Sun and skin: daily sunscreen, sun protection and oral nicotinamide

Thompson et al. (New England Journal of Medicine, 1993; PMID 8377777): 588 adults aged 40 or older in Victoria, Australia, sunscreen cream against base cream for one summer; keratoses fell by 0.6 per person on sunscreen and rose by 1.0 on base cream (difference 1.53), fewer new lesions (rate ratio 0.62) and more remissions (odds ratio 1.53), with a dose-response relation. Darlington et al. (Archives of Dermatology, 2003; PMID 12707092), a separate group in Nambour: the ratio of keratosis counts was 1.20 on daily sunscreen against 1.57 on discretionary use, a 24% reduction, about 1 keratosis prevented per person. Naylor et al. (Archives of Dermatology, 1995; PMID 7857113): fewer new precancerous lesions on sunscreen in a small double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. trial in Texas. Susanto et al. (Clinical and Experimental Dermatology, 2026; PMID 41671392) summarized the sunscreen trials as reducing keratoses by 24 to 51% across three trials. Independent groups agree, but keratoses are precursor lesions, not cancer: a surrogate endpoint A lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome., capped at B.

Green et al. (Lancet, 1999; PMID 10475183), Nambour, 1,621 adults for 4.5 years: the number of squamous cell tumors was lower on daily sunscreen (1115 against 1832 per 100,000; rate ratio 0.61), but the number of people with a first new squamous cell cancer did not differ significantly (rate ratio 0.88, 95% CI 0.50 to 1.56). van der Pols et al. (Cancer Epidemiology, Biomarkers A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. and Prevention, 2006; PMID 17132769), 8 further years of follow-up of the same trial: squamous cell tumor rates almost 40% lower (rate ratio 0.62, 95% CI 0.38 to 0.99). The Cochrane review (Sanchez et al., 2016; PMID 27455163) found only this one trial and rated the evidence low quality. One trial, never repeated by another group, positive on tumor counts but not on people affected: C.

Green et al. (Journal of Clinical Oncology, 2011; PMID 21135266): 10 years after the Nambour trial ended, 11 new primary melanomas in the daily sunscreen group against 22 in the discretionary group (hazard ratio How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. 0.50, 95% CI 0.24 to 1.02; P = .051); invasive melanomas 3 against 11 (hazard ratio 0.27, 95% CI 0.08 to 0.97). Melanoma was not the trial's primary endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score., the overall result sits on the line of no effect, it rests on 33 cases, and no second trial exists. The Task Force review (Lin et al., 2011; PMID 21282699) judged it unclear whether sunscreen prevents melanoma. A single trial on a secondary, follow-up endpoint: C.

Green et al. (Lancet, 1999; PMID 10475183): no difference in basal cell carcinoma by person (rate ratio 1.03) or by tumor count. van der Pols et al. (2006; PMID 17132769): no significant reduction over 8 further years. Pandeya et al. (American Journal of Epidemiology, 2005; PMID 15800267): time to first basal cell cancer did not differ (hazard ratio 1.04); tumors that came back trended lower without reaching significance (hazard ratio 0.82, 95% CI 0.59 to 1.15). Sanchez et al., Cochrane (2016; PMID 27455163): risk ratio 1.03 (95% CI 0.74 to 1.43). Tested and no benefit found: D on Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale..

Hughes et al. (Annals of Internal Medicine, 2013; PMID 23732711): 903 Nambour participants younger than 55; skin surface casts graded by assessors blinded to treatment; skin aging over 4.5 years was 24% less on daily sunscreen (relative odds 0.76, 95% CI 0.59 to 0.98), and the daily sunscreen group showed no detectable increase in skin aging. The authors note missing outcome data and modest power. One trial, not repeated: C.

Gallagher et al. (JAMA, 2000; PMID 10865273): 458 Vancouver schoolchildren randomized, 309 analyzed; children given SPF 30 sunscreen developed fewer new moles over 3 years (median 24 against 28; P = .048), with a much larger effect in freckled children; Lee et al. (Journal of the American Academy of Dermatology, 2005; PMID 15858467) found the difference on the trunk. Harrison et al. (Cancers, 2023; PMID 36980647), a cluster trial in 25 Townsville childcare centers: children wearing sun-protective clothing and hats acquired fewer new moles (median 12.5 against 16; 24.3% fewer after 3.5 years). Mole counts are a risk marker for melanoma, not melanoma (surrogate), and each form of protection rests on one trial: C.

Chen et al., ONTRAC (New England Journal of Medicine, 2015; PMID 26488693): 386 people with at least two nonmelanoma skin cancers in the previous 5 years, 500 mg nicotinamide twice daily or placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received. for 12 months; new nonmelanoma skin cancers 23% lower (95% CI 4 to 38); squamous cell cancers 30% lower (95% CI 0 to 51); basal cell cancers 20% lower, not significant; actinic keratoses 11 to 20% lower; no benefit after the tablets stopped. Funded by the National Health and Medical Research Council of Australia. No second phase 3 trial in people who are not immunosuppressed has been reported. Meta-analyses A study that pools the numbers from several trials into one combined estimate. disagree: Mainville et al. (Journal of Cutaneous Medicine and Surgery, 2022; PMID 35134311) found a reduction (rate ratio 0.50, 95% CI 0.29 to 0.85, 5 trials, 552 patients, heterogeneity How much the results of the pooled trials differ from each other. High heterogeneity makes a combined estimate less reliable. explained by risk of bias), while Tosti et al. (Nutrients, 2023; PMID 38201930), pooling immunocompetent and transplant patients, found insufficient evidence (rate ratio 0.82, 95% CI 0.61 to 1.12). A single positive phase 3 trial not repeated by another group: C.

Allen et al., ONTRANS (New England Journal of Medicine, 2023; PMID 36856616): 500 mg twice daily for 12 months did not lower keratinocyte cancers, squamous or basal cell counts, or keratoses in immunosuppressed transplant recipients. Zhang et al. (Transplantation Proceedings, 2023; PMID 37838527): no reduction in keratoses in a 21-person pilot. Tested and no benefit found: D on Route 2.

No randomized trial of sun-protection counseling has measured skin cancer incidence as an outcome. Henrikson et al. (JAMA, 2018; PMID 29558557), the Task Force review of 21 trials (20,561 people): no trials assessed skin cancer outcomes in children; counseling produced small to moderate increases in self-reported sun protection behavior, with no consistent reduction in sunburn in children (3 trials) or adults (6 trials). The one adult trial with a melanoma count promoted skin self-examination, a detection program, and found 0 against 1 diagnosis. Lin et al. (Annals of Internal Medicine, 2011; PMID 21282699) also found counseling increased sun-protective behavior and reduced indoor tanning. No trial on the stated endpoint: D on Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale..