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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 (about 1 month)

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 (5 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 (9 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

    Within multivitamin formulations, vitamin D is one fat-soluble constituent absorbed enterically then hydroxylated hepatically without inter-nutrient mechanistic modulation.

  • Small vessel disease

    Vitamin D modulates endothelial nitric oxide synthesis and blood-brain barrier integrity; deficiency exacerbates inflammatory cerebral small vessel disease.

  • Vitamin D

    Vitamin D is a secosteroid prohormone whose active metabolite calcitriol regulates calcium-phosphate homeostasis and skeletal mineralization.

News & Publications

  • 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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  • Supplemental vitamin D is linked to a 40% lower risk of Alzheimer's in cognitively healthy older adults. alz-journals.onlinelibrary.wiley.com
    Vitamin D Alzheimer's Aging Dementia Supplements

    As the global population ages and the risk of Alzheimer’s disease increases, identifying lifestyle factors that may prevent or forestall the disease is becoming increasingly important. A recent study found that people who take vitamin D supplements are 40% less likely to develop Alzheimer’s than those who don’t supplement.

    The study involved more than 12,000 cognitively healthy older adults. Researchers gathered information about the participants' vitamin D supplementation practices and whether they developed Alzheimer’s over 10 years.

    They found that participants who took any form of supplemental vitamin D (D2, D3, or D3 with calcium) had a 40% lower risk of developing Alzheimer’s than non-supplementers. This effect was more robust in women, those with normal cognition, and people without the APOE4 gene (a risk factor for Alzheimer’s).

    These findings suggest that supplemental vitamin D protects against Alzheimer’s. However, this was an observational study, so other factors might have influenced the participants' Alzheimer’s risk. For example, those who took supplemental vitamin D had higher education than those who didn’t. Research suggests that higher educational attainment is associated with a lower risk of Alzheimer’s.

    Nevertheless, vitamin D is essential for human health, and most people living in the U.S. have low vitamin D levels, potentially driving the growing number of Alzheimer’s cases. Learn more about vitamin D’s effects on the brain in this episode featuring Dr. Rhonda Patrick.

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  • Vitamin D shapes neurodevelopment, influencing the development of dopamine-producing neurons and, ultimately, the risk of schizophrenia. onlinelibrary.wiley.com
    Vitamin D Brain Pregnancy Micronutrients Mental Health Development Schizophrenia Dopamine

    Vitamin D plays a crucial role in the early development of dopamine-producing neurons, shedding light on the potential neurodevelopmental origins of schizophrenia. Abnormalities in dopamine signaling are at the heart of this complex mental health disorder, and a recent study suggests that vitamin D deficiency during pregnancy influences these pathways, increasing the risk of schizophrenia in offspring.

    Researchers examined nerve growth, synapse formation, and dopamine release in various dopamine-producing cells exposed to vitamin D over time. They focused on SH-SY5Y cells—which can mature into dopaminergic (dopamine-releasing) neurons—and other brain cells.

    They found that vitamin D increased neuron outgrowth and branching in dopaminergic cells, enhancing the production and release of dopamine. It also altered the expression and distribution of critical presynaptic proteins involved in dopamine release, further supporting its role in dopaminergic development.

    These findings suggest vitamin D is crucial for developing and maturing dopamine-producing neurons. They provide new insights into how maternal vitamin D levels might influence the risk of schizophrenia in offspring by affecting early dopamine signaling pathways. Evidence suggests that vitamin D synergizes with omega-3 fatty acids to support neurodevelopment. Learn more about this relationship in this peer-reviewed article coauthored by Dr. Rhonda Patrick.

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  • High-dose dietary vitamin D allocates excess calories to muscle growth instead of fat storage. pubmed.ncbi.nlm.nih.gov
    Vitamin D Exercise Fat Muscle

    Fat tissue produces leptin, a hormone that communicates with the brain to regulate energy balance. When fat mass increases, leptin levels in the blood also rise, signaling the brain to curb appetite and increase energy use. However, in obesity, the body’s sensitivity to leptin is reduced, blunting these regulatory effects. A recent study in mice found that vitamin D allocates excess calories to muscle growth instead of fat storage by regulating leptin and myostatin, a hormone involved in muscle growth.

    Researchers fed mice diets containing low, moderate, or high doses of vitamin D for four weeks to induce deficient, normal, and high vitamin D concentrations, respectively. Then, they measured changes in the animals' blood concentrations of leptin and myostatin and assessed their strength.

    They found that high doses of vitamin D increased leptin production and sensitivity while decreasing myostatin production. These changes elicited a greater allocation of excess calories to muscle and linear growth instead of fat storage.

    These findings suggest that high-dose vitamin D could effectively manage obesity and related conditions by redirecting calories from fat storage to muscle growth. They also highlight the interplay between vitamin D, leptin, and myostatin. Learn more about vitamin D in our comprehensive overview article.

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  • Low vitamin D status increases the risk of premature death from all causes by 97 percent. nutritionj.biomedcentral.com
    Vitamin D Mortality Blood Pressure

    Vitamin D is a steroid hormone stored in the body’s liver and fatty tissues. 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. A recent study found that people with the lowest vitamin D concentrations are 97 percent more likely to die prematurely.

    Researchers measured vitamin D concentrations in more than 19,000 adults with high blood pressure who participated in the National Health and Nutrition Examination Survey. They tracked the participants' health and dietary supplement usage for about nine years and assessed their risk of dying prematurely from all causes.

    They found that participants with vitamin D concentrations less than 25 nanomoles per liter (nmol/L) were 97 percent more likely to die prematurely, and those with concentrations between 25 and 49.9 nmol/L were 71 percent more likely. However, people with high blood pressure who took supplemental vitamin D were 25 percent less likely to die prematurely, with the greatest benefits observed with higher doses and among those without diabetes or cardiovascular disease.

    These findings from this study suggest that vitamin D supplementation reduces the risk of premature death in people with high blood pressure. Many medications accelerate vitamin D inactivation, including commonly prescribed blood pressure medications such as nifedipine and spironolactone. Learn more about vitamin D in our comprehensive overview article.

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  • Higher vitamin D levels are linked to 18 percent lower dementia risk in older adults with prediabetes. pubmed.ncbi.nlm.nih.gov
    Vitamin D Alzheimer's Diabetes Genetics Dementia

    Lifestyle and nutritional factors influence the risk of dementia, particularly among people with prediabetes – a condition characterized by elevated blood sugar levels that are not high enough to be classified as diabetes. A recent study found that higher vitamin D levels may reduce the risk of developing dementia in older adults with prediabetes.

    Researchers drew on data collected from a large cohort of more than 34,000 older adults enrolled in the UK Biobank, all of whom had prediabetes but did not have dementia at the start of the study. They measured the participants' blood vitamin D levels and monitored them for the development of dementia, including Alzheimer’s disease and vascular dementia, for approximately 12 years. Their analysis also considered genetic variations that could influence the relationship between vitamin D levels and dementia risk.

    They found that participants with higher blood vitamin D levels were 18 percent less likely to develop any type of dementia, with similar findings for Alzheimer’s disease and vascular dementia. The protective effect of vitamin D was particularly robust in participants who did not carry polymorphisms (genetic variants) related to the vitamin D receptor, highlighting a potential interaction between genetics and vitamin D levels in dementia risk.

    These findings suggest that maintaining adequate levels of vitamin D benefits brain health, especially in older adults with prediabetes, a group at elevated risk for dementia. They add to the growing body of evidence supporting the importance of vitamin D for overall health and emphasize the need for further research to understand the mechanisms behind its protective effects on the brain. Learn more about vitamin D in our comprehensive overview article.

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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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  • Vitamin D supplementation associated with a 40 percent reduction dementia risk, particularly for females and cognitively normal people.
    Vitamin D Brain Aging Dementia

    Vitamin D is a steroid hormone that plays critical roles in many physiological processes, including blood pressure regulation, immune function, and cell growth. Findings from a new study suggest that vitamin D prevents dementia. People who took vitamin D were 40 percent less likely to develop dementia than those who didn’t.

