Taking vitamin D2 might lower the body’s levels of the more efficient form of vitamin D, vitamin D3, according to new research from the University of Surrey, John Innes Centre and Quadram Institute Bioscience.
Many people take vitamin D supplements to support their bone and immune health and meet the UK government recommendation of 10 micrograms (µg) each day, especially during the winter months.
There are two forms of vitamin D supplements available: vitamin D2 and vitamin D3. Researchers have found that taking vitamin D2 supplements can lead to a drop in the body’s concentration of vitamin D3, which is the form our bodies naturally produce from sunlight and use most effectively to raise overall vitamin D levels.
The study, published in Nutrition Reviews, analysed data from randomised controlled trials and found that vitamin D2 supplementation resulted in a reduction in vitamin D3 levels compared to those not taking a vitamin D2 supplement. In many of the studies, the vitamin D3 levels went lower than in the control group.
Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK. However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2.
Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey’s Nutrition, Exercise, Chronobiology & Sleep Discipline
This research supports a previous study published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, which suggests that vitamin D2 and D3 do not have identical roles in supporting immune function. Vitamin D3 has a modifying effect on the immune system that could fortify the body against viral and bacterial diseases
We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signalling system in the body – a key part of the immune system that provides a first line of defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.
Professor Colin Smith, University of Surrey
Further research into the different functionalities of vitamin D2 and D3 should be a priority in deciding whether vitamin D3 should be the first-line choice of vitamin D supplement, subject to individual requirements.
The findings from the current study suggest that magnesium also increases the gut synthesis of vitamin D, which does not go to the blood and takes effect locally.
Photo by Danilo Alvesd on Unsplash
Researchers from Vanderbilt University Medical Center have demonstrated in a precision-based clinical trial that a magnesium supplement increases gut bacteria in humans that have been shown to synthesise vitamin D and inhibit colorectal cancer carcinogenesis.
However, the effect was observed primarily in females – an outcome that the researchers surmised may be attributable to the role that oestrogen plays in shifting magnesium from circulation into cellular uptake.
Intestinal microbiome data and colonoscopy results were analysed from participants who were randomised by whether they had the TRPM7 genotype, which plays a crucial role in regulating magnesium and calcium uptake.
Previously, the investigators showed in the same randomised trial that magnesium enhances the synthesis of vitamin D and increases the blood levels of vitamin D. The findings from the current study suggest that magnesium also increases the gut synthesis of vitamin D, which does not go to the blood and takes effect locally.
“Our previous study showed magnesium supplementation increased blood levels of vitamin D when vitamin D levels were low,” said Qi Dai, MD, PhD, professor of Medicine. “The current study reveals that magnesium supplementation also increases the gut microbes which have been shown to synthesise vitamin D in the gut without sunlight and locally inhibit colorectal cancer development.”
The participants were divided into two arms, one that received the magnesium supplement and another that received a placebo. Their gut microbiome was analysed from stools, rectal swabs and rectal tissues. Among participants with adequate TRPM7 function, the magnesium supplement increased Carnobacterium maltaromaticum and Faecalibacterium prausnitzii, which were previously found to work synergistically to increase vitamin D and decrease colorectal carcinogenesis. Among those with inadequate TRPM7 function, the magnesium supplement reduced the abundance of F. prausnitzii in rectal mucosa.
Among 236 participants who all had a history of colorectal polyps, 124 underwent colonoscopies after completing the trial with a 3.5-year median follow-up time. A higher abundance of F. prausnitzii in rectal mucosa was associated with an almost threefold increase in developing additional polyps.
The potential role of vitamin D in preventing and treating colorectal cancer (CRC) has attracted growing research interest – especially as CRC rates are rising, particularly among younger adults. This isn’t a new area of study. Low vitamin D levels have long been linked to a higher risk of developing colorectal cancer.
One large study involving over 12 000 participants found that people with low blood levels of vitamin D had a 31% greater risk of developing CRC compared to those with higher levels. Similarly, another study reported a 25% lower CRC risk among individuals with high dietary vitamin D intake.
Data from the Nurses’ Health Study – a long-term investigation of American nurses – showed that women with the highest vitamin D intake had a 58% lower risk of developing colorectal cancer compared to those with the lowest intake.
Now, a review highlights vitamin D’s promise in colorectal cancer prevention and treatment – but also underscores the complexity and contradictions in current research.
While observational data, which follow people’s use of vitamin D, and mechanistic studies, to investigate how vitamin D works in the laboratory, suggest protective effects, this isn’t confirmed by larger trials.
In fact, randomised controlled trials (RCTs), in which some people receive vitamin D and others don’t, the gold standard by which treatments are judged, reveal inconsistent outcomes. This highlights the need for a balanced approach to its integration into public health strategies.
Vitamin D is synthesised in the skin in response to sunlight and exerts its biological effects through vitamin D receptors (VDRs) found throughout the body, including in colon tissue. When activated, these receptors help regulate gene activity related to inflammation, immune response and cell growth – processes central to cancer development and progression.
