Studies Reveal (Almost) Irrefutable Evidence For The Root Cause Of Acne

By Seppo | Cause

Not too long ago a person at forums was complaining that despite ‘doing all the right things’ her acne just wouldn’t go away. She then went on to complain how acne is maddeningly confusing and how nothing seems to work. Needless to say, acne, and trying to get over it, had made her utterly confused.

I believe this confusion as to what acne is how to treat is the biggest obstacle between you and clear skin. It leads you to merry-go-round where you try one thing after another. Desperation starts creeping in when you don’t see the results you expect, and that makes you vulnerable to quacks promoting unscientific and dubious methods.

Today I’m going to share with you a couple of studies that provide antidote to the confusion. We are going to talk about 3 new studies that provide even more evidence that inflammatory damage at the skin is the root cause of acne.

Acne severity correlates with inflammation level

A study published in January 2013 provides quite damning evidence. In the study Saudi Arabian researchers compared measures of inflammatory damage between acne patients and people with clear skin. They further divided the patients to three groups: mild, moderate and severe, according to acne severity.

This graph shows measures of inflammatory damage. For copyright reasons I can’t use their graphs, but I reproduced them from the data.

Chart showing oxidative stress in acne patients and controls with healthy skin

Source: Biochemical Markers of Oxidative and Nitrosative Stress in Acne Vulgaris: Correlation With Disease Activity.

As you can see, there’s a clear correlation between acne severity and inflammatory damage. The graph shows measures for both protein oxidation (the blue bars) and lipid peroxidation (damage to fats, the red bars). But the details don’t really matter to us. What matters is the overall trend showing higher levels of inflammatory damage as acne goes from mild to moderate to severe.

On the flip side, they also looked into antioxidant activity. Here are the results for antioxidant enzymes. This chart shows measures for two very important antioxidant enzymes glutathione and superoxide dismutase. Much like vitamins C and E, these enzymes neutralize free radicals and other inflammatory molecules.

Chart showing levels of antioxidant enzymes in acne patients vs. healthy controls

Source: Biochemical Markers of Oxidative and Nitrosative Stress in Acne Vulgaris: Correlation With Disease Activity.

Again we see a similar pattern. People with clear skin show higher levels of these antioxidants and that the levels drop as acne gets worse.

Of course correlation doesn’t equal causation. These data don’t prove that inflammation causes acne. And if these were the only data, I would be careful not to jump to unwarranted conclusions. But these are not the only data, not even close. In the earlier posts I have covered more data on inflammation and the potential role of topical antioxidants.

Acne lesions show inflammatory damage

Another study published in Novermber 2012 provides more evidence. The earlier study measured markers of inflammatory damage and antioxidant enzymes in the blood. This study measured similar things in actual pimples. For the study the researchers took skin samples from people with varied severities of acne, again divided into mild, moderate and severe categories. They also took control samples from people with clear skin.

Results show that people with severe acne showed 2 to 4 fold higher levels of inflammatory damage than people with mild or moderate acne. Similarly, antioxidant enzyme readings were significantly lower in people with severe acne than the other participants. For the most part, there was not much difference between people with mild acne and those with clear skin.

Study: Antioxidant supplements reduce acne by 50%

Late 2012 Iraqi researched published a study that shows antioxidant supplementation can reduce acne by 50%. A few such studies have been published earlier, but those were quite low quality and as such we can’t draw strong conclusions from them. This study was placebo-controlled, which makes this much better.

Placebo control is important because, though it doesn’t seem like that, the placebo effect is very strong in acne. For example, it’s been pointed out that the placebo effect may account for about 50% of all the positive effects seen in studies using oral and topical antibiotics. Without placebo-control we can never know how much of the observed effect was due to the treatment and how much due to various placebo effects. The internet is full of stories of people getting better after ridiculous and implausible ‘therapies’ – most such stories can probably be explained with placebo, and that’s another reason why you shouldn’t put too much faith into those stories. What ‘works’ for them may not work for you.

Back to the study. At the beginning of the study they measured the levels of glutathione (GSH), malondialdehyde (MDA) and interleukine -8 (IL-8). Glutathione is an antioxidant enzyme and malondialdehyde and interleukine -8 are measures of inflammation.


Clear skin





60% lower




59% higher




66% higher

Again the same pattern emerges. Acne patients show much higher level of systemic inflammation (they are under higher oxidative stress in medical speak).

Here’s a graph from the study that again shows a correlation between glutathione (antioxidant) level and acne severity. As antioxidant level drops the number of pimples goes up.

Chart showing correlation between glutathione level and acne severity

The study also showed similar graphs for other measures of inflammation. I’m not going to post them here, but the study is open-access so you can check them out for yourself.

