Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What is selenium?
Selenium is a micronutrient which has antioxidant properties by means of selenoproteins which play many important functions in the body. They actually are contained in many different foods. The amount of selenium we get from diet is closely linked to the amount of selenium in the soil.
What foods contain selenium?
Basically there is a large variability in different countries as the amount of selenium in soil will influence the amount of selenium in different natural foods. For example, in the US where the level of selenium in soil is extremely high, selenium will be contained in the vast majority of meat, seafood, bread, cereals and so on.
In the UK there are also several different sources of selenium, both red and white meat, seafood, vegetables, fruit. The amount of selenium in the UK is generally lower than in the US but is within the optimal range to optimise selonoprotein activities.
How much selenium should we intake per day?
There is a physiological range of selenium in the body which is around 70-90 ng/ml which corresponds to an amount of selenium of about 50 µg per day. So there is a set threshold of selenium from natural sources which obviously will have an impact on the levels of selenium in the blood and therefore on the activities of selenoproteins which again play many important functions in the body.
We can say that generally speaking the Western population do have enough selenium from natural foods to optimise selenoprotein activities. The likelihood that someone in the general healthy adult population may have selenium deficiency is quite marginal at least in the UK.
What forms do selenium supplements come in?
There are basically two forms of selenium – organic selenium which is selenium methionine – and inorganic selenium which is selenites and selenates.
Most of the available selenium supplements on the market are organic forms of selenium – selenium methionine. This is also the most efficient form of selenium as opposed to inorganic selenium.
What was previously known about selenium and the risk of heart disease?
The story of selenium in relation to heart disease begins with the appearance of an endemic cardiomyopathy in North East of China in the province of Keshan. Basically there was a very high prevalence of a cardiac myopathy in newborns which was discovered to be linked to selenium deficiency due to a lack of selenium in the soil in that region of China – North East China.
This goes back to the 70’s. In that area of China because of this common cardiomyopathy there were concerns about selenium deficiency as the underlying cause and therefore Chinese scientists implemented some interventions using a selenium supplement which was actually able to reverse the condition. We are talking about an area of China with extremely low levels of selenium – the blood level was lower than 5ng (whereas it should be between 70 and 90ng).
After that there’s been a long standing interest into examining whether selenium status and selenium supplements may play a role also in chronic disease prevention. There’s been some observational epidemiological studies conducted from the 80’s onwards, mainly in Finland, showing an observational association between low levels of selenium in the blood and high risk of cardiovascular disease outcomes such as myocardial infarction primarily. Again that evidence was from Finland which at that time did have relatively low levels of selenium as compared to other countries.
However, this was evidence coming from observational studies which can not prove causality. In order to prove causality we need to conduct clinical trials. From the 90’s onwards there have been some clinical trials addressing the potential efficacy of a selenium supplementation on many chronic disease outcomes including cancer and cardiovascular disease.
One of the early studies was a trial on the nutritional prevention of cancer in the Eastern part of the US. I was part of this clinical trial looking at the effect of selenium supplements on chronic outcomes including cancer and cardiovascular disease. At that time we did not find any evidence for the efficacy of selenium in reducing the risk of cardiovascular disease – this was based on 8 years of 200µg of selenium per day in American adults coming from the East of the US. However, it is important to note that the levels of selenium in the US population are already adequate to optimise selenoprotein activities.
There has been another big trial, again in the US, called SELECT which examined the effect of supplementation with selenium – again 200µg per day and/or vitamin E – on cancer primarily but also cardiovascular disease. The trial was stopped after 5 years because of potential increased risk of cancer in people taking vitamin E and also because of the potential increased risk – although it was not significant – of diabetes in people taking selenium supplements.
In the nutritional prevention of cancer trial we also looked at the effect of selenium supplementation on type 2 diabetes risk. For the first time we actually found an increased risk of diabetes in that study in people taking selenium supplements. This was a surprising result and also had a lot of media attention because, especially in America, there were major expectations for the use of selenium supplements for preventing primarily cancer and also for cardiometabolic disease including diabetes.
After those findings were published in Annals of Internal Medicine in 2007, there has been an explosion of interest around this issue – whether or not selenium may increase risk of diabetes. Also because selenium supplements in US are quite common – not as much as single ingredient supplements which are rarely consumed although I think 1% of Americans take selenium supplement as a single ingredient – but selenium is contained in many multivitamins which are quite widely used both in the US, the UK and many other countries.
What did your review involve?
This was a Cochrane review with funding from the National Institute for our research in the UK to examine the effects of providing selenium supplements to healthy adults in order to prevent the appearance of cardiovascular disease. We actually found 12 clinical trials, which were included in our review, in which nearly 20,000 healthy adults were randomly assigned to receive either selenium supplements or a placebo.
