel cells, which govern the sense of touch.

The second layer of skin is the dermis. It lies beneath the epidermis and is connected through an intercellular membrane. At it’s thickest, it is 3mm (on the back) and .3mm at it’s thinnest (on the eyelids). It is composed of the glands of the skin (sweat and oil), collagen and elastin connective tissues, blood vessels, and nerves.

The third layer, the hypodermis, is the deepest layer and consists primarily of fat, connective tissue, large blood vessels, and nerves. It is important for regulating body temperature as well as skin temperature.


The Epidermis

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The epidermis is perhaps the most important layer of the skin and understanding the epidermis allows us to understand product penetration and efficacy. It is the layer most  affected by UV, inflammation, skin diseases, cigarette smoke and cigarette smoking, as well as skin cancer.

It is one of the most metabolically active layers of skin, synthesizing lipids and containing what is needed to form the lipid layer. It is the layer that houses the most free radical scavengers such as vitamin E and C, and contains large amounts of natural ceramides as well as glycosaminoglycans.

It is broken down into four distinct layers:

  • Stratum corneum (SC)
  • Stratum granulosum (SG)
  • Stratum spinosum (SS)
  • Stratum basale (SB)

The stratum corneum is the thickest, outermost layer. Flattened keratinocytes (corneocytes) or “dead cells” have no nuclei, though they do retain some of their metabolic and signalling functions. They are abundant in keratin, which they gain on their progression from deep within the SB to the very top SC. This layer also contains only 10-15% water, which is held in the cell’s cytoplasmic gel and intercellular channels (spaces between cells). The younger you are, the more water is present. As we age, the skin’s ability to hold onto water decreases. They serve to protect the skin from water loss as well as injury. As skin gets pushed upwards, it results in the sloughing of these surface “scales,” known as desquamation.

The Langerhans cells are also found in the epidermis. They are typically found in the lower layers of the epidermis and comprise roughly 5% of the total epidermal cell population. These cells carry antigens from the epidermis to the lymphatic system to be eliminated. They are also the cells most sensitive and susceptible to damage from UV rays. Even small amounts of UV (<10 minutes of exposure) can result in damage to the Langerhans cells, which inhibits the skin’s entire immune response. As we age, we lose Langerhans cells, which may be why skin diseases and skin cancers increase with age.

When we are young, it takes roughly 28 days for a cell to travel from the SB to the SC. This process plummets as we age, dropping to roughly 37 days at age 50. Products like Retin-A are designed to speed this process up by communicating with the cells.

In the deepest layer of the skin, the SB, is where cells reproduce through mitosis (one cell dividing into two). One cell remains in the SB and another travels upward, to the surface of the SC. As the cells migrate, they secrete lipids that create cohesion between the cells and help the epidermis hold moisture. This is why it is so crucial to consider the appropriate products to use on your skin, as it is what maintains this health.1023px-Major_events_in_mitosis.svg

The skin’s exfoliation process is controlled through enzymes. These enzymes break down, allowing the skin cells to be shed. However, if this process is not working as it should, skin cells accumulate, causing hyperkeratosis (many skin conditions are conditions of hyperkeratosis, such as keratosis pilaris forms, for example).

The SC also contains a layer of natural moisturizing factors (NMF), which are hydrosoluable (able to dissolve in water) and hygroscopic (able to retain water) substances that regulate the permeability of the SC. Harsh soaps wash away the NMF, rendering skin fragile and dry.

Skin pigmentation is also formed at the deepest layer of the epidermis. Excessive melanin production can be caused by sun/UV exposure (getting a tan), hormonal imbalances (melasma), or trauma to the skin (post-inflammatory hyperpigmentation). In the case of UV exposure, melanocytes rush to create melanin in an attempt to protect the skin from UV damage.

Touch is controlled by the Merkel cells, which are modified epidermal cells with a receptor. They are named after the scientist, Friedrish Sigmund Merkel, who first described them.

Together, melanocytes, Merkel cells, and Langerhans cells account for 13-20% of the total epidermal cells.


The Dermis

The second layer of skin, it is about 10-40x thicker than the epidermis. It houses the hair follicles, sebaceous glands, and the two types of sweat glands as well as capillaries and nerves.

The dermis is perhaps best known for the housing of collagen and elastin, which makes up roughly 70% of dermal proteins and holds the water found in the dermis. Collagen is also responsible for wound healing by producing very thin collagen fibers are which gain thickness (I like to think of them like the strands of muscle being built on Hosts in Westworld). The dermis is made of a network of other fibers that are responsible for hydration, resistance to pressure, and orientation of other proteins.

