Say the words “nitric oxide” to the average acne guru and he probably won’t bat an eyelid. On this website we’ve discussed how nitric oxide accelerates wound healing, but it’s never ever been in the premier league of acne molecules.
Until now. An interesting new study has emerged showing that topical nitric oxide generated by nanoparticles can slash inflammation and curtail p.acnes bacteria by 95%.
The first question is clearly – what is nitric oxide? Well first of all, don’t confuse it with nitrous oxide AKA laughing gas. Nitric oxide is a gas manufactured by your body using nitric oxide synthase and l-arginine, which is most important for vasodilation. In other words, it relaxes your blood vessels and is critical for blood pressure control. Nitric oxide is needed to protect bodily organs from ischemic damage (damage caused by restriction of blood supply).
By improving blood flow, this gas can work wonders for heart health and male sexual function. In fact, the Nobel Prize in 1998 was awarded for the discovery of nitric oxide’s role in cardiovascular health. The nitric oxide precursor l-arginine is also a key ingredient in many workout formulas. By widening your blood vessels it can give you the “ripped” look with extremely large, freaky veins that look like hosepipes. Nitric oxide also improves the delivery of nutrients to all your muscles and thus is great for exercise recovery in any kind of sport, whether you’re an Olympian or a hard-core skier with aching thighs.
One other role of nitric oxide in the body is regulating inflammation. Nitric oxide is actually a free radical, but under normal bodily conditions it has anti-inflammatory effects on sites of excessive inflammation. Previously, these seemed fairly insignificant for acne prevention, until a month ago…
Nitric oxide is being investigated as a new acne drug!
For the last year or so, a US biotech start-up called Novan Therapeutics has been developing an acne treatment based on nanoparticles which slowly release nitric oxide into the skin. Two weeks ago, they released the results of a highly positive study.
According to the researchers, nitric oxide is highly beneficial for lowering inflammation but its effect is short lived. Nitric oxide’s half-life in the body is only a few seconds. Therefore, they created extremely tiny nanoparticles (at the size of 1 billionth of a meter) which released nitric oxide very slowly and applied them to the skin.
The result? Nitric oxide substantially lowered inflammation in the skin both by killing p.acnes bacteria itself, and by preventing the body’s innate immune response to that bacteria. Chronic inflammation is one of two root causes of acne, both from internal bodily factors (an overactive immune system) and outside irritants (harsh cosmetics, air pollution). P.acnes is important to tackle because it triggers that inflammation when your immune system shows up to destroy it.
Many different concentrations of nitric oxide were used and p.acnes was highly sensitive to all of them. To demonstrate the antibacterial activity against P. acnes, bacteria were incubated with varying doses of NO nanoparticles for 4 hours. Nitric oxide was highly effective at killing P. acnes, with application resulting in only 8.9% and 4.6% survival for two different concentrations of the nanoparticles.
Basically, p.acnes was reduced by 91.1% and 95.4% or in other words, p.acnes was absolutely massacred. Unlike harsh topical treatments such as Benzoyl Peroxide, it achieved this reduction without demonstrating any cytotoxicity; it didn’t harm or inflame human skin cells.
The results on inflammation were similarly promising. One of the researchers involved, Dr Friedman, commented that “the nano particles inhibits the activation of a newly recognized but exceedingly important inflammatory pathway that is directly tied to the formation of an acne lesion, called the NLRP3 inflammasome. Research has shown that our bodies already regulate this pathway with nitric oxide”.
Apparently, nitric oxide can downregulate a vast swathe of inflammation associated with acne. The doctor mentioned that this NLRP3 inflammasome pathway has been shown in other studies to be regulated by nitric oxide too.
Hence, the study found that an extremely broad range of pro-inflammatory chemicals were inhibited, including TNF-a, interleukin 8, interleukin 6, and interleukin-1beta. They are all chemicals which can redden and inflame acne and create the necessary damage for new pimples to form.
Acne patients, for example, were found in this study to have substantially higher levels of interleukin-8 in their skin than clear skinned people. The scientists commented that “We were able to demonstrate altered immunoreactivity of IL-8 in inflammatory acne vulgaris compared to normal skin. Targeted therapy to block IL-8 production may hold promise in limiting the deleterious effects of IL-8-mediated inflammatory response”.
Nitric oxide seems to be one such a targeted therapy. Novan Therapeutics is now performing further trials and they hope to release a nitric oxide based acne cream in the future. Compared to what we previously knew about NO’s benefits for wound healing, its promised acne-clearing powers have now reached the next level of potency.
What does this mean for acne patients?
Well, nitric oxide levels are far from fixed in the human body. There are numerous foods and nutrients which can provide the ingredients for your body to make higher amounts; in this article we discussed how watermelon is packed with citrulline, which converts to arginine and helps to increase NO substantially.
Other foods with natural (not carcinogenic synthetic ones) nitrates can also increase NO, like celery and parsley. If you take steps to organise a diet that’s optimal for nitric oxide production, you could allow your immune system to produce greater amounts at your skin and thus enjoy all the acne-clearing benefits outlined above.
