Sebum

Sebaceous Gland High Magnification

What is Sebum?

Sebum is a naturally occurring substance that moisturizes, lubricates and protects the skin and hair. Sebum is produced by the sebaceous glands of mammals. Healthy sebum production is essential for the integrity and normal function of the skin as a protective organ. Sebum is also an important source of energy (food) for acne-causing Propionibacterium acnes bacteria.

Human skin is composed of three primary layers: the stratum corneum, the epidermis, and the dermis. The outermost layer of the skin, the stratum corneum, functions as the primary barrier to the external environment, preventing water loss and the invasion of microorganisms. Sebum is secreted to the stratum corneum from the sebaceous glands and helps maintain an effective, hydrophobic barrier.

The chemical composition of sebum and the rate of sebum production varies from individual to individual, and can even vary depending where on the body the sebum is produced. Normal sebum levels help to maintain healthy skin, but abnormal sebum production or composition can contribute to a variety of diseases, including acne.

Acne symptoms are often associated with sebum overproduction, which can increase the incidence of clogged pores, stimulate inflammation, provide nutrients for bacterial growth. Overproduction of sebum is generally the result of excessive growth and activity of the sebaceous glands. Overactive sebaceous glands and sebum overproduction can be caused by many factors, such as hormones, genetics, stress and environmental stimuli.

The Composition of Sebum

Composition of Human Sebum
Composition of Human Sebum

Sebum is a complex mixture of naturally produced fats, oils, waxes, cholesterols and other molecules. It is important to point out that the fats and oils present in sebum do not originate directly from the fats and oils consumed in the diet. Rather, sebum is manufactured and stored by the sebaceous glands under the direction of a highly specialized biological process.

Most mammals (but not whales and dolphins) produce some sort of sebum, and each animal has its own unique blend. In addition to sebaceous glands and sebum, there are other structures in the skin that produce a sebum-like mixture called “epidermal lipids”.

Differences in Sebum Composition Between Normal and Acne Prone Skin (Pappas)
Differences in Sebum Composition Between Normal and Acne Prone Skin (Pappas)

Human sebum is composed primarily of glycerides, free fatty acids, wax esters and squalenes. Glycerides are more commonly known as “fats” and are molecules of two or three free fatty acids connected together by a glycerol backbone. Free fatty acids are the building blocks of glycerides and other molecules. They are composed of a polar head group and a non-polar (aliphatic tail). Wax esters are molecules composed of fatty acids linked to fatty alcohols by an ester bond. Squalenes are hydrophobic chains of carbon atoms that serve as the basic building block for naturally occuring steroids and other types of signal molecules.

The Role of Sebum in Acne Vulgaris

Several research studies have found a direct relationship between increased sebum secretion and increased acne symptoms. People with sebaceous gland disorders (e.g. sebaceous hyperplasia) that lead to very high sebum levels often have severe forms of acne and other skin diseases. However, there are several possible explanations for how sebum production may contribute to acne, and there is not unanimous agreement between experts when it comes to explaining this relationship.

Sebaceous Gland Hyperplasia (Smith)
Sebaceous Gland Hyperplasia (Smith)

The most common explanation for why elevated sebum production leads to acne symptoms is that increased sebum production leads to increased follicular plugs (clogged pores). Clogged pores create an low oxygen (hypoxic) environment that supports the growth of acne-causing P. acnes bacteria. Sebum is also a source of food for P. acnes bacteria. The accumulation of sebum within plugged follicles provides ideal growing conditions for P. acnes bacteria and can lead to large numbers of these bacteria growing in the skin.

Research has also found that sebum itself can lead to increased inflammation. Byproducts of the sebum metabolism may cause the accumulation of molecules that trigger an inflammatory immune response. It is possible that this mechanism is at work in some individuals with inflammatory acne.

Research has also shown that people with abnormally high sebum production tend to make sebum that has a different composition than the sebum from people with normal levels. Apparently, people with acne tend to have decreased levels of free fatty acids, but increased levels of glycerides and squalene. Some scientists have proposed that these compositional changes play a role in the development of acne symptoms..

The Regulation of Sebum Production

The proliferation of sebaceous glands and production of sebum is directly regulated by a complex system of hormones and other cellular signals. Going deeper, these hormonal signals are controlled by an even more complex balance that includes genetics, environmental conditions, metabolic conditions, stress, diet, injury and many other factors. Despite this extraordinary complexity, scientists have begun to unravel the central relationships in sebaceous gland biology.