Collagen in the dermis also acts as a structural support system that holds the nerves, glands, and blood vessels in this layer while providing the skin with strength and elasticity. Its production begins with procollagen, which goes through a series of changes to become regular collagen. Procollagen decreases over time, which is why skin gets drier, wrinkles, and loses elasticity as a person ages.

In undamaged skin, collagen and elastin fibers make up for 2-4% of the dermis.


The Hypodermis

The hypodermis or the subcutaneous layer is the last layer of skin, tucked just below the dermis. This is what gives skin its shape and acts as a thermal insulator, shock absorber, and nutritional depot. Attached firmly to the lower surface of the dermis, it glides fairly smoothly over deeper fascia, giving skin mobility. The fat of the tissue protects nerves and other underlying tissue. It is not present in the thinnest parts of the skin, such as the eyelids.

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Skin Anatomy and Physiology – Glands of the Skin

Skin Anatomy and Physiology – Glands of the Skin

The skin is the body’s largest organ, and as such, performs many key functions. It is a barrier, protecting the body from external elements, injury, and oxidation. It regulates body temperature through regulation of moisture loss, which helps the body adapt to changing ambient conditions. It also is your largest sensory organ and plays a tremendous role in the immune system, thanks to Merkel and Langerhan cells.

Skin care products play a large role in maintaining these key functions. As an example, sunscreen protects against UV radiation, and thus, premature ageing as well as preservation of the skin’s immune response. Moisturizers can reduce excessive bacteria, acne formation, and maintain a healthy barrier function, which reduces water loss from the skin that is associated with dehydration.

The presence of sweat glands also helps the body eliminate harmful substances from the metabolic activities of the intestines and liver. The skin is also loaded with glands that secrete hormones and respond to the other hormones in the body, for better or for worse.


The skin has a number of glands throughout. These are important for cooling, protection, and secreting substances that can be harmful if allowed to remain in the body for too long, such as cholesterol and minerals.

The most important glands that I will discuss in a bit of detail are the sebaceous glands (oil glands) as well as the sweat glands (eccrine and apocrine glands).

Pilosebaceous+Unit_+most+commonly+on+face,+chest+and+back.jpgSebaceous glands are attached to the same duct that contains the hair follicle (pilosebaceous duct), which is situated in the dermis — the second layer of skin. A complete pilosebaceous duct contains one hair follicle and one sebaceous gland, though some skin may contain multiple sebaceous glands per follicle, resulting in oilier skin. These sebaceous glands are responsible for the oil that is secreted onto the skin, and have ducts that open onto the upper portion of the follicle, near the top of the dermis. The face and the back contain the highest number of sebaceous glands per square inch, where the palms of the hands and soles of the feet contain none.

This oil prevents excessive evaporation of water, and contains some anti-fungal properties, but excessive oil can be associated with acne, while insufficient amounts are often associated with drier skin types.

eccrine-sweat-glands-2Sweat glands are also abundant through the skin, and there are two types: apocrine and eccrine. Eccrine glands are the most common, found throughout the body as glands that open directly onto the skin as pores. As you can imagine, they are most commonly found on the palms of the hands and soles of the feet. They are also the glands that tend to be hyperactive in conditions like hyperhidrosis (excessive sweating). Apocrine glands are most commonly found in the “smellier” parts of the body, such as the armpits and groin. They are positioned along the hair follicle, above the sebaceous glands, and secrete their fluids out onto the hair and eventually, the skin. While the areas of these glands are most associated with having a particular smell, this is not due to the fluid being secreted, but the skin’s flora that is pushed out along the hair follicle with the fluid. apocrine-sweat-glands-2.gif

All sweat glands secrete fluids composed mainly of water, lactic acid, urea, waste, and bacteria-fighting substances, though the primary function of these glands is to cool and regulate body temperature, not just to remove waste from the body.

One common myth of all sweat glands is that sweat “purifies” the pore and thus, the skin, resulting in less acne or breakouts. Some people feel this is why they break out more when they work out. However, it is important to note that congestion — the plug that causes acne — in the pore occurs much deeper than where these glands are situated and sweat does not clean out this waste.

As I’ve noted before, skin is fairly acidic, maintaining a pH of roughly 4.4-5.6. This protective layer of sebum and perspiration from the glands forms a protective layer known as the “acid mantle.” Maintaining this mantle helps the skin ward off infection, prevents the growth of bacteria, and allows for normal exfoliation of the surface dead cells. This is why harsh skin care is especially damaging for skin, particularly harsh soaps.


Hopefully this was educational! Tomorrow, I will share with you about the layers of the skin — something I’ve discussed a bit on this blog but will go a bit more into depth on, including the skin cell types and how it all ties together to create this organ.

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