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    Features

    Vitamin D: A Fixture of Supplementation and Fortification

    The most widely-supplemented nutrient continues to prevail in large-scale studies on immunity, healthy aging, and more.

    Vitamin D: A Fixture of Supplementation and Fortification
    By Mike Montemarano, Associate Editor01.20.23
    Half of dietary supplement users have taken vitamin D in the past year thanks to recognition for its role in a plethora of human health issues. Compared to most other nutrients, adequate intake levels of vitamin D are typically rare in the Western diet.

    Certain types of people are more prone to vitamin D deficiency for a number of reasons. Obesity, insufficient exposure to sunlight, old age, higher skin concentrations of melanin, and a host of medical conditions can all affect the likelihood that someone becomes vitamin D deficient.

    While data is lacking from many countries, it is estimated that 1 billion people globally have a deficiency in vitamin D, and approximately 50% of the population is thought to have a suboptimal vitamin D intake. National Health and Nutrition Examination Survey (NHANES) data from 2005-2006 suggested that nearly half of the U.S. population (42%) had a deficiency in vitamin D.1

    Vitamin D has a primary function of bone mineralization through increasing the uptake of calcium, magnesium, and phosphorous in the intestine. Beyond the fact that vitamin D deficiency shares strong correlations with a range of chronic diseases, its wide-ranging antioxidant and inflammatory-modulating activities also suggest the vitamin may support cardiovascular health, immune function, and cancer risk.

    A significant portion of the U.S. population takes vitamin D supplements. According to the Council for Responsible Nutrition’s most recent annual consumer survey on dietary supplements, 75% of Americans used at least one dietary supplement in 2022. Vitamin D supplements were used by half (50%) of supplement users, second only to multivitamins (70%), which also often contain vitamin D.

    This represented a rise in the use of single-ingredient vitamin D supplements by 10% since 2020. Almost half (49%) of supplement users told pollsters they changed their supplement use since the pandemic began.

    Emerging Sources

    Vitamin D is found in dietary supplements in two forms: vitamin D2 (ergocalciferol) and D3 (cholecalciferol), which differ slightly in molecular structure. D3 is typically preferred as it more quickly elevates circulating vitamin D levels in the bloodstream and has a longer half-life. 

    Vitamin D3 is traditionally of animal origin, and in dietary supplements, it’s naturally present in fish oil and can be synthesized from lanolin, an oily material found in sheep’s wool.

    Up until recently, vitamin D2 was the only vegan version of vitamin D, and it is typically sourced from certain plant or mushroom species that produce it in response to UV light exposure.

    Aside from D3 being more readily absorbed by the body, there are no known drastic differences in clinical effects between the two forms of the vitamin. However, a 2022 blood analysis study published in Frontiers in Immunology found that D3 and D2 have overlapping but different effects on the human immune system, suggesting that functional equivalence shouldn’t always be assumed in studies related to bacterial and viral infections.2

    Through emerging extraction technologies, companies are seeking to gain an edge by meeting today’s consumer preference for novel plant-based alternatives and have developed methods to derive D3 from certain plant sources. Today’s supply chain disruptions may also provide further incentive to diversify sources of vitamin D, and many natural options exist alongside synthesis from lanolin.

    Ingredient supplier AIDP, for instance, offers VegD3, a vegan, organic form of vitamin D3 sourced from algae, one of the few plant sources of cholecalciferol. Recently, the company announced findings of a bioavailability study that found the ingredient raised blood concentrations of vitamin D3 at a rate which brought participants who were deficient in the nutrient to sufficient levels by the end of a seven-day intervention period.

    Meanwhile, PLT Health Solutions offers Earthlight Whole Food Vitamin D made from mushrooms. The ingredient has approval as a food additive from the U.S. FDA and Novel Foods Approval in the EU.

    Additionally, ingredient supplier ESB Development Ltd. has developed a vegan version of vitamin D3 extracted from an edible form of wild-harvested lichen. 

    There are certainly sustainable credentials and other front-of-pack quality claims to pursue for companies that stick with lanolin-based D3. For instance, Frezzor New Zealand launched a vitamin D3 supplement locally sourced from 100% grass-fed, free-range sheep in order to have full traceability of its raw material. The wool used by the company is upcycled following annual shearing of sheep’s coats.

    Research Highlights

    Research on vitamin D has continued to strengthen the nutrient’s position as a cornerstone in both the healthy aging and immune support categories.

    A 2022 study of over 300,000 participants of the U.K. Biobank found that vitamin D deficiency was a significant risk factor for all-cause mortality, cardiovascular disease mortality, and cancer mortality.3 Across the mortality risks, there was a linear correlation between vitamin D status and mortality, with benefits appearing to plateau at 75 nmol/L. The fully-adjusted odds for all-cause mortality were 36% higher for participants at 25 nmol/L compared to 50 nmol/L, the latter of which is considered sufficient.

