Inflammation and oxidative stress

Inflammation and oxidative stress

Our understanding of the role inflammation plays in acne has evolved a lot during the past two decades. In the earliest studies, inflammation was blamed on infiltration and overgrowth of the bacteria P. Acnes. But work done by experimental dermatologists has called this view into question. While there’s no doubt that the P. Acnes bacteria plays a role in acne formation, many researchers now believe it enters the picture only later, and that we can attribute the blame for acne squarely to inflammation.

Before going on, we should define our terms. On this page, I talk a lot about oxidative stress and inflammation, and it’s important that we understand what these things mean.

  • Oxidative stress refers to an imbalance between reactive oxygen species (ROS), commonly known as free radicals, and the antioxidants that neutralize them. Without sufficient antioxidants to neutralize them, free radicals cause oxidative damage to cells they come in contact with.
  • Inflammation is a complex process by which the body responds to injury and ‘harmful stimuli’. In the case of acne, the triggers include cellular damage as a result of oxidative stress, damage to fatty acids in sebum, leakage of bacterial toxins from the gut, and overgrowth of bacteria in blocked skin pores.

Role of inflammation in acne formation process

Samples taken during the growth cycle of a pimple show inflammation even in the earliest stages of comedo formation. This means that there’s inflammation in the microcomedo even before bacterial colonization.

As a pimple progresses through the ‘acne cycle‘, inflammation gets more severe. Skin scraping studies show up to four times more inflammation in the later stages. (source).

Cell culture studies have shown that inflammation can stimulate:

  • Keratin production
  • Sebum production
  • Skin cell growth

In other words, it seems that inflammation can do everything it takes to start the acne formation process. Let’s take it a step further and see how this happens.

Lipid peroxidation

Lipid peroxidation refers to oxidative damage to fats (lipids). In this process, free radicals steal electrons from the lipids in the cell membranes. In relation to acne, we are talking about damage to sebum by UV rays, pollution, chemicals, and other ‘oxidative insults’.

Lipid peroxidation is not a new theory for explaining acne. It was first proposed by the University of Chicago researcher Allan L. Lorincz in 1965. His work was followed by other investigators who showed lipid peroxidation in acne and put forward a hypothesis that the free radical damage to sebum initiates the acne formation process. More support came from other research that showed both benefits from antioxidants and higher levels of inflammation in acne patients. Despite this evidence, lipid peroxidation theory of acne never fully gained support in mainstream dermatology and was mostly forgotten.

In 2010 Drs. Whitney Bowe and Alan C Logan published a paper that resurrected the old lipid peroxidation theory of acne. In the paper, they reviewed not only the earlier studies but also evidence from experimental dermatology research over the past two decades.

Let’s take a look at this theory and see how nicely it fits with everything else we know about acne.

Oxidative damage to squalene triggers the acne cycle

Most acne patients produce more sebum than people with clear skin. Sebum is a waxy substance composed of triglycerides, fatty acids and other fatty substances. Out of these, squalene seems to be the most relevant for acne. Squalene makes up 10% to 20% of sebum but seems to be the one substance that’s the most elevated in acne patients. For some reason, acne-prone skin produces proportionally more squalene. For example, a 2009 study showed squalene makes up 15% of sebum, while the average for acne patients was 20%. The study also showed acne patients produced 59% more sebum. Putting these two figures together, acne patients had 112% more squalene than people without acne.

The problem with squalene is that it is an unsaturated fat and thus quite fragile. When exposed to UV radiation, it undergoes massive degradation into squalene peroxides. Squalene peroxides are not only highly inflammatory but also comedogenic. Animal studies show that squalene peroxide applied to rabbit ears produces a comedo, and the size of the comedo is related to the degree of damage the squalene suffered. These studies also showed hyperkeratosis and increased sebum production as a result of the squalene peroxide exposure. Studies as far back as 50 years found increased levels of squalene peroxides in acne patients. Modern studies have confirmed this (source).

A 2014 study showed that people with mild acne had 79% more squalene peroxide in sebum than people with clear skin. After four weeks of treatment with retinol and vitamin E cream, squalene peroxide levels dropped by 56%. Similarly, the treated areas showed much less hyperkeratinization and inflammation.

It’s starting to look increasingly likely that the initial oxidative damage to squalene is the trigger that kick-starts the acne formation process. Without this initial inflammatory insult, a pimple might never form. Earlier we discussed how oxygen depletion in the blocked skin follicle creates an ideal environment for P. Acnes bacteria to grow and thrive.

Squalene peroxide molecules deplete oxygen levels further by scavenging oxygen molecules inside blocked pores.

Failure of antioxidant protection in acne-prone skin

More clues to the puzzle come from antioxidant studies. Vitamin E is a major antioxidant in the skin. It’s transported to the skin via sebum. Studies have shown a continuous and much higher flow of vitamin E to the areas of skin that produce more sebum. For example, the sebum collected from the cheeks contained 20 times more vitamin E than the sebum collected from the forearms (source).

Researchers believe that the primary task of vitamin E in the skin is to protect squalene from oxidative damage. There is a very tight correlation between squalene and vitamin E secretion, such that when squalene secretion increases, so does vitamin E secretion.