As you can see below, there are numerous other studies suggesting that nitric oxide can lower inflammation in the skin more generally:
- This study examined whether nitric oxide drugs were useful for relieving inflammatory skin conditions. Hence, they added compared the most commonly prescribed anti-inflammatory drug, hydrocortisone, to a version of hydrocortisone with NO included. They found that hydrocortisone plus NO produced a much faster reduction in skin inflammation than regular hydrocortisone (which is a type of catabolic steroid). The scientists commented that nitric oxide could prevent the very earliest stages of inflammation, by preventing the recruitment of immune system leucocytes to the site of inflammation. There was also an interesting quote right at the beginning of the article: “The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years”.
- This study by Paul-Clarke et al again analysed the effect of combining NO with cortisol drugs. Again, their NO based cortisone drug (called NCX-1015) was far more potent at relieving skin inflammation. Quote: “In conclusion we show that NCX-1015 is more potent than prednisolone in controlling several, though not all, parameters of acute and chronic inflammation”.
- A later study in 2002 by the same authors combined nitric oxide with cortisones to produce the same NCX-1015 combination again, and once again compared it with the anti-inflammatory drug called prednisolone. They found that dosing of rats with NCX-1015 lowered all parameters of inflammation. Prednisolone did the same, but the benefits were noticeably inferior. Prednisolone also had the side effect of eroding the rat’s skeletons, but the nitric oxide drug didn’t. The scientists were very enthusiastic about nitric oxide, although there haven’t been many studies in the ten years since then.
Nitric oxide’s more widely understood role in inflammation is as follows. Your immune system phagocytes are armed with inducible nitric oxide synthase (iNOS) which is the main catalyst to produce nitric oxide. When nitric oxide is required, it is created upon activation by one of two possible immune agents; either interferon gamma or tumour necrosis factor alpha.
So when is NO required in inflammatory processes? Apparently, the production from iNOS is triggered in order to kill microorganisms. NO is a free radical, but compared to other free radicals, which are pure evil when it comes to acne, NO is safe because its half-life is so short. It kills its target and calls it a day. NO secretion by your immune system has been shown to kill many bacterial strains and parasites, like Leishmania and even malaria.
It’s no wonder then that nitric oxide can kill p.acnes so effectively. Many bacterial strains are evolving nitric oxide defence mechanisms and becoming resistant, but it seems that p.acnes has failed miserably.
As for inflammation, we previously had no idea of the mechanism involved but now we have scientists saying it inhibits the little known inflammatory pathway called NLRP3 inflammasome.
Nitric oxide – the preliminary judgement
We don’t have enough evidence on whether increasing nitric oxide across the entire body will kill acne the same way. With zinc we have studies revealing 54.1% of acne patients are deficient, with omega 3s we have fish oil slashing acne by 42%. With nitric oxide we currently have nothing because while this gas lowers inflammation and kill p.acnes successfully on the face, the effect when applied topically would be highly concentrated. Spread across the whole body, NO’s benefits would be more diluted, or it might only affect acne when applied topically full-stop.
On the plus side, the mechanism is plausible; if you provide more resources for your body to manufacture NO then more will be released at the site of inflammation. The topical study showed a massive 95% reduction of p.acnes; just a fraction of that would be terrific. There are indications that nitric oxide deficiency is common too, because it’s a critical vasodilator and high blood pressure is plaguing millions of people.
The truth is that we don’t know the truth yet. But my gut feeling is that experimenting with nitric oxide could be rewarding.
Nitric oxide’s benefits as a vasodilator are very far-reaching across the body. Boosting NO lowers your blood pressure substantially, can enhance your sexual function, and is favoured by athletes and bodybuilders for increasing resistance to pain and the flow of nutrients to muscles.
Could the anti-inflammatory powers be equally as potent? Nobody knows, but it’s a smart idea to eat two of the foods that boost nitric oxide levels daily. You could experiment by eating four or five such foods (see list below) and monitoring the results for three weeks.
You could notice miracles. Increased blood flow itself should have its own advantages. Nitric oxide should maximise the delivery of important nutrients like vitamin E and vitamin A to your skin. A small intestine with extra blood flow is known to break down and absorb nutrients more effectively.
Nitric oxide can also increase blood flow to the brain and that could relieve stress and anxiety. Nitric oxide has some interesting effects on mental function actually; one study found that chronic nitric oxide deficiency was far more common in people suffering from Alzheimer’s disease.
Overall, it’s far from proven that increasing nitric oxide levels will kill acne but experimenting is a superb idea.
How to increase nitric oxide levels
If you want to boost your nitric oxide levels for an experiment then good news – there’s no shortage of foods that can do that. Firstly, you’ve got to understand how nitric oxide is synthesised in the body. By far the biggest ingredient is the amino acid l-arginine, and this is combined with oxygen and a cofactor called NADPH.
The whole process is stimulated by nitric oxide synthase, but the big cheese you have to focus on is arginine. Any food that boosts arginine levels in the body will translate into increased NO levels.
