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Vitamin D

Vitamin D featured article

Introduction

Vitamin D is a fat-soluble vitamin that is stored in the liver and fatty tissues of the body. Perhaps best known for its role in maintaining calcium balance and bone health, vitamin D is critical in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer.

Vitamin D is a controversial topic in the scientific community and has contributed to much debate regarding terminology, testing, optimal blood concentrations, repletion strategies (including dose, frequency, and vitamer), and outcomes.

This article provides an overview of a wide range of topics related to vitamin D, including its biosynthesis, recommended intakes, mechanisms, and physiological actions.

Biosynthesis of vitamin D is a multi-step process.

Unlike other vitamins – trace nutrients that...

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Episodes

vitamin d

Why Vitamin D Deficiency Accelerates Brain Aging

Posted on May 13th 2025 (7 days)

Dr. Rhonda Patrick discusses a study that found vitamin D supplementation was associated with a 40% lower risk of dementia.

vitamin d

What's the Optimal Level of Vitamin D?

Posted on January 22nd 2025 (4 months)

In this clip, Drs. Rhonda Patrick and Peter Attia discuss vitamin D sources, optimal levels, and supplementation challenges.

vitamin d

More People Would Supplement With Vitamin D If They Knew THIS

Posted on September 30th 2024 (8 months)

In this clip, Dr. Rhonda Patrick discusses vitamin D insufficiency, sun vs. supplements, and the roles of magnesium and vitamin K.

Topic Pages

  • Multivitamins

    Multivitamin and multimineral supplements are used by nearly one-third of adults to improve health and mitigate disease risk.

  • Small vessel disease

    Small vessel disease is a generic term that describes dysfunction of blood vessels that occurs with aging and contributes to cognitive decline, cardiovascular disease, frailty, and stroke.

  • Vitamin D

    Vitamin D is a hormone that plays critical roles in many physiological processes, such as blood pressure regulation, immune function, and cell growth.

News & Publications

  • Exercise doesn't just release vitamin D from fat stores—it potentially alters the hormone's metabolism and offers a route to restore vitamin D availability in obesity, where supplementation often falls short. www.technologynetworks.com
    Vitamin D Exercise Obesity

    Vitamin D, a fat-soluble nutrient, is sequestered in adipose tissue, limiting its circulation—an effect amplified in obesity. Obese adults, for example, exhibit a 57 % smaller rise in circulating vitamin D₃ after whole-body ultraviolet exposure and are more than half as likely to reach sufficient vitamin D levels than normal-weight adults. Against this backdrop, the VitaDEx randomized trial showed that ten weeks of indoor exercise during winter sharply attenuated seasonal vitamin D loss and fully preserved its active hormone, 1,25(OH)₂D₃—without weight loss or supplementation.

    • Active hormone maintained: Exercise fully prevented the winter decline in 1,25(OH)₂D₃, while controls experienced a 15 % drop. (The precursor 25-hydroxy-vitamin D fell only 15 % in exercisers versus 25 % in sedentary controls.)
    • Adipose sequestration puzzle: Contrary to expectations, adipose vitamin D concentrations remained largely unchanged. “Exercise did not drive a greater decrease in adipose tissue concentrations of vitamin D…there was no correlation between the change in serum 25(OH)D and changes in adipose vitamin D₃ concentrations.”
    • Mechanistic pivot: Researchers suggested possible transient vitamin D mobilization, depot-specific effects, or direct metabolic adaptations improving vitamin D efficiency. They speculated that regular physical activity might enable “more ‘efficient’ vitamin D metabolism, making better use of the available substrate to generate the active metabolite without tipping the balance into a negative feedback loop.”

    Taken together, the findings indicate exercise is not merely releasing vitamin D from fat stores; it is altering the flux and enzymatic handling of the hormone, offering a route to restore endocrine availability where supplementation often fails in obesity.

