Tag: vitamin D

Five Years of Vitamin D Supplements Fails to Prevent Diabetes

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Using significantly higher doses of vitamin D than recommended for five years did not affect the incidence of type 2 diabetes in elderly men and women, according to a new study from the University of Eastern Finland which appears in Diabetologia.

In population studies, low levels of vitamin D in the body have been associated with a higher risk of type 2 diabetes, but such observational studies cannot directly prove a causative link. Experimental studies have shown that the use of significantly higher doses of vitamin D than recommended slightly reduces the risk of developing type 2 diabetes in individuals with impaired glucose metabolism, ie, those with prediabetes. In contrast, no effects have been observed in individuals without prediabetes. However, the studies with non-prediabetic subjects have used relatively small doses of vitamin D or have been short-term. Until now, there has been no research data on the effects of long-term use of high doses of vitamin D on the risk of type 2 diabetes in individuals without glucose metabolism disorders.

In the Finnish Vitamin D Trial (FIND) conducted at the University of Eastern Finland from 2012 to 2018, 2 495 men aged 60 and older and women aged 65 and older were randomised for five years into either a placebo group or groups receiving either 40 or 80 micrograms of vitamin D3 per day. In the statistical analyses of the now-published sub-study, 224 participants who were already using diabetes medications at the start of the study were excluded. Comprehensive information was collected from the participants on lifestyle, nutrition, diseases, and their risk factors. Data was also obtained from national health registers. About one-fifth were randomly selected for more detailed examinations, and blood samples were taken from them.

During the five years, 105 participants developed type 2 diabetes: 38 in the placebo group, 31 in the group receiving 40 micrograms of vitamin D3 per day, and 36 in the group receiving 80 micrograms of vitamin D3 per day. There was no statistically significant difference in the number of cases between the groups.

In the more closely studied group of 505 participants, the blood calcidiol level, which describes the body’s vitamin D status, was on average 75nmol/L at the start, and only 9% had a low level, ie, below 50nmol/L. After one year, the calcidiol level was on average 100nmol/L in the group that used 40 micrograms of vitamin D per day and 120nmol/L in the group that used 80 micrograms of vitamin D per day. There was no significant change in the placebo group. The effects of vitamin D on blood glucose and insulin levels, body mass index, and waist circumference were examined during the first two years of the study, but no differences were observed between the groups.

The findings of the FIND study reinforce the view that the use of higher doses of vitamin D than recommended does not significantly affect the risk of developing type 2 diabetes in individuals without prediabetes and who already have a good vitamin D status. So far, there is no research data on whether high doses of vitamin D can be beneficial in preventing type 2 diabetes in individuals without prediabetes but with vitamin D deficiency.

Source: University of Eastern Finland

For Healthy Adults, New Guideline Recommends only Daily Allowance of Vitamin D

Guideline recommends vitamin D higher than the recommended daily allowance for children, pregnant people, adults over 75 and adults with prediabetes

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Healthy adults under the age of 75 are unlikely to benefit from taking more than the daily intake of vitamin D recommended by the Institutes of Medicine (IOM) and do not require testing for vitamin D levels, according to a new Clinical Practice Guideline issued today by the Endocrine Society. For children, pregnant people, adults older than 75 years and adults with high-risk prediabetes, the guideline recommends vitamin D higher than the IOM recommended daily allowance.

Vitamin D use and blood vitamin D levels have been associated with many common diseases. However, whether vitamin D supplementation lowers the risk of these diseases and what vitamin D blood levels are needed for better health have been debated for years.

In this new guideline, the panel of experts established guidelines for vitamin D use and testing for vitamin D levels in healthy persons without established indications for vitamin D treatment or testing. The guideline relied on clinical trials to develop the recommendations.

The guideline, titled “Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the August 2024 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.

