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Metabolic switch may bring on chronic fatigue syndrome

Metabolic switch may bring on chronic fatigue syndrome

Chronic fatigue syndrome seems to be caused by changes in the body’s metabolism

By Andy Coghlan

https://www.newscientist.com/article/2121162-metabolic-switch-may-bring-on-chronic-fatigue-syndrome

It’s as if a switch has been flicked. Evidence is mounting that chronic fatigue syndrome (CFS) is caused by the body swapping to less efficient ways of generating energy.

Also known as ME or myalgic encephalomyelitis, CFS affects some 250,000 people in the UK. The main symptom is persistent physical and mental exhaustion that doesn’t improve with sleep or rest. It often begins after a mild infection, but its causes are unknown. Some have argued that CFS is a psychological condition, and that it is best treated through strategies like cognitive behavioural therapy.

But several lines of investigation are now suggesting that the profound and painful lack of energy seen in the condition could in many cases be due to people losing their ability to burn carbohydrate sugars in the normal way to generate cellular energy.

Instead, the cells of people with CFS stop making as much energy from sugar as usual, and start relying more on lower-yielding fuels, such as amino acids and fats. This kind of metabolic switch produces lactate, which can cause pain when it accumulates in muscles.

Together, this would explain both the shortness of energy, and why even mild exercise can be exhausting and painful.

Øystein Fluge of Haukeland University Hospital in Bergen, Norway, and his colleagues studied amino acids in 200 people with CFS, and 102 people without it. The levels of some amino acids in the blood of women with CFS was abnormally low – specifically for the types of amino acid that can be used by the body as an alternative fuel source.

These shortfalls were not seen in men with CFS, but that could be because men tend to extract amino acids for energy from their muscles, instead of their blood. And the team saw higher levels of an amino acid that’s a sign of such a process.

“It seems that both male and female CFS patients may have the same obstruction in carbohydrate metabolism to energy, but they may try to compensate differently,” says Fluge.

Both sexes had high levels of several enzymes known to suppress pyruvate dehydrogenase (PDH), an enzyme vital for moving carbohydrates and sugars into a cell’s mitochondria – a key step for fully exploiting sugar for energy.

Fluge thinks PDH is prevented from working in people with CFS, but that it can spontaneously recover.

Several studies have now hinted that defects in sugar burning can cause CFS, but there is still uncertainty over how exactly this is disrupted. However, a picture is emerging. Something makes the body switch from burning sugar to a far less efficient way of making energy.

“We don’t think it’s just PDH,” says Chris Armstrong at the University of Melbourne in Australia, whose research has also uncovered anomalies in amino acid levels in patients. “Broadly, we think it’s an issue with sugar metabolism in general.”

The result is not unlike starvation, says Armstrong. “When people are facing starvation, the body uses amino acids and fatty acids to fuel energy for most cells in the body, to keep glucose levels vital for the brain and muscles as high as possible.”

“We think that no single enzyme in metabolism will be the answer to CFS, just as no single enzyme is the ‘cause’ of something like hibernation,” says Robert Naviaux of the University of California at San Diego, who has found depletion of fatty acids in patients suggesting they were diverted as fuel.

So what could flick the switch to a different method of metabolism? Fluge’s team thinks that a person’s own immune system may stop PDH from working, possibly triggered by a mild infection.

His team has previously shown that wiping out a type of white blood cell called B-cells in CFS patients seems to relieve the condition. These white blood cells make antibodies, and Fluge suspects that some antibodies made to combat infections may also recognise something in PDH and disable it.

The team is now conducting a large trial in Norway of the cancer drug rituximab, which destroys the cells that make antibodies, in people with CFS. Results are expected next year.

Together, these metabolic approaches are suggesting that CFS has a chemical cause. “It’s definitely a physiological effect that we’re observing, and not psychosomatic, and I’ll put my head on the block on that,” says Armstrong. However, he adds that psychological and brain chemistry factors might be involved in some cases.

Permanent link to this article: https://animatedscience.co.uk/2017/metabolic-switch-may-bring-on-chronic-fatigue-syndrome

Why hasn’t the US eradicated the plague?

Why hasn’t the US eradicated the plague?

  • 15 October 2015
Dry gangrene, caused by the plagueImage copyrightScience Photo Library

It’s nearly 50 years since the US landed men on the moon, but Americans are still dying from a disease that ravaged Europe in the Middle Ages. Why hasn’t the US eradicated the plague?

The Black Death caused about 50 million deaths across Africa, Asia and Europe in the 14th Century. It wiped out up to half of Europe’s population.

Its last terrifying outbreak in London was the Great Plague of 1665, which killed about a fifth of the city’s inhabitants. Then there was a 19th Century pandemic in China and India, which killed more than 12 million.

