Hec­tic lives don’t have to go hand-in-hand with feel­ing drained. Read on to find out how the lat­est re­search will elim­i­nate tired­ness for good. Plus, turn to p74 for tips on ban­ish­ing fa­tigue

BBC Earth (Asia) - - Front Page - WORDS BY SI­MON CROMPTON


Can you keep your eyes open long enough to read this fea­ture? We won’t be of­fended if you can’t. The Royal Col­lege of Psy­chi­a­trists says that one in five of us feels un­usu­ally tired at any one time, and one in ten feels per­ma­nently fa­tigued. Tired­ness and fa­tigue are be­hind 20 per cent of UK doc­tor con­sul­ta­tions, ac­cord­ing to a re­cent sur­vey of GPs. No won­der doc­tors are reg­u­larly jot­ting down a handy new acro­nym – TATT (Tired All The Time) – in pa­tient notes. Or that UK sales of en­ergy drinks shot up by 155 per cent be­tween 2006 and 2014.

Tired­ness is no joke. Sleep de­pri­va­tion brings a heavy men­tal and phys­i­cal toll. Around 20 per cent of ac­ci­dents on ma­jor roads are sleep-re­lated, ac­cord­ing to the Depart­ment of Trans­port. Plus, peo­ple who are sleep-de­prived lose the abil­ity to be pos­i­tive-minded, which re­searchers from the Univer­sity of Penn­syl­va­nia say is likely to in­crease the like­li­hood of de­pres­sion. There’s also ev­i­dence that sleep de­pri­va­tion in­creases the risk of obe­sity, heart dis­ease, di­a­betes and stroke.

Even if you’re get­ting enough sleep, feel­ing con­stantly fa­tigued can be bad for you. Re­search from the Univer­sity of Alabama has found that work­ing hard while fa­tigued in­creases blood pres­sure. This is be­cause tired peo­ple in­crease their ef­fort to make up for their di­min­ished ca­pa­bil­ity when they want to ac­com­plish a task.

For those with con­di­tions such as chronic fa­tigue syn­drome (CFS/ME) and can­cer, it se­verely re­stricts qual­ity of life. For mil­lions of oth­ers, un­ex­plained tired­ness reg­u­larly rum­bles in the back­ground. Is there some­thing wrong with us? Are we the vic­tims of hec­tic 24-hour life­styles? Why are we tired all the time?

Un­til now, lit­tle has been known about the bi­o­log­i­cal pro­cesses that re­sult in what we call tired­ness or fa­tigue. Only in re­cent decades, with grow­ing con­cern about the preva­lence of con­di­tions such as CFS/ME, has re­search money been in­vested into the causes of long-term fa­tigue. And it is be­com­ing clear that, al­though there is a wide spec­trum of tired­ness types, they are all linked and their causes in­ter­act.

Prof Ju­lia New­ton, direc­tor of the New­cas­tle Cen­tre for Fa­tigue Re­search at New­cas­tle Univer­sity, ex­plains the causes of tired­ness via a clas­sic bell-shaped curve graph. “At the thin end of the curve, there are peo­ple who just need to get some sleep and get their life­style in order. At the other thin end of the curve there are clearly peo­ple who have di­ag­nosed or un­di­ag­nosed ill­ness that is caus­ing fa­tigue. And then, there’s ev­ery­thing else in the wide mid­dle part of curve.”

The wide mid­dle is the com­plex bit, cov­er­ing tired­ness caused by com­bi­na­tions of many en­vi­ron­men­tal, life­style and health fac­tors. And re­cent re­search is be­gin­ning to re­veal how ge­net­ics, cell func­tion, in­flam­ma­tion and the brain’s re­sponse to light may all have an un­der­ly­ing role in this tired­ness ‘main­stream’.