Studies looking at antioxidant levels in acne-prone and healthy skin show that the antioxidant protection is overwhelmed in acne patients. For example, one study showed 30% more squalene peroxide and 20% less vitamin E in the sebum taken from acne-prone skin (source).

To compensate for the higher demand of antioxidants in the skin, acne patients draw from the body’s antioxidant reserves at a much higher rate than individuals with clear skin. We can see this from studies comparing blood antioxidant and oxidant values between acne patients and people with clear skin. One study showed:

  • Vitamin A: 33% lower in acne patients
  • Vitamin C: 40% lower
  • Vitamin E: 45% lower
  • Beta-carotene: 65% lower

Other studies have also shown lower levels of other important elements, though not such dramatic differences. For instance, lower levels of zinc and selenium have been found in acne patients (source, source). Both selenium and zinc support the body’s antioxidant pathways. Other studies have further shown depleted levels of antioxidant enzymes and higher levels of oxidative stress and inflammation in acne patients (source).

Other studies have shown that blood levels substances that indicate oxidative stress and inflammation correlate with acne severity.

All these studies suggest that acne patients are under higher inflammatory load than people with clear skin. This applies both to systemic inflammation throughout the body and local inflammation in the skin.

Is this inflammation a cause or a consequence of acne? We can’t say for sure yet. But given everything else we know about acne, it seems likely that inflammation is one of the triggers that kicks off the acne cycle.

Especially when we consider that there are several studies showing topical and oral antioxidants can effectively treat acne. These studies show almost universally positive results, and added to everything else we know, they further support inflammation and oxidative stress as the villains behind acne.

Sources of inflammation

One reason I like the inflammatory theory of acne is that it helps to explain how so many seemingly different things can trigger acne. Inflammation can come in many forms and varieties, but we can categorize it to external and internal sources.

External sources of inflammation include:

  • UV rays from sunlight
  • Ozone in smog and air pollution
  • Contact allergy from irritants or allergens
  • Damage to the skin barrier function from alkaline soaps or chemicals, such as chlorine in swimming pools
  • Harsh chemicals in personal care products
  • Frequent rubbing, friction, and other forms of physical contact with the skin

Benzoyl peroxide

I must mention benzoyl peroxide (BP) here. As you know, it’s widely used in acne treatment products. Several decades of clinical experience and research have proven it effective in treating acne. But despite its effectiveness, it can cause problems for some people. You often hear individuals with acne complain that BP worked initially, but after a while, it not only stopped working but also started irritating the skin. Others complain that benzoyl peroxide dries the skin excessively.

I believe that we can explain these with the oxidative effect of benzoyl peroxide. BP works by forming free radicals that destroy the acne-causing bacteria. Unfortunately, benzoyl peroxide is anything but a precision weapon, and it also inflicts oxidative damage to healthy skin cells. And with this oxidative damage comes depletion of antioxidants. One study showed that a single application of 10% BP depleted 93.2% of the vitamin E in the skin. Another study showed a 95% reduction in vitamin E and a 70% reduction in vitamin C in the sebum following BP application (source). With such drastic effect on the skin, it’s easy to see how overuse can cause problems.

I believe that overuse of benzoyl peroxide and other harsh acne treatment products is one the leading causes of irritant-type acne.

This doesn’t mean you shouldn’t use benzoyl peroxide. Studies have shown it can reduce acne and inflammation in the skin. Perhaps by killing the bacteria and keeping the skin pores open BP prevents an even greater source of inflammation. What this means is that you should be careful with benzoyl peroxide and keep the potential danger in mind. Use it only as much as you need and support the antioxidant system with supplements and topical application of antioxidants.

Moving on to internal sources of inflammation, these can include:

  • Gut issues
  • Smoking
  • Stress
  • Sleep deprivation
  • Unhealthy diet, such as eating too much sugar or trans-fats
  • Allergic or sensitivity reaction to foods
  • Infections

We’ll talk more about these in the inflammatory-type acne section.


Let’s summarize a bit. Though research is yet to confirm this fully, here’s one way how acne develops. People with acne produce significantly more sebum than people with clear skin, and they produce even more squalene. Due to its unsaturated form, squalene is fragile and prone to oxidative damage.

The skin is constantly exposed to oxidative insults; from UV rays to air pollution to chemicals in personal care products.

Because unchecked oxidation is destructive, humans evolved a complicated antioxidant system to protect against runaway oxidation.

Due to higher levels of oxidation-prone squalene, acne patients need more antioxidants in the skin. These antioxidants are drawn from the body’s reserves, and if the supplies run dry, squalene is left vulnerable to the ever-present oxidative damage. This initial inflammatory damage starts the acne cycle by increasing keratin and sebum production, which clogs the skin follicle. The squalene peroxides deplete the oxygen levels in the blocked follicle. This oxygen-poor, sebum-rich environment helps the P. Acnes bacteria to multiply rapidly and colonize the follicle, which in turn creates runaway inflammation that eventually leads to an inflammatory pimple.

About Me

Hi, I am Acne Einstein(a.k.a. Seppo Puusa). I'm a bit of a science nerd who is also passionate about health. I enjoy digging through medical journals for acne treatment gems I can share here. You can read more about my journey through acne and how I eventually ended up creating this.