Background Randomised controlled trials demonstrating improved longevity are needed to justify high-dose vitamin D supplementation for older populations. Objectives To demonstrate the feasibility of a large trial (n ≈ 20,000) of high-dose vitamin D in people aged 65–84 years through general practitioner (GP) practices, and to cluster randomise participating practices between open-label and double-blind randomisation to compare effects on recruitment, compliance and contamination. Design Twenty GP practices were randomised in matched pairs between open-label and double-blind allocation. Within each practice, patients were individually randomised to vitamin D or control (i.e. no treatment or placebo). Participants were invited to attend their GP practice to provide a blood sample and complete a lifestyle questionnaire at recruitment and again at 2 years. Randomisation by telephone followed receipt of a serum corrected calcium assay confirming eligibility (< 2.65 nmol/l). Treatment compliance was reported by quarterly follow-up forms sent and returned by e-mail or post (participant choice). GP visits and infections were abstracted from GP records. Hospital attendances, cancer diagnoses and deaths were ascertained by linkage to Hospital Episode Statistics and national registration through NHS Digital. Setting GP practices in England. Participants Recruitment opened in October 2013 and closed in January 2015. A total of 1615 registered patients aged 65–84 years were randomised: 407 to vitamin D and 421 to no treatment in open practices; 395 to vitamin D and 392 to placebo in blind practices. Interventions There was a 24-month treatment period: 12 monthly doses (100,000 IU of vitamin D3 or placebo as 5 ml oily solution) were posted after randomisation and at 1 year (100,000 IU per month corresponds to 3300 IU per day). Reminders were sent monthly by e-mail, text message or post. Main outcome measures Recruitment, compliance, contamination and change in circulating 25-hydroxyvitamin D [25(OH)D] from baseline to 2 years. Results Participation rates (randomised/invited) were 15.0% in open practices and 13.4% in double-blind practices (p = 0.7). The proportion still taking study medication at 2 years was 91.2% in open practices and 89.2% in double-blind practices (p = 0.4). The proportion of control participants taking > 400 IU vitamin D per day at 2 years was 5.0% in open practices and 4.8% in double-blind practices. Mean serum 25(OH)D concentration was 51.5 nmol/l [95% confidence interval (CI) 50.2 to 52.8 nmol/l] with 82.6% of participants < 75 nmol/l at baseline. At 2 years, this increased to 109.6 nmol/l (95% CI 107.1 to 112.1 nmol/l) with 12.0% < 75 nmol/l in those allocated to vitamin D and was unaltered at 51.8 nmol/l (95% CI 49.8 to 53.8 nmol/l) in those allocated to no vitamin D (no treatment or placebo). Conclusions A trial could recruit 20,000 participants aged 65–84 years through 200 GP practices over 2 years. Approximately 80% would be expected to adhere to allocated treatment (vitamin D or placebo) for 5 years. The trial could be conducted entirely by e-mail in participants aged < 80 years, but some participants aged 80–84 years would require postal follow-up. Recruitment and treatment compliance would be similar and contamination (self-administration of vitamin D) would be minimal, whether control participants are randomised openly to no treatment with no contact during the trial or randomised double-blind to placebo with monthly reminders. Trial registration Current Controlled Trials ISRCTN46328341 and EudraCT database 2011-003699-34. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 10. See the NIHR Journals Library website for further project information.

Conflicts of interestNone declared.The British Isles are often thought to have a mild climate-winters with little snow and temperatures generally above freezing, while summers are seldom if ever uncomfortably hot. But in one respect the British climate is extreme: we get very little bright sunshine. The British Isles are located so far north that for 6 months of the year the sun is not strong enough to enable vitamin D synthesis in exposed skin. In summer the sky is often cloudy or overcast and, even when the sun is strong and bright, the air temperature may be too cold for clothes to be removed comfortably.This lack of sunlight leads to a low vitamin D level in the British and Irish population and this is now being recognized as a major cause of ill health. And government advice to stay out of the sun in the middle of the day, which is the best time for vitamin D synthesis in the skin, adds to the problem.In this article I consider the problem of vitamin D insufficiency from the earliest days of human settlement in these islands up to the present day. I outline recent findings about the consequences of vitamin D insufficiency for health. And I suggest that optimum health is more likely to be achieved by safe sunbathing without burning than by the SunSmart advice presently advocated by government and Cancer Research UK (CR-UK). Evolution of white skinHumans evolved in tropical Africa-we now know that for sure. Modern human beings (Homo sapiens) first colonized northern Europe some 20 000 years ago following the ice age. 1 The climate of northern Europe provided a new evolutionary challenge to humankind. In tropical Africa there is generally plenty of sunlight every day of the year whereas in northern Europe we have a vitamin D winter when synthesis of the vitamin is impossible.White skin synthesizes vitamin D six times faster than dark skin, 2 enabling efficient use to be made of short sunny periods on cloudy days. A white skin also enables better use to be made of the thin sunlight that we get at the beginning and end of the summer season, thus extending the period when vitamin D can be synthesized for growth and reproduction. This must have given white skin a strong selective advantage during the colonization of northern Europe. 3 Low levels of vitamin D are a cause of infertility 4 and seem to be associated with an increased risk of tuberculosis. 5,6 These two factors together were probably responsible for a strong selection pressure that fixed skin colour genes favouring greater production of vitamin D, so enabling more successful reproduction and enhanced survival of the species.Women and children have lighter skins than adult men. 7 It has been suggested that this enables them to make best use of small amounts of sunlight for good reproduction and growth while men, who traditionally spent more time foraging in the open, had darker skins that protected them from sun damage. Industrial lifestyle brings low levels of vitamin DOur lifestyle has changed drastically in the last 200 years and in the last 40 years ...

The British Isles have a very cloudy climate and as a result receive fewer hours of clear sunlight than most other industrial regions. The majority of people in these islands have low blood levels of vitamin D [25(OH)D] all year round. Few food products are fortified with vitamin D in the UK and the government does not recommend any vitamin D supplement for most adults in the UK. Diseases associated with vitamin D insufficiency such as cancer, heart disease, diabetes (types 1 and 2) and multiple sclerosis are more frequent in the UK, and particularly in Scotland, than in many other European countries and some, such as multiple sclerosis and diabetes (types 1 and 2), are increasing in incidence. Present knowledge suggests that the risk of some chronic diseases could be reduced if vitamin D intake or sun exposure of the population were increased. Yet policy and public health recommendations of the UK government and its agencies (e.g. the Health Protection Agency, the Food Standards Agency) and of Cancer Research UK have failed to take full account of established and putative benefits of vitamin D and/or sunshine. The epidemic of chronic disease in the UK, which is associated with and caused at least in part by vitamin D insufficiency, has not been adequately recognized by these agencies, and too often measures taken by them have been misguided, inappropriate or ineffective.

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