“The goal of this guideline was to address the vitamin D requirements for disease prevention in a generally healthy population with no underlying conditions that would put them at risk of impaired vitamin D absorption or action,” said Marie Demay, M.D., of Harvard Medical School and Massachusetts General Hospital in Boston, Mass. Demay is the chair of the panel that developed the guideline. “Healthy populations who may benefit from higher dose vitamin D supplements are those 75 and older, pregnant people, adults with prediabetes, and children and adolescents 18 and younger, but we do not recommend routine testing for vitamin D levels in any of these groups.”

Key recommendations from the guideline include:

  • We suggest against vitamin D supplements at doses beyond the reference dietary intakes recommended by the IOM in healthy adults under 75 years old.
  • We identified the following populations that may benefit from supplementation above the intakes recommended by the IOM because of the potential to reduce specific health risks:
    • Children and adolescents 18 and younger—potential to prevent nutritional rickets and to reduce the chance of respiratory infections.
    • Individuals 75 and older—potential to lower mortality risk.
    • Pregnant people—potential to reduce risk of pre-eclampsia, intra-uterine mortality, preterm birth, small-for-gestational age birth and neonatal mortality.
    • People with prediabetes—potential to reduce progression to diabetes.
  • In adults ages 50 years and older who have indications for vitamin D supplementation or treatment, we suggest daily, lower-dose vitamin D instead of non-daily, higher-dose vitamin D.
  •  We suggest against routine testing for 25-hydroxyvitamin D levels in any of the populations studied, since outcome-specific benefits based on these levels have not been identified. This includes 25-hydroxyvitamin D screening in people with dark complexion or obesity.

Even though the evidence on the role of vitamin D in health and disease has increased over the last decade, the panel noted many limitations in the available evidence. For example, many of the large clinical trials were not designed for several of the outcomes that they reported, and the studied populations had vitamin D blood levels that most would consider adequate to begin with. Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

Source: The Endocrine Society

Not Just Sunlight – Individual Factors Influence Vitamin D Production

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A new study from Trinity College Dublin sheds light on the complexities of achieving optimal vitamin D status across diverse populations. The study, which was recently published in the journal Clinical Nutrition, showed that individual factors like age, sex and body mass index significantly affected vitamin D levels generated from sunlight exposure.

Despite substantial research on the determinants of vitamin D, levels of vitamin D deficiency remain high. Dr Margaret M. Brennan, Research Assistant, Department of Public Health and Primary Care, School of Medicine, Trinity College and first author, said:

“We hope this work can highlight the significant differences in vitamin D levels among different ethnic groups at northern latitudes and contribute to efforts to address the long-standing population health issue of vitamin D deficiency.”

The authors analysed data from half a million participants from the United Kingdom (UK,) and for each person, they calculated the individualised estimate of ambient ultraviolet-B (UVB) level, which is the wavelength of sunlight that induces vitamin D synthesis in the skin.

A comprehensive analysis of key determinants of vitamin D and their interactions revealed novel insights. The first key insight is that ambient UVB emerges as a critical predictor of vitamin D status, even in a place like the UK, which receives relatively little sunlight. The second is that age, sex, body mass index (BMI), cholesterol level, and vitamin D supplementation significantly influence how individuals respond to UVB. For example, as BMI and age increase, the amount of vitamin D produced in response to UVB decreases.

Professor Lina Zgaga, Associate Professor of Epidemiology, Department of Public Health and Primary Care, School of Medicine, Trinity College and the principal investigator, said:

“We believe our findings have significant implications for the development of tailored recommendations for vitamin D supplementation. Our study underscores the need to move away from a one-size-fits-all approach towards personalised strategies for optimising vitamin D status.”

Source: Trinity College Dublin

Probiotics plus Vitamin D may Boost Cognition in Schizophrenia

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Previous studies have questioned whether gut microbe imbalances and vitamin D deficiency may be linked to schizophrenia. New research published in Neuropsychopharmacology Reports now indicates that taking probiotics plus vitamin D supplements may improve cognitive function in individuals with the disease.

