Acne is the most common diagnosis made in the dermatology office. It is incredibly common in the general population. Some estimates state that up to 85% of teenagers, 42-50% of people in their twenties, and 20-25% of people in their thirties experience acne. Acne is even present among individuals over the age of forty. Acne is defined as the presence of white heads, black heads, pimples, or large, red, sometimes painful bumps. Some people have mild cases that can be controlled with store-bought face washes, and others have severe cases necessitating a dermatologist to prescribe strong oral medications.
There are 4 major routes to developing acne: excessive skin cell development, overproduction of sebum (a product from oil glands), a very specific bacteria called Propionibacterium acnes, and inflammation. There are many causes of each of these elements, but a large cause is the genetics of acne that refers to the genes passed down from your parents. But our genetics can be modified by the environment (i.e. diet), making acne more or less likely in any one person. This modification is called epigenetics.
What Is Epigenetics?
DNA is the building block that contains our hereditary material, or our genetics. Historically, scientists thought that the sequence of our DNA is what determines who we are. However, recent researchers have found that our body actually modifies the expression of our DNA. There are 3 major ways our bodies do this: methylation, chromatin modification, and noncoding RNAs.
Methylation turns genes off, and demethylation (removing the methylation) turns genes on.
Chromatin is the large package that contains the DNA in each and every cell in the body. Chromatin modification makes the package easier or harder to open, making DNA more or less accessible to be read and translated.
Noncoding RNAs (nRNAs) are small pieces of DNA that can cover up and hide parts of DNA to turn genes off or make genes more visible to turn them on.
These changes in DNA expression are collectively called epigenetics. The exact reasons that influence when and which genes get turned on or off is still under intensive research; however, both external environmental factors and our internal genetic programming play a role in epigenetics and the genetics of acne.
Excessive Skin Cell Development
Your skin has an abundance of cells that are constantly growing and shedding. Ever heard of the term “dead skin cells?” That expression is true! On the surface of your skin are dead skin cells that connect with each other to create a water-tight barrier. In acne, cells stay longer than they should and continue to adhere to each other. The problem arises when they block the pores in your skin, causing a buildup of stuff like oils and bacteria underneath the skin surface leading to irritation.
Dairy is commonly blamed for acne and here’s why. Milk has noncoding RNAs that are absorbed in the gut and found in a person’s bloodstream after consumption. These noncoding RNAs decrease the activity of a gene, p53. This gene prevents cells from growing and reproducing too much by forcing cells that are no longer needed to die. When milk nRNAs decrease p53 activity, the skin cells are not told to die quickly enough, so they multiply.[7,8] Milk nRNAs also decrease methylation of certain genes by preventing the activation of an enzyme called DNMT1. This enzyme adds methyl groups to genes to turn them off. When milk nRNAs turn off DNMT1, it ends up turning genes on. DNMT1 works with p53 to turn off a gene called survivin. As it sounds, this gene allows cells to survive longer than they should. So milk nRNAs turn on survivin and allow skin cells to stick around and block pores. Once the pores are blocked, the other factors involved in acne continue to contribute to acne development.
Overproduction of Sebum
People always talk about “oily skin” or “dry skin,” but where is this oil coming from? There are oil glands at the base of every hair on your skin. On the face, these hairs are very small, but still have oil glands that produce a substance called sebum, which most people call oil. Sebum is special in that it contains triglycerides, a type of fat, and lipoperoxides, a substance similar to fat. Triglycerides are great sources of food for the bacteria on the skin. Lipoperoxides can stimulate more sebum production and can cause inflammation if they get deeper into the skin. So sebum feeds the bacterium Propionibacterium acnes, allowing it to thrive and multiply and causing inflammation if a pore is blocked.
Hormones like the androgen hormones stimulate the oil glands. The androgen hormone receptor is the target for androgens to turn on the oil glands. Diet may impact androgens in the body. The explanation for this is through epigenetics. The androgen receptor is turned off by a factor called FoxO1. It turns out carbohydrates that have a high glycemic index increase insulin, another hormone, and a factor called IGF-1. Both insulin and IGF-1 turn off FoxO1. Once FoxO1 is off, the androgen receptor is turned on and sebum is produced, leading to acne.
Bacteria are all over the body, especially on the face. Propionibacterium acnes (P. acnes) is the bacteria that normally lives in your pores, but different people have different types of this bacteria. Some types can be more irritating and cause worsened acne. People that have more severe acne usually have a stronger reaction to the bacteria, so it’s not necessarily the bacteria that causes the acne but the body’s response to the bacteria that causes the most problems.
Another bacterium, Staphylococcus epidermidis (S. epidermidis), commonly found on the skin of most people, can decrease the inflammatory response to P. acnes through epigenetics. One study found that a nRNA called miR-143 prevents the start of a pathway that usually results in inflammation. This pathway is initiated through a protein called toll-like receptor-2 (TLR-2). In acne, P. acnes causes TLR-2 to be produced and stimulated to create inflammation. S. epidermidis produced miR-143 prevents TLR-2 from being formed, preventing inflammation and acne development by P. acnes.