We need to clarify that the vast majority of participants in this review were mainly living in the US where people are already well-nourished and consume large amounts of selenium from natural foods.
What were the findings of your review?
Compared to taking a placebo, selenium supplements in our review did not lead to any statistically significant difference in the risk of death due to cardiovascular disease or any other cause, or in the occurrence of non-fatal cardiovascular disease events. So basically overall there was no effect of selenium supplementation on both cardiovascular mortality and morbidity.
As far as the possible adverse side effects of selenium supplementation, especially in the terms of potential increased risk of diabetes as suggested by early evidence including my own studies. This review is cannot definitely rule this out because actually selenium supplements in our review were found to be correlated with a small increase in the risk of diabetes but this was not large enough to be statistically significant.
Minor side effects reported in the largest trial included hair loss and skin problems. So I think overall in summary we can say that the limited evidence available at this time does not support the use of selenium supplements as a means of preventing cardiovascular disease in healthy people.
I want to emphasise that most of the participants included in this trial come from a population in the US where people have adequate or high selenium status. So in that context there is really no biological rational to think that providing additional selenium from supplements will have any impact on selenoprotein activities and therefore beneficial effect on the anti-oxidant potential and the prevention of chronic disease.
On the other hand, when we go beyond the physiological range of selenium there could be the possibility of harmful effects. That is why we need more biological mechanistic evidence to see whether high levels of selenium may produce an increased risk of diabetes.
What impact do you think this study will have?
This is not a trivial public health issue, because the use of selenium-enriched foods, supplements and fertilizers has increased in recent years in many years again because of the perception that selenium may reduce the risk of cardiovascular disease, cancer and other chronic conditions.
This applies also to the UK where there is quite a large market around the use of dietary supplements and around 30% of British adults do use some sort of supplementation. These people take supplements because they believe they will have benefits in terms of longevity or prevention of long term disease.
Importantly, we know from surveys that the supplement users tend to be healthier, tend to be well-educated, and tend to already engage in a healthy lifestyle. So, those are the people who are least likely to need to use supplements because supplementation should be adopted when there is deficiency. In the generally healthy adult population, at least in the UK, it is extremely rare that someone may have deficiency for selenium or other micronutrients.
So the implication is that in the general adult population using selenium supplements does not seem justified and should not be encouraged at least at the present time.
What further research do you think needs to be done into selenium and the risk of heart disease?
I think there is a gap in terms of the effect of selenium supplementation in less well-nourished populations where the dietary intake of the element is lower. As I said before, most of the clinical trials come from the US, so we need to conduct more clinical trials in populations that may have lower levels of selenium and therefore supplementation may produce additional benefits on top of the selenium in natural foods.
Most of these trials so far were cancer-prevention trials – to look primarily at the effect of selenium on prostate cancer – so most of the trials recruited male participants. We have a relative lack of evidence on the effect of selenium supplementation in cardiovascular disease in women - that’s another gap of the evidence that we need to fill.
We also need to look at the potential impact of the genetics of some of the selenoproteins linked to selenium status which also may play a role in cardiovascular risk and other chronic disease, so I think we also need to incorporate some genetic analysis. This may have an impact on individual responses to selenium supplements.
We need more evidence from:-
countries with low levels of selenium
clinical trials, especially in women
studies looking at the potential role of genetic variants of selenoproteins
Where can readers find more information?
They can find our paper here: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009671/abstract
There is a very comprehensive review by Professor Margaret Rayman at the University of Surrey, who is a worldwide expert on selenium, that was published in The Lancet 2012: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2961452-9/abstract
About Dr Saverio Stranges
Dr. Stranges is an Associate Clinical Professor of Cardiovascular Epidemiology in the Division of Health Sciences at University of Warwick, where he has been since August 2006.
Dr. Stranges is originally from Italy, where he completed his medical school, and specialty training in Preventive Medicine. Thereafter, he moved to the US (2002-06) to complete his doctoral training and carry out post-doctoral work in Cardiovascular Epidemiology.
Dr. Stranges started his academic career as an Assistant Professor in the Department of Social and Preventive Medicine in the School of Public Health at the State University of New York in Buffalo.
His research primarily focuses on the epidemiology and prevention of cardiovascular disease and type 2 diabetes. Specifically, Dr Stranges has been involved in a number of research outputs on the role of nutrition and micronutrients, primarily selenium, in cardiovascular and metabolic disease in several populations across Europe and US.
Among the others: Nutritional Prevention of Cancer Trial, Western New York Health Study, National Health and Nutrition Examination Survey (USA); National Diet and Nutrition Survey, Whitehall II Study (UK); EPIC Study, Olivetti Heart Study (Italy). Specifically, Dr Stranges led a series of secondary analyses from the Nutritional Prevention of Cancer (NPC) Trial that examined the effect of long-term supplementation with selenium on cardiovascular disease and type 2 diabetes.