For the study, 70 adults with schizophrenia were randomised to take a placebo or probiotic supplements plus 400 IU vitamin D daily for 12 weeks. Severity of the disease and cognitive function were evaluated by tests called the Positive and Negative Syndrome Scale (PANSS) and the 30-point Montreal Cognitive Assessment (MoCA), respectively.

A total of 69 patients completed the study. The MoCA score increased by 1.96 units in the probiotic-containing supplement group compared with the placebo group. Also, the percentage of patients with MoCA scores of 26 or higher (indicating normal cognition) rose significantly in the intervention group. Between-group differences in PANSS scores were not significant.

“Probiotics may be a novel way to treat mental disorders by regulating gut microbiota,” said corresponding author Gita Sadighi, MD, of the University of Social Welfare and Rehabilitation Sciences, in Iran.

Source: Wiley

Rickets in the Industrial Revolution Driven by Low Vitamin D

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Rickets ran rife in children following the Industrial Revolution, but University of Otago-led research has found factory work and polluted cities aren’t entirely to blame for the period’s vitamin D deficiencies.

In a study published in PLOS One, researchers sampled teeth from a cemetery site in industrial era England, looking for microscopic markers of nutritional disease.

Lead author Dr Annie Sohler-Snoddy, Research Fellow in Otago’s Department of Anatomy, says they uncovered some of the first clear evidence of seasonal vitamin D deficiency in an archaeological sample.

She says it has been known for many years that there was an increase in rickets, a childhood bone disease caused by vitamin D deficiency, in 18th and 19th Century Europe.

“It has been assumed that this was due to more people, including children, working long hours indoors, living in crowded housing and in smog-filled environments, all of which reduce the amount of sunlight that reaches a person’s skin, which is the main way humans make vitamin D.”

However, new bioarchaeological methods enabled the researchers to get a much clearer picture of how vitamin D deficiency affected the people living in industrial England, rather than looking at bone deformities alone.

The study, from Otago, Durham University, University of Edinburgh, University of Brighton, and University of Queensland, found markers associated with vitamin D deficiency in the interior part of 76% of the teeth analysed.

In many samples, these occurred regularly, in annual increments.

“This shows clear evidence of seasonal vitamin D deficiency in the teeth of people living in the north of England.

“This is exciting because it highlights that latitude and seasonal lack of sunlight was a major factor in the amount of vitamin D these people could make in their skin – it’s more complicated than the factors associated with the industrial revolution like working indoors more,” Dr Sohler-Snoddy explains.

Poor vitamin D status is associated with several negative health outcomes including increased risk for infectious diseases, cardiovascular disease, and cancers.

Vitamin D deficiency has been an ongoing problem in society and Dr Sohler-Snoddy believes it is important to study what happened in the past in order to inform modern approaches to the ailment.

“We tend to think of archaeological human remains as belonging to a different world, but our biology hasn’t changed in the last 200 years.

“Teeth provide a really important source of information for archaeologists as they form in a very precise chronology and, importantly, their tissues do not change over the lifespan. This means that they lock in a record of a person’s development and this stays with them until they die, or the tooth is lost.

“Understanding how vitamin D deficiency impacted past populations and why gives us an important deep-time perspective on the disease,” she says.

Source: University of Otago

Vitamin D Supplements don’t Prevent Fractures in Children

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A major clinical trial has found that vitamin D supplements do not increase bone strength or prevent bone fractures in children with vitamin D deficiency. The findings, published in Lancet Diabetes & Endocrinology, challenge widely held perceptions relating to the effects of vitamin D on bone health.

Around one-third of children have at least one fracture before the age of 18. This is a major global health issue, as childhood fractures can lead to life years of disability and/or poor quality of life. The potential for vitamin D supplements to improve bone strength has attracted growing interest in recent years, based on vitamin D’s role in promoting bone mineralisation. But there have been no clinical trials to test whether vitamin D supplements can prevent bone fractures in children.