    Press Release: Regular Exercise Helps Maintain Vitamin D Levels During Winter
    Study: Exercise without Weight Loss Prevents Seasonal Decline in Vitamin D Metabolites: The VitaDEx Randomized Controlled Trial

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  • Nearly half of people with type 2 diabetes have multiple micronutrient deficiencies—the most common being vitamin D. nutrition.bmj.com
    Vitamin D Diabetes Micronutrients Magnesium Vitamin B12 Insulin Metformin

    Micronutrient deficiencies contribute to insulin resistance, a key driver of type 2 diabetes, but researchers still don’t fully understand their role in the disease’s progression. A recent study found that nearly half of people with type 2 diabetes suffer from multiple micronutrient deficiencies, with vitamin D being the most prevalent.

    Researchers analyzed data from studies investigating links between micronutrient deficiencies and type 2 diabetes. Their analysis included 132 studies and more than 52,000 participants.

    They found that 45% of people with type 2 diabetes had multiple micronutrient deficiencies. Women with the disease were more likely to have deficiencies, with 48% affected compared to 41% of men. Vitamin D deficiency was the most common, affecting 60% of participants, followed by magnesium (42%) and vitamin B12 (28%)—the latter being especially prevalent among people with type 2 diabetes who were taking metformin. The prevalence of deficiencies also varied by region.

    These findings suggest that micronutrient deficiencies are widespread in people with type 2 diabetes, particularly among women. Check out our many resources on micronutrients, including vitamin D and magnesium, and the long-term health consequences of deficiencies.

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  • Vitamin D promotes tooth remineralization, reducing the risk of cavities. www.ncbi.nlm.nih.gov
    Vitamin D Inflammation Dental

    Tooth decay – a risk factor for cavities and tooth loss – often begins as white spots on the enamel, an early sign of demineralization. Strategies that promote tooth remineralization can reduce the need for invasive dental procedures. A 2022 study found that vitamin D promotes tooth remineralization, potentially reducing the risk of cavities.

    Researchers gave 40 healthy adults vitamin D supplements (1,000 IU) for six weeks. They collected saliva samples from the participants at the beginning of the intervention and again at the third and sixth weeks. They exposed healthy, extracted teeth to an acidic solution to mimic the changes in pH that normally occur in the mouth in response to foods and beverages, causing demineralization. Then, they exposed the teeth to the saliva samples for 12 hours and assessed their mineral content, a measure of hardness.

    They found that the amount of calcium and phosphorus in the teeth decreased considerably after exposure to the acidic solution – an indicator of demineralization. However, both minerals increased in the teeth after exposure to saliva collected from participants taking vitamin D.

    These findings suggest that vitamin D promotes tooth remineralization, potentially reducing the risk of cavities. They also align with other findings showing that vitamin D helps treat gingivitis (gum disease), a major cause of tooth loss.

    Vitamin D is a fat-soluble vitamin and hormone that participates in many physiological processes, including calcium balance, blood pressure regulation, immune function, and cell growth. Poor vitamin D status drives the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Learn more about vitamin D in our comprehensive overview article.

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  • Vitamin D increases muscle strength and mass without altering body weight in mice. www.biorxiv.org
    Vitamin D Obesity Aging Metabolism Hormones Muscle

    Vitamin D, best known for maintaining calcium balance and bone health, is critical in many physiological processes, including blood pressure regulation, immune function, and cell growth. Evidence now suggests vitamin D also influences body composition and muscle strength. A recent study in mice showed that high vitamin D intake increased muscle strength and mass without altering body weight.

    Researchers fed mice one of three diets, providing low, normal, and high doses of vitamin D for four weeks to achieve deficient, insufficient, and sufficient vitamin D concentrations, respectively. At the end of the fourth week, they assessed the animals' grip strength (a measure of muscle function) and body composition.

    They found that compared to low or normal vitamin D intake, high intake increased grip strength and lean mass and decreased fat mass without altering the animals' weights. High intake also impaired myostatin production and increased the animals' leptin sensitivity and energy expenditure without altering their activity levels.

    Leptin is a satiety hormone that signals the brain to balance energy. When body fat increases or decreases, blood concentrations of leptin change accordingly. Higher leptin levels signal the brain to reduce hunger and boost energy use. However, in obesity, the body becomes less responsive to leptin, dulling its effects on appetite and energy expenditure.

    These findings suggest that vitamin D influences body composition and metabolism by preferentially allocating calories toward muscle development and overall growth rather than fat storage. They also highlight the intricate relationship between obesity and vitamin D status. Learn more about vitamin D in our comprehensive overview article.

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  • Exercise, vitamin D, and cognitive training boost cognitive function. link.springer.com
    Vitamin D Exercise Brain Aging Dementia

    Changes in brain function and connectivity often occur many years before the clinical manifestation of cognitive impairment and dementia. A new study shows that lifestyle modifications, including exercise, vitamin D intake, and cognitive training, improve functional brain connectivity in older adults with mild cognitive impairment.

    The study involved 120 older adults (ages 60 to 80 years) with mild cognitive impairment. The participants engaged in 30 minutes of cognitive training and 60 minutes of exercise three times a week for 20 weeks. Thirty-eight of the participants received vitamin D supplements, while the remainder received a placebo. Researchers measured the participants' functional brain connectivity using MRI before and after the interventions.

    They found that physical exercise alone, exercise combined with cognitive training, or exercise combined with both cognitive training and vitamin D supplementation increased functional brain connectivity in regions of the brain’s default mode network, including the hippocampus and angular gyrus.

    The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.

    This study’s findings suggest that lifestyle behaviors, particularly exercise, enhance functional brain connectivity, potentially staving off age-associated cognitive decline. Learn more about the effects of exercise on the brain in this episode featuring Dr. Axel Montagne.

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  • Vitamin D protects against high glucose-induced pancreatic β-cell dysfunction via AMPK- NLRP3 inflammasome pathway pubmed.ncbi.nlm.nih.gov
    Vitamin D Insulin

    Vitamin D protects pancreatic beta cells in type 2 diabetes.

    Chronic inflammation is a principal driver of many of the pathological processes that accompany type 2 diabetes, a metabolic disorder characterized by hyperglycemia (high blood glucose) and subsequent pancreatic beta cell dysfunction. Findings from a recent study suggest that vitamin D blocks activation of the NLRP3 inflammasome, preventing inflammation-driven impairment of pancreatic beta cells.

    The NLRP3 inflammasome is a large, intracellular complex that plays critical roles in immune function. Its activation triggers the release of the proinflammatory proteins interleukin (IL)-1 beta and IL-18, promoting inflammation and cell death. People who have type 2 diabetes exhibit upregulated NLRP3 inflammasome activation. However, AMP-activated protein kinase (AMPK), an enzyme that participates in metabolic regulation, blocks NLRP3 activation.

    The investigators conducted a three-part study. First, they evaluated the vitamin D status of 399 adults with type 2 diabetes and 78 healthy adults. There was no significant difference in vitamin D status between the two groups. Although males tended to have higher vitamin D concentrations than females, vitamin D deficiency was common among both sexes, with approximately 80 percent of males deficient and 91 percent of females deficient. The investigators then assessed the participants' beta cell function following a meal. They found that higher vitamin D concentrations were associated with greater beta cell function, but this correlation was seen in males only.

    In a second experiment, the investigators fed rats either a normal diet or a high-glucose diet (designed to induce beta cell dysfunction) for five weeks. They supplemented half of the rats in both diet groups with vitamin D. At the end of five weeks, they found that among rats that ate the high-glucose diet, those that received vitamin D had lower blood glucose levels than those that did not. The rats that received vitamin D also had greater insulin secretion – an indicator of healthy beta cell function.

