New insights into the health benefits of vitamin D supplementation

In this article, Christiane Lippert (pictured), Global Product Manager, Vitamins and Delivery Systems at Lycored, discusses the role of this essential nutrient and new research that examines the value of combined vitamin D supplementation.

Vitamin D: the inside story
Vitamin D is both a fat-soluble vitamin obtained from the diet and a type of secosteroid hormone made in the body. Necessary in vertebrates to maintain normal levels of blood calcium and phosphate, it’s essential for healthy bones, teeth, muscle contraction, cellular function, metabolism and immunity.

The discovery of the vital roles that vitamin D plays in human health is inextricably linked to the story of rickets, a bone-softening disease in children that was particularly rife in the West from the 16th until the early 20th century and is still relatively common today in the Middle East, Africa and Asia.¹

By the late 1700s, cod liver oil and sunlight were both being advocated for its prevention and cure, but it was only in the 1920s that scientists identified the common curative factor as vitamin D and described the chemical structure of its two most important forms for humans: D2 (ergocalciferol) and D3 (cholecalciferol).^2,3

Vitamin D2 is derived from fungi and yeast and is found in fortified products such as breakfast cereals, margarine and plant-based milk.

Vitamin D3 can be obtained from a small range of foods of animal origin, including oily fish, cod liver oil and egg yolks, but most is synthesised in the lower layers of the epidermis when UVB rays directly strike the skin and convert cutaneous 7-dehydrocholesterol to previtamin D3.

Both vitamins D2 and D3 are biologically inactive and must be processed by the liver and kidneys to produce the active form of vitamin D: calcitriol. 

The scale of vitamin D deficiency
Vitamin D deficiency is associated with cognitive decline, depression, hypertension, cardiovascular disease, type 2 diabetes, Parkinson’s disease and cancer. Although it might seem that the easiest way to boost vitamin D levels is to ensure exposure to sunlight, it’s not quite that simple.

Limiting factors include latitude (above 35°, UVB rays are typically not intense enough to produce vitamin D all year round), chronic conditions (such as kidney disease, inflammatory bowel disease and obesity), skin pigmentation (people with darker skin synthesise less vitamin D than those with lighter complexions), cultural mores (such as wearing clothes that cover the body and face for religious reasons) and an age-related decline in the ability to efficiently synthesise vitamin D.⁴

Little wonder that an estimated one billion people worldwide are deficient in this key vitamin.⁵ The role of supplementation is therefore looking increasingly important, particularly in the light of recent research into the benefits of vitamin D — both on its own and in combination with other nutrients.

Vitamin D status alone and in combination: implications for health
A recent groundbreaking Australian study revealed a direct link between the increased risk of cognitive decline and dementia, lower brain volumes and vitamin D deficiency, with genetic analysis indicating a causal effect.

The researchers suggest that up to 17% of dementia cases might be avoidable by boosting vitamin D levels to a normal range.⁶

Meanwhile, in the first randomised study of its kind, scientists from the University of South Australia used a new genetic method to find strong evidence linking low levels of vitamin D with premature death (with the risk of death being proportionate to the degree of deficiency).⁷

Senior investigator Professor Elina Hyppönen said that “this underlined the importance of maintaining sufficient vitamin D levels throughout the year in the elderly, in those with health vulnerabilities and in those not acquiring enough vitamin D from healthy sun exposure and dietary sources.”

This supports earlier research by Mark, et al., that demonstrates that D3 slows ageing in C. elegans (nematode worms) in a dose-dependent fashion by several mechanisms, including by reducing oxidative stress, which could explain why so much human age-related disease is linked to vitamin D deficiency.⁸

Furthermore, a recent prospective trial found an association between low levels of both vitamin D and K and increased all-cause mortality risk, with the risk being greater than that found between low vitamin D or vitamin K status alone — indicating a powerful synergistic effect.⁹

Data from the China Stroke Prevention Trial also showed a significantly increased risk of ischaemic stroke in a hypertensive population with low blood levels of both vitamin D and K.¹⁰

Vitamin D has also been shown to inhibit the growth of cancer cells by regulating the genes responsible for cell proliferation, with observational studies indicating an inverse association between circulating vitamin D blood levels and total cancer risk.

Combining high-dose vitamin D3 supplements with omega-3 fatty acids, along with a simple home-strength exercise programme — as per the DO-HEALTH double-blind randomised clinical trial — showed a cumulative reduction in cancer risk in a healthy, active and vitamin D-deficient elderly cohort.¹¹

Delivering optimal dosage
One problem with vitamin D3 supplementation is that the nutrient oxidises easily, is sensitive to light and usually needs to be kept in a vacuum in the dark, which presents problems during both production and storage.

Using precision microencapsulation technology significantly reduces the deterioration of the active ingredient; in benchmarking tests with a competitor product, encapsulated Lycored Capsudar showed no loss during production and degraded by 35% during a 2-year shelf-life in a pectin gummy application (compared with 70% in the competitor product for the same period).

Lycored offers a range of Capsudar vitamin D2 and D3 products that provide the key advantages of encapsulation. These include nutrient protection, limiting interactions with other actives and, last but not least, shelf-life stability, allowing 77% lower overages compared with competitor products.

This all translates into reduced throwaways from early expiration, more convenient shipping/storage and, potentially, smaller servings for gummies or tablets owing to the lower volumes of coated material required.

Furthermore, Capsudar D2 100E costs approximately 45% less per million doses compared with one competitor offering an encapsulated product — illustrating that all encapsulation types are not equal. For those focused on softgels, Lycored also offers vitamin D2 and D3 in liquid suspensions.  

References

1. A.L Creo, et al., “Nutritional Rickets Around the World: An Update,” Paediatrics and International Child Health 37(2), 84–98 (2017).
2. J.H.L O’Riordan and O.L.M. Bijvoet, “Rickets Before the Discovery of Vitamin D,” BoneKEy Reports 3, 478 (2014).
3. G. Jones, “100 Years of Vitamin D: Historical Aspects of Vitamin D,” Endocrine Connections 11(4): e210594 (2022).
4. https://lpi.oregonstate.edu/mic/vitamins/vitamin-D/.
5. P. Lips, “Worldwide Status of Vitamin D Nutrition,” Journal of Steroid Biochemistry and Molecular Biology 121, 297–300 (2020).
6. S.S. Navale, et al., “Vitamin D and Brain Health: An Observational and Mendelian Randomized Study,” American Journal of Clinical Nutrition 116, 531–540 (2022).
7. J.P. Sutherland, A. Zhou and E. Hyppönen, “Vitamin D Deficiency Increases Mortality Risk in the UK Biobank,” Annals of Internal Medicine 175(11), 1552–1559 (2022).
8. K.A. Mark, et al., “Vitamin D Promotes Protein Homeostasis and Longevity Via the Stress Response Pathway Genes skn-1, ire-1 and xbp-1,” Cell Reports 17, 1227–1237 (2016).
9. A.J. van Ballegooijen, et al., “Combined Low Vitamin D and K Status Amplifies Mortality Risk: A Prospective Study,” European Journal of Nutrition 60, 1645–1654 (2021).
10. Y. Wei, et al., “Joint Association of Low Vitamin K1 and D Status with First Stroke in General Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT),” Frontiers in Neurology 13: 881994 (2022).
11. H.A. Bischoff-Ferrari, et al., “Combined Vitamin D, Omega-3 Fatty Acids and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial,” Frontiers in Aging 3: 852643 (2022).