At a cel­lu­lar level, sci­en­tists are in­creas­ingly look­ing at the role of mi­to­chon­dria – the power packs in ev­ery hu­man cell – in de­ter­min­ing how tired we feel. Mi­to­chon­dria are minia­ture or­gans (or­ganelles) that con­vert oxy­gen, sugar, fats and pro­tein into a form of chem­i­cal en­ergy, called ATP, which the body uses to fuel the brain and mus­cles. Dis­eases af­fect­ing the mi­to­chon­dria cause fa­tigue, so re­cent re­views of re­search sug­gest that fa­tigue is closely as­so­ci­ated with mi­to­chon­dria not work­ing prop­erly be­cause the body is not pro­duc­ing par­tic­u­lar enzymes, for ex­am­ple.

Stud­ies into CFS/ME by Amer­i­can fa­tigue ex­pert Dr Robert Navi­aux have shown that the con­di­tion is char­ac­terised by changes in mi­to­chon­dria func­tion. Navi­aux be­lieves that these changes may be trig­gered by stres­sors such as in­fec­tion, or phys­i­cal and psy­cho­log­i­cal trauma.

Navi­aux cites new lit­er­a­ture in­di­cat­ing that stress can prompt meta­bolic changes which make or­gan­isms go into hi­ber­na­tion-like states such as tor­por, di­a­pause and aes­ti­va­tion. “Each of these is an en­ergy con­ser­va­tion state that per­mits sur­vival un­der con­di­tions of en­vi­ron­men­tal stress at the ex­pense of a de­crease in the abil­ity to al­lo­cate en­ergy for daily work or ac­tiv­ity,” he says. “Mi­to­chon­dria are cen­tral con­trol points for each of these pro­cesses.”

This ex­ploratory re­search about the meta­bolic ori­gins of fa­tigue may link with other stud­ies sug­gest­ing that some­times tired­ness has un­der­ly­ing but undis­cov­ered phys­i­cal ori­gins. For ex­am­ple, re­cent stud­ies have in­di­cated that se­vere fa­tigue is as­so­ci­ated with raised lev­els of lep­tin, a hor­mone pro­duced in fat tis­sue which sig­nals to the brain that the body has ad­e­quate en­ergy stores. This raises the prospect that too much lep­tin – pos­si­bly from too much body fat – means we nat­u­rally feel less en­er­getic: if we don’t need food we don’t need to go out and do some­thing about it. This links with anec­do­tal ev­i­dence that in­ter­mit­tent fast­ing and re­duc­ing body fat can im­prove peo­ple’s en­ergy lev­els.


It also links with re­search in­di­cat­ing that peo­ple with CFS/ ME can have high lev­els of lep­tin and sim­i­lar in­flam­ma­tion-pro­duc­ing sub­stances called cy­tokines. Cy­tokines, which are also pro­duced in fat, are re­leased dur­ing im­mune re­sponses. Stud­ies have shown that low-grade in­flam­ma­tion robs mice of their en­ergy to run on a wheel. This sug­gests that un­der­ly­ing tis­sue in­flam­ma­tion – whether it’s in re­sponse to a virus, a long-term con­di­tion or a prob­lem with cy­tokine reg­u­la­tion – can be enough to make us feel weary. Sci­en­tists in the Nether­lands have now started a ma­jor new trial to find out whether anakinra, an anti-in­flam­ma­tory drug that blocks a par­tic­u­lar cy­tokine, brings an im­prove­ment in peo­ple with CFS/ME.

New­ton is clear that these re­lated un­der­ly­ing phys­i­cal vul­ner­a­bil­i­ties may be a fac­tor in ev­ery­one’s con­tin­u­ing tired­ness – not just those with a di­ag­nosed con­di­tion. “The day-to-day fa­tigue that GPs see def­i­nitely re­lates to chronic ill­ness. The two aren’t sep­a­rate,” she says.


There’s new re­search to sug­gest some of us may sim­ply have been born with a phys­i­cal and psy­cho­log­i­cal susceptibility to tired­ness.

