Vitamin D may help prevent rheumatoid arthritis, suggests study

Vitamin D

Vitamin D

Original here

“Vitamin D may help prevent rheumatoid arthritis, suggests study,” is the headline in The Guardian. This is in reference to a UK-based laboratory study looking into whether vitamin D could be used to suppress inflammation in individuals with rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease, which means the immune system mistakenly attacks the body’s own cells. In rheumatoid arthritis, the immune system targets the cells that line the joints, causing them to become swollen (inflamed), stiff and painful.

Previous laboratory research has suggested that vitamin D has anti-inflammatory effects, so the current researchers wanted to see if it could help inflammatory conditions such as rheumatoid arthritis.

They analysed samples of joint fluid from people with rheumatoid arthritis and found that vitamin D did not have the expected anti-inflammatory effect that it usually does in healthy joint fluid. This was because it had a limited impact on the immune system cells, so making these immune system cells responsive to vitamin D could offer a new way to prevent flare-ups of the disease.

It could be that regularly taking a vitamin D supplement may prevent rheumatoid arthritis developing in the first place, but this is pure speculation at the moment.

For now, regardless of possible effects on inflammation, it’s recommended that all adults take a daily supplement containing 10mcg of vitamin D during the autumn and winter months. Continuing to take it during the spring and summer may have limited benefits but should be entirely safe.

Where did the story come from?

The study was carried out by a team of researchers from University College London and several institutions in Birmingham. It was funded by the European Union, National Institutes of Health, Arthritis Research UK and the Royal Society Wolfson Research Merit Award.

The study was published in the peer-reviewed Journal of Autoimmunity on an open-access basis, so it can be viewed online for free.

The Guardian’s coverage was generally balanced. However, its headline could be interpreted as referring to a much more advanced stage of research than actually was the case. The study didn’t look at the effects of giving vitamin D supplements to people with rheumatoid arthritis – it only looked at levels of vitamin D and inflammatory cells in samples in a laboratory setting.

What kind of research was this?

This was a laboratory study aiming to investigate whether vitamin D could suppress inflammation in individuals with rheumatoid arthritis and whether this effect, if confirmed, may have potential in the prevention or treatment of inflammatory disorders.

Previous laboratory research has suggested that vitamin D may be able to reduce the immune response when necessary. However, this has only involved tests on blood samples from healthy individuals. The researchers of this study wanted to look at the effects of vitamin D in individuals with inflammatory disease.

Laboratory studies are useful as early-stage research for getting an indication of biological processes and how things may work in the body. However, many more stages would be needed to better understand the role of vitamin D in rheumatoid arthritis before getting to the point of conducting a randomised controlled trial (RCT) to see whether taking vitamin D supplements would actually improve symptoms in individuals with the condition.

What did the research involve?

The researchers took samples of joint synovial fluid from 15 individuals with rheumatoid arthritis aged between 40 and 85. Synovial fluid acts much like biological engine oil by helping to keep the joints lubricated.

They analysed the samples for levels of specific white blood cells (T helper cells) and inflammatory proteins involved in the type of immune response associated with rheumatoid arthritis.

To compare responses with healthy tissue, the researchers also looked at anonymised blood samples from age- and gender-matched donors from the National Blood Service in Birmingham, UK.

The researchers cultured (grew in the lab) specific subtypes of T helper cells – Th1 and Th17 cells – known to have a role in inflammatory conditions such as rheumatoid arthritis. They then looked at the effect of vitamin D on these cells.

What were the basic results?

The researchers found that vitamin D was better able to suppress the production of inflammatory proteins by Th17 cells in the healthy blood samples than it was in the rheumatoid arthritis samples.

Vitamin D had no effect on Th1 immune cells in either of the samples.

Looking for a possible explanation, they found that vitamin D may have a reduced anti-inflammatory effect in people with rheumatoid arthritis because, in general, vitamin D had a limited effect on a type of T helper cell known as memory T cells. People with rheumatoid arthritis are thought to have higher-than-average levels of memory T cells in their synovial fluid.

How did the researchers interpret the results?

