The health benefits of selenium: it's much more important than you think
image: USGS
Researchers from our College of Medicine, Biological Sciences and Psychology have been involved in a groundbreaking international study to find out what role selenium plays in the human body. The element is known to be essential for health – but only in minute amounts. Trace levels of selenium are found in a wide variety of vegetables and meat products and are determined by the chemical composition of the local soil.
This presents a problem because, when studying complex biological systems, a good way to find out what something does is to remove it. But required selenium levels are so low and its trace presence is so widespread that deleting it from someone’s diet would be as impractical as it is unethical. Nevertheless, there is another way…
Selenium switch – the gene
- Structure of the SBP2 protein.
Within the human body, selenium occurs in the form of an amino acid called selenocysteine or ‘Sec’ which is a constituent part of about 25 proteins. The formation of these selenoproteins is mediated by a protein known as SBP2 which is short for SECISBP2 which in turn is short for ‘Sec insertion sequence-binding protein 2’ (at this level of science even the abbreviations have abbreviations).
A paper published last month in the Journal of Clinical Investigation reports on two individuals with a defective SBP2 gene which leaves them unable to manufacture most of the known human selenoproteins. In other words, it’s not that they’re not getting any selenium, it’s that they can’t metabolise it. This is an extremely rare condition – and a valuable opportunity for molecular biochemists.
Selenoproteins fulfil many roles including metabolising hormones from the thyroid gland in the neck; and thyroid function tests (TFTs) are among the most common routine biochemical tests in hospitals. The two individuals described in the paper were already receiving treatment for various medical conditions but it was their highly abnormal TFT results which first flagged them up as possibly suffering from selenium deficiency.
The patients were an adult male and a small boy, first identified at ages 35 and two respectively and studied over a couple of years. The patients were not related and in neither case did anyone in their immediate family share the defective SBP2 gene.
Selenium symptoms – the effects
- Skin tests on the adult patient: each spot was exposed to UV radiation for 90 minutes. Note that the reaction to the penultimate dose was so extreme that the highest dose wasn't tested.
In the case of the adult patient, symptoms included weak muscles, general fatigue and discoloured fingers – a condition called Raynaud’s disease which is caused by spasms in the local blood vessels. In addition he had long-term hearing problems (despite treatment in childhood), rotatory vertigo (ie. a frequent ‘room spinning’ sensation), a history of speech difficulties and a distorted hip joint resulting in the condition commonly known as ‘knock-knees’ – more properly called ‘genu valgus’ – which made walking and running difficult.
As if all that wasn’t problem enough, in his teens the patient had developed an unexplained (at the time) extreme sensitivity to light. Also his testicles had become twisted, requiring one to be removed (a wince-inducing process with the disarmingly elegant name ‘orchidectomy’). Although the other testicle remained fully intact, the man was infertile and could produce no sperm.
One of the most curious observations concerned the patient’s body mass index; his normal BMI masked a raised fat mass index and a reduced lean mass index (ie. his increased body fat balanced out his small, weak muscles to give him a normal weight for his height). Lots of body fat often indicates problems in metabolising insulin but, to the researchers’ surprise, in this case the patient’s insulin levels were normal; in fact, in that respect he was a veritable picture of health.
Could all of these conditions be attributed in some way to the absence of selenoproteins? Being so young, the second patient displayed fewer symptoms but there was already noticeable muscle weakness, identifiable hearing loss and a low insulin level (causing hypoglycaemia when the child was asleep for long periods). Of course, with both patients being male and relatively young, we don’t yet know what effects SBP2 deficiency might have on women or old people.
Selenium science – the research
An international team including scientists from Australia, Sweden, France, Italy, Cambridge, UCL, Great Ormond Street, Dartford and Leicester set to examining the two cases, studying not only the levels of the various selenoproteins themselves but also a whole range of other factors across numerous metabolic pathways.
What they found was that the symptoms fell into two groups. Some were directly attributable to the absence of specific selenoproteins which have particular roles in the metabolic pathways of certain organs and tissues. For example, three selenoproteins that should occur in semen were greatly reduced in the patient’s sperm-free seminal fluid.
The other group of symptoms were those which were caused indirectly by an excess of a free radicals. From the age of 13, the adult patient had been extremely sensitive to ultraviolet radiation and was only able to go outside lathered in high-factor sun-cream. Skin biopsies showed raised levels of peroxides and other reactive oxygen molecules.
Selenoproteins have important antioxidant properties and their absence allowed free radical levels to increase within the patient’s cells until eventually the resultant cell damage manifested itself as photosensitivity. Because the effects of such oxidative stress are cumulative, the patient may yet develop further symptoms and the other, younger patient is likely to experience similar problems in due course.
This is all fascinating – but what can be done for these two people and others who might share the same defective gene? Additional selenium in the diet won’t have any effect because there’s already enough, it’s just not being metabolised. However, treatment with known antioxidants such as ascorbic acid may help to alleviate symptoms in the second group – research into this is now underway, building on the information documented in the current paper.
Marcus S Cooke, jointly appointed to our Department of Cancer Studies and Molecular Medicine and Department of Genetics, Mahsa Karbaschi from our Department of Cancer Studies and Molecular Medicine and John Schwabe from our Department of Biochemistry all contributed to the multi-author study which is the first time that the full biological importance of this essential trace element has been analysed.
- Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans (doi:10.1172/JCI43653)