In the study 56 acne patients were divided into 4 groups. 3 of the groups received one of the 3 studied antioxidant supplements while the 4th group received a placebo pill. The antioxidants were silymarin (milk thistle) (210 mg/day), N-Acetylcystein (NAC) (1200 mg/day) or selenium (200 mcg/day). NAC is a precursor to glutathione and can increase glutathione level in the body. Similarly selenium acts as a coenzyme in glutathione antioxidant reactions. The authors write that silymarin is believed to act as a potent antioxidant in human tissue.

Here are the results.

Chart showing the effect of 3 antioxidant supplements on acne severity

As you can see, the reduction in pimple count is practically linear for both N-Acetylcystein and silymarin supplements. After 8 weeks both supplements reduced acne lesions by about 50%. Selenium supplementation also showed a nice reduction, if not quite as quick as with the other 2 supplements. In contrast, there was no real change in the placebo group. I should note that this study was single-blinded, so the participants didn’t know which supplement they received.

This reduction in acne lesions was mirrored in increase in glutathione levels and reduction in measures of systemic inflammation. In other words, acne and systemic inflammation went down hand in hand.

Pretty encouraging results – especially considering what we discussed above.

There’s also older data that show low levels of glutathione in people with skin problems, and that combined supplementation with selenium and vitamin E increases glutathione levels and improves skin condition.

NAC supplementation may cause adverse effects

In the comment section Bob alerted me to the possibility of side-effects from NAC supplementation. He mentioned that NAC may increase histamine level and thus cause hives or rash.

Unfortunately I couldn’t find any studies on adverse effects of NAC supplementation at doses used for acne. NAC is used as antidote for paracetamol poisoning and in that context we do have safety data.

Adverse effects include:

  • Nausea
  • Vomiting
  • Flushing
  • Rashes
  • Itching of the skin
  • Angioedema (swelling of the skin)
  • Constricting of airways (similar to what happens in asthma)

The paper Adverse reactions associated with acetylcysteine mentions that side-effects are more common when NAC is given intravenously. When given orally (as in supplements) side-effects are milder. The doses used for treating paracetamol poisoning are quite a big higher, but not orders of magnitude, than doses used to treat acne.

Risk factors include: history of drug allergies and asthma.

As Bob mentioned in the comments, NAC may increase histamine levels in some people, and this is one of the reasons for side-effects. Anti-histamine drugs and paracetamol can alleviate the side-effects.

Does this mean you shouldn’t take NAC? I don’t think so. The papers mention that in the vast majority of cases side-effects are mild and easily treated. I would start with a smaller dose to see if you get any adverse reactions. If you notice any adverse effects, consider using to sillymarin instead.

What does this mean to you?

By now you may think ‘OK, this is mildly interesting. It looks like inflammation can cause acne, but what does it mean to me? Eat more fruits and vegetables?’ Good point, so let’s move away from the dusty scientific papers and back to the real world where acne doesn’t obey fancy Excel-graphs.

This may be stating the obvious, but preventing and controlling acne means keeping inflammation in check. Unfortunately this is where neat the theory ends and the messy real world begins. The problem is that inflammation is such a fundamental function in the human body that there are countless things that affect it.

How you can reduce inflammation depends on what causes the inflammation in your body. Here are some common possibilities:

  • Gut problems allow inflammatory molecules to escape the gut and into systemic circulation. I believe that this is one of the little-known and the most underestimated causes of acne.
  • Chronic stress and persistent negative emotional states are very likely to trigger inflammation in the skin. In Clear for Life I wrote how a neurotransmitter called substance P can trigger an inflammatory response in the skin. There’s also evidence that substance P can increase sebum production and contribute to clocked pores. There’s no data on acne, but a study on psoriasis patients showed that injection of substance P triggered a psoriatic flare – even in people not prone to getting psoriasis. Substance P is released during psychological stress.
  • Sugar and dairy products can increase sebum production and thus increase antioxidant demand in the skin.
  • Inflammatory reaction to gluten is a possible cause, as are other allergic or sensitivity reactions to food.
  • Chemicals in acne treatment and personal care products can cause skin irritation for some people.

The exact treatment plan is different for everybody, but here are some things that are likely to be helpful:

  • Healthy diet that’s low in sugar and refined carbohydrates and high in fruits, vegetables, protein and healthy fats.
  • Drinking 4 to 5 cups of green tea per day.
  • Use antioxidant cream or moisturizer.

For more details feel free to read other posts on the skin, or, even better, get my book. Clear for Life packs all of this into an easy to understand and follow program. You can get it from here.


About the Author

Seppo Puusa, a.k.a. AcneEinstein shares rational advice about natural and alternative acne treatments. Read more about me and my acne struggles at the page.

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