    The study involved more than 12,000 older adults who did not have dementia at enrollment. Researchers categorized the participants based on their vitamin D exposure: those exposed to vitamin D before dementia onset and those not exposed before dementia onset. They also examined different forms of vitamin D (calcium + vitamin D, cholecalciferol [D3], and ergocalciferol [D2]) to see if their effects on dementia rates varied and explored potential interactions with other risk factors for dementia, such as age, sex, education, race, cognitive function, depression, and apolipoprotein E4 (APOE4) status.

    They found that participants exposed to vitamin D had a 40 percent lower risk of developing dementia. They were also dementia-free longer than those without vitamin D exposure. These effects were evident across various forms of vitamin D. Further analysis revealed that sex, cognitive status, and APOE4 status influenced the extent of vitamin D’s effects on dementia risk. For example, females, people with normal cognitive function, and those who did not carry the APOE4 gene variant seemed to gain greater protection against dementia.

    These findings suggest that vitamin D supplementation holds promise as a preventive measure for dementia, especially for people at higher risk of developing the condition. However, more research is required to fully understand the mechanisms behind this association and establish specific vitamin D supplementation guidelines to reduce dementia risk. Learn more about vitamin D in our comprehensive overview article.

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  • Maternal vitamin D deficiency linked to potential developmental disorders, emphasizing a role in dopamine signaling. neurosciencenews.com
    Vitamin D Brain Omega-3 Neurotransmitter Schizophrenia Dopamine

    Dopamine is a neurotransmitter best known for its role in motor, motivation, and pleasure control. A new study highlights vitamin D’s influence on dopamine signaling and emphasizes its essential role in the normal development of dopamine-producing cells.

    Researchers developed three cell lines to mimic the natural process of embryonic development, during which cells differentiate (specialize) into dopamine-producing neurons. Then they cultured the cells in the presence or absence of vitamin D.

    They found that vitamin D participated in neuronal growth and branching, the rearrangement of presynaptic proteins, and the production and release of dopamine. The researchers posited that glial-derived growth factor, a vitamin D-dependent factor that promotes dopamine neuron differentiation, was the mechanism driving these effects.

    These findings suggest that vitamin D plays multiple roles in dopamine signaling, with potential implications for neurodevelopmental disorders like schizophrenia, ADHD, and autism. They also underscore the importance of adequate maternal vitamin D status during pregnancy.

    Interestingly, vitamin D and omega-3 fatty acids may synergistically work to support neurodevelopment further. Read this open-access peer-reviewed article by Dr. Rhonda Patrick to learn more.

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  • Vitamin D may boost neurodevelopment, reducing childhood behavioral problems. jamanetwork.com
    Vitamin D Brain Behavior Mental Health Development

    Although vitamin D is best known for its role in bone health, this fat-soluble vitamin participates in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Now, new research shows that vitamin D also supports neurodevelopment. Young children who received supplemental vitamin D were less likely to have neurobehavioral problems later in childhood than those who didn’t.

    Researchers gave 346 infants either low-dose (400 IU) or high-dose (1,200 IU) vitamin D daily from two weeks to two years of age. Then, when the children were between six and eight years old, their parents completed questionnaires regarding their children’s behavior, particularly internalizing behaviors, such as depression, anxiety, and withdrawal. They also collected information about the mothers' prenatal vitamin D status.

    They found that nearly 12 percent of the children on low-dose vitamin D exhibited internalizing behaviors between the ages of six and eight. However, fewer than 6 percent of those on the high-dose vitamin D exhibited internalizing behaviors, even after considering other factors that influence behavior, such as sex, maternal depression, and living in a single-parent household. Notably, 48 children in the low-dose group whose mothers had low prenatal vitamin D levels exhibited more internalizing behaviors than those in the high-dose group, suggesting that vitamin D supplementation in early childhood compensated for low prenatal exposure.

    These findings highlight yet another role of vitamin D in human health. Learn more about vitamin D in our overview article.

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  • Vitamin D may be critical in building strong muscles and combating obesity. www.biorxiv.org
    Vitamin D Obesity Muscle

    Poor strength and muscle mass are linked with many disease states, including obesity, diabetes, and chronic inflammation. A new study in mice shows that vitamin D is critical in building and maintaining muscle. Mice with higher vitamin D levels had greater strength and muscle mass and less fat mass than those with lower levels.

    Researchers fed mice three different diets over a period of 12 weeks to induce deficient, normal, and high blood concentrations of vitamin D. They measured the animals' strength and body composition before and after each dietary intervention. They also measured levels of myostatin (a hormone that inhibits muscle growth) and leptin (a hormone that maintains bodyfat stores) in the animals' blood.

    They found that vitamin D-deficient mice had poor strength and low muscle mass. Boosting vitamin D levels to normal (20-30 ng/mL) increased the animals' muscle strength but did not increase muscle mass. However, raising vitamin D to high concentrations increased both strength and muscle mass. This increase occurred without a corresponding weight increase but with a decrease in fat mass, implying that vitamin D redistributed dietary calories from fat to muscle. Higher vitamin D concentrations were associated with reductions in myostatin levels and increases in leptin levels.

    These findings suggest that high vitamin D concentrations decrease myostatin production and increase leptin production, redirecting excess calories to muscle growth instead of fat storage. Learn more about the health benefits of 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 may reduce the risk of developing Alzheimer's disease. www.sciencedaily.com
    Vitamin D Brain Alzheimer's Aging

    Taking vitamin D may prevent Alzheimer’s disease, a new study shows. People who took vitamin D were 40 percent less likely to develop Alzheimer’s disease than those who did not.

    The study involved more than 12,000 adults who were dementia-free at the time of enrollment. Participants provided information about their vitamin D intake and underwent regular cognitive evaluations over a period of 10 years.

    Even after taking other risk factors into account, such as age, sex, education, race, cognitive diagnosis, depression, and whether they carried the APOE4 gene, people who took vitamin D were 40 percent less likely to develop Alzheimer’s disease during the study period than those who did not. APOE4 carriers who took vitamin D were 33 percent less likely to develop the disease than carriers who did not. Interestingly, women were more likely than men to develop Alzheimer’s disease, but taking vitamin D countered this effect.

    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 plays critical roles 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. Evidence suggests that low vitamin D concentrations are linked with severe outcomes in COVID-19.

    The findings from this large study suggest that vitamin D protects the brain against Alzheimer’s disease. The researchers did not measure the participants' blood vitamin D concentrations, so they could not identify cutoffs that define risk. However, the Endocrine Society has determined that vitamin D concentrations less than 20 ng/mL (50 nmol/L) define “deficiency,” and concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency.” They also recommend widespread testing for at-risk populations. Learn more about vitamin D in our overview article.

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  • Vitamin D deficiency may cause the brain to age faster. www.valleycentral.com
    Vitamin D Brain Aging

    According to findings from a recent study, the brains of people with vitamin D deficiency age faster than those with adequate vitamin D levels. This is particularly true for males.

    Researchers measured blood vitamin D concentrations in the blood of more than 1,800 healthy adults. Then they scanned the participant’s brains to assess their brain aging. They calculated the participants' brain age based on chronological age and brain volume.

    They found that participants with vitamin D deficiency (which the researchers defined as less than 16.08 nanograms (ng) per milliliter (ml) for the purposes of this study) were more likely to have accelerated brain aging, as evidenced by lower total brain and gray matter volumes. Interestingly, the association between low vitamin D concentrations and older brain age was only statistically significant for male participants.

    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 plays critical roles in many physiological processes. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including osteoporosis, multiple sclerosis, and cancer.

    Although the researchers that conducted this study used 16.08 ng/ml as the cutoff for vitamin D deficiency, public health experts and physicians disagree regarding the appropriate cutoffs and terminology that define vitamin D status. Learn more about vitamin D in our overview article.

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  • High vitamin K1 intake cuts hip fracture hospitalizations by nearly half. pubs.rsc.org
    Vitamin D Aging Vitamin K

    Women with the highest vitamin K1 intake were nearly half as likely to require long-term hospitalization due to hip fracture compared to women with the lowest intake, a recent study shows. Those with higher vitamin K1 intake were nearly one-third less likely to experience any kind of fracture that required hospitalization.

    Researchers tracked hip fractures among more than 1,300 older women (70 years and older) living in Australia for about 15 years. They also assessed the women’s vitamin K1 intake using food frequency questionnaires and measured their blood vitamin D concentrations.