But the disease has not been consigned to the dustbin of history. It is endemic in Madagascar, the Democratic Republic of Congo and Peru. What’s perhaps more surprising is that it is still killing people in the US.

There have been 15 cases in the US so far this year – compared to an average of seven, according to the Centers for Disease Control and Prevention (CDC) – and the figure of four deaths is higher than in any year this century.

Bar charts showing US plague cases and deaths from 2000 to 2015

The bacterium responsible – Yersinia pestis – was introduced to the US by rat-infested steamships in 1900, according to Daniel Epstein of the World Health Organization (WHO).

“Plague was pretty prevalent, with epidemics in Western port cities. But the last urban plague was in Los Angeles in 1925. It spread to rural rats and mice, and that’s how it became entrenched in parts of the US,” he says.

The disease – typically transmitted from animals to humans by fleas – has a 30-to- 60% fatality rate if left untreated, however, antibiotics are effective if patients are diagnosed early.


The plague

Plague bacteria, Yersinia pestisImage copyrightScience Photo Library
  • More than 80% of US cases have been bubonic plague, the most common form, which affects the lymph nodes and causes gangrene (see picture at top of page)
  • There are two other types, septicaemic, an infection of the blood, and pneumonic, which infects the lungs
  • It can be hard to identify the disease in its early stages because symptoms, which usually develop after three to seven days, are flu-like – a laboratory test can confirm diagnosis

Most cases occur in summer, when people spend more time outdoors.

“The advice is, take precautions against flea bites and don’t handle animal carcasses in plague-endemic areas,” says Epstein.

The areas in question are New Mexico, Arizona, California and Colorado, according to the CDC. All of this year’s cases originated in those states, or in other states west of the 100th meridian, which Dr Amesh Adalja, an infectious-disease specialist at the University of Pittsburgh’s Center for Health Security, refers to as “the plague line”.

“Prairie dogs are the main reservoir for plague, and they tend to be west of the 100th meridian,” he says. The geography and climate of the Western US suits them, he explains, and the fact that they are “social animals” helps the infected fleas to spread.

Prairie dog in CaliforniaImage copyrightGetty Images
Image captionYersinia pestis thrives in prairie dogs’ fleas

Black-footed ferrets and the Canada lynx are other particularly susceptible species, says Dr Danielle Buttke, an epidemiologist at the US National Park Service.

It’s the existence of this “animal reservoir” that makes the plague hard, if not impossible, to eradicate, experts say.

The only human disease eradicated so far, smallpox, does not exist in animals. It’s the same with polio, which remains endemic in two countries – Afghanistan and Pakistan. The WHO is working towards to eradicating polio and last month announced that it is no longer endemic in Nigeria. (It has, however, returned to Syria, since the civil war.)

“Unless we exterminate rodents, [the plague] is always going to be around,” Epstein argues.

California Department of Public Heath workers treat the ground to ward off fleas at the Crane Flat campground in Yosemite National Park, California, on 10 AugustImage copyrightReuters
Image captionPublic health workers treat the ground in Yosemite National Park to get rid of fleas

On the other hand, scientists at the National Wildlife Health Center have been working with parks to develop oral vaccines to protect black-footed ferrets and prairie dog – prairie dogs seem to prefer peanut butter-flavoured baits, research shows.

An injectable vaccine for black-footed ferrets has also been created. So maybe it will be possible to rid animals of the disease, at least in the most popular national parks.

Generally, research into the disease is in a “vibrant” state, according to Adalja, with scientists trying to improve ways of diagnosing it, and to develop an effective human vaccine.

The reason? The plague has been classified as a “category A bioweapon”, he says. An average of seven cases of plague per year is one thing, but the risk of biological warfare, even if it’s a remote one, is quite another.

Permanent link to this article: https://animatedscience.co.uk/2015/why-hasnt-the-us-eradicated-the-plague

Caffeinated plants give bees a buzz

Caffeinated plants give bees a buzz

Permanent link to this article: https://animatedscience.co.uk/2015/caffeinated-plants-give-bees-a-buzz

Roar of the rutting stag: why men have deep voices

Roar of the rutting stag: why men have deep voices

http://gu.com/p/3j7ev

Permanent link to this article: https://animatedscience.co.uk/2015/roar-of-the-rutting-stag-why-men-have-deep-voices-2

How to treat your brain during revision time

How to treat your brain during revision time

http://gu.com/p/3btcq

Permanent link to this article: https://animatedscience.co.uk/2014/how-to-treat-your-brain-during-revision-time

Why an octopus’s suckers don’t stick its arms together

Why an octopus’s suckers don’t stick its arms together

http://gu.com/p/3p9eb

Permanent link to this article: https://animatedscience.co.uk/2014/why-an-octopuss-suckers-dont-stick-its-arms-together

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