    Finally, they conducted an in vitro experiment to evaluate the effects of vitamin D on INS1e cells, a well-established model for studies of pancreatic islet beta cell function. They found that vitamin D inhibited hyperglycemia-induced NLRP3 activation and IL-1 beta production, leading to lower levels of inflammation. Further investigation revealed that vitamin D upregulated AMPK production in the cells, which likely contributed to the reduction of inflammation.

    These findings suggest that vitamin D inhibits NLRP3 activation via enhanced AMPK production, thereby reducing inflammation due to high blood sugar in mice with type 2 diabetes. Learn more about the beneficial effects of vitamin D in our overview article.

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  • New research identifies critical differences between the two types of vitamin D, with vitamin D2 having a questionable impact on human health. www.sciencedaily.com
    Vitamin D Immune System Autoimmunity

    Vitamins D2 and D3 exert differing effects on the human immune system.

    Scientists have identified five forms of vitamin D, but the two primary forms relevant to human health are ergocalciferol, commonly referred to as vitamin D2 (produced by invertebrates), and cholecalciferol (produced by mammals), commonly referred to as vitamin D3. Prescription vitamin D supplements in the United States typically provide D2, but over-the-counter dietary supplements and fortified foods typically provide D3. Considerable controversy exists regarding the bioequivalence of D2 and D3. Findings from a recent study suggest that D2 and D3 exert differing effects on the human immune system.

    Vitamin D modulates both innate and adaptive immune responses via its interactions with immune cells, including antigen presenting cells, B cells, and T cells. Evidence suggests that people with vitamin D deficiency are at greater risk of viral infection and autoimmune disorders. This is in keeping with the widely held belief that a principal role of vitamin D is to restrain, or balance, immune system activity.

    The study was part of a previous randomized placebo-controlled trial involving healthy white European and South Asian females who received 15 micrograms (600 IU) of vitamin D2 or D3 every day for 12 weeks during the winter months, when sun exposure was limited. Participants also consumed vitamin D-fortified foods (orange juice and tea biscuits) daily. The investigators used microarray analysis to measure changes in 97 of the participants' blood transcriptome (the full range of RNA molecules an organism produces) and weighed the changes against any influence of ethnic background.

    They found that while the effects of both D2 and D3 showed some overlap, the two forms of the vitamin showed distinct differences in terms of changes to gene expression. In particular, D3 switched off the activity of genes involved in the regulation of the innate and adaptive immune systems. The investigators posited that these changes could make the immune system more tolerant and therefore less likely to promote autoimmunity. They also noted that vitamin D3 (and not D2) had a dramatic effect on genes involved in activation of interferon, which plays important roles in providing protection against pathogens and cancer. The investigators' analysis revealed that some of the variation in overall gene expression was likely due to ethnic differences among the participants.

    These findings suggest that vitamins D2 and D3 exert differing effects on the human immune system, with D3s effects modulating tolerance and immunoreactivity. They also may have relevant implications for supplementation with vitamin D.

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  • More evidence having poor vitamin D status before infection increases COVID-19 severity and death risk. www.eurekalert.org
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays key roles in several physiological processes, including immune function. Robust evidence demonstrates links between poor vitamin D status and severe outcomes following infection with SARS-CoV-2, the virus that causes COVID-19. Now, findings from a recent study suggest that poor vitamin D status prior to infection with SARS-CoV-2 increases the risk of severe disease and/or death from COVID-19.

    During an infection, vitamin D deficiency can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes, such as acute respiratory distress syndrome and death in COVID-19. Research suggests that supplemental vitamin D during hospitalization with COVID-19 improves outcomes. Vitamin D levels may drop during a viral infection, however, so measuring pre-infection status provides a more accurate assessment of the vitamin’s protective effects.

    The authors of the study reviewed the medical records of 253 patients whose vitamin D levels had been measured two weeks to two years prior to testing positive for COVID-19. They categorized the patients according to disease severity (critical, severe, moderate, or mild). They classified the patients' vitamin D status as deficient, below 20 nanograms per milliliter (ng/ml); insufficient, 20 to 29.9 ng/ml; adequate, 30-39.9 ng/ml; or high-normal, above 40 ng/mL.