    They found that nearly 11 percent of the women experienced a hip fracture and 28 percent experienced any type of fracture that required hospitalization during the study period. When compared to women with the lowest vitamin K1 intake, those with the highest intake were 49 percent less likely to require hospitalization due to hip fracture and were 31 percent less like to require hospitalization due to any type of fracture. This was true regardless of the women’s vitamin D status.

    Vitamin K is a fat-soluble vitamin that participates in blood clotting, bone metabolism, prevention of blood vessel mineralization, and regulation of various cellular functions. The body has limited vitamin K storage capacity, so the body recycles it in a vitamin K redox cycle and reuses it multiple times. Naturally occurring forms of vitamin K include phylloquinone (vitamin K1) and a family of molecules called menaquinones (vitamin K2). Vitamin K1 is synthesized by plants and is the major form of vitamin K in the diet.

    The findings from this study suggest that vitamin K1 is essential for bone health in older women and underscore the importance of adequate dietary intake of this essential nutrient. The study investigators noted that just one or two servings of vitamin K1-rich foods daily were sufficient to achieve levels high enough to protect against fracture. Sources of vitamin K1 include kale, Swiss chard, spinach, and other green leafy vegetables.

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  • Vitamin D may protect against dementia and cognitive impairment. apple.news
    Vitamin D Brain Alzheimer's Dementia

    People with higher brain concentrations of vitamin D were 25 to 33 percent less likely to develop dementia or cognitive impairment, a recent study has found. Those with higher vitamin D concentrations also performed better on tests of cognitive function than those with lower concentrations.

    The study involved 290 participants enrolled in the Rush Memory and Aging Project who had undergone regular physical and cognitive assessments when they were alive and agreed to donate their brains for study upon their deaths. Researchers measured concentrations of vitamin D in four regions of the participants' brains and reviewed the participants' cognitive assessments.

    They found that higher brain concentrations of vitamin D were associated with 25 to 33 percent lower odds of having dementia or mild cognitive impairment at the last assessment before death. Participants with higher vitamin D concentrations had better word recall, working memory, episodic memory, and perceptual speed – the ability to compare similarities and differences quickly and accurately among sets of letters, numbers, objects, pictures, or patterns.

    The findings from this study suggest that vitamin D is neuroprotective. 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 plays critical roles in many physiological processes. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Learn more about vitamin D in our overview article.

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  • Osteoporosis therapy consisting of estrogen, vitamin D and calcium reduced prevalence of severe periodontitis in postmenopausal women by 44%. (2017) www.sciencedaily.com
    Vitamin D Hormones Inflammation Estrogen Calcium

    From the article:

    In the Menopause article “Association between osteoporosis treatment and severe periodontitis in postmenopausal women,” 492 postmenopausal Brazilian women aged 50 to 87 years, 113 in osteoporosis treatment and 379 not treated, were evaluated to determine whether osteoporosis treatment could help increase the bone mineral density in their jaws and, subsequently, improve overall oral health.

    The study found that the rate of occurrence of severe periodontitis was 44% lower in the postmenopausal osteoporosis-treatment group than in the untreated group. Treatment consisted of systemic estrogen alone or estrogen plus progestin, as well as calcium and vitamin D supplements, for a minimum of six months.

    “Osteoporosis can occur throughout the body, including the jaw, and lead to an increased risk of periodontal disease,” says Dr. JoAnn Pinkerton, NAMS executive director.

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  • A meta-analysis of more than 884 studies (RCTs) finds omega-3, folic acid and CoQ10 among the micronutrients that reduce cardiovascular risk. (2022) www.sciencedaily.com
    Vitamin D Vitamin C Omega-3 Melatonin Magnesium Curcumin Selenium Folate Zinc Polyphenol Carotenoids Cardiovascular Supplements

    Omega-3 fatty acids, folic acid, and CoQ10 reduce the risk of cardiovascular disease.

    Some nutritional components benefit cardiovascular health, but others have no effect on cardiovascular health or may even harm it, according to a recent study. Nutritional components providing the greatest benefit include omega-3 fatty acids, folic acid, and coenzyme Q10 (CoQ10), a vitamin-like compound produced in the body.

    Researchers analyzed the findings of more than 880 trials involving more than 880,000 participants that investigated the benefits of various macronutrients, micronutrients, and bioactive compounds on cardiovascular health.

    They found that the nutritional components had varied effects on cardiovascular health. For example, while omega-3 fatty acids, folic acid, and CoQ10 reduced the risk of cardiovascular disease, selenium and vitamins C, D, and E had no effect on the risk for either cardiovascular disease or type 2 diabetes (which often coincides with cardiovascular disease). On the other hand, beta-carotene (a vitamin A precursor) increased the risk of death from all causes. The researchers did not investigate the effects of the various nutritional components in combination versus alone.

    This analysis demonstrates that nutrition plays important roles in maintaining cardiovascular and metabolic health and supports the findings of large, epidemiological studies that have demonstrated that adherence to dietary patterns that are rich in omega-3 fatty acids, folic acid, and CoQ10, such as the Mediterranean Diet, for example, improves cardiometabolic health.

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  • Vitamin D deficiency increases the odds of all-cause mortality by 25%, a mendelian randomization study suggests. (2022) doi.org
    Vitamin D Cancer Mortality Cardiovascular

    From the publication:

    Participants: 307 601 unrelated UK Biobank participants of White European ancestry (aged 37 to 73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25-(OH)D) and genetic data.

    Measurements: Genetically predicted 25-(OH)D was estimated using 35 confirmed variants of 25-(OH)D. All-cause and cause-specific mortality (cardiovascular disease [CVD], cancer, and respiratory) were recorded up to June 2020.

    Results: There were 18 700 deaths during the 14 years of follow-up. The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped, and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases. Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L.

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  • Vitamin D and estradiol may synergistically help protect against metabolic syndrome. (2019) www.sciencedaily.com
    Vitamin D Hormones Cholesterol Estrogen Triglycerides Blood Pressure Blood Sugar Metabolic Syndrome

    From the article:

    Metabolic syndrome has emerged as a major public health concern, affecting 30% to 60% of postmenopausal women worldwide.

    […]

    The cross-sectional study included 616 postmenopausal women aged 49 to 86 years who were not taking estrogen and vitamin D/calcium supplements at the beginning of the trial. It concluded there was a positive correlation between vitamin D and estradiol.

    Specifically, higher vitamin D was associated with a favorable lipid profile, blood pressure, and glucose level. Estradiol was negatively associated with cholesterol, triglycerides, and blood pressure. These results suggest a synergistic role of vitamin D and estradiol deficiency in developing metabolic syndrome in postmenopausal women.

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  • Low vitamin D levels promote brain aging. www.sciencedirect.com
    Vitamin D Brain Aging

    Low vitamin D levels promote brain aging and loss of brain volume and gray matter.

    A recent study found that the brains of people with low vitamin D levels age faster. Having high vitamin D levels may protect the brain, however.

    Researchers measured vitamin D levels and reviewed MRI brain studies of more than 1,800 adults to identify associations between vitamin D levels and total brain, gray matter, and hippocampal volumes. They found that having low vitamin D levels was closely tied to brain aging. As vitamin D levels decreased, total brain and gray matter volumes decreased as well, particularly in males.

    Between the ages of 30 and 40 years, the connections between cells in a person’s brain begin to diminish, causing the brain to shrink in volume. The rate of shrinkage increases as a person reaches the age of 60, impairing thinking, memory, and executive function. The loss of brain volume is a hallmark of Alzheimer’s disease.

    These findings suggest that vitamin D plays a role in protecting the brain from the effects of aging. Vitamin D plays many other roles in human health. Learn more about vitamin D in our overview article.