The researchers suggested: “Restoration of 1,25(OH)2D3 [the chemical formula for vitamin D] responses in memory T cells may provide a new strategy for treatment of inflammatory diseases such as rheumatoid arthritis.”

However, because vitamin D was found to have a limited effect on the T cells from the site of inflammation, they cautioned: “Vitamin D supplementation is unlikely to be successful as treatment for established active rheumatoid arthritis patients.”

Conclusion

Previous research has suggested that vitamin D has anti-inflammatory effects, so this laboratory study investigated whether vitamin D could be used to suppress inflammation in individuals with rheumatoid arthritis, to prevent flare-ups of symptoms.

However, it found that adding vitamin D to joint fluid samples from people with rheumatoid arthritis had limited success in suppressing the inflammatory response compared with the effect it has on blood from healthy donors. It seems that the memory T cells in the joint fluid samples taken from people with rheumatoid arthritis are not responsive.

If it were possible to make these cells respond to vitamin D, then this could be a new avenue for treatment. But if anything, it seems more likely that vitamin D may have potential as a way to prevent inflammatory conditions like rheumatoid arthritis from developing in the first place.

While this is an interesting possibility, this early-stage study only looked at a very small sample of people. Further laboratory studies would be needed to better understand the role of vitamin D in inflammatory conditions before research could move on to trial vitamin D supplements in the prevention or treatment of these conditions.

For the moment, we know that vitamin D is essential to keep bones, teeth and muscles healthy. It can be created by the body from direct sunlight and can also be found in a few food sources such as:

oily fish

red meat

liver

egg yolks

In the spring and summer months, most people should be able to get all the vitamin D they need from natural sunlight exposure, but taking a daily supplement of 10mcg of vitamin D is recommended during the autumn and winter months. However, there should be no risk to your health if you also choose to take a 10mcg supplement during spring and summer.

It’s advised that breastfed babies up to 1 year old should be given an 8.5 to 10mcg supplement, while children from 1 to 4 years old should be given a 10mcg supplement.

How to Naturally Overcome Vitamin D Deficiency

Vitamin D

Vitamin D

How to Naturally Overcome Vitamin D Deficiency

For more information on Vitamin D go here. For getting more Vitamin D from food this article will be of use.

Oh and for info on multiple sclerosis and vitamin d here.

Interestingly fibromyalgia, diabetes, and lupus are warning signs of Vitamin D deficiency!

Vitamin D levels reach dangerously low in winter months

Vitamin D

Vitamin D

Vitamin D, also known as ‘the sunshine vitamin’, is good for us in so many ways. Unlike other nutrients it is not provided by the food we eat, but the exposure we have to the sun. It is required for the absorption of calcium and promotes healthy bones, teeth and muscle growth, as well as supporting our immune system. Recent studies have also shown that vitamin D protects against colds.

Despite the undeniable benefits of the vitamin, new research has found that only 19% of people have been tested for their Vitamin D levels in the past and of those tested over two thirds (64%) had noticeably low numbers.

In addition to this, 66% of parents and children do not take vitamin D tablets and 78% were not aware that the government recommends that everybody (including babies and children) should take a vitamin D supplement every day.

A mix of environmental, lifestyle and nutrition habits as well as confusion over how best to manage sun exposure have all led to these reduced vitamin D levels within the UK population.

Our primary source of vitamin D is bright sunshine on the skin (face, arms and neck). However, in the UK it’s impossible to get the required amount of sunshine in the autumn and winter months, to enable the skin to make adequate vitamin D levels.

We can get some vitamin D from a healthy diet, but not the healthy amount needed. The Department of Health issued new guidelines in 2016 which said that everyone, without exception, needs to supplement their vitamin D intake, especially during the colder, darker autumn and winter months when most of us spend most of our time indoors.

And some key population groups are at risk all year round, such as those with darker skin, people who always cover up outdoors, elderly people in care or those who don’t go out very often, babies and young children – and people who spend most of their lives in an urban environment.
60% of people living in urban areas have inadequate vitamin D levels in the winter. 16% of people in London have inadequate levels all year round as UVB rays are blocked by cloud cover or pollution and never reach us.