    They found that patients categorized as having critical or severe COVID-19 disease were 14 times more likely to have pre-infection vitamin D deficiency than patients with moderate or mild disease. Patients with vitamin D deficiency were more likely to have coexisting illnesses, such as diabetes, high blood pressure, and chronic obstructive pulmonary disease and were 11 times more likely to die from COVID-19, compared with those who had vitamin D sufficiency.

    These findings suggest that pre-infection vitamin D deficiency markedly increases the risk of critical or severe disease and death in patients with COVID-19. Learn more about the importance of vitamin D in COVID-19 in this episode featuring frontline physician Dr. Roger Seheult.

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  • Sunlight reduces the risk of developing early-onset multiple sclerosis. www.sciencedaily.com
    Vitamin D Multiple Sclerosis Autoimmunity

    Exposure to ultraviolet (UV) light is critical for maintaining many aspects of human health. For example, compounds present in the skin react to UV light, initiating the production of vitamin D, a steroid hormone that participates in many physiological processes. Similarly, photoreceptors in the eyes respond to UV exposure, modulating the regulation of circadian rhythms. Findings from a new study suggest that early life exposure to ultraviolet light reduces the risk of developing early-onset multiple sclerosis (MS).

    Multiple sclerosis is an autoimmune disorder characterized by the progressive destruction of myelin – the insulating sheath that surrounds nerves and facilitates neural transmission. The disease affects approximately 3 million people worldwide and is twice as likely to manifest in women than men. Symptom onset typically occurs between the ages of 20 and 50 years, but as many as [5 percent of people with MS experience early onset](https://pubmed.ncbi.nlm.nih.gov/11205364/], with symptoms manifesting during childhood or young adulthood.

    The study involved 322 children and young adults with MS (ages 3 to 22 years) and 534 healthy participants of similar ages and sexes. All the participants (or their parents) provided information about their medical history, place of residence, and sun exposure.

    The authors found that among the participants who reported having spent fewer than 30 minutes outside per day during the previous summer, 19 percent had MS, while only 6 percent did not. When they accounted for other risks associated with MS, such as smoking or being female, they found that those who spent 30 to 60 minutes outside per day were 52 percent less likely to develop MS, compared to those who spent fewer than 30 minutes outside per day.

    These findings suggest that early life UV exposure reduces the risk of developing MS. Although these findings were based on observational data and do not assign causality, the authors of the study pointed out that they align with results of other studies suggesting that low UV exposure is associated with other neurological diseases, including Parkinson’s disease, Alzheimer’s disease, and other forms of dementia. Although there is no cure for Parkinson’s disease, evidence suggests that the fasting-mimicking diet may be beneficial in treating the condition. Learn more about the fasting-mimicking diet in this episode featuring Dr. Valter Longo.

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  • Vitamin D treatment reduces the risk of severe outcomes, including death, in patients with COVID-19 www.mdpi.com
    Vitamin D COVID-19

    Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes, such as acute respiratory distress syndrome (ARDS) and death in COVID-19. Findings from a recent study suggest that supplementation with calcifediol, an intermediate molecule in the production of the active form of vitamin D, reduces the risk of death due to COVID-19.

    Unlike other vitamins – trace nutrients that must be consumed in the diet – vitamin D is a steroid hormone that is produced in the body. Its synthesis occurs in a stepwise manner that begins in the skin following exposure to ultraviolet light and ends in the kidneys with the production of 1α,25-dihydroxyvitamin D, or 1,25(OH)2D, the active steroid hormone.

    The retrospective cohort study involved 537 patients living in Spain who were hospitalized with COVID-19 during a three-month period in early 2020. Of these patients, 79 received vitamin D treatment providing 532 micrograms (~21,000 IU) of calcifediol on the first day of their hospital stay, and 266 micrograms of calcifediol (~9,300 IU) on days 3, 7, 14, 21, and 28. The primary outcome measure was death during the first 30 days of hospitalization.