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  • Several environmental and lifestyle factors can lower testosterone levels. (2020) www.tandfonline.com
    Vitamin D Diet Obesity Sleep Hormones Stress Magnesium Testosterone Zinc Polyphenol Oxidative Stress

    From the publication:

    Many factors, including external, environmental and internal factors, influence testosterone levels. The impact of energy intake derived from a testosterone-boosting diet depends on a human body mass. In the case of people of healthy body mass, insufficient energy intake may result in a reduction in testosterone levels in men. The same energy deficit in obese people, may, in turn, result in a neutral or positive impact on the levels of the hormone. Undoubtedly, nutritional deficiency, and particularly of such nutrients as zinc, magnesium, vitamin D, together with low polyphenols intake, affects the HPG [hypothalamic–pituitary–gonadal] axis. The levels of mental and oxidative stress can also adversely impact the axis. The higher the cortisol levels in a human body, or the higher its daily fluctuation, the lower the testosterone levels. What is more, the effect seems to be strengthened by excessive body weight, which is related to the increased oxidative stress affecting the functions of the Leydig cells. Other factors which might disrupt testosterone synthesis may be the length and quality of sleep. Even though the issue is relatively unknown, it appears that both sleep deprivation (shorter than five hours) and low quality of sleep (sleeping with the light on, sleeping during the day, under the influence of alcohol) impact the testosterone levels negatively.

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  • Vitamin D deficiency increases mortality risk in the UK Biobank, Mendelian randomization study finds. (2022) www.sciencedaily.com
    Vitamin D Mortality

    From the publication:

    Published in Annals of Internal Medicine, the study found that the more severe the vitamin D deficiency, the greater the risk of mortality.

    […]

    “Our study provides strong evidence for the connection between low levels of vitamin D and mortality, and this is the first study of its kind to also include respiratory disease related mortality as an outcome.

    […]

    The Mendelian randomization study evaluated 307,601 records from the UK Biobank. Low levels of vitamin D were noted as less than <25 nmol/L with the average concentration found to be 45.2 nmol/L. Over a 14-year follow up period, researchers found that the risk for death significantly decreased with increased vitamin D concentrations, with the strongest effects seen among those with severe deficiencies.

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  • Meta-analysis of clinical trials did not find any evidence to support beneficial effect of vitamin D supplementation on testosterone levels. (2019) doi.org
    Vitamin D Hormones Testosterone

    From the publication:

    In this systematic review and meta‐analysis of RCTs, vitamin D supplementation had no significant effect on TT [total testosterone] and SHBG in men. In term of intervention, treatment duration (<16 or ≥16 weeks), type of prescription (weekly or daily), daily doses of vitamin D supplementation (<3,000 IU/day or ≥ 3,000 IU/day) and baseline 25(OH)D [40 nmol/L or lower or higher than 40 nmol/L] and TT [total testosterone] levels confirmed the null finding in total analysis. Our results are consistent with the current systematic review (Trummeret al., 2018), which found conflicting results about the effect of vitamin D supplementation on TT in men in RCTs and observa‐tional studies.

    […]

    The main outcome of this study reaffirmed the null effect of vitamin D supplementation on TT and SHBG in men. To solve this problem in the future, we recommend further studies that consider the effect of vitamin D over a longer period in men with hypogonadism and severe vitamin D deficiency.

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  • Claimed associations between vitamin D deficiency and low testosterone could reflect nonbiological correlations, meta-analysis suggests. (2021) onlinelibrary.wiley.com
    Vitamin D Hormones Testosterone

    From the publication:

    Eligibility criteria for the study selection were (i) observational case-control studies involving men with 25(OH)D <20 ng/mL (cases) and ≥20 ng/mL (controls) (ii) availability of mean ± standard deviation (SD) of total testosterone levels in both groups.

    […]

    Overall, at the pooled estimate of eighteen carefully selected case-control studies, vitamin D deficiency was associated with a slight, albeit just significant, decrease in circulating total testosterone levels but the result was burdened with a large between‑study heterogeneity. Noteworthy, when studies were grouped according to health-related characteristics of the populations under investigation, a significant positive association between 25(OH)D and testosterone levels, along with a noticeable decrease in heterogeneity, could only be demonstrated in studies of patients with frailty states, including men with advanced age and/or documented chronic comorbidities. This indicated that the significant association arising from the overall analysis reflected the inclusion of studies on frail series. In the sub-group of studies carried out in ‘non-frail’ populations, besides the loss of the statistical significance in the association between lower 25(OH)D and lower testosterone, a large between-study heterogeneity persisted. […] Taken together these data suggest that the claimed association between vitamin D deficiency and low testosterone could reflect nonbiological correlations due to similar distributions of shared risk factors and confounders.

    […]

    Further studies are warranted to elucidate a possible direct clinical contribution of Leydig cell dysfunction to vitamin D deficiency in men with frailty states related to chronic illnesses.

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  • In overweight men with vitamin D deficiency, testosterone levels increased significantly after taking 3320 IU of vitamin D daily for one year. (2011) pubmed.ncbi.nlm.nih.gov
    Vitamin D Obesity Hormones Testosterone

    From the publication:

    Healthy overweight men undergoing a weight reduction program who participated in a randomized controlled trial were analyzed for testosterone levels. The entire study included 200 nondiabetic subjects, of whom 165 participants (54 men) completed the trial. Participants received either 83 μg (3,332 IU) vitamin D daily for 1 year (n = 31) or placebo (n =2 3). Initial 25(OH)D concentrations were in the deficiency range (< 50 nmol/l) and testosterone values were at the lower end of the reference range (9.09-55.28 nmol/l for males aged 20-49 years) in both groups. Mean circulating 25(OH)D concentrations increased significantly by 53.5 nmol/l in the vitamin D group, but remained almost constant in the placebo group. Compared to baseline values, a significant increase in total testosterone levels (from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l; p < 0.001), bioactive testosterone (from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l; p = 0.001), and free testosterone levels (from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l; p = 0.001) were observed in the vitamin D supplemented group. By contrast, there was no significant change in any testosterone measure in the placebo group. Our results suggest that vitamin D supplementation might increase testosterone levels. Further randomized controlled trials are warranted to confirm this hypothesis.

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  • Low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke, genetic analyses suggest causal effect unisa.edu.au
    Vitamin D Brain Aging Dementia

    Vitamin D deficiency is associated with the development of dementia.

    Vitamin D is a fat-soluble vitamin that plays critical roles 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, cancer, and COVID-19. Evidence from a recent study suggests that vitamin D deficiency is associated with the development of dementia.

    Health experts disagree on the terminology and cutoffs used to determine vitamin D status. The Institute of Medicine (IOM) has determined that serum vitamin D concentrations less than 30 nmol/L (less than 12 ng/mL) place people “at risk for vitamin D deficiency”; those ranging from 30 to 50 nmol/L (12 to 20 ng/mL) place some populations “at risk for inadequacy”; and those of 50 nmol/L (20 ng/mL) or greater are considered “sufficient.” However, the Endocrine Society has suggested that vitamin D concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency,” and those less than 20 ng/mL (50 nmol/L) define “deficiency.”

    The study involved more than 425,000 healthy adults (ages 60 to 73 years) enrolled in the UK Biobank study who had undergone magnetic resonance imaging (MRI) studies to assess brain volumes and whose vitamin D status was known. The investigators categorized the participants according to their vitamin D status based on literature and Institute of Medicine and Endocrine Society Clinical Practice guidelines. They collected information about the participants' demographics, lifestyles, and various health factors and tracked the participants for approximately 10 years. Then they used Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population, to identify causal links between vitamin D status and brain health, dementia, and stroke.

    They found that lower total brain volume tended to reflect a higher rate of dementia and stroke. The participants with low vitamin D concentrations were more likely to have lower brain volumes, an increased risk for dementia and stroke, and more white matter hyperintensities (brain lesions that indicate small vessel disease) than those with high concentrations. Vitamin D conferred the greatest protection against dementia at concentrations of 50 to 74.9 nmol/L. The Mendelian randomization revealed that participants whose concentrations were less than 25 nmol/L were 54 percent more likely to develop dementia.

    These findings suggest that low vitamin D increases a person’s risk for dementia. The authors suggested that as many as 17 percent of dementia cases might be prevented by achieving vitamin D sufficiency (50 nmol/L). Learn more about the beneficial health effects of vitamin D in our overview article.