Office workers and most indoor occupations reduce your time to be outdoors. A recent survey showed that 15% of workers spend no time outside in a nature-like environment during the working week and only 30% take a proper lunch-break. People on nightshifts often sleep at the key time of day when the sun can help your vitamin D levels.

Here to discuss the UK’s lack of Vitamin D and the impact of this is author and international speaker Dr. John Briffa. Emilee interview him on behalf of PatienTalk.Org and includes a discussion on the relationship between vitamin d and multiple sclerosis.

Dr John Briffa is a practising doctor, author and international speaker. He is prize-winning graduate of University College London School of Medicine, where he also gained a BSc degree in Biomedical Sciences. Dr Briffa is a leading authority on the impact of nutrition and other lifestyle factors on health and illness. He is dedicated to providing individuals with information and advice they can use to take control of their health and optimise their energy and vitality.

Dr Briffa is a former columnist for the Daily Mail and the Observer, and former contributing editor for Men’s Health magazine. He has contributed to over 50 newspaper and magazine titles internationally, and is a previous recipient of the Health Journalist of the Year award in the UK.

Vitamin D may prevent asthma worsening for some

Vitamin D

Vitamin D

Vitamin D supplements protect against severe asthma attacks,” The Daily Telegraph reports.

The headline was prompted by a review that pooled data from seven trials comparing taking vitamin D supplements with a placebo in people with asthma.

The researchers wanted to see whether vitamin D reduced the risk of severe asthma episodes that needed hospitalisation or treatment with oral steroids, referred to as “asthma exacerbations”.

Overall, the researchers found vitamin D supplements reduced the risk of asthma exacerbations by 26%. Further analysis found the protective effect was only seen in people who were vitamin D deficient to start with.

But the main limitation of this evidence is the small number of exacerbations that occurred. For example, in two trials there were no asthma exacerbations, in another only a single event.

And only 92 people from the data were vitamin D deficient at the start. This means the risk estimates are based on small numbers, which may make them less accurate.

It’s currently recommended that certain groups, including those at risk of vitamin D deficiency and children aged one to four, take vitamin D supplements all year round.

All adults and children are advised to consider taking 10 micrograms (mcg) a day of vitamin D during the autumn and winter months, when there is less sunlight.

Find out what to do during an asthma attack.

 

Where did the story come from?

The study was carried out by researchers from Barts and The London School of Medicine and Dentistry, Queen Mary University of London, and other institutions in the UK, US, Ireland, Poland and Japan.

Funding was provided by the Health Technology Assessment Programme, which is run by the UK’s National Institute for Health Research (NIHR).

The study was published in the peer-reviewed journal The Lancet: Respiratory Medicine.

The UK media’s reporting is generally accurate, but official guidelines haven’t changed on the basis of the results of this study.

 

What kind of research was this?

This systematic review and meta-analysis pooled data from people with asthma taking part in randomised controlled trials that compared vitamin D supplementation with an inactive placebo.

Previous meta-analysis of trial data has suggested that vitamin D may reduce the risk of asthma attacks and exacerbations of asthma.

But it’s not known whether this effect is influenced by the person’s vitamin D level to start with, so the researchers set out to investigate this.

A systematic review of randomised controlled trials (RCTs) is the best way of gathering the available evidence on the effects of an intervention.

But when it comes to trials on nutritional supplements, RCTs can vary considerably in how the treatment is given. And when the outcome of interest is relatively rare – in this case, asthma exacerbations – it can be difficult to be sure how much of the effect is down to the intervention.

 

What did the research involve?

The reviewers identified placebo-controlled trials of vitamin D supplementation (D2 or D3) in people with asthma that reported incidence of asthma exacerbations as an outcome.

The trials included had to be double-blinded in design, where neither the participants nor the assessors knew if a person was taking vitamin D or a placebo.

The reviewers collected individual patient data from the trials, contacting study investigators for clarity or to gather missing data.