When excess skin cells block sebum from exiting the skin’s pores, the sebum and bacteria have no place to go, but to overgrow within the pore. When this happens, the body responds with inflammation.
Carbohydrates that have a high glycemic index increase a specific nRNA, miRNA-21. Increased levels of miRNA-21 have been shown to decrease FoxO1, which results in increased androgen receptor activity as previously mentioned.[13,14] More importantly, macrophages that are white blood cells important in acne inflammation contain miRNA-21, leading to release of signals that stimulate inflammation. A specific chemical involved in inflammation is interleukin-17 (IL-17). Vitamin A and vitamin D both have been shown to decrease the production of the IL-17 gene and decrease the formation of a specific type of white blood cell, Th17, involved in acne.
Acne is a frustrating condition that has a lot of factors working all at once. Epigenetics helps to explain how some of these factors can be controlled so that acne can be controlled in turn. Diet has been rumored for decades to impact acne. Epigenetics explains how diet impacts acne development and will continue to explain how various factors of the environment affect the genetics of acne.
Table 1 –Epigenetics of High Carbohydrates on Skin Sebum (Oil) Production
Effects of High Carbohydrates
Insulin and IGF-1 Levels
(High insulin and IGF-1 turn off FoxO1)
Activity of FoxO1
(Low activity of FoxO1 means that the androgen receptor is more active)
Activity of the Androgen Receptor
(High activity of the androgen receptor means that more sebum is produced in the skin)
Sebum (Oil) Production
(High sebum means more food for P. acnes and lipoperoxides, another source of inflammation)
(High miRNA 21 decreases FoxO1 and increases inflammation)
* This Website is for general skin beauty, wellness, and health information only. This Website is not to be used as a substitute for medical advice, diagnosis or treatment of any health condition or problem. The information provided on this Website should never be used to disregard, delay, or refuse treatment or advice from a physician or a qualified health provider.
Knutsen-Larson S, Dawson AL, Dunnick CA, et al. Acne vulgaris: pathogenesis, treatment, and needs assessment. Dermatol Clin.2012;30(1):99-106, viii-ix; PMID: 22117871 Link to research.
Collier CN, Harper JC, Cafardi JA, et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol.2008;58(1):56-59; PMID: 17945383 Link to research.
Zaenglein AL, Graber EM, Thiboutot DM. Chapter 80. Acne Vulgaris and Acneiform Eruptions. In: Goldsmith LA, Katz SI, Gilchrest BA, et al., eds. Fitzpatrick's Dermatology in General Medicine, 8e. New York, NY: The McGraw-Hill Companies; 2012.
Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun.2013;41:1-5; PMID: 23375849 Link to research.
Suh DH, Kwon HH. What's new in the physiopathology of acne? Br J Dermatol.2015;172 Suppl 1:13-19; PMID: 25645151 Link to research.
Baier SR, Nguyen C, Xie F, et al. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J Nutr.2014;144(10):1495-1500; PMID: 25122645 Link to research.
Melnik BC. Milk disrupts p53 and DNMT1, the guardians of the genome: implications for acne vulgaris and prostate cancer. Nutr Metab (Lond).2017;14:55; PMID: 28814964 Link to research.
Le MT, Teh C, Shyh-Chang N, et al. MicroRNA-125b is a novel negative regulator of p53. Genes Dev.2009;23(7):862-876; PMID: 19293287 Link to research.
Melnik BC. Linking diet to acne metabolomics, inflammation, and comedogenesis: an update. Clin Cosmet Investig Dermatol.2015;8:371-388; PMID: 26203267 Link to research.
Webster GF, Indrisano JP, Leyden JJ. Antibody titers to Propionibacterium acnes cell wall carbohydrate in nodulocystic acne patients. J Invest Dermatol.1985;84(6):496-500; PMID: 3158714 Link to research.
Xia X, Li Z, Liu K, et al. Staphylococcal LTA-Induced miR-143 Inhibits Propionibacterium acnes-Mediated Inflammatory Response in Skin. J Invest Dermatol.2016;136(3):621-630; PMID: 26739093 Link to research.
Jeremy AH, Holland DB, Roberts SG, et al. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol.2003;121(1):20-27; PMID: 12839559 Link to research.
Lei BX, Liu ZH, Li ZJ, et al. miR-21 induces cell proliferation and suppresses the chemosensitivity in glioblastoma cells via downregulation of FOXO1. Int J Clin Exp Med.2014;7(8):2060-2066; PMID: 25232387 Link to research.
Song W, Wang L, Wang L, et al. Interplay of miR-21 and FoxO1 modulates growth of pancreatic ductal adenocarcinoma. Tumour Biol.2015;36(6):4741-4745; PMID: 25623117 Link to research.
Agak GW, Qin M, Nobe J, et al. Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D. J Invest Dermatol.2014;134(2):366-373; PMID: 23924903 Link to research.