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.

Relative rates of cancers and deaths in Australian communities with PFAS environmental contamination associated with firefighting foams: A cohort study using linked data.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that are potentially harmful to health. We examined if rates of selected cancers and causes of deaths were elevated in three Australian communities with local environmental contamination caused by firefighting foams containing PFAS. The affected Australian communities were Katherine in Northern Territory, Oakey in Queensland and Williamtown in New South Wales. METHODS: All residents identified in the Medicare Enrolment File (1983-2019)-a consumer directory for Australia's universal healthcare-who ever lived in an exposure area (Katherine, Oakey and Williamtown), and a sample of those who ever lived in selected comparison areas, were linked to the Australian Cancer Database (1982-2017) and National Death Index (1980-2019). We estimated standardised incidence ratios (SIRs) for 23 cancer outcomes, four causes of death and three control outcomes, adjusting for sex, age and calendar time of diagnosis. FINDINGS: We observed higher rates of prostate cancer (SIR=1·76, 95 % confidence interval (CI) 1·36-2·24) in Katherine; laryngeal cancer (SIR=2·71, 95 % CI 1·30-4·98), kidney cancer (SIR=1·82, 95 % CI 1·04-2·96) and coronary heart disease (CHD) mortality (SIR=1·81, 95 % CI 1·46-2·33) in Oakey; and lung cancer (SIR=1·83, 95 % CI 1·39-2·38) and CHD mortality (SIR=1·22, 95 % CI 1·01-1·47) in Williamtown. We also saw elevated SIRs for control outcomes. SIRs for all other outcomes and overall cancer were similar across exposure and comparison areas. INTERPRETATION: There was limited evidence to support an association between living in a PFAS exposure area and risks of cancers or cause-specific deaths.

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.

Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study.

BACKGROUND: Acute lymphoblastic leukaemia is the most common childhood cancer in more-developed countries but it has few recognised risk factors or preventive measures. We aimed to determine and assess the risk factors associated with this disease. METHODS: From 1984 to 1992, we investigated known and suspected risk factors for common acute lymphoblastic leukaemia diagnosed in a population-based case-control study of children aged 0-14 years in Western Australia. 83 children in the study group came from the sole referral centre for paediatric cancer in the state and 166 controls matched for age and sex were recruited through a postal survey of people randomly selected from the state electoral roll. We interviewed mothers of 83 study and 166 control children (82% and 74%, respectively, of those eligible). Fathers completed a self-administered questionnaire. FINDINGS: We recorded a protective association between iron or folate supplementation in pregnancy and risk of common acute lymphoblastic leukaemia in the child (odds ratio 0.37 [95% CI 0.21-0.65]; p=0.001). For iron alone, the odds ratio was 0.75 (0.37-1.51); only one mother took folate without iron. Further analyses of folate use with or without iron (0.40; 0.21-0.73) showed that the protective effect varies little by time of first use of supplements or for how long they were taken. The association was not weakened by adjustment for potentially confounding variables. INTERPRETATION: Our results, though unexpected, suggest that folate supplementation in pregnancy reduces the risk of common acute lymphoblastic leukaemia in the child.

Vegetarian diet in mild hypertension: effects of fat and fiber.

Recently, a relatively small reduction in systolic blood pressure (approximately 5 mm Hg) was estimated to substantially reduce the numbers of major coronary events. The blood pressure reduction is about the same as the difference seen between typical ovolactovegetarians and omnivores. This paper reviews the evidence for the blood pressure-lowering effects of a vegetarian diet on those with elevated blood pressure. It also reviews whether the effect on blood pressure of a vegetarian diet can be attributed either to elevation of the dietary P:S ratio or to fiber intake alone.

Dietary fat intake and blood pressure: a double blind controlled trial of changing polyunsaturated to saturated fat ratio.

The effect on blood pressure of elevating the dietary polyunsaturated/saturated fat (P/S) ratio was assessed in a double-blind, randomized control trial. Fifty-four healthy, normotensive volunteers aged between 20 and 59 years were randomly allocated either to a control group who ate a low P/S ratio diet throughout, or to one of two experimental groups who ate a high P/S ratio diet for one of two six-week experimental periods. Other nutrient changes were avoided. Twenty-four-hour diet records showed substantial changes in the P/S ratio when on the high P/S ratio diet, and no change in the control group or either experimental group when on the low P/S ratio diet. Relative concentrations of linoleic acid in plasma and cheek cell phospholipids were significantly increased when on the high P/S ratio diet. Changes in blood pressure, before and after adjustment for other possible confounding factors, were not related to changes in P/S ratio. It was concluded that an increase in P/S ratio per se cannot account for the previously reported blood pressure lowering effect of a vegetarian diet.

Dietary-induced changes in the fatty acid composition of human cheek cell phospholipids: correlation with changes in the dietary polyunsaturated/saturated fat ratio.

Healthy normotensive volunteers aged 20 to 59 yr were randomly allocated either to a control group or to one of two experimental groups. The control group ate a low P/S ratio diet for 12 wk while the first experimental group ate a high P/S ratio diet for 6 wk followed by a low P/S ratio diet for the next 6 wk. The second experimental group ate a low P/S ratio diet in the first 6 wk followed by a high P/S ratio diet for the next 6 wk. Dietary P/S ratio, plasma linoleic acid (18:2), and cheek cell phospholipid 18:2 levels were compared in each dietary group at the end of the 1st and 2nd 6 wk. On change from a low to a high P/S ratio diet, there was a 36% increase in the proportion of 18:2 in the cheek cell phospholipids in comparison with the proportion existing before the change. This was associated with an increase in the proportion of 18:2 in the plasma lipids of this group. No reduction in the proportion of 18:2 in the cheek cell phospholipids was apparent in the control group or the group which changed from a high to a low P/S ratio diet, although in the latter group there was a reduction in the proportion of 18:2 in the plasma lipids. As the phospholipid fatty acid composition of human cheek cells reflects dietary lipid status under certain conditions, this observation may be useful in dietary and nutritional studies, particularly as human cheek cells can be obtained in a noninvasive manner.