They also collected information on participants’ age, gender, ethnicity, BMI, blood vitamin D concentration at the start of the study, and any other factors that might influence the results (confounders).

The main outcome of interest was incidence of asthma exacerbations needing treatment with oral steroids. They also looked at emergency hospital attendance or admissions and any adverse effects associated with supplementation.

Eight trials were eligible for inclusion, but patient data couldn’t be obtained for one, leaving a total of seven studies and 978 participants available for analysis. Trials came from six different countries (one from the UK), and about a third of the participants were children.

Vitamin D dosing varied from a single dose (an injection or infusion) every two months (100,000 international units, IU) to daily dosing (500 to 2,000 IU per day) or a mixture of the two. Treatment duration ranged from 15 weeks to one year.

Baseline blood vitamin D levels ranged from undetectable to 187nmol/L. Vitamin D deficiency is generally accepted to be less than 25nmol/L, so this threshold was used in the study.

 

What were the basic results?

Asthma exacerbations needing oral steroid treatment were rare. In two trials there were no exacerbations, and in another there was only one.

When pooling the participants, in all seven studies vitamin D supplementation was associated with a 26% reduced risk of asthma exacerbation needing steroid treatment (relative risk (RR) 0.74, 95% confidence interval (CI) 0.56 to 0.97).

A similar risk reduction was found when researchers just looked at the four individual studies with several exacerbations.

There was no difference between groups in the proportion of people having at least one exacerbation, but vitamin D helped reduce the risk of multiple exacerbations.

Vitamin D supplements reduced the rate of exacerbations in people with vitamin D levels less than 25nmol/l (0.33, 95% CI 0.11 to 0.98), but this was based on data from only 92 participants.

Among the 764 participants who weren’t vitamin D deficient, there was no significant effect, regardless of their age, gender and ethnicity.

Vitamin D didn’t increase the risk of serious adverse events, and there were no cases of high blood calcium or kidney stones reported.

 

How did the researchers interpret the results?

The researchers concluded: “Vitamin D supplementation reduced the rate of asthma exacerbations requiring treatment with systemic corticosteroids overall.

“We did not find definitive evidence that effects of this intervention differed across subgroups of patients.”

 

Conclusion

This review gathers the available trial evidence to address the specific question of whether giving people with asthma vitamin D supplements could have an effect on how many asthma exacerbations they have.

The review has many strengths. It only included double-blind trials, where participants and assessors didn’t know if people were taking vitamin D or a placebo.

Researchers also made careful attempts to gather all relevant data and information on confounding factors, and all but one trial had a low risk of bias.

But there are some limitations to bear in mind:

With the relatively small number of trials and participants, the outcome of interest – exacerbations needing steroid treatment – was quite rare. Three trials recorded no exacerbations, and a third only one. Analyses based on a small number of events can give less precise risk estimates.

The main aim was to see whether a person’s vitamin D levels to begin with had an effect. The researchers found there was: the benefit was only seen in people who were vitamin D deficient to start with. But only 92 people fell into this category, so again the small number of events in this sample may give a less reliable result.

The dosing and duration of treatment varied from study to study. Along with the small sample and low number of events, this makes it difficult to know what could be an optimal dose for children or adults to take.

This study, and the research it’s based on, isn’t able to tell us whether there should be a change in guidelines for people with asthma. It’s too soon to recommend they take vitamin D supplements, regardless of whether or not they’re deficient.

Current guidelines recommend everyone should consider taking a vitamin D supplement of 10mcg a day in the autumn and winter months, when there is less sunlight. People can get all the vitamin D they need from sunlight and some dietary sources in the spring and summer.

Babies who are breastfed, all children aged one to four years, pregnant and breastfeeding women, and people at risk (such as those who are indoors a lot) are advised to take a supplement all year round.

Vitamin D supplements are available from most pharmacists and are usually safe to take as long as you don’t regularly take more than 100mcg (4,000 IU) a day.

Children under 10 years should not take more than 50mcg a day, and babies under one year should not take more than 25mcg a day.