Working with partners in Mongolia, a setting with a particularly high fracture burden and where vitamin D deficiency is highly prevalent, researchers from led by Queen Mary University of London and the Harvard T.H. Chan School of Public Health conducted a clinical trial to determine if vitamin D supplementation would decrease risk of bone fractures or increase bone strength in schoolchildren.

This study is also the largest randomised controlled trial of vitamin D supplementation ever conducted in children. Over the course of three years, 8851 schoolchildren aged 6-13 living in Mongolia received a weekly oral dose of vitamin D supplementation.

Testing revealed that 95.5% of participants had vitamin D deficiency at baseline, and study supplements were highly effective in boosting vitamin D levels into the normal range. No effect was seen on fracture risk or on bone strength, measured in a subset of 1438 participants using quantitative ultrasound.

The trial findings are likely to prompt scientists, doctors and public health specialists to re-consider the effects of vitamin D supplements on bone health.

Dr Ganmaa Davaasambuu, Associate Professor at the Harvard T.H. Chan School of Public Health, said:

“The absence of any effect of sustained, generous vitamin D supplementation on fracture risk or bone strength in vitamin D deficient children is striking. In adults, vitamin D supplementation works best for fracture prevention when calcium is given at the same time – so the fact that we did not offer calcium alongside vitamin D to trial participants may explain the null findings from this study.”

Professor Adrian Martineau, Lead of the Centre for Immunobiology at Queen Mary University of London, added:

“It is also important to note that children who were found to have rickets during screening for the trial were excluded from participation, as it would not have been ethical to offer them placebo (dummy medication). Thus, our findings only have relevance for children with low vitamin D status who have not developed bone complications. The importance of adequate vitamin D intake for prevention of rickets should not be ignored, and UK government guidance recommending a daily intake of 400 IU vitamin D remains important and should still be followed.”

Source: Queen Mary University of London

Five Years of High-dose Vitamin D Reduced Atrial Fibrillation Risk

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Taking higher-than-recommended doses of vitamin D for five years reduced the risk of atrial fibrillation in older adults, according to a randomised controlled study conducted in Finland and published in the American Heart Journal.

Atrial fibrillation is the most common arrhythmia, the risk of which increases with age, and which is associated with an increased risk of stroke, heart failure and mortality. Vitamin D has been shown to have an effect, for example, on the atrial structure and the electrical function of the heart, suggesting that vitamin D might prevent atrial fibrillation.

Conducted at the University of Eastern Finland in 2012–2018, the main objective of the Finnish Vitamin D Trial (FIND) was to explore the associations of vitamin D supplementation with the incidence of cardiovascular diseases and cancers. The five-year study involved 2 495 participants, men aged 60 and older, and women aged 65 and older, who were randomised into three groups: one placebo group and two vitamin D3 supplementation groups, with one of the groups taking a supplement of 40µg (1600 IU) per day, and the other a supplement of 80µg (3200 IU) per day. All participants were also allowed to take their personal vitamin D supplement, up to 20µg (800 IU) per day, which at the beginning of the study was the recommended dose for this age group. Participants had no diagnoses of cardiovascular disease or cancer at baseline, and they completed comprehensive health-related questionnaires, both at the beginning. Data on the occurrence of diseases and deaths were also obtained from Finnish nationwide health registers. Approximately 20% of participants were randomly selected for more detailed examinations and blood samples.

During the five-year study, 190 participants were diagnosed with atrial fibrillation: 76 in the placebo group, 59 in the 40µg group, and 55 in the 80 micrograms group. The risk of atrial fibrillation was 27% lower in the 40µg group, and 32% lower in the 80 micrograms group, when compared to the placebo group. In the sub-cohort selected for more detailed examinations, the mean baseline serum calcidiol concentration, which is a marker of the body’s vitamin D concentration, was relatively high, 75nmol/l. After one year, the mean calcidiol concentration was 100nmol/L in the 40µg group, and 120nmol/l in the 80µg group. No significant change in the calcidiol concentration was observed in the placebo group.