    Another study of a U.K. Biobank population of similar size was published in 2021. Researchers analyzed vitamin D’s role specifically for the risk of developing cardiovascular disease (CVD) and CVD mortality. According to the authors, it could be inferred that the lowest blood concentrations of vitamin D in the population nearly doubled the risk of CVD compared to what was seen in the healthy control group, and there was a similar association for systolic and diastolic blood pressure.4

    For seniors, having optimal vitamin D blood concentrations is associated with significant reductions in all-cause mortality for a range of conditions. A study published in Nutrients last year on osteoarthritis patients who participated in NHANES concluded that the lowest mortality rates in a group of 4,750 occurred at blood concentrations of vitamin D of 84.5 nmol/L.5

    One of the largest interventional studies on vitamin D ever conducted, dubbed the VITAL study, was published early last year in BMJ. In this randomized, double blind, placebo controlled trial, 25,871 participants aged 55 and older took 2,000 IU of vitamin D alone or in combination with 1,000 mg of omega-3 fatty acids, or matching placebos. While vitamin D did not have a significant effect on the primary endpoint of cardiovascular outcomes, researchers found the risk of developing an autoimmune disease was reduced by 39% in the vitamin D arm of the study.6

    Awareness

    Consumer awareness campaigns continue to promote the use of vitamin D for immune support, and several studies designed to offer high-quality evidence on vitamin D and COVID-19 are still in the works.

    The Council for Responsible Nutrition (CRN) has developed a consumer resource called “Vitamin D & Me!” which provides a central place for the public to review results of 13 meta-analyses and several studies with findings on the interactions between vitamin D status/supplementation and COVID-19 outcomes. Users can browse based on observational/intervention studies, and look at specific populations, such as children, pregnant women, and seniors.

    Across the 13 meta-analyses, which were generated from more than 100 human clinical trials, most research found an association between blood concentrations of vitamin D and reduced incidence and severity of COVID-19. One meta-analysis linked vitamin D intervention following a COVID-19 diagnosis with reductions in mortality rates. 

    Data gathered from the early days of the pandemic continues to roll out, including large-scale interventional studies. One survival study appearing in Nature analyzed outcomes of 15,968 patients from Andalusia, an autonomous community near Spain, in which a prescription of vitamin D or its metabolites within 15-30 days of hospitalization were recorded. Researchers found a 33% reduction in mortality when vitamin D2 was prescribed 15 days before hospitalization, and a 25% reduction in mortality for cholecalciferol (reductions were 27% and 12%, respectively, when adjusted to 30 days before hospitalization).7

    Meanwhile, the International Alliance of Dietary Supplement Associations (IADSA) has developed its “Mind The Gap” consumer education campaign to focus on increasing the use of essential nutrition products.

    Recently, the organization led an awareness campaign about the widespread issue of micronutrient deficiency, following a recent study in The Lancet, which found that previous estimates of global malnutrition were substantial under-estimates. That publication also estimated more than half of pre-school children and over two thirds of non-pregnant women of reproductive age worldwide have at least one micronutrient deficiency.8

    The authors warned about the consequences of these micronutrient deficiencies, which include compromised immune systems, constrained physical and cognitive development in children, increased risk of diabetes and heart disease, reduced educational outcomes, and limitations on human potential. While the authors specifically looked at deficiencies in vitamin A, iron, folate, and zinc because these deficiencies can cause severe morbidity and death, deficiencies in other micronutrients also likely exist at rates well beyond what is expected. The widely held belief that 2 billion people are suffering with at least one micronutrient deficiency is likely to be a “major underestimate,” the researchers concluded.

    As a result of the research, the Global Alliance for Improved Nutrition (GAIN) and the Micronutrient Forum both called for increased fortification of popular foods with essential vitamins and minerals, biofortification of staple crops, and supplements targeting pregnant women and children.

    IADSA also called attention to recent international policy recommendations that older adults ensure adequate vitamin D and calcium intake in order to reduce the risk of fall injuries. The European Commission now has an approved health claim for vitamin D and a reduced risk of falling for men and women ages 60 and older, while the U.S. National Institute on Aging has publicly recommended adequate vitamin D and calcium intakes in order to prevent fracture risk when falling. 

    References

    1. Forrest, K. et al. (2011). Prevalence and correlates of vitamin D deficiency in U.S. adults. Nutrition Research. 31(1):48-54. doi: 10.1016/j.nutres.2010.12.001
    2. Durrant, L. et al. (2022). Vitamin D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome. Frontiers in Immunology. doi: 10.3389/fimmu.2022.790444
    3. Sutherland, J. et al. (2022). Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Nonlinear Mendelian Randomization Study. Annals of Internal Medicine. doi: 10.7326/M21-3324
    4. Zhou, A. et al. (2022). Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk. European Heart Journal. 43(18):1731-1739. doi:10.1093/eurheartj/ehab809
    5. Wang, J. et al. (2022). Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in Osteoarthritis Patients: Results from NHANES III and NHANES 2001-2018. https://doi.org/10.3390/nu14214629
    6. Hahn, J. et al. (2022). Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. https://doi.org/10.1136/bmj-2021-066452
    7. Loucera, C. et al. (2021). Real World evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients. Scientific Reports. 11, 23380. https://doi.org/10.1038/s41598-021-02701-5
    8. Stephens, G. et al. (2022). Micronutrient deficiencies among preschool-aged children and women of reproductive age worldwide: a pooled analysis of individual-level data from population-representative surveys. Volume 10, Issue 11, E1599, November https://doi.org/10.1016/S2214-109X(22)00367-9
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