Of course it isn’t that simple, so here’s a list of secret weapons known to boost nitric oxide…
Watermelon – we already covered this healthy fruit extensively in this article. It’s well known for boosting NO but why? Watermelon is bursting with the amino acid l-citrulline, which is a precursor to arginine in the body. Citrulline is increasingly beloved by athletes and you’ve now got supplement companies making products like citrulline malate. For some reason, citrulline boosts arginine levels in the body better than arginine itself, so watermelon is terrific.
Celery – one of the best nitric oxide-boosting foods ever. It’s packed full of natural nitrates which can easily convert to nitric oxide once you get them inside you. In fact, celery contains so many nitrates that organic meat producers use celery powder as an alternative to artificial nitrites for curing pork and making bacon.
Other nitrate rich foods – any other food will work, including the likes of beetroot, spinach, cabbage, parsley, radishes, collard greens and carrots. What happens with natural nitrates is that the benign bacteria on your tongue converts them to nitritines. When you then swallow the nitritines, the bacteria in your gut converts them to nitric oxide. Important note: remember to avoid harsh chemical mouthwashes since they can decimate the friendly bacteria in your mouth required for the conversion. Use my secret for a healthy mouthwash instead.
Eat Brazil nuts – they’re packed with natural arginine, not to mention other acne clearing benefits like being the world’s best source of selenium.
Sunlight – a lot of acne patients are terrified of sunlight because of the free radicals generated by UV ray exposure. Well, they can be a problem but only in excessive levels. You need sunlight to make vitamin D, which can clear acne in endless different ways.
Furthermore, UV light directly triggers your skin to synthesis nitric oxide. Researchers at the University of Edinburgh found out that when sunlight hits the skin, nitric oxide is released into the bloodstream instantly. Have you ever noticed how the veins on your arms become way more prominent after spending a day at a sunny beach? This is why.
In my eBook Annihilate Your Acne, we discussed how if you strengthen your skin with nutrition, you can spend far longer in the sun without fear of getting cancer or getting burnt.
Ginseng – a few weeks ago we discussed how Korean (or Panax) ginseng is a prime herbal supplement for boosting nitric oxide production. It contains plant saponins called ginsenosides which inhibit inflammation and boost NO production through some unknown mechanism. We talked about how ginseng can thus accelerate your old acne’s healing process, but in light of the new studies and information, ginseng is now a more powerful herb than ever before.
If you’re going to buy a ginseng supplement then watch out, because fake dealers have sprung up everywhere. Remember to buy authentic Korean ginseng, rather than the common Siberian ginseng which unfortunately lacks the medically important ginsenoside compounds. Your best option is this Solgar Full Potency Korean Ginseng Root.
Cocoa powder – cocoa is packed full of antioxidants and endless healthy compounds, whether it be theobromine, flavonoids, magnesium, or vitamin E. Hence, this study found that cocoa can crank up your NO production to massive levels. This study and this study found the same. I can testify for this benefit because prior to discovering the truth I always wondered why my veins became so prominent after eating 20 grams of dark chocolate. In fact, I just ate some and my veins are like garden hoses as I type this.
Eat some chocolate, but make sure that it is DARK chocolate at all costs, because the chocolate has to have a high cocoa content or it won’t work. Organic, 85% plus cocoa chocolate is perfect. As for the myth about chocolate causing acne, you can discover the truth in this article.
Laughter – a dead easy strategy that seems unbelievable. Nevertheless, this study found that when men watched a comedy film for 60 minutes or more, their levels of nitric oxide ended up substantially higher than men in the control group. The scientists found that mirthful laughter boosts heart function as well, and serum dopamine levels.
It’s actually a little known fact that actions like laughing and smiling can affect your hormones and neurotransmitters very strongly. In this article we discussed how changing your body language can slash stress hormones by 25%.
Resveratrol – a terrific supplement for lowering inflammation and making your antioxidants more effective. It’s also terrific for boosting nitric oxide as it can increase levels of the critical nitric oxide synthase enzyme. This study and this study both found increased NOS. Resveratrol is well known to protect against cardiovascular disease and so is nitric oxide.
You can get resveratrol through dark chocolate, red grapes, and red wine, or you can take a high quality supplement. It’s best to eat organic red grapes as they’ve got tons of antioxidants too. Red wine seems to provide enough resveratrol to work; this study found that red wine also increased activation of nitric oxide synthase.
Resveratrol has the benefit of extending lifespan too. The world’s oldest woman of all time, Jeanne Calment of France, claimed to have drunk red wine every day and eaten a pound of chocolate a week. Read more about resveratrol here.
In 1992 nitric oxide was proclaimed as “molecule of the year” for its newly emerging role in vasodilation. Well, it’s time has come again; this may be the year when it’s potentially astonishing benefits for acne finally come to light.
There’s substantial evidence that increasing your body’s production of nitric oxide can lower inflammation in the skin and help to kill p.acnes more efficiently. Therefore it’s a smart idea to follow the strategies above to boost your levels.
At the same time you might also enjoy the following: improved heart health, superior blood flow, improved healing of muscles after exercise, and clarity of mental thinking thanks to more blood flow to the brain.
Watch this space. With Novan Therapeutics steamrollering ahead with research and development on nitric oxide, it’s only a matter of time before more benefits for acne come to light.
Thanks for reading!