Re­searchers from the Univer­sity of Ed­in­burgh an­a­lysed the ge­netic make-up of 111,749 peo­ple who in­di­cated they felt tired in the two weeks be­fore sam­ples were col­lected for the UK Biobank. They found a ge­netic link be­tween those who re­ported tired­ness and those prone to di­a­betes, schizophre­nia, high choles­terol or obe­sity. “This raises the pos­si­bil­ity of a ge­netic link be­tween tired­ness and vul­ner­a­bil­ity to phys­i­o­log­i­cal stress,” said the team, led by Prof Ian Deary. How­ever, the re­searchers also said that the ma­jor­ity of peo­ple’s dif­fer­ences in self-re­ported tired­ness can be put down to en­vi­ron­men­tal causes rather than ge­netic fac­tors. So how we live our lives, and what hap­pens to us, is of first im­por­tance.

And the sig­nif­i­cance of our re­la­tion­ship to day­light is be­com­ing in­creas­ingly clear. For decades, we’ve been told that keep­ing reg­u­lar habits and sleep­ing hours is im­por­tant. Now, re­search has con­firmed the im­por­tance of a part of the brain called the suprachi­as­matic nu­cleus (SCN), a group of cells in the hy­po­thal­a­mus that re­sponds to light sig­nals fed from the eye. When it’s light, the SCN mes­sages other parts of the brain to re­lease hor­mones which make us feel alert, and when it’s dark it sig­nals for the re­lease of hor­mones that make us feel sleepy, like mela­tonin.

If our habits are reg­u­lar, our brain ad­justs to re­lease hor­mones at the right time. If they’re not, we end up in con­stant con­flict with our nat­u­ral cir­ca­dian rhythm. The blue imi­ta­tion day­light emit­ted from com­puter screens and smart­phones can con­fuse our SCN fur­ther, es­pe­cially if we’re us­ing our screens at night. Our brain is tricked into think­ing it’s day when it’s not, and we end up feel­ing awake when we should be sleepy, so we don’t get such a good night’s rest.

There’s in­creas­ing pub­lic and sci­en­tific in­ter­est in us­ing what are known as ‘chrono­bi­otic agents’ to ad­just the body clock to counter sleep prob­lems, tired­ness and mood dis­or­ders. Stud­ies in­ves­ti­gat­ing whether tak­ing mela­tonin tablets re­duces fa­tigue have been mixed, and doc­tors warn against overuse of the sup­ple­ment. But some new types of an­tide­pres­sants, such agome­la­tine, work by reg­u­lat­ing cir­ca­dian rhythms and there’s ev­i­dence they im­prove day­time func­tion­ing and re­duce fa­tigue.

Some of us are tired for the sim­plest of rea­sons, yet

un­aware of it, says New­ton. She sees hun­dreds of pa­tients in her fa­tigue clinic in New­cas­tle, and for many the cause is al­most too ob­vi­ous for them to see. “It’s amaz­ing how many peo­ple don’t as­so­ciate their day­time fa­tigue with poor night-time sleep,” she says. “Some­times it’s sim­ply a mat­ter of get­ting enough sleep. Peo­ple tend to just carry on do­ing what they’ve al­ways done and don’t rest prop­erly.

“Peo­ple are amazed when I ask them to do an ac­tiv­ity di­ary, and then I ask: ‘Well, when ac­tu­ally do you rest?’ And they say: ‘I’m rest­ing here, when I’m on Face­book’. And I have to tell them, sorry, but that’s not rest­ing.

“We’re in a so­ci­ety on a tread­mill. We’re all push, push, push. And some­times that just isn’t sus­tain­able, phys­i­cally and men­tally.”

The eye de­tects light, send­ing sig­nals to the brain’s suprachi­as­matic nu­cleus, where the body’s ‘cir­ca­dian clock’ is housed

A mi­to­chon­drion, a cell’s ‘power pack’, has a highly folded in­ner mem­brane that’s packed with sub­stances in­volved in the cre­ation of ATP, which the body uses for en­ergy

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