    During the study period, 20 percent of patients who did not receive vitamin D treatment died. More of the patients in the untreated group had chronic kidney disease, but fewer had diabetes, cancer, high blood pressure, or other cardiovascular diseases, compared to the treated group. They also had low oxygen saturation levels and were more likely to have elevated inflammatory markers. Twenty-five percent of this group developed ARDS. Only 5 percent of those who received vitamin D treatment died, and only 10 percent of these developed ARDS, even though the patients in this group were more likely to have comorbidities (coexisting health conditions) compared to the untreated group.

    These findings suggest that vitamin D reduces the risk of severe outcomes, including death, in patients with COVID-19. The authors of the study noted that this small study was observational in design, possibly limiting the interpretation of these findings. They also noted that although none of the patients in this cohort were assessed for vitamin D deficiency, most of the people who live in southern Spain tend to be deficient during the time of year when the study was conducted.

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  • Vitamin D deficiency exacerbates inflammation and Alzheimer's pathology in mice. pubmed.ncbi.nlm.nih.gov
    Vitamin D Alzheimer's

    Currently selected for this coming member’s digest by team member Melisa B.

    Adequate exercise is one of the most effective lifestyle interventions to improve aging, but many people, especially older adults, can find it difficult to exercise. In a study published this month, researchers tested the effects of resveratrol as an adjuvant therapy to exercise for older adults with physical limitations.

    The word “adjuvant” has roots in Latin that mean “helping toward.” Adjuvant therapies are add-ons that may improve the effectiveness of other interventions. Resveratrol is known to activate mitochondria through a protein called PGC-1α, the master regulator of mitochondrial biogenesis. Therefore, resveratrol may boost the benefits of exercise by enhancing mitochondrial adaptation in skeletal muscle.

    The purpose of this randomized controlled pilot study was to determine the safety and feasibility of chronic exercise combined with resveratrol supplementation. The investigators split a group of 60 adults (average age, 71 years) with physical limitations into three groups. All three groups completed supervised walking and whole-body resistance training twice weekly for 12 weeks. One group took 500 milligrams of resveratrol daily, another took 1,000 milligrams of resveratrol daily, and the third group took a placebo. The participants completed a battery of physical function tests and gave blood so the researchers could measure markers of cardiovascular risk.

    On average, participants completed 82 percent of their exercise sessions and took 85 percent of their resveratrol doses, indicating that the intervention was acceptable for most participants. The rate of adverse events was similar between groups with an average of nine events, indicating that the intervention was safe. Pilot studies are not designed to evaluate the effect of the study intervention on health; however, the authors reported some promising early results. Participants in the 1,000 milligram group exhibited a clinically-significant increase of 449 meters in their 6-minute walk test and increased levels of citrate synthase, a common marker of mitochondrial volume.

    The authors are planning a large-scale clinical trial to build on these preliminary results.

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  • Free, circulating levels of vitamin D predict future disease risk in aging men better than measures of total vitamin D. scienmag.com
    Vitamin D

    Vitamin D plays critical roles in many physiological processes, such as calcium balance, blood pressure regulation, immune function, and cell growth. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Data from a study presented at the European Endocrine Society’s recent conference suggest that free, circulating levels of vitamin D predict future disease risk in aging men better than measures of total vitamin D.

    Vitamin D is a steroid hormone synthesized in the body in a multistep process following skin exposure to ultraviolet B light. The primary end-products in the process are 25-hydroxyvitamin D, or 25(OH)D (the major circulating form of vitamin D) and 1α,25-dihydroxyvitamin D, or 1,25(OH)2D (the active steroid hormone). The vast majority of these end-products in serum is bound to the vitamin D binding protein](https://academic.oup.com/jcem/article-abstract/63/4/954/2674725?redirectedFrom=fulltext). Total measures of 25(OH)D) and 1,25(OH)2D are associated with death rates from all causes. Some researchers have posited that only the free, unbound portion of vitamin D can exert its biological effects.

