“The sunshine vitamin D is likely to be the oldest hormone to be produced almost from the beginning of time when eukaryotes began to evolve in the oceans more than 1-1/2 billion years ago,” he wrote in a new review published in the journal Nutrients.
Flash forward to today, and the science recognizes that essentially every tissue and cell in the body not only has a vitamin D receptor but can produce 1,25-dihydroxyvitamin D3, the active form of the vitamin.
From sea creatures to rickets
Dr. Holick reports that while phytoplankton produced vitamin D2 as hormone, vitamin D3 might have first been metabolized and activated as vertebrate life forms emerged from the calcium-rich oceans onto calcium-poor land.
“During exposure to sunlight, land vertebrates would have produced vitamin D3 in their skin, which would have entered their circulation and increased the efficiency of calcium absorption,” he wrote, emphasizing the close connection between sunlight, vitamin D and calcium for maintaining a healthy skeleton.
By the 16th century, this intimate relationship was reinforced by another evolution – the migration of the population to crowded and air-polluted cities. This was accompanied by a crippling bone-deforming disorder in children (think Tiny Tim from the novel “A Christmas Carol”) that continued to spread widely from Europe to the industrialized cities of the United States into the 20th century.
“It was the deficiency of sunlight causing the devastating skeletal disease known as English disease and rickets that provided the first insight as to the relationship of sunlight and the cutaneous production of vitamin D3,” Dr. Holick wrote.
The discovery of vitamin D
On June 19, 1922, the New York Times reported that a team led by U.S. biochemist Dr. E. V. McCollum “‘captured’ a hitherto unknown vitamin, which has been labeled vitamin D, the specific purpose of which is the protection of bone growth and the prevention of the disease known as rickets.”
Over the next couple decades, science confirmed skin exposure to ultraviolet light (from the sun or artificial radiation) or ingestion of either vitamin D2 (from plant sources) or D3 (from animal sources like cod liver oil) could prevent rickets by correcting phosphate and calcium levels in the blood. It was later determined that vitamin D contributed to bone health by stimulating intestinal calcium absorption.
“Within a few years, these interventions resulted in the essential eradication of rickets in the industrialized countries,” Holick noted. “Vitamin D fortification was so popular worldwide that beer, soda pop, hot dogs, custard and even soap and shaving cream were fortified.”
Isolating the active form
In his review, Dr. Holick recounts his prominent role in the identification of the major circulating form of vitamin D3 in humans as a graduate student in Dr. Hector DeLuca's laboratory at the University of Wisconsin-Madison.
Not long after, the lab made an even bigger discovery – isolating and identifying the active hormone of vitamin D3 as 1,25-dihydroxyvitamin D3 through lipid extraction of 1,450 chicken intestines dosed with 100 IUs of vitamin D3. Dr. Holick acknowledged the contributions of the Kodicek and Norman labs towards the structural identification of this active form.
“Vitamin D coming from the skin during sun exposure or from diet first goes to the liver and then to the kidneys to get activated to 1,25-dihydroxyvitamin D,” Dr. Holick told NutraIngredients-USA. “This hormone has a receptor called the vitamin D receptor in the nucleus of most cells in the body.”
From there, it unlocks the genetic information that supports blood calcium levels, improves bone health and reduces the risk for acute and chronic illnesses, he explained.
Hoffman-La Roche, more commonly known as Roche, introduced chemically synthesized 1,25-dihydroxyvitamin D3, clinically known as calcitriol, as a FDA-approved pharmaceutical in the early 1970s.
Looking ahead
Dr. Holick points to epidemiology studies linking vitamin D deficiency with a multitude of chronic illnesses from multiple sclerosis to COVID-19 and associates a circulating concentration of vitamin D of 40-60 ng/mL with the reduction of cardiovascular disease, neurocognitive dysfunction, several cancers and infectious diseases.
“Vitamin D has by no means revealed all its biologic functions and clinical potential,” Dr. Holick added. “It is hoped that there will be a resolution for recommendations for how much vitamin D and sensible sun exposure is necessary for maximum health."
Coming up: A century of the sunshine vitamin part II
Source: Nutrients 2023, 15(3), 593
doi: doi.org/10.3390/nu15030593
“The One-Hundred-Year Anniversary of the Discovery of the Sunshine Vitamin, D3: Historical, Personal Experience and Evidence-Based Perspectives”
Author: Michael Holick