The role of vitamin B3 in reducing non-melanoma skin cancer

Cancer Council NSW helped fund one of the biggest discoveries in skin cancer research – that vitamin B3 can help reduce non-melanoma skin cancers. Five years after this grant ended, we have caught up with lead researcher, Professor Diona Damian, to hear the latest on her pioneering work.

It all began in 2008, when Cancer Council NSW awarded a research grant to Professor Diona Damian and her team at the University of Sydney.  Over the next three years, the researchers led the way globally in exploring a new approach to tackling skin cancer.

“We were interested in finding new ways of preventing and treating skin cancer, because that’s our national cancer. It’s the most common cancer in Australia, more than four times as common as all other cancers put together”, Professor Damian said.

Breakthrough findings

When Professor Damian’s team began their work, they knew that even low doses of UV radiation from the sun could cause skin cancer. UV radiation does this not only by damaging the DNA in skin cells, but also by suppressing our skin’s immune defences. Professor Damian had already tested a number of compounds which could potentially prevent this sunlight-induced immune suppression, and found that a form of vitamin B3, called nicotinamide, had the greatest potential.

Thanks to Cancer Council NSW funding, her team was able to prove that nicotinamide, either as a topical lotion or a daily tablet, is highly effective in providing immune protection. Nicotinamide does this by replenishing cellular energy, which also enables faster and more efficient DNA repair following sun exposure.

A landmark clinical trial

Since her Cancer Council NSW project grant concluded, Professor Damian’s research on nicotinamide has made incredible progress. Her team won a grant from the National Health and Medical Research Council to undertake a landmark skin cancer prevention clinical trial called ONTRAC (“Oral Nicotinamide To Reduce Actinic Cancer”).

The trial was conducted across the Royal Prince Alfred and Westmead Hospitals and included 386 patients who were randomly assigned to receive either a twice daily dose of nicotinamide or a placebo for one year. All the patients had been diagnosed with at least two non-melanoma skin cancers in the previous 5 years, which meant they were at a high risk of developing more cancers.  During the twelve months of study, this group of patients collectively grew 800 new skin cancers.

What did the trial discover?

• The final results of ONTRAC were published in the New England Journal of Medicine and made international headlines.
• The team found that at 12 months, the rate of non-melanoma skin cancers was 23% lower in the nicotinamide group than in the placebo group.
• The number of precancerous lesions was also 13% lower among the people taking nicotinamide compared to those not taking nicotinamide.

The impact

Nicotinamide is widely accessible as an inexpensive, over-the-counter vitamin supplement, so the discovery that it is effective in protecting against non-melanoma skin cancer and precancerous lesions has been a game changer. In recognition of this achievement, Dr Andrew Chen, a final year PhD student who worked with Professor Damian on the trial, won The Rising Star PhD Student Award in 2016 at the NSW Premier’s Awards for Outstanding Cancer Research.

Who can use nicotinamide to prevent skin cancer?

Professor Damian emphasised that using nicotinamide to prevent skin cancer is a high-dose treatment rather than a supplement.  “This treatment is only for people with a defined medical condition – multiple skin cancers.”

“It’s not suitable for the general population, as we do not have any evidence that it would be beneficial in a lower risk setting.”

Before taking nicotinamide, people should consult with their dermatologist or general practitioner to see whether nicotinamide is suitable for them. It is also very important that people planning to take vitamin B3 take the amide form, nicotinamide, and not the nicotinic acid form. “Nicotinic acid has a range of unpleasant side effects – including flushing, headache and low blood pressure – that we don’t see with nicotinamide”, says Professor Damian.

Moving forward with this research

Exploring nicotinamide for melanoma

Looking ahead, Professor Damian hopes that nicotinamide will continue to reduce rates of non-melanoma skin cancer among people at high risk – but the work does not end here. In fact, her team is now determining how the immunoprotective effects of nicotinamide might help prevent melanoma as well as non-melanoma skin cancer.

“Laboratory studies so far have provided encouraging results, but we now need a large scale clinical trial in people at high risk of melanoma.”

Nicotinamide and supressed immune systems

A second avenue of research will investigate whether nicotinamide can help people who are at risk of aggressive skin cancers because they have a chronically supressed immune system.

“The skin’s immune system is a key defence against skin cancer, and people who have had organ transplants must remain immune suppressed for life in order to prevent rejection of their new kidney, liver or heart.”

“These patients develop 50 times as many cancers as people with intact immunity, but we don’t yet know whether nicotinamide will be safe and effective in this setting. We have now obtained funding for a Phase 3 trial in transplant recipients to help answer this question.

Research meets clinical practice

These days, Professor Damian divides her time between research and clinical practice. “The clinical practice for me now is mainly skin cancer patients, many of whom have participated in our trials as high-risk patients.”

“They are the patients who inspire you and trigger you to find answers to their questions. It’s about observing a need and finding simple but effective ways to reduce the burden of our most common cancer.”

Learn more about the different types of skin cancer.