90th Anniversary Commentary: Vitamin D Is Critical for Human Nutrition, but Research Is Still Needed to Identify Optimal Blood Concentrations and Intake Levels for Human Health
The Journal of Nutrition, Vol148, Issue 10, 1 Oct 2018, Pages 1686–1687, https://doi.org/10.1093/jn/nxy122
Marian L Neuhouser
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Exactly 90 years ago in 1928, the Nobel Prize in Chemistry was awarded to Dr. Adolf Windhaus for his work on sterols and their relation to vitamins, specifically vitamin D (1, 2). It is only fitting for this 90th anniversary commemoration of The Journal of Nutrition that we remember some of the seminal scientific discoveries in nutrition science published in the Journal, including important discoveries concerning vitamin D and human health. The work of Dr. EV McCollum, Dr. AF Hess, Dr. LJ Unger and countless others contributed to our current scientific understanding of the role of vitamin D in human nutrition (3–5).
Vitamin D is the name given to a group of secosteroids with similar molecular structure and hormone-like functions (6, 7). Vitamin D has been primarily recognized for its ability to maintain proper blood concentrations of both calcium and phosphorous, regulate parathyroid hormone concentrations, and related roles in prevention of bone diseases, such as vitamin D-related rickets, osteomalacia, and age-related fractures (6, 7). More recently, interest has arisen around vitamin D's potential role in chronic disease prevention. Although data are insufficient to date to alter nutritional requirements for anything other than bone health (7), the scientific community recognizes several roles for vitamin D, which have been extensively reviewed (7–9).
The early work on vitamin D in the first half of the 20th century was almost exclusively focused on discoveries showing that the “antirachitic factor” was present in certain foods, such as cod liver oil and cottonseed oil, but could also be produced by exposure to UV light. It was not until the mid-1930s that the chemical structures of the various vitamin D isomers were identified, as well as the discovery of the formation of 7-dehydrocholesterol from cholesterol through irradiation (2). In 1970, Drs. Suda, DeLuca, and Tanaka published a seminal article in the Journal (10) in which a rodent model was used to confirm that the primary circulating form of vitamin D was 25-hydroxyergocalciferol (now known as 25-hydroxyvitamin D). Briefly, the series of experiments used: 1) depletion/repletion to test 25-hydroxyergocalciferol's effect on bone calcification and the dose needed to treat rickets; 2) absorption experiments demonstrating that 25-hydroxyergocalciferol was the form of the vitamin needed to promote gut calcium absorption and transport in a timely manner; and 3) that 25-hydroxyergocalciferol was an effective bone mineralizing agent. This series of experiments confirmed their earlier experimental finding that the primary circulating form of vitamin D was 25-hydroxyergocalciferol (i.e., the hydroxylated form), and now also gave the important finding that in order for vitamin D3 to be effective for bone health and to act as the “antirachitic agent”, it needed to be hydroxylated as 25-hydroxyergocalciferol; this was the required form of the vitamin for maximum function (10).
Over the ensuing 40 y, basic and human nutrition research has continued for vitamin D. Although many important articles on the structure, function, absorption, and metabolism of vitamin D have been published (11, 12), debate continues regarding human nutritional requirements. In 2005, the Journal published an article by Dr. Bruce Hollis that was presented, in part, during the symposium “Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency” (13). This symposium was sponsored by the American Society for Nutrition as part of Experimental Biology 2004 held in Washington, DC. In his report, Dr. Hollis presented a rationale for establishing a new (higher) DRI for vitamin D. His rationale was based on knowledge of human evolution where, presumably, the first hominids living on the African continent (an area with plentiful sunshine and substantial cutaneous synthesis of vitamin D) migrated into areas at higher latitudes with lower year-round exposure to the sun's UV radiation required for vitamin D synthesis. Dr. Hollis goes on to posit that because humans evolved in areas with plentiful solar UV exposure, “normal” serum 25-hydroxyvitamin D concentrations should not be based on the general population, but rather on the concentrations observed in individuals with high UV exposure to the skin such as lifeguards and other outdoor workers who are minimally clothed (13). He goes on to suggest that DRI should be set in a manner such that the general population would achieve the blood concentrations of lifeguards and others who regularly have high UV exposure with minimal clothing. This approach, however, should be considered very cautiously. Using the distributions of circulating 25-hydroxyvitamin D in such a select group of individuals only tells us what the distributions could be if everyone had light skin and lived in a climate where outdoor work was conducted on a routine basis with minimal clothing. That is, it could tell us what human capacity (i.e., an upper threshold) might be for cutaneous synthesis of vitamin D, but that is a separate question from establishing nutritional requirements, or what the proper concentrations should be (and intake to achieve such concentrations) for promotion of health and disease prevention.
Six years after Dr. Hollis's report, the Institute of Medicine (IOM) published their report on DRIs for vitamin D and calcium (7). In this report, new DRIs for vitamin D were established and included an Upper Limit. At the time of the IOM report, skeletal health remained the primary health outcome for establishing DRIs because evidence was insufficient at the time to support a strong association with other health conditions. In the ensuing years, research has continued to flourish on the role of vitamin D in human nutrition and health. Whether Hollis’ declaration is correct that current DRIs (even the 2011 DRIs) are still too low, or whether the optimal serum concentrations should be higher than those declared by the 2011 IOM report, remains to be seen. Research evidence must accumulate to the level necessary for proper evaluation and review. Much of the newer research is focused on the role of vitamin D and chronic disease risk, such as cardiovascular disease, cancer, and diabetes, which are the major causes of morbidity and mortality in the United States and globally. It is possible that the amount of vitamin D needed for chronic disease prevention is different from that needed to preserve bone health. Fortunately, the National Academies of Sciences, Engineering, and Medicine (formerly the IOM) recognizes that DRIs for deficiency may differ from DRIs for chronic disease prevention. A 2017 report provided guiding principles and methods for use by future DRI committees as they consider nutrition needs for chronic disease prevention (14). As the debate continues over the optimal levels of vitamin D required for human nutrition, particularly for chronic disease prevention, the National Academies report will provide a strong framework for evidence evaluation to guide policy recommendations for the general population.
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