“Multiple sclerosis could be prevented through daily vitamin D supplements”

"Multiple sclerosis could be prevented through daily vitamin D supplements"

“Multiple sclerosis could be prevented through daily vitamin D supplements”

 

“Multiple sclerosis could be prevented through daily vitamin D supplements” reports The Times, stating that scientists have found the first causal link between the “sunshine vitamin” and a gene that increases the risk of the incurable neurological condition, known as MS.

The news comes from research into how vitamin D interacts with the genes that make certain people more likely to develop MS. The researchers claim their study strongly implies that vitamin D deficiency increases the risk of developing MS among susceptible individuals. This study was not attempting to find a cure or treatment for MS.

The Times reports that spending more time in the sun (which makes the body produce vitamin D) might protect against the condition. However, exposure to high levels of sunlight can damage the skin and cause cancer. The newspaper also suggests the use of vitamin supplements by pregnant women might reduce their children’s risk of the condition. Current advice for pregnant women is that they can choose to take up to 10 micrograms of vitamin D a day and to contact their GP for specific advice.

Although preliminary, this important study does point the way to future research into the actions of vitamin D and particularly the complex interactions between sunlight, vitamin D and genes.

Where did the story come from?

This study was conducted by Prof. George Ebers, Dr Julian Knight and colleagues from Oxford University, John Radcliffe Hospital and various institutions in Canada. The study was funded by the Multiple Sclerosis Society of Canada, the Scientific Research Foundation and the Multiple Sclerosis Society of the United Kingdom. It was published online in the peer reviewed journal PLoS genetics.

What kind of scientific study was this?

 

This genetic and laboratory study looked at whether there might be a relationship between vitamin D and genetic susceptibility for MS. The authors explain that MS is an inflammatory disease of the nervous system.

One particular area in the genome (genetic make up) on chromosome 6, called the Major Histocompatibility Complex (MHC), is reported to have the greatest genetic influence on a person’s risk of MS. Within this MHC one particular section called the HLA-DRB1 locus is known to influence MS risk. Having one particular variation of this locus, called the HLA-DRB1*15 haplotype, increases the risk of MS three fold.

There is also evidence to suggest that environmental factors act at a population level to influence the geographical distribution of MS. This is unusual, and even in populations of the same ethnicity the risk can vary by up to three times depending on geographic location. There is also a trend for a higher incidence of the disease in areas with less sunshine, such as Scotland and Northern European countries.

This has led to the suggestion that sunshine and particularly vitamin D, which is synthesised in the body in response to sunlight, may be connected to the environmental causes of MS. This study aimed to look at whether vitamin D might directly affect the function of specific genes within the MHC.

Once in the body vitamin D can switch certain genes on. To do this it needs to bind to a protein called the vitamin D receptor (VDR), which in turn binds to a particular sequence of the letters in the DNA called vitamin D response elements (VDREs).

To investigate this, the researchers used a computer program to look at genes within the MHC for VDREs in DNA from a person with the HLA-DRB1*15 haplotype on both of their copies of chromosome 6. They looked at the HLA-DRB1, -DQA1 and -DQB-1 genes, and at the DNA around them, as well as the IL2RA and IL7RA genes.

The computer program identified a piece of DNA that looked like a VDRE. The researchers then carried out a case-control study in 322 people to see if its sequence varied in people with MS (cases) and people without MS (controls). These people were all homozygous for (had two copies of) the HLA-DRB1*15 haplotype. The researchers also looked at the DNA from 168 people who did not carry this high-risk haplotype, but were homozygous for other haplotypes, which were not associated with increased risk of MS, or conferred only a modest increase in risk.

To further test whether vitamin D could bind to the VDRE-like sequence, the researchers carried out experiments where they mixed the VDR with a piece of DNA containing the VDRE-like sequence. This was to see if  there was evidence that the two were specifically binding to each other. Cells were then grown in the laboratory that were homozygous for the HLA-DRB1*15 haplotype. Half of the cells were treated with vitamin D for 24 hours, and the other half had no vitamin D. The researchers then used specific techniques to see if the VDRE was bound to the VDRs.