Several of the central factors that control sebum production have been identified and are currently being investigated by scientists. The major regulators of sebaceous gland activity include:

Androgens

Androgens Drive Muscle Growth
Androgens Drive Muscle Growth

Androgens are male sex hormones, like testosterone. Acne symptoms commonly develop in males during adolescence, when levels of androgen hormones in the body are their highest. Androgens drive the development of many male characteristics, like muscle and body hair growth. They also stimulate the proliferation of sebaceous glands, particularly those located on the face, chest and upper back.

Individuals with excessively high levels of androgen hormones tend to have higher levels of sebaceous gland proliferation, sebum production and acne vulgaris. Women with elevated androgen levels tend to have higher levels of acne and hirsuitism (excess body hair growth). The effect of androgens on sebaceous gland activity is also why the use of anabolic steroids, which increase androgen levels, can cause acne symptoms.

Estrogens

Estrogen Molecule
Estrogen Molecule

Estrogens are female sex hormones. In most cases, estrogens antagonize (suppress) the effects of androgen hormones. This relationship partially explains why acne symptoms tend to change over the course of a woman’s menstrual cycles, or during and after pregnancy. Men do not usually produce significant levels of estrogen hormones. Estrogens may also directly modulate sebaceous gland activity, although this relationship is not well studied.

Insulin-Like Growth Factor 1 (IGF-1)

IGF-1 is a protein hormone that is produced in the liver and is similar in structure to insulin. Researchers have reported that high IGF-1 levels correlate with elevated sebum production. Levels of IGF-1 tend to be highest during adolescence. Since insulin is similar in structure to IGF-1, it is possible that elevated levels of insulin could cause increased sebum production.

Insulin levels are often elevated in individuals who consume a high glycemic diet (high sugar/carbohydrate), or who have Type 2 diabetes. This relationship could explain the observed correletion between high glycemic diets, obesity and increased incidence of acne vulgaris. Increased IGF-1 has also been linked to milk consumption, although these studies are not necessarily conclusive. IGF-1 hormone production is stimulated by human growth hormone (hGH).

Retinoids

Retinoids are intercellular signalling molecules that are derived from Vitamin A. Retinoid is the generic name for a diverse class of related molecules that play essential roles in many human biological systems, including development of the human embryo. The proliferation of sebaceous glands and the production of sebum is directly controlled by specific retinoid signal molecules. Accutane (Isotretinoin, 13-cis-retinoic acid) is a retinoid that is a powerful anti-acne drug. Binding of Isotretinoin molecules to specialized receptors on the surface of sebocyte cells causes them to slow down their growth and sebum production. The natural balance of different retinoids in the body has a direct impact on sebaceous gland activity.

Environmental Conditions

Seasonal Variation in Sebum Production (Youn)
Seasonal Variation in Sebum Production (Youn)

Recent research has shown that sebum secretion levels change in response to seasonal and environmental changes. While the changes are not drastic, researchers observed that sebum secretion levels were highest during the summer. These changes may be due to the increased fluidity of sebum in warmer conditions, or something else entirely.

Generally speaking, acne sufferers tend to observe an improvement in their acne symptoms during the summer, although this could be more directly related to factors such as UV light exposure or stress levels, than to sebum production. Overall, the research indicates that sebum production is modulated by environmental conditions, although it is less clear whether these normal fluctuations play a role in the development of acne or other skin conditions.

Stress

Stressed Out
Stress

Several research studies have reported that there is a direct correlation between stress and increased acne symptoms. However, other research studies have found that stress does not appear to increase the levels of sebum production. While it is well understood that stress can modulate levels of certain hormones, like cortisol, it does not appear that these pathways directly impact sebaceous gland activity.

Treatments for Excessive Sebum Production

For acne patients with abnormally high levels of sebum production, decreasing sebum production will often improve acne symptoms. There are several medications available that can decrease sebaceous gland activity and sebum production, including:

Retinoids

Retinoids are the most common course of treatment for individuals with hyperactive sebaceous glands and abnormally high sebum production. Retinoids can be an effective acne treatment for many people. Retinoids cause side effects related to decreased sebum production, such as dry and sensitive skin.