Preclinical studies have shown that the active form of vitamin D (calcitriol) can suppress inflammation, boost immune surveillance (the immune system’s ability to detect abnormal cells), inhibit tumour blood vessel growth and regulate cell division – a key factor in cancer development, as demonstrated in my recent research.
Epidemiological studies, which track health outcomes across large populations over time, consistently find that people with higher blood levels of vitamin D have a lower risk of developing CRC. This paints a hopeful picture, suggesting that something as simple as getting more vitamin D – via sun exposure, diet, or supplements – could lower cancer risk.
But the story gets more complicated.
Mixed results
When it comes to medical decision-making, randomised controlled trials (RCTs) are the gold standard. These studies randomly assign participants to receive either a treatment (like vitamin D) or a placebo, helping eliminate bias and isolate cause-and-effect relationships.
Unfortunately, RCTs on vitamin D and CRC have produced mixed results.
For example, the VITAL trial – a major RCT involving over 25 000 participants – found no significant reduction in overall colorectal cancer incidence with 2000 IU/day of vitamin D supplementation over several years.
However, a meta-analysis of seven RCTs did show a 30% improvement in CRC survival rates with vitamin D supplements, suggesting potential benefits later in the disease course rather than for prevention.
On the other hand, the Vitamin D/Calcium Polyp Prevention Trial found no reduction in the recurrence of adenomas (pre-cancerous growths) with supplementation, raising questions about who benefits most, and at what dosage.
Adding to the uncertainty is the question of causation. Does low vitamin D contribute to cancer development? Or does the onset of cancer reduce vitamin D levels in the body? It’s also possible that the observed benefits are partly due to increased sunlight exposure, which itself may have independent protective effects.
The big picture
These discrepancies highlight the importance of considering the “totality of evidence” – treating each study as one piece of a larger puzzle.
The biologic plausibility is there. Observational and mechanistic studies suggest a meaningful link between vitamin D and lower CRC risk. But the clinical evidence isn’t yet strong enough to recommend vitamin D as a standalone prevention or treatment strategy.
That said, maintaining sufficient vitamin D levels – at least 30ng/mL – is a low-risk, cost-effective health measure. And when combined with other strategies like regular screening, a healthy diet, physical activity, and personalised care, vitamin D could still play a valuable role in overall cancer prevention.
Vitamin D is not a miracle cure – but it is part of a much broader picture. Its role in colorectal cancer is promising but still being defined. While it’s not time to rely on supplements alone, ensuring adequate vitamin D levels – through sun exposure, diet, or supplements – remains a smart choice for your health.
Colorectal cancer is a complex disease, and tackling it requires an equally nuanced approach. For now, that means focusing on evidence-based lifestyle changes, regular screenings, and staying informed as new research unfolds.
Low vitamin D levels in the first trimester of pregnancy are associated with higher rates of preterm birth and decreased foetal length, according to a new study led by researchers in the Penn State Department of Nutritional Sciences. This research provides evidence that early pregnancy or even preconception may represent critical time points for intervening with women who have low vitamin D status, to optimise pregnancy outcomes.
“More than 25% of women who are pregnant or lactating have lower than recommended levels of vitamin D,” Gernand said, explaining that prior research has demonstrated the effect of vitamin D on foetal skeletal growth, maternal immune function at the foetal interface, and the development of the placenta in pregnant women. “A lot of the development early in pregnancy requires vitamin D, so we conducted this study to better understand how early-pregnancy vitamin D status is related to pregnancy outcomes.”
Most prior studies on vitamin D status in pregnant women have measured vitamin D concentrations starting in the second trimester or later, the researchers said. The researchers said this study, to their knowledge, is the first to examine both first and second trimester maternal vitamin D status in relation to longitudinal foetal growth and pregnancy outcomes.
The researchers at Penn State partnered with colleagues at the University of Utah to test blood samples from 351 women collected as part of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which was funded by the National Institute of Child Health and Human Development and recruited pregnant women across the United States between 2010 and 2013.
According to the Institute of Medicine, less than 50nmol/L represents an insufficiency of vitamin D. When the researchers compared outcomes for women with vitamin D insufficiency (less than 50nmol/L) to women with sufficient vitamin D (more than or equal to 50nmol/L), they found no statistical differences in pregnancy outcomes. However, when the researchers compared pregnancy outcomes across a wider range of vitamin D concentrations, they found that pregnant women with first trimester vitamin D concentrations lower than 40 nmol/L were four times more likely to experience a preterm birth compared to women with vitamin D concentrations more than or equal to 80nmol/L.
Despite the higher risk of preterm birth in women with low vitamin D status, the researchers cautioned that these results were based on a very low number of preterm births in this study and recommend that additional, larger studies be conducted.
The researchers also observed an association between first-trimester vitamin D concentrations and certain foetal growth patterns. Women with higher levels of vitamin D experienced a small but statistically significant increase in foetal length.
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.
Guideline recommends vitamin D higher than the recommended daily allowance for children, pregnant people, adults over 75 and adults with prediabetes
Photo by Michele Blackwell on Unsplash
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 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.
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.”
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.
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.
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.”