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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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  • Vitamin D supplementation may improve cardiorespiratory fitness and muscle strength (randomized controlled trial, n=74) pubmed.ncbi.nlm.nih.gov
    Vitamin D Exercise Muscle Aerobic Strength Supplements

    From the abstract:

    Cardiorespiratory fitness and muscle strength were measured before and after supplementation through maximal treadmill tests and dynamometry, respectively. Wilcoxon tests were used to compare intragroup results and the Mann-Whitney test to examine intergroup differences. There was an increase in the serum concentration of vitamin D in participants who ingested the supplementation. Cardiorespiratory fitness improved after supplementation through increases in the values of maximum oxygen consumption of 28% (p < .001). Muscle strength in left hand grip increased 18% in participants who received the supplement (p = .007). Sixty days of cholecalciferol supplementation improved cardiorespiratory fitness and upper limb muscle strength.

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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 and magnesium co-supplementation improves behavior and mental health in children with ADHD. bmcpediatr.biomedcentral.com
    Vitamin D ADHD Magnesium

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral condition. Characterized by inattention and/or hyperactive or impulsive behavior that interferes with functioning, learning, or development, ADHD affects as many as 7 percent of children and nearly 3 percent of adults worldwide. Findings from a study published earlier this year suggest that vitamin D and magnesium co-supplementation improves behavior and mental health in children with ADHD.

    A growing body of evidence suggests that nutritional inadequacies play critical roles in neurobehavioral and neuropsychiatric conditions, including ADHD, autism spectrum disorder, bipolar disorder, and schizophrenia. A common feature of these disorders is dysfunction of the body’s serotonin pathway. Serotonin is a neurotransmitter and hormone produced in the brain. It regulates social cognition (how people interact socially) and influences decision making. Serotonin levels are often diminished in people who have neurobehavioral or neuropsychiatric disorders.

    Vitamin D is a steroid hormone produced in the body in response to ultraviolet light exposure. Its synthesis relies on the activity of six enzymes that catalyze the various reactions in the pathways that activate or deactivate the vitamin. Ultimately, these enzymes modulate the extent of vitamin D-dependent gene expression in the body as well as vitamin D’s participation in various biological pathways. All of these enzymes are magnesium dependent, and evidence suggests that magnesium deficiency impairs vitamin D metabolism. Vitamin D influences serotonin synthesis via its actions on tryptophan hydroxylase 2, a rate-limiting enzyme involved in serotonin production. Interestingly, scientists have identified several tryptophan hydroxylase 2 gene variants associated with ADHD.

    The marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also play roles in serotonin pathways. EPA increases serotonin release by reducing certain types of prostaglandins (proinflammatory molecules). DHA modulates serotonin action by increasing cell membrane fluidity, promoting serotonin receptor accessibility.

    The Endocrine Society classifies “sufficiency” as 30 nanograms per milliliter (ng/ml) or higher (40 to 60 ng/ml is “optimal”); “insufficiency” as 21 to 29 ng/ml; and “deficiency” as less than 20 ng/ml. Based on these classifications, approximately 70 percent of people living in the United States have vitamin D insufficiency and 40 percent have deficiency. In addition, dietary intake of marine omega-3 fatty acids is low. Robust evidence suggests that poor vitamin D status and suboptimal intake of omega-3s contribute to serotonin pathway dysfunction, ultimately contributing to the pathophysiology of neurobehavioral and neuropsychiatric disorders.

    The authors of the present study conducted a randomized, double blind, placebo-controlled clinical trial involving 66 children (6 to 12 years of age) who had been diagnosed with ADHD. Half of the children received both 50,000 IU of vitamin D weekly plus 6 milligrams per kilogram of body weight per day of magnesium for eight weeks. The other half of the children received a placebo. The children’s parents completed questionnaires regarding the children’s mental health before and after the intervention.

    At the end of the eight-week period, serum vitamin D and magnesium concentrations were markedly increased in the children who received the supplemental vitamin D and magnesium, compared to those who received the placebo. In addition, the children who received the supplemental vitamin D and magnesium exhibited fewer emotional, behavioral, and social problems, compared with the children who received the placebo.

    These findings suggest that co-supplementation with vitamin D and magnesium improves behavior and mental health among children with ADHD. This was a small study, however, so further well-designed studies with larger sample sizes are needed to confirm these effects.

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  • Co-supplementation with magnesium and vitamin D aids weight loss, improves mood, and reduces systemic inflammation. pubmed.ncbi.nlm.nih.gov
    Vitamin D Obesity Inflammation Depression Magnesium IL-6

    For decades, deficiencies in micronutrients such as magnesium and vitamin D have been linked to conditions such as depression and obesity, as well as their associated hallmarks of systemic inflammation. These observations raise questions about whether certain nutritional inadequacies might play a causal role in these conditions and whether supplementation may help regulate symptom severity. Now, a recent randomized double-blind placebo-controlled clinical trial reveals that co-supplementation with magnesium and vitamin D significantly decreases depression scores and body weight in healthy women with obesity.

    The study recruited 102 women with obesity (body mass index, 30–40; ages, 20-45 years) with mild-to-moderate depression and no indication of other health issues such as hormonal dysfunction, autoimmune disease, or diabetes. The study investigators randomly allocated the women to one of four groups to receive varying combinations of a weekly soft gel containing 50,000 international units (IU) of vitamin D, a daily tablet of 250 milligrams magnesium, and/or a placebo. The groups comprised:

    1) Co-supplementation: weekly vitamin D + daily magnesium

    2) Vitamin D only: weekly vitamin D + daily magnesium placebo

    3) Magnesium only: daily magnesium + weekly vitamin D placebo

    4) Control: weekly vitamin D placebo + daily magnesium placebo

    The investigators collected participants’ blood samples at baseline and following eight weeks of supplementation. The samples revealed that while the women on average had adequate baseline serum levels of magnesium and borderline-adequate levels of vitamin D, their health outcomes and biomarkers nonetheless showed the greatest improvements as a result of co-supplementation with both micronutrients. For instance, women who received both magnesium and vitamin D lost more weight over the duration of the intervention compared to all the other groups, in the absence of any observed changes in their dietary patterns. They also showed the greatest average reduction in depression scores over time, although all participants (including controls) exhibited some degree of symptom relief after the eight-week intervention - an observation the researchers attributed in part to the placebo effect.

    The women’s blood samples revealed a similar picture, with co-supplementation outperforming all other conditions (although individual supplementation with either vitamin D or magnesium still yielded significant improvements over controls). For instance, combining magnesium and vitamin D achieved the greatest reduction in plasma levels of pro-inflammatory tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6). It also generated the highest boost in brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1) – a protein widely known for its involvement in regulating autophagy and longevity-promoting genes.

    These findings reveal that co-supplementation with a weekly 50,000 IU dose of vitamin D and a daily 250 mg of magnesium can aid weight loss, enhance mood, and improve a host of blood biomarkers pertaining to systemic inflammation, brain functioning, and longevity. Moreover, the fact that positive health outcomes can be observed despite an absence of marked micronutrient deficiencies raises the possibility that current medical guidelines on adequate ranges of plasma levels and RDAs for vitamin D and magnesium, respectively, may be insufficiently high for optimal health outcomes.

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  • Vitamin D improves outcomes among breast cancer survivors. www.newswise.com
    Vitamin D Breast Cancer

    Breast cancer is the most common cancer in women worldwide, with nearly 2.6 million new cases diagnosed in 2020. Robust evidence demonstrates that nutritional factors may mediate the risk of many types of cancer. Findings presented at the annual conference of the American Society of Clinical Oncology suggest that vitamin D status influences outcomes among breast cancer survivors.

    Vitamin D is a fat-soluble vitamin stored in the liver and fatty tissues. It plays key roles in several physiological processes. Research suggests that vitamin D exerts anti-cancer properties through its effects on the regulation of cell growth.

    The current study involved nearly 4,000 women with breast cancer who were enrolled in the Pathways Study, an ongoing investigation of breast cancer survivorship. The study presenters measured vitamin D concentrations (measured in nanograms per milliliter, ng/ml) in blood samples collected from the women at the time of diagnosis. They categorized the women’s status as deficient (< 20 ng/ml), insufficient (20 to < 30 ng/ml), or sufficient (≥30 ng/ml) and then conducted a statistical analysis to determine if vitamin D status was related to the women’s survival. They also looked at factors that could influence vitamin D status, such as genetic variants, body mass index, race/ethnicity, and supplemental vitamin D intake.