    The authors of the study drew on data from the European Male Ageing Study, which involved nearly 2,000 men between the ages of 40 and 79 years. They measured total and free levels of 25(OH)D) and 1,25(OH)2D in the men’s blood.

    They found that low total 25(OH)D) and 1,25(OH)2D levels among the men were associated increased risk of death. However, only low free 25(OH)D but not free 1,25(OH)2D levels predicted death from all causes. It’s noteworthy that this was an observational study, and the causal relationships and underlying mechanisms were not identified.

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  • Different forms of vitamin D have distinct impacts on muscle mass and strength. www.medicalnewstoday.com
    Vitamin D Muscle

    The loss of muscle mass and strength, known as sarcopenia, is a significant problem in aging, affecting both healthspan and quality of life. Findings from a recent study suggest that vitamin D affects muscle function through diverse metabolic pathways.

    Clinicians determine a person’s vitamin D status by measuring 25-hydroxyvitamin D3, or 25(OH)D3 — the inactive circulating form of vitamin D. However, a new technique, high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS), allows researchers to quantify additional vitamin D metabolites. While these other metabolites, part of what is termed the vitamin D metabolome, are present in low concentrations in the blood, they can perform critical functions in tissues, such as muscles.

    Previous research has examined the relationship between vitamin D and muscle function yielding inconsistent results; however, these studies have mainly focused on 25(OH)D3. The current study investigated whether other vitamin D metabolites are associated with muscle function.

    The cross-sectional study involved 116 healthy adults who performed handgrip and lower limb strength tests, while a subset of 85 participants consented to thigh muscle biopsies. The authors assessed the participants' vitamin D status using LC-MS/MS, steroid metabolites from urine samples, and the expression of 92 genes from the muscle biopsies. The authors also measured lean body mass and body fat percentages.

    Only 14 percent of participants had normal vitamin D levels, while 28 percent had insufficient levels, and 58 percent were found to be deficient. Subjects with a higher percent body fat had lower vitamin D levels. Participants with higher muscle mass had higher active vitamin D levels. Those with higher active, but not inactive vitamin D levels scored better on the muscle strength tests. The authors observed that the expression of 24 skeletal muscle genes correlate with levels of serum 25(OH)D3.

    These findings highlight the complex relationship between vitamin D, gene expression, and muscle function. They suggest that the maintenance of muscle mass and strength is complicated, and it may be more appropriate to measure other vitamin D forms rather than just 25(OH)D3.

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  • Low magnesium levels impair vitamin D metabolism. www.sciencedaily.com
    Vitamin D Magnesium

    Vitamin D is an essential nutrient that plays critical roles in several physiological processes. Poor vitamin D status has been implicated in the pathogenesis of many acute and chronic diseases. A 2018 review suggested that magnesium is essential for vitamin D metabolism.

    Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to pre-vitamin D. Subsequent processes in the liver and kidneys convert the pre-vitamin to calcitriol, the active form of the vitamin. The enzymes that catalyze these processes require magnesium.

    Approximately 42 percent of people living in the United States are vitamin D deficient. The authors of the review pointed out that approximately one-third of otherwise healthy adults are magnesium deficient. Although many people take vitamin D supplements, without sufficient magnesium, the body cannot properly metabolize vitamin D, promoting calcification of blood vessels, a critical factor in the development of atherosclerosis and coronary heart disease. Conversely, people whose magnesium levels are sufficiently high require less vitamin D supplementation to achieve healthy levels.

    The recommended dietary allowance for magnesium for adults between the ages of 31 and 50 years is 420 milligrams for men and 320 milligrams for women per day. According to the authors of the study, the typical American diet provides less than half of these amounts. Dietary sources of magnesium include green leafy vegetables, nuts, legumes, and fish.

    It’s noteworthy that poor vitamin D status is associated with poor outcomes in COVID-19. Listen to this clip in which Dr. Rhonda Patrick describes how vitamin D might reduce the risk of acute lung injury in COVID-19.