Only two randomised trials tried to test whether vitamin D supplementation reduces AF risk in healthy adults, and they did not observe an effect when using doses of 10µg (400 IU) or 50µg (2000 IU) per day. Further confirmation of the present results from the FIND study is therefore needed before doses of vitamin D that significantly exceed current recommendations can be recommended for preventing atrial fibrillation. The FIND study has previously published findings showing no association with the incidence of other cardiovascular events or cancers.

Source: University of Eastern Finland

Low Maternal Vitamin D Levels may Increase Schizophrenia Risk of Offspring

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Neuroscientists published in the Journal of Neurochemistry, shows that maternal levels of vitamin D are key in the development of dopaminergic neurons, which are thought to be involved in schizophrenia.

Professor Darryl Eyles has built on past research out of his laboratory at the Queensland Brain Institute linking maternal vitamin D deficiency and brain development disorders, such as schizophrenia, to understand the functional changes taking place in the brain.

Schizophrenia is associated with many developmental risk factors, both genetic and environmental. While the precise neurological causes of the disorder are unknown, what is known is that schizophrenia is associated with a pronounced change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain’s ‘reward molecule’.

Professor Eyles has followed the mechanisms that might relate to abnormal dopamine release and discovered that maternal vitamin D deficiency affects the early development and later differentiation of dopaminergic neurons.

The team at the Queensland Brain Institute developed dopamine-like cells to replicate the process of differentiation into early dopaminergic neurons that usually takes place during embryonic development.

They cultured the neurons both in the presence and absence of the active vitamin D hormone. In three different model systems they showed dopamine neurite outgrowth was markedly increased. They then showed alterations in the distribution of presynaptic proteins responsible for dopamine release within these neurites.

“What we found was the altered differentiation process in the presence of vitamin D not only makes the cells grow differently, but recruits machinery to release dopamine differently,” Professor Eyles said.

Using a new visualisation tool known as false fluorescent neurotransmitters, the team could then analyse the functional changes in presynaptic dopamine uptake and release in the presence and absence of vitamin D.

They showed that dopamine release was enhanced in cells grown in the presence of the hormone compared to a control.

“This is conclusive evidence that vitamin D affects the structural differentiation of dopaminergic neurons.”

Leveraging advances in targeting and visualising single molecules within presynaptic nerve terminals has enabled Professor Eyles and his team to further explore their long-standing belief that maternal vitamin D deficiency changes how early dopaminergic circuits are formed.

The team is now exploring whether other environmental risk factors for schizophrenia such as maternal hypoxia or infection similarly alter the trajectory of dopamine neuron differentiation.

Eyles and his team believe such early alterations to dopamine neuron differentiation and function may be the neurodevelopmental origin of dopamine dysfunction later in adults who develop schizophrenia.

Source: University of Queensland

Daily Vitamin D Could Reduce Cancer Mortality

Vitamin D intake could reduce cancer mortality in the population by 12% – provided the vitamin is taken daily. This was the result of an evaluation of 14 studies of the highest quality conducted at the German Cancer Research Center with a total of almost 105 000 participants.

Vitamin D deficiency is widespread worldwide and is particularly common among cancer patients. Averaged over the year, the vitamin D blood levels of about 15% of German adults are below the threshold for a pronounced vitamin D deficiency*. In contrast, in a study of colorectal cancer patients, researchers diagnosed vitamin D3 deficiency in 59% of participants, which was also associated with unfavourable prognosis.