    They found that women categorized as having sufficient vitamin D concentrations had better survival outcomes than women categorized as deficient. Supplemental vitamin D intake, body mass index, and race/ethnicity had the greatest influence on vitamin D concentrations, and genetic variants had only a minor influence. Black women had the lowest vitamin D concentrations among the cohort, possibly contributing to their poorer outcomes following breast cancer diagnosis.

    Although these findings have not been peer-reviewed, they suggest that vitamin D status influences outcomes among breast cancer survivors and underscore the need for further research to assess the roles that vitamin D plays in cancer.

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  • Vitamin D deficiency increases addictive behaviors. www.eurekalert.org
    Vitamin D Addiction

    Opioid use disorder is defined as a problematic pattern of opioid use that leads to serious impairment or distress. It has emerged as a public health crisis in the United States, affecting as many as two million people aged 12 years and older. A multifaceted approach to reducing opioid use disorders involves targeting preventable environmental factors in addition to restricting opioid prescriptions. One group of researchers investigated the effects of vitamin D status on reward-seeking behaviors like opioid use and sunlight exposure in mice.

    Opioid drugs are highly addictive due to their effects on the reward-seeking centers in the brain. Previous research suggests sunbed tanning may be addictive in ways similar to effects of opioids. Exposure to ultraviolet (UV) light causes the skin to produce vitamin D. It also induces the production of beta-endorphins, which are natural opioids with addictive properties. Humans' UV light-seeking behavior may have developed as an evolutionary strategy to maintain adequate vitamin D levels. Whether vitamin D status has an effect on UV light-seeking or prescription opioid-seeking behavior is unclear.

    To assess the relationship between vitamin D levels and opioid use disorder, the authors analyzed data from the National Health and Nutrition Examination Survey (NHANES), a long-term study collecting lifestyle and health data from participants in the United States. To determine the effects of vitamin D deficiency on opioid reward sensitivity, opioid-seeking behavior, and pain, the researchers performed multiple experiments with normal mice, mice without functioning vitamin D receptors, and mice without functioning opioid receptors.

    Compared to NHANES participants with normal serum vitamin D levels (greater than 20 nanograms per milliliter), those with insufficient vitamin D levels (12 to 20 nanograms per milliliter) were 1.27 times more likely to have opioid use disorder. Participants with vitamin D deficiency (less than 12 nanograms per milliliter) were 1.62 times more likely to have opioid use disorder. In mice, vitamin D deficiency increased the rewarding and pain-relieving effects of UV exposure through altered gene expression in key brain regions. Finally, vitamin D deficiency sensitized mice to the pain-relieving and rewarding effects of opioid drugs, while restoring vitamin D levels to normal decreased both UV-seeking and opioid-seeking behavior.

    The authors concluded that the addictive effects of sunlight exposure may be an evolutionary strategy to maintain adequate vitamin D levels and that opioid-seeking may be a consequence of vitamin D deficiency. Their results imply that obtaining and maintaining adequate vitamin D levels through UV light exposure or supplementation may help prevent or treat opioid use disorder.

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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 supplementation and sunlight improve athletic performance. www.ncbi.nlm.nih.gov
    Vitamin D

    Vitamin D regulates over 900 genes in the body that affect the immune, musculoskeletal, and endocrine systems, among others. Previous research has shown that vitamin D deficiency may decrease athletic performance. A study published in early 2020 in soccer players demonstrates the importance of maintaining year-round adequate vitamin D levels for athletes.

    Estimates suggest that 60 percent of outdoor and 64 percent of indoor athletes may have insufficient vitamin D levels (defined as less than 30 ng/ml), which may impair aerobic capacity and muscle recovery. High-dose supplementation of 5,000 IUs per day has been associated with increased vertical jump height and decreased sprint times.

    Twenty-eight professional soccer players completed the study, which took place in three stages from January to September. In January, all players completed 10 days of sun exposure while training in Cyprus (latitude of 34 degrees north, 33 degrees east). Next, half of the players consumed 6,000 IU of vitamin D per day for 6 weeks and half consumed a placebo. In September at the end of the season, the researchers measured changes in serum vitamin D, serum testosterone, body composition, sprint times, and leg power compared to January.

    The authors reported that both sun exposure and supplementation increased serum vitamin D levels, serum testosterone levels, and muscle mass, and decreased 5-meter sprint times. However, they noted that most players did not achieve high levels of vitamin D (greater than 50 ng/ml) by September, which may have affected their results.

    The authors concluded that vitamin D insufficiency is a problem among athletes, even following summer sun exposure at southern latitudes. They recommended year-round supplementation to support optimal vitamin D status and maximize athletic performance.

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  • High-dose vitamin D booster therapy reduces the risk of death among COVID-19 patients. www.mdpi.com
    Vitamin D COVID-19

    A growing body of evidence suggests that vitamin D plays a critical role in preventing and treating COVID-19. Observational data demonstrate that people who take vitamin D regularly are 34 percent less likely to develop COVID-19. Findings from a recent study show that high-dose vitamin D booster therapy reduces the risk of death among COVID-19 patients.

    The retrospective, cross-sectional observational study involved 986 COVID-19 patients admitted to two hospitals in the United Kingdom (Royal Preston Hospital and University Hospitals of Leicester) over a period of approximately seven months in 2020. The authors of the study categorized the patients according to their vitamin D status: replete (> 50 nmol/L), insufficient (25 to 50 nmol/L), or deficient (< 25 nmol/L), and whether they received high-dose vitamin D booster therapy or not.

    The average age of the participants at Royal Preston Hospital was 76 years, and their average vitamin D levels were 45 nmol/L (insufficient). The average age of the participants at University Hospitals of Leicester was 70 years, and their average vitamin D levels were 43 nmol/L (insufficient). A total of 151 of the patients received vitamin D booster therapy; 66 percent of these received 40,000 IU weekly, and 32 percent received 20,000 IU weekly.

    The data from this observational study indicated that those who received vitamin D therapy were 87 percent less likely to die from COVID-19, regardless of their baseline vitamin D levels. Clinical trials using varying vitamin D doses and frequencies are critical to determining whether vitamin D is indeed causal in the fight against COVID-19. Some randomized controlled trials have shown that weekly and daily vitamin D doses are protective against respiratory infections but single monthly doses are not. Furthermore, inter-individual variation in response to vitamin D supplementation is fairly common. In a sample of 35 healthy young people given 8,000 IU of vitamin D, 14 were high responders, 11 were mid responders, and 10 were low responders

    The time and circumstances surrounding administration are important, too. For example, one recent study involving just 208 COVID-19 patients found no benefit when seriously ill patients received vitamin D roughly 10 days after symptom onset in conjunction with other treatments, including dexamethasone. The FMF team has identified several flaws in this study’s design and implementation.

    First, the patients who received vitamin D had more pre-existing conditions (obesity, high blood pressure, and diabetes) than the patients who received the placebo at baseline, so one would expect these patients to have worse outcomes, regardless of supplementation. In addition, there is considerable discordance between the primary endpoints: More of the patients who received vitamin D died, but fewer were admitted to the ICU or were ventilated, an anomaly that suggests the caregivers were not blinded and were biased to undertreat the vitamin D group.

    Perhaps the greatest flaw is how underpowered the study is. With a sample size of only 208 participants, the authors of the study would have 80 percent power to detect a 50 percent difference in hospital length-of-stay. Setting the bar such that hospitalization stays need to be cut in half for vitamin D to be deemed successful is unrealistic. Even if vitamin D supplementation did cut hospitalization in half, there is still a 20 percent chance the study would not show it. (For comparison, millions of people are prescribed low dose “baby” aspirin to prevent a major coronary event despite the fact that 265 people would have to be treated in order for just one person to actually benefit from it.)

    Finally, title of the article is incorrect. As explained in this article in Nature, studies never prove the null hypothesis, they only reject or fail to reject it. In this study, the null hypothesis is that there is no difference in outcome between vitamin D and a placebo. Because the findings in this study did not reach statistical significance, it failed to prove there is a difference but did not prove that there was no difference.

    A randomized controlled trial to investigate the prophylactic use of vitamin D for reducing COVID-19-associated hospitalization and mortality (VIVID Trial) is currently underway and is still recruiting participants. This type of trial may be the best hope for proving the clinical benefit of vitamin D in COVID-19 since people would take vitamin D before illness occurs. Hospital-based treatment trials are challenging because patients are already very sick, and it may be too late for vitamin D to be protective.