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  • Majority of COVID-19 patients found to be vitamin D deficient. www.medrxiv.org
    Vitamin D COVID-19

    Several factors increase the risk of death due to COVID-19, including hypertension, obesity, male sex, advanced age, living at a northern latitude, and coagulopathy. Interestingly, poor vitamin D status is associated with all of these factors. Findings from a small, retrospective study revealed that vitamin D deficiency was a common feature among the majority of COVID-19 patients with severe outcomes.

    The study involved COVID-19 patients treated in the intensive care unit (ICU) at a tertiary care academic medical center in the United States. Of 20 COVID-19 patients for whom vitamin D levels were available, 13 were treated in the ICU. Of those, 11 (nearly 85 percent) were vitamin D deficient. All of the ICU patients under the age of 75 were vitamin D deficient.

    The authors of the study noted that COVID-19-related death and vitamin D deficiency are more common among African Americans. They also suggested that vitamin D deficiency contributes to the severity of COVID-19 outcomes via impairment of the immune system and prothrombotic effects.

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  • Vitamin D can suppress cytokine storms in COVID-19 patients reducing mortality. news.northwestern.edu
    Vitamin D COVID-19

    A cytokine storm is an excessive release of pro-inflammatory molecules that occurs during severe COVID-19 and is a common cause of death. A new study suggests that vitamin D could reduce the risk of developing a cytokine storm and decrease COVID-19 mortality.

    Vitamin D is a fat-soluble vitamin that plays essential roles in numerous physiological processes including the regulation of blood pressure, calcium homeostasis, and immune function. Previous work on other coronaviruses demonstrates that vitamin D can counteract a cytokine storm by strengthening the innate immune response and inhibiting the adaptive immune system from over-responding to a viral infection. COVID-19 mortality varies across countries and age groups, with the elderly being particularly susceptible.

    Previous research has suggested a connection between vitamin D deficiency and C-reactive protein (CRP), a protein that increases in the blood in response to inflammation and infection. Furthermore, elevated blood levels of CRP are indicative of severe COVID-19. The current study used large-scale data to investigate whether there is an association between vitamin D deficiency and the severity of COVID-19.

    The authors of the study examined COVID-19 data from patients in ten countries, together with vitamin D and CRP data from previous studies. They estimated that patients with normal vitamin D levels had a 15.6 percent reduced risk of severe COVID-19 compared to patients with severe vitamin D deficiency.

    These findings suggest that vitamin D could suppress the cytokine storm in COVID-19 patients and reduce disease severity. More research is needed to determine if these findings hold true when vitamin D levels are measured directly.

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  • Poor vitamin D status prevalent among patients with acute respiratory distress syndrome. www.atsjournals.org
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays critical roles in several physiological processes, including blood pressure regulation, calcium homeostasis, and immune function. Approximately 70 percent of people living in the United States have low vitamin D levels. Findings of a study presented at a 2016 scientific conference suggested that vitamin D insufficiency is associated with increased risk for developing acute respiratory distress syndrome (ARDS).

    ARDS is a severe form of acute lung injury characterized by rapid breathing, shortness of breath, and a low blood oxygen level and can lead to respiratory failure and death. It commonly occurs with viral illnesses, including influenza and COVID-19.

    The retrospective study, which drew on data collected as part of a multicenter randomized controlled trial, involved 476 patients diagnosed with ARDS. The patients' vitamin D status was assessed upon admission to the hospital. Vitamin D levels less than 20 ng/ml were considered “low.”

    The assessments indicated that approximately 90 percent of the patients had low vitamin D levels, even when the data were adjusted for age and severity of illness. The patients with low vitamin D levels spent an average of six days longer on mechanical ventilation compared to patients with higher levels. These findings suggest that poor vitamin D status contributes to increased risk for developing ARDS and influences disease outcomes associated with ventilator needs.

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