Vitamin D: One hundred years on
The year 2022 will feature in history books for a number of reasons; but in the world of nutrition, it marks the Centenary of the landmark investigation by Dame Harriette Chick and her co-workers. Exactly 100 years ago, working with malnourished children in a clinic in Vienna (Austria) shortly after the First World War, they showed that rickets in children could be prevented or cured by cod-liver oil supplementation. Cod liver oil was subsequently recognized as a particularly rich source of vitamin D (Chick et al. 1922).
A century later, vitamin D remains at the forefront of research and a specially curated Virtual Issue of Nutrition Bulletin, available free-to-access online at Vitamin D: 100 years of research - 1922-2022: Nutrition Bulletin (wiley.com) has drawn together 14 papers published in the journal over the past 10 years on the topic. Included among these is an editorial (Buttriss & Lanham-New 2022) which summarises the history of vitamin D over the last century.
Dame Harriette Chick was awarded the British Nutrition Foundation (BNF) Prize in 1974 for her contribution to nutrition research. By then already a Centenarian, she chose her ground breaking research on vitamin D in Austria, 50 years previously, as the theme for her BNF Annual Lecture (Chick 1976), presenting the chemical, clinical and sociological aspects of her story. Dame Harriette worked at the Lister Institute of Preventative Medicine, London, UK from 1905 to 1970, and she and colleagues were sent to Vienna by the Accessory Food Factor Committee of the Medical Research Council to investigate whether the diseases affecting the population were the result of vitamin deficiencies.
Over the past century, many researchers – far too many to mention here – have contributed to our current understanding of vitamin D and its role as a pro-hormone. Notable among these was a British doctor, Dr Edward Mellanby (Mellanby 1919), who had become concerned about the very high incidence of rickets in the UK, especially in Scotland. Following a series of trials, Mellanby realised that puppies fed a diet based on the oatmeal-rich Scottish diet (and coincidentally housed indoors), developed rickets which could be prevented or cured by the addition of cod liver oil. Mellanby concluded that it “seems probable that the cause of rickets is a diminished intake of an anti-rachitic-factor which is either fat-soluble factor A”, (later known as vitamin A) “or has a similar distribution”.
Again in 1922, a key experiment by McCollum and co-workers (McCollum et al. 1922) showed that heated, oxidized cod liver oil could cure rickets in rats but could not prevent xerophthalmia (now known to be a symptom of vitamin A deficiency). The antirachitic factor was given the name vitamin D (as B and C had already been used for water-soluble factors and the anti-scurvy factor, respectively).
Meanwhile, an entirely different cure for rickets had emerged, namely ultraviolet (UV) light. It had long been acknowledged that fresh air and sunshine were effective in the prevention of rickets, and in 1921 it was proposed that the seasonal incidence of rickets was due to seasonal variations in sunlight exposure (Hess & Unger 1921). Support for this was evident in the work of Chick et al. in Vienna, who observed that sunlight would cure rickets in young children just as well as cod liver oil (Chick et al. 1922). Using X-ray analysis, Dame Harriette and her co-workers showed conclusively that rickets had a marked winter incidence; that protection against its development in young children in winter could be achieved by diet (none of the infants given cod liver oil developed rickets) and that infants in the first 6 months of life were particularly susceptible to rickets.
In his 1973 BNF Prize Lecture, Dr Egon Kodicek (a researcher in Cambridge) described how understanding of the role of UV light, in converting a precursor of vitamin D in the skin into an active form of the vitamin, followed on a few years after the work in Vienna. He also summarized work by himself and others, over the following 50 years, that built on these important discoveries a century ago (Kodicek 1974a; Kodicek 1974b). In 1969, a specific binding protein for vitamin D, the vitamin D receptor, was identified and the metabolism of vitamin D in the liver and kidney to its active forms was elucidated. It was Fraser and Kodicek (1970) who demonstrated the conversion in the kidney of the liver-hydroxylated vitamin D metabolite, 25-hydroxy vitamin D3 (25-OH-D3), to what was later identified as calcitriol (1,25-(OH)2D3) (Holick et al. 1971).
In a relatively recent historical overview, Professor Hector DeLuca from Wisconsin University (USA) (DeLuca 2008), summarizes keys discoveries such as the conversion of vitamin D to its hormonal form, its regulation and the evolving picture of its molecular mechanism of action. He discusses how it has long been recognized that calcitriol circulates as a hormone in the blood, regulating the concentrations of calcium and phosphate in the bloodstream and promoting growth and remodelling of bone. Furthermore, over time, evidence continues to emerge to show that vitamin D’s role extends far beyond mineralization of the skeleton to include, for example, muscle function, the immune system, and treating the skin disorder psoriasis (see Lanham-New et al 2022).
During the coronavirus pandemic, vitamin D’s role in the immune system (Hewison 2012; 2022) was explored in considerable depth by researchers as well as policy makers (Lanham-New et al. 2020), in part triggered by the higher incidence of extreme coronavirus symptoms in communities recognised to be at greater risk of lower serum vitamin D concentrations. A paper in Nutrition Bulletin (and included in the Virtual Issue) by Gibson Moore (2021) provides a summary of work in this area.
These developments in understanding the role of vitamin D, which began more than a century ago, underpin the science that supports policies to tackle the incidence of rickets that continue to this day. Progress is brought right up to date in a summary of a ‘hot topics’ workshop held in 2021 (Lanham-New et al, 2022; available in the Virtual Issue).
A longer version of this article (Buttriss & Lanham-New 2022) – link below - outlines the success (or otherwise) of efforts to eradicate rickets and improve vitamin D status over the past 100 years, summarising current UK government policy and the Department of Health’s call for evidence on strategies to improve intakes and health disparities, and the on-going challenges and options for future public health strategies in relation to vitamin D, including new government legislation allowing gene editing (e.g. vitamin D enriched tomatoes). The paper also provides a flavour of the vitamin D papers published in Nutrition Bulletin over the past 10 years; the full papers can be accessed in the Virtual Issue at Vitamin D: 100 years of research - 1922-2022: Nutrition Bulletin (wiley.com) and a longer version of this blog is here Vitamin D: One hundred years on - Buttriss - Nutrition Bulletin - Wiley Online Library
Fact sheets for the general public on vitamin D are available from the British Dietetic Association (BDA) - Vitamin D | British Dietetic Association (BDA) – and from the British Nutrition Foundation (BNF) – Vital vitamin D! vitalv-3.pdf (nutrition.org.uk)
AUGUST 11, 2022