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  • Vitamin D is a cost-effective means to reduce the number of cancer deaths. febs.onlinelibrary.wiley.com
    Vitamin D Cancer

    Cancer is the second leading cause of death worldwide, claiming the lives of nearly 10 million each year. As the number of cancer drugs has increased in recent years, so too have the costs associated with their use. Findings in a recent report indicate that vitamin D may reduce the number of cancer deaths, saving thousands of dollars.

    The authors of the study drew on data regarding age- and sex-specific cancer deaths in the German Center for Cancer Registry. They estimated the costs of cancer treatment and years of living lost in people over the age of 50 years since most cancer deaths occur in this age group and because most vitamin D trials are conducted in older adults. They also estimated the costs of vitamin D supplementation and summarized the findings from three recent meta-analyses investigating the effects of vitamin D supplementation on cancer deaths.

    The authors estimated that the end-of-life cancer costs in Germany were more than $48,000 USD per patient, but the cost of vitamin D supplementation $30 USD per year. They estimated that 1,000 IU of vitamin D daily would reduce cancer deaths in Germany by 13 percent, or about 30,000 lives, at a savings of more than $308 million USD.

    These findings suggest that vitamin D is a cost-effective means to reduce cancer deaths, especially among older adults. Learn how vitamin D slows epigenetic aging – a driver of cancer – in this episode featuring Dr. Steve Horvath.

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  • Regular use of supplemental vitamin D reduces the risk of developing COVID-19. academic.oup.com
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays key roles in several physiological processes, including immune function. Research indicates that people who take supplemental vitamin D are less likely to have acute respiratory tract infections. Findings from a new study suggest that regular use of supplemental vitamin D reduces the risk of developing 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 in COVID-19.

    The study involved nearly 8,300 adults enrolled in the UK Biobank study who had been tested for COVID-19. The investigators collected information about the participants' demographics and health status, use of vitamin D supplements (as well as other vitamins), and circulating vitamin D levels.

    The authors found that people who took vitamin D regularly (daily or weekly) tended to be older, have better overall health, and to take other supplements. They also had higher levels of circulating vitamin D. Notably, they were 34 percent less likely to develop COVID-19 compared to people who did not take vitamin D.

    Although this was an observational study and causation cannot be established, these findings suggest that regular vitamin D supplementation is beneficial in reducing the risk of developing COVID-19. The authors posited that the protective effects of vitamin D are attributable to the vitamin’s capacity to maintain cell junctions to reduce the risk of infection; enhance cellular innate immunity; or modulate the renin-angiotensin-system.

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  • Vitamin D supplementation improves cognitive function and lengthens telomeres in people with mild cognitive impairment. pubmed.ncbi.nlm.nih.gov
    Vitamin D

    Some scientists have proposed mild cognitive impairment as a transitional stage before the development of Alzheimer’s disease, one of the most common causes of dementia. Epidemiological evidence suggests that vitamin supplementation may support cognitive function. New research demonstrates reduced oxidative stress and improved cognition after 12 months of vitamin D supplementation.

    Current evidence suggests that lifestyle factors like diet influence the progression of cognitive decline by increasing or decreasing oxidative stress that damages the brain. Previous studies have demonstrated the association between telomere length, a marker of DNA integrity, and mild cognitive impairment or Alzheimer’s disease progression. Vitamin D supplementation has been shown to improve working memory; however, the mechanisms that drive these improvements are unknown.

    The randomized placebo-controlled study involved 183 participants who had mild cognitive impairment. Approximately half of the participants took 800 international units of vitamin D daily for one year, and the remainder took a placebo. The authors of the study assessed the participants' cognitive function and measured key biomarkers, including telomere length and markers of oxidative stress.

    Participants who took vitamin D performed significantly better on tests of cognitive function. Supplementation also increased telomere length and decreased markers of oxidative stress in the blood.

    The authors believe their findings are consistent with previous studies demonstrating the protective effects of vitamin D in the brain. The optimal dose of vitamin D is unknown and likely varies between individuals, limiting the ability to interpret these results. The authors also noted that blood markers of oxidative stress may not be a reliable measure of the brain environment. Future research should include more participants and a longer length of supplementation.

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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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  • Vitamin D reduces the risk of developing high blood pressure among children of women with preeclampsia. www.sciencedaily.com
    Vitamin D Pregnancy

    Preeclampsia is a condition characterized by high blood pressure during pregnancy. The condition typically manifests around the 20th week of pregnancy and carries considerable risk to both the mother and infant. Children of women who had preeclampsia during pregnancy are more likely to develop high blood pressure in childhood or adolescence. Findings from a recent study suggest that vitamin D reduces the risk of developing high blood pressure among children of women with preeclampsia.

    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 skeletal health, vitamin D also plays roles in aspects of cardiovascular health, including the regulation of blood pressure.

    The authors of the analysis drew on data from the Boston Birth Cohort, a large, prospective cohort study that included more than 750 mother-child pairs. They collected data regarding maternal preeclampsia, childhood and adolescent systolic blood pressures (from multiple readings), and cord blood vitamin D concentrations, as well as maternal demographics, smoking status, and pre-pregnancy body mass index, a proxy for body fatness.

    They found that the children of women who had preeclampsia during pregnancy were more likely to have higher systolic blood pressure in early childhood and/or adolescence. However, higher cord blood vitamin D concentration – an indicator of higher vitamin D exposure in the womb – negated this effect.

    These findings suggest that maternal vitamin D levels in women who have preeclampsia during pregnancy influence whether their children develop high blood pressure. Clinical trials investigating the efficacy of vitamin D supplementation in women with preeclampsia and long-term follow-up of their children are needed to confirm.

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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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  • High-dose vitamin D reduces blood pressure variability among adults age 60 years and older. academic.oup.com
    Vitamin D

    High blood pressure is a major cause of disease and death worldwide. A person’s blood pressure varies throughout the day in response to changes in physical and mental activities, sleep, and other stimuli. High variability may increase a person’s risk for cardiovascular disease. Findings from a new study suggest that high-dose vitamin D reduces blood pressure variability.

    Vitamin D is a steroid hormone that participates in many aspects of human health, including regulation of the renin-angiotensin-aldosterone system, an endocrine system that plays key roles in blood pressure control. Some evidence suggests that vitamin D deficiency increases a person’s risk for high blood pressure.

    The randomized, double-blind trial involved 250 men and women over the age of 60 years who were enrolled in a larger study of people with arthritis. Half of the participants received high dose (2000 IU) vitamin D3 and the other half received a standard dose (800 IU) daily for 24 months. The participants monitored their blood pressure at home, checking it every 20 minutes during the day and every hour during their sleep, using a home-based ambulatory monitor.

    Over the two-year period, both groups of participants experienced minor reductions in their systolic blood pressures. But those taking the high dose vitamin D saw improvements in their blood pressure variability. Unfortunately, this study did not have a placebo group, so determining whether vitamin D reduces blood pressure is not possible.

    These findings demonstrate that vitamin D supplementation may be useful in reducing blood pressure variability, but more research is needed to confirm.

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  • Vitamin D supplementation reduces risk of developing vertigo. www.aan.com
    Vitamin D Supplements

    Vitamin D is a steroid hormone that plays critical roles in many aspects of human health. Findings from a new study suggest that vitamin D supplementation reduces the risk of developing vertigo in people who are deficient.

    Vertigo is a condition characterized by the false sensation of movement, such as spinning, swaying, or tilting. The most common form of vertigo is benign paroxysmal positional vertigo (BPPV), which affects roughly one-third of all adults at least once in their lifetime. BPPV is caused when small stones called canaliths, which are located in the inner ear, dislodge and move into the semicircular canals – the area of the ear that regulates balance. The typical treatment for BPPV involves canalith repositioning maneuvers, also known as Epley maneuvers, a strategy used to relocate the inappropriately positioned canaliths.

