Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.

Therapeutic mammaplasty is a safe and effective alternative to mastectomy with or without immediate breast reconstruction.

BACKGROUND: Therapeutic mammaplasty (TM) may be an alternative to mastectomy, but few well designed studies have evaluated the success of this approach or compared the short-term outcomes of TM with mastectomy with or without immediate breast reconstruction (IBR). Data from the national iBRA-2 and TeaM studies were combined to compare the safety and short-term outcomes of TM and mastectomy with or without IBR. METHODS: The subgroup of patients in the TeaM study who underwent TM to avoid mastectomy were identified, and data on demographics, complications, oncology and adjuvant treatment were compared with those of patients undergoing mastectomy with or without IBR in the iBRA-2 study. The primary outcome was the percentage of successful breast-conserving procedures in the TM group. Secondary outcomes included postoperative complications and time to adjuvant therapy. RESULTS: A total of 2916 patients (TM 376; mastectomy 1532; mastectomy and IBR 1008) were included in the analysis. Patients undergoing TM were more likely to be obese and to have undergone bilateral surgery than those having IBR. However, patients undergoing mastectomy with or without IBR were more likely to experience complications than the TM group (TM: 79, 21·0 per cent; mastectomy: 570, 37·2 per cent; mastectomy and IBR: 359, 35·6 per cent; P < 0·001). Breast conservation was possible in 87·0 per cent of patients who had TM, and TM did not delay adjuvant treatment. CONCLUSION: TM may allow high-risk patients who would not be candidates for IBR to avoid mastectomy safely. Further work is needed to explore the comparative patient-reported and cosmetic outcomes of the different approaches, and to establish long-term oncological safety.

ANTECEDENTES: La mamoplastia terapéutica (therapeutic mammaplasty, TM) puede ser una alternativa a la mastectomía, pero hay pocos estudios bien diseñados que hayan evaluado el éxito de esta estrategia o hayan comparado los resultados a corto plazo de la TM con la mastectomía con o sin (+/-) reconstrucción mamaria inmediata (immediate breast reconstruction, IBR). Para comparar la seguridad y los resultados a corto plazo de la TM y la mastectomía +/- IBR se combinaron los datos de los estudios nacionales iBRA-2 y TeaM. MÉTODOS: En el estudio TeaM se identificó el subgrupo de pacientes al que se realizó una TM para evitar la mastectomía y se compararon los datos demográficos, las complicaciones, los resultados oncológicos y el tratamiento adyuvante con las pacientes sometidas a mastectomía +/- IBR del estudio iBRA-2. La variable principal fue el porcentaje de éxito de la cirugía conservadora de mama en el grupo TM. Las variables secundarias fueron las complicaciones postoperatorias y el intervalo de tiempo hasta el inicio del tratamiento adyuvante. RESULTADOS: Se incluyeron en el análisis 2.916 pacientes (TM n = 376; mastectomía n = 1.532; IBR n = 1.008). La TM era más frecuente en pacientes obesas o en las sometidas a cirugía bilateral en comparación con las pacientes con IBR. Sin embargo, las pacientes sometidas a una mastectomía +/- IBR tenían más probabilidades de desarrollar complicaciones que las del grupo TM (TM n = 79, 21,0%; mastectomía n = 570, 37,2%; mastectomía y IBR n = 359, 35,6%; P < 0,001). La conservación de la mama fue posible en el 87% de las pacientes con TM y el procedimiento no retrasó el inicio del tratamiento adyuvante. CONCLUSIÓN: La TM puede permitir que pacientes de alto riesgo que no serían candidatas a IBR eviten la mastectomía de una forma segura. Se necesitan más trabajos para comparar los resultados percibidos por las pacientes y los estéticos de las diferentes estrategias terapéuticas y establecer la seguridad oncológica a largo plazo.

The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer.

BACKGROUND: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort. METHODS: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence. RESULTS: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar. CONCLUSIONS: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice.