Antioxidants supplements deadly?

1. Mejia, Paula. “Antioxidants May Lead to Cancer Spread, Study Says.” Newsweek. 17 October 2015. Available http://www.newsweek.com/antioxidants-may-lead-cancer-spread-study-says-384528
2. Piskounova E, Agathocleous M, Murphy MM, et al. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature. 2015.
3. Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. The New England journal of medicine. 2015;373(17):1618-1626.

Anti-oxidants and Skin Cancer

Major news outlets hyped the dangers of antioxidant consumption from sources such as “blueberries,” citing they may promote tumor metastasis.[1]

The original study’s aim was to better understand metabolic changes in metastatic tumors. The authors first characterized the potential of human melanoma lines to form new tumors when explanted into immunodeficient mice.  Successfully metastasizing melanomas were found to have higher levels of NADPH, a critical enzyme within the folate pathway that recycles glutathione, which is known to help with oxidative stress. To test whether increased glutathione promotes tumor metastasis, three highly metastatic melanoma cell lines were injected into mice and received either subcutaneous N-acetyl cysteine (NAC) or control. The authors found a 10-fold increase in tumor formation with NAC (p<0 .0001="" p="">

A separate phase 3 double-blind randomized control trial published this week showed that antioxidant compounds might also have protective effects in cancer. Investigators tested vitamin B3 in the prevention of skin cancer in patients with a history of previous non-melanoma skin cancers. The rationale for using Vitamin B3 is that Vitamin B3 is a precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-factor for ATP production, which is otherwise depleted with UV-radiation induced DNA damage. The study included 386 patients who underwent dermatological evaluations every 3-month for 18-months to evaluate for new skin lesions. The results showed that at 12-months, there were 23% fewer new non-melanoma skin cancers with a number needed to treat (NNT) of 2.2 for basal cell carcinoma and 5.0 for squamous cell carcinoma. Vitamin B3 also led to a 13% greater decline in the number of actinic keratoses from baseline in the nicotinamide group vs. the placebo group, which equates to 3 – 5 fewer per patient on average. However how the number of actinic keratoses corresponds to risk of recurrent malignancy is unclear. There was no comparative benefit during the 6-month post-intervention surveillance period after nicotinamide was discontinued nor were there any adverse effects throughout the study.[3] Overall this study provides support for the role of vitamin B3 as a chemoprevention agent in patients at high risk for recurrent non-melanoma skin cancer as it is safe, well tolerated and cheap. However it remains unclear whether this will lead to true clinical benefit as non-melanoma tumors are frequently slow growing and easy to excise. Larger and longer studies are necessary to assess effects on morbidity and mortality.

These two recent studies present opposing conclusions regarding the harm or benefit of antioxidants in cancer. One possibility is that antioxidants provide a protective effect during tumor initiation but a deleterious effect during tumor progression. This could explain why Vitamin B3/nicotinamide decreases the risk of new tumors while NAC promotes melanoma metastasis. Alternatively, the biology of non-melanoma and melanoma tumors may be different. Either way, the role of antioxidants in cancer is likely to be more complex than represented in the popular press. Additional pre-clinical and clinical trials will be essential to further understand the effects of antioxidants on cancer.

http://www.clinicalcorrelations.org/?p=8732