They then investigated if the VDRE could affect how genes are switched on in living cells. They took a piece of DNA containing the VDRE and attached it to a gene that produces a protein that can cause a light-producing reaction under certain conditions (called a reporter gene because of the ability to tell if it is switched on or off). This piece of DNA was then inserted into cells in the laboratory to see whether exposing the cells to vitamin D caused the reporter gene to be switched on. The researchers repeated this experiment using the variant forms of the VDRE found in the no- or moderate-MS-risk haplotypes.

Finally, the researchers investigated whether having the VDRE could affect the switching on of the HLA-DRB1 gene. They did this by comparing the level of HLA-DRB1 protein on the surface of cells that carried two copies of the HLA-DRB1*15 and cells that carried two copies of the less active VDRE variant haplotypes. They also looked at how treating these cells with vitamin D affected levels of HLA-DRB1.

What were the results of the study?

The researchers identified a possible site for vitamin D binding (a possible VDRE) in the region that controls the switching on of the HLA-DRB1 gene (called its promoter region). They found no variations in this possible VDRE sequence in people who had two copies of the high risk HLA-DRB1*15 haplotype, regardless of whether they had MS or not.

However, people who had two copies of the haplotypes that were not associated with MS, or conferred only a modest risk of MS, did have variations within the possible VDRE that might affect vitamin D binding. Tests in the laboratory showed that the VDR protein could bind to the potential VDRE when mixed together, and that the two would bind to each other in cells grown in the laboratory.

They also found that the VDRE could lead to switching on of reporter genes in the presence of vitamin D in cells in the laboratory, but that the variants of VDRE found in the lower risk MS haplotypes did not. Cells that had two copies of the HLA-DRB1*15 haplotype, and therefore the working VDRE, had higher levels of HLA-DRB1 protein than those that did not. Treating the cells that had two copies of the HLA-DRB1*15 haplotype with vitamin D increased the levels of this protein even more, but did not affect the other cells.

What interpretations did the researchers draw from these results?

The researchers say that their study provides further support for vitamin D as a strong environmental risk factor for MS. They say that their findings “imply direct interactions between HLA-DRB1, the main genetic susceptibility locus for MS, and vitamin D, a strong candidate for mediating the environmental effect”. They also say that as there is a high frequency of vitamin D insufficiency in the general population their data support the case for supplementation to reduce the number of people who have MS.

What does the NHS Knowledge Service make of this study?

This is important research and will be of major interest to people living with MS. However, this study concentrated on susceptibility to MS among populations, rather than looking for a cure or treatment to help those already living with the condition. “These are exciting advances, but unfortunately we have yet to find and solve the cause of MS. what I think we’ve done is add another piece to the jigsaw” said Dr Julian Knight, one of the authors.

Multiple genetic and environmental factors play a role in the development of MS, and this work advances scientific understanding of how these factors interact. This particular study focused on how vitamin D might interact with sections of the DNA of certain susceptible people.

Although The Times speculates that pregnant women might reduce their child’s risk of developing MS by taking vitamin D supplements, the authors state that the decision to use supplements “should still be between the patient and their physician”. Current NICE guidance states that pregnant or breastfeeding women may choose to take up to 10 micrograms of vitamin D a day and that women should speak to their GP for specific advice.
The newspaper also discusses the possibility of changing the recommended sun exposure limits. While sunlight does stimulate vitamin D production, the dangers of high levels of sun exposure are well documented, and sunbathing to increase vitamin D levels may be harmful. In addition, the study did not compare whether sunlight or supplements are a better source of vitamin D, but only looked at the chemical and biological interaction of vitamin D and genes in a laboratory.

This work will undoubtedly lead to further research into the risk factors behind MS, and potentially other serious conditions. Simon Gillespie, Chief Executive of the Multiple Sclerosis Society said that the research “is, of course, only part of the story, but what strikes me is opportunities and avenues for future research that it opens up.” At present trials are being conducted into whether vitamin D supplements can improve the symptoms of people living with MS.

The Multiple Sclerosis Society can give individuals further advice on this study through their website and helpline, on 0808 800 8000.