Isotretinoin (Roaccutane) 20mg Capsules
Isotretinoin (Roaccutane)

The oral retinoid Isotretinoin (Accutane) is a potent anti-acne medication that can dramatically reduce sebum production. For many individuals, treatment with isotretinoin can lead to significant, long-lasting improvement in their acne symptoms. However, Accutane can have significant side effects, causes severe birth defects in pregnant women, and is tightly controlled in many countries.

Topical retinoid medications are commonly used to treat acne and other skin conditions. Popular topical retinoids include tretinoin (Retin-A), adapalene (Differin), tazarotene (Tazorac) and isotretinoin (Isotrex). These treatments also decrease sebum production, although the effect is often less dramatic than that of oral retinoids.

Retinoids are also used in Naturopathic acne treatments. Retinoids are naturally present in some plant extracts, such as Rose Hip Seed Oil.

Androgen Inhibitors

Spironolactone 25mg Tablets
Spironolactone 25mg Tablets

Androgen Inhibitors can block the activity of the androgen hormones that stimulate sebum production.  Androgen inhibitors like spironolactone (Aldactone) and cyproterone (Androcur) can partially block the effects of androgen hormones and decrease sebaceous gland activity. Androgen Inhibitors are available in both oral and topical formulations.

Hormonal Contraceptive medications can also block the effect of androgen hormones. Both anti-androgen medications and birth control medications are usually reserved for use in females, because their effects can disrupt the normal function of the male hormone system.

Light and Laser Treatments

Photodynamic Therapy (PDT) Acne Treatment
Photodynamic Therapy (PDT)

Light and Laser Treatments have become increasingly popular for the treatment of acne and other skin disorders. Certain light and laser treatments, like Photo Dynamic Therapy (PDT) and Diode Laser Therapy, can be used to directly target the sebaceous glands. Damaging the sebaceous glands with laser treatments can decrease the production of sebum at the treatment site. Depending on the specific type of laser treatment, these effects can be semi-permanent.

References

Transient Receptor Potential Vanilloid-1 Signaling as a Regulator of Human Sebocyte Biology. Toth, et al. 2009.
Comparative Chemistry of Sebum. Nikkari. 1974.
Comprehensive analysis of the major lipid classes in sebum by rapid resolution high-performance liquid chromatography and electrospray mass spectrometry. Camera, et al. 2010.
Quantitative evaluation of sebum lipid components with nuclear magnetic resonance. Robosky, et al. 2008.
Sebaceous gland lipids. Picardo, et al. 2009.
Variation in Sebum Fatty Acid Composition Among Human Adults. Green, et al. 1984.
Sebaceous gland lipids: friend or foe? Smith, et al. 2007.
Sebum analysis of individuals with and without acne. Pappas, et al. 2009.
Does facial sebum excretion really affect the development of acne? Youn, et al. 2005.
Sebum output as a factor contributing to the size of facial pores. Roh, et al. 2006.
Comparison of sebum secretion, skin type, pH in humans with and without acne. Kim, et al. 2006.
Can sebum reduction predict acne outcome? Janiczek-Dolphin, et al. 2010.
Human Neutrophils Convert the Sebum-derived Polyunsaturated Fatty Acid Sebaleic Acid to a Potent Granulocyte Chemoattractant. Cossette, et al. 2008.
Peroxisome Proliferator-Activated Receptors Increase Human Sebum Production. Trivedi, et al. 2006.
Sebum Free Fatty Acids Enhance the Innate Immune Defense of Human Sebocytes by Upregulating b-Defensin-2 Expression. Nakatsuji, et al. 2010.
Control of Human Sebocyte Proliferation in Vitro by Testosterone and 5-DHT is Dependent on the Localization of the Sebaceous Glands. Akamatsu, et al. 1992.
Differentiation of the sebaceous gland. Niemann. 2009.
Correlation of facial sebum to serum insulin like growth factor-1 (IGF-1) in patients with acne. Vora, et al. 2008.
The Role of Specific Retinoid Receptors in Sebocyte Growth and Differentiation. Kim, et al. 2000.
The Effect of Marked Inhibition of Sebum Production with 13-Cis-Retinoic Acid on Skin Surface Lipid Composition. Strauss, et al. 1980.
Regional and seasonal variations in facial sebum secretions: a proposal for the definition of combination skin type. Youn, et al. 2005.
Study of Psychological Stress, Sebum Production and Acne Vulgaris in Adolescents. Yosipovitch, et al. 2007.

Sebaceous Gland High Magnification