    The randomized controlled trial involved nearly 1,000 adults with confirmed BPPV who had undergone successful canalith repositioning maneuvers. Approximately half of the participants were randomly assigned to receive 400 IU of vitamin D and 500 milligrams of calcium carbonate twice a day for a year if their serum vitamin D level was lower than 20 ng/ml – a level considered deficient. The other half of the participants simply received follow-up care with no supplementation. The primary outcome was the annual recurrence rate of BPPV.

    At the end of the study, participants who took the supplemental vitamin D and calcium were 24 percent less likely to develop BPPV than those who did not. Even greater reductions were seen in participants whose vitamin D levels were 10 ng/mL or less, with a 45 percent reduction in incidence. Slightly more than one-third of the participants who took the supplements had another episode of vertigo, but nearly one-half of those in the observation group had one.

    These findings demonstrate that vitamin D and calcium supplementation may be beneficial in preventing vertigo, especially among people who are vitamin D deficient.

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  • Severe vitamin D deficiency in people with COVID-19 associated with greater risk of death than those with normal levels. pubmed.ncbi.nlm.nih.gov
    Vitamin D COVID-19

    Severe vitamin D deficiency in people with COVID-19 associated with greater risk of death than those with normal levels.

    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 plays critical roles in immune function. Recent evidence suggests that vitamin D deficiency is associated with poor outcomes in COVID-19. Findings from a new study suggest that poor vitamin D status increases the risk of death from COVID-19.

    The authors of the retrospective, observational study analyzed data collected from 42 patients with acute respiratory failure due to COVID-19 who were treated in Bari, Italy, during a six-week period during the spring of 2020. The authors of the study classified the patients according to their vitamin D status: normal, insufficient, moderate deficiency, or severe deficiency. According to the Endocrine Society, vitamin D concentrations less than 20 ng/mL (50 nmol/L) define “deficiency,” and concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency.”

    They found that 81 percent of the patients had low vitamin D status. After ten days of of hospitalization, patients with severe vitamin D deficiency were 50 percent more likely to die, while those with vitamin D levels greater than or equal to 10 ng/mL had a 5 percent chance of death.

    These findings indicate that severe vitamin D deficiency may predict poor prognosis in patients with poor vitamin D status, suggesting that adjunctive treatment that involves vitamin D repletion might improve disease outcomes. Learn more about the role of vitamin D in COVID-19 in this clip featuring Dr. Rhonda Patrick.

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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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  • A randomized controlled trial finds that magnesium is important for modulating vitamin D levels by both increasing and lowering them. www.sciencedaily.com
    Vitamin D Magnesium Vitamin A Dairy

    Participants that were low in vitamin D at the start of the clinical trial were able to successfully raise the levels of the major form of circulating vitamin D (25-hydroxyvitamin D3) if they took a magnesium supplement along with their vitamin D supplement. Surprisingly, participants that had high 25-hydroxyvitamin D3 levels at the start of the trial actually lowered their levels to a more normal range after supplementing with magnesium and vitamin D.

    Both in vitro and animal studies have indicated that magnesium deficiency affects enzymes which synthesize and metabolize vitamin D metabolites.

    Based off of recent NHANES data ~45% of the US population does not meet the daily requirement for magnesium which is 310 mg/day for adult females and 400 mg/day for adult males.

    Magnesium is found at the center of a chlorophyll molecule which is what is responsible for giving plants their green color. That should make it obvious that leafy greens are a great source of magnesium. One cup of cooked spinach contains 156 mg.

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  • VITAL study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer www.eurekalert.org
    Vitamin D Cancer Heart Disease Omega-3 Vitamin A

    Finally, the highly anticipated result of the VITAL Study are in - at least for the major endpoints CVD and cancer.

    While at first sight they may seem disappointing and have already prompted the usual, overgeneralizing negative reports from many media outlets, there are some remarkable findings if you look more closely - such as a whopping 77% reduced risk for heart attacks in African Americans taking fish oil (all those media who are now sweepingly reporting that fish oil dies “not reduce CVD”, without mentioning this, such as MdMag*, musk ask themselves whether they are looking at the results through racist glasses, as the investigators certainly didn’t make a secret of this remarkable finding).

    With regard to vitamin D, the results certainly don’t support the strong effect on cancer risk suggested by some observational studies, but there seems to be a modest effect building up over time, and given the fact that 2000 IU is a rather modest dose indeed and not expected to raise the blood level by more than 10 ng/ml, the jury is far from out on vitamin D and cancer.

    Anyway, this is a very high quality trial providing the researchers with a treasure-trove of data that will be subject to many auxillary studies. I’m particularly curious about the upcoming studies regarding autoimmune and mental health endpoints.

    *https://www.mdmag.com/conference-coverage/aha-2018/vital-study-supplements-of-omega3s-or-vitamin-d-do-not-reduce-cvd-or-cancers

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  • Supplemental Vitamins and Minerals for CVD Prevention and Treatment - ScienceDirect www.sciencedirect.com
    Vitamin D Vitamin C Vitamin E Vitamin B12 Calcium Vitamin A Dairy

    Hi Rhonda,

    First off, I’m a big fan and I love your podcasts. The one thing I’m not such a fan of though, is the supplement craze.

    Do you have any comments on this study? By the looks of it, the only supplement worth taking is folic acid and B-vitamins (which is something I am considering, since I rarely eat meat).

    In my mind, if you predominantly eat plant-based wholefoods (vegetables, berries and fruits, legumes, grains, nuts and seeds in that order), molluscs every now and then (once a month-ish) (and I do eat a bit of egg and cheese on occasions), is supplementation really necessary or even desired?

    I’m a mid-twenties guy, who exercises a lot (stretching/yoga and running everyday, weights/calisthenics 3-6days/wk and intervals 2days/wk) and I strive to “optimize” my health and fitness (although I do feast on junk in social occasions every blue moon). I intermediate fast every day, every now and then I do a 2-4 day fast, and I meditate daily). Do you have any recommendations for other healthy habits I could implement? Sorry for the digression, I’d be happy with just an answer in regards to the study :)

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  • women with blood levels of vitamin D in the 60 ng/ml range had an 80% lower breast cancer risk compared to women with less than 20 ng/ml. www.sciencedaily.com
    Vitamin D Breast Cancer Vitamin A

    A pooled analysis of randomized controlled trials and prospective studies finds that women with blood levels of vitamin D in the 60 ng/ml range had an 80% lower breast cancer risk compared to women with less than 20 ng/ml.

    Another randomized controlled trial found that men given 4,000 IU of vitamin D per day slowed cancer progression and improved tumors in men with low-grade prostate cancer (compared to men given placebo).

    In a 2009 paper published in the Annals of Epidemiology by the authors of this study, they recommended vitamin D levels between 40 to 60 ng/ml based on lowest all-cause mortality data.

    Many factors regulate how much vitamin D3 a person makes from UVB exposure from the sun. These factors include geographic location/time of year since some northern latitudes do not get UVB exposure certain times of the year, how much pigmentation a person has since melanin acts as a natural sunscreen and blocks UVB radiation, age since the aging process makes the production of vitamin D3 from the sun much less efficient, body fat since vitamin D3 is less bioavailable to mobilize from the skin into the bloodstream with increasing fat mass, and other factors such as sunscreen and time spent in the sun.

    The best way to know how much vitamin D to supplement with is to get a blood test before and after supplementation.

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  • A vitamin D supplement containing the active form prevented autism is mice that were engineered to be predisposed. www.sciencealert.com
    Vitamin D Serotonin Autism Vitamin A

    A supplement containing the active form of vitamin D was shown to prevent autistic-like behaviors in mice that are predisposed to them. The active vitamin D was given to pregnant mice during the first trimester and this prevented deficits in social interaction, basic learning, and stereotyped behaviors. While this study did not find a mechanism, I published a study in 2014 suggesting that low maternal vitamin D may increase the risk of autism because vitamin D controls the production of serotonin. Serotonin acts as a brain morphogen during early brain development and it shapes the structure and wiring of the developing brain. Low brain serotonin during development has also been linked to autism. It is unclear what maternal vitamin D levels are optimal but I like to shoot for levels between 40-60 ng/ml based on all-cause mortality studies. Levels above 30 ng/ml are considered sufficient. I like to measure vitamin D levels even after supplementation to make sure that I am getting the right amount (not too low or high). I take between 2,000 IU to 4,000 IU of vitamin D3 per day, depending on the season.

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