Potential effects of vitamin D supplementation and the development or prognosis of cancer have already been investigated in numerous studies. “Based on current studies, vitamin D3 supplementation probably does not protect against developing cancer, but it could reduce the likelihood of dying from cancer. However, previous studies on cancer mortality have yielded very different results, and we were interested in the reasons for this,” said Ben Schöttker, an epidemiologist at the German Cancer Research Center. “By re-evaluating all previous studies on the topic, we wanted to help produce robust results on this issue, which is so relevant to population health.

To investigate the effectiveness of vitamin D3 on cancer mortality in the population and on the survival of cancer patients, Ben Schöttker and colleagues conducted a systematic literature search that identified 14 studies with a total of nearly 105 000 participants. The researchers considered only studies of the highest quality whose participants had been randomly assigned to the vitamin D3 arm or the placebo arm.

When all 14 studies were pooled, no statistically significant results emerged. However, when the studies were divided according to whether vitamin D3 was taken daily in a low dose** or in higher doses administered at longer intervals**, a large difference was seen. In the four studies with the infrequent higher doses, there was no effect on cancer mortality. In contrast, in the summary of the ten studies with daily dosing, the researchers determined a statistically significant twelve percent reduction in cancer mortality.

“We observed this twelve percent reduction in cancer mortality after untargeted vitamin D3 administration to individuals with and without vitamin D deficiency. We can therefore assume that the effect is significantly higher for those people who are actually vitamin D deficient,” says Ben Schöttker. He explains the better efficacy of daily doses of vitamin D3 by the more regular bioavailability of the active agent, the hormone 1,25-dihydroxyvitamin D, which is only produced by reactions of vitamin D in the body and can presumably inhibit tumor growth.

A more detailed analysis of the studies with daily intake further revealed that people aged 70 and older benefited most from vitamin D3 therapy. In addition, the effect was most evident when vitamin D intake was started before the cancer diagnosis.

Hermann Brenner, epidemiologist and prevention expert at DKFZ, adds: “This work underlines the great potential of vitamin D3 administration in the prevention of cancer deaths. Regular intake at low doses** is associated with almost negligible risk and very low cost.”

* The threshold blood 25-hydroxyvitamin D level used for vitamin D deficiency was 30 nmol/L (= 12 ng/ml). If individuals with less severe vitamin D deficiency (blood 25-hydroxyvitamin D level < 50 nmol/L (= 20 ng/mL)) are added, slightly more than half of Germans have at least one deficiency. However, there are also guidelines that use other thresholds. Since the vitamin D level in the blood depends primarily on the tanning of the skin, this percentage also varies greatly with the seasons.

** In the studies, daily low doses were 400 to 4000 IU per day, and higher-doses administered at longer intervals were 60 000 to 120 000 IU once per month or less.

Source: German Cancer Research Center

Vitamin D may be Necessary for Effective Immunotherapy in Skin Cancer

3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

Vitamin D has many effects on the body, including regulation of the immune system. New research indicates that for patients with advanced skin cancer, it may be important to maintain normal vitamin D levels when receiving immunotherapy in the form of immune checkpoint inhibitors. The findings are published in CANCER.

To see whether levels of vitamin D might impact the effectiveness of immune checkpoint inhibitors, investigators analysed the blood of 200 patients with advanced melanoma both before and every 12 weeks during immunotherapy treatment.

A favourable response rate to immune checkpoint inhibitors was observed in 56.0% of patients in the group with normal baseline vitamin D levels or normal levels obtained with vitamin D supplementation, compared with 36.2% in the group with low vitamin D levels without supplementation. Progression‐free survival in these groups was 11.25 and 5.75 months, respectively.

“Of course, vitamin D is not itself an anti-cancer drug, but its normal serum level is needed for the proper functioning of the immune system, including the response that anti-cancer drugs like immune checkpoint inhibitors affect,” said lead author Łukasz Galus, MD, of Poznan University of Medical Sciences, in Poland. “In our opinion, after appropriately randomised confirmation of our results, the assessment of vitamin D levels and its supplementation could be considered in the management of melanoma.”

Source: Wiley