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The Fatigue Biomarker Index & Sleep Deprivation

Blog written by John Kalns

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An Experiment in Exhaustion

The fatigue biomarker index was discovered during an experiment in which volunteers were asked to participate in exhausting physical work over the span of 10 hours. As participants became increasingly exhausted, our team searched for differences in the composition of their saliva (shoutout to Dr. Brent Ruby at the University of Montana! Kudos for leading the team that took on the exercise challenge portion of the study).


Looking at Peptides

Rather than making assumptions about what we might find, we looked for changes in the levels of most of the small proteins (or peptides) present in saliva. We ignored peptides whose concentrations were below a certain level because we thought that it would be too difficult going forward to develop a reliable test if levels were very small. After examining about 4,000 peptides, our main observation was that the abundance of these small molecules in individuals remained about the same over time, with the exception of about 30 that changed as volunteers grew more and more exhausted.

Out of these candidates, two peptides in particular were interesting. When we looked at the ratio of these two peptides, we found that this ratio was the best predictor of physical exhaustion. In fact, the ratio changed by about 1,000 times from a rested state to a fatigued state. This response was amazing and very robust!

Besides intense physical exertion, we know that fatigue can be caused by a variety of different things. For example, two factors that increase fatigue are illness and lack of high-quality sleep. Most Americans don’t know much about starvation, but if you try fasting (not eating) for a couple of days, you will discover a very strange state of profound fatigue and mental clarity.

One thing we were able to do was conduct a study to determine if sleep deprivation also caused a change in our fatigue biomarker index. This study was published in a peer-reviewed journal, which you can find here.

The big message from this study was that the index detects fatigue that is caused by sleep deprivation. The graph on the right shows our main finding: sleep-deprived people have very different levels of the fatigue biomarker index (compared to people that aren’t sleep-deprived), and the graph shows these huge differences. This was interesting because we now knew that the fatigue biomarker index measures fatigue that is caused by both intense physical exertion as well as lack of sleep.


Are People Honest About How Tired They Are?

Sometimes when I talk to people, they bring up that knowing how tired you are is “just common sense,” and that everybody has a pretty good idea of how tired they are.

When we first sent this paper out for peer-review, one reviewer stated that asking someone how fatigued they felt was the most sufficient way to measure fatigue, and that the entire concept of an objective laboratory test that measures fatigue is pointless. But the learned scholar might not have considered one thing: people may not report their level of fatigue honestly.

For instance, consider that people work dangerous jobs and should not be performing tasks if they are seriously fatigued. Driving a car is another example of a dangerous activity in which fatigue can be hazardous – high levels of fatigue are implicated in many accidents. So the question remains: are people honest about just how tired they are? In many cases, the answer is no.


Surveys and Assessments

Here’s the point: During this study we took a fatigue survey (POMS fatigue sub-scale) and had volunteers perform a cognitive assessment. The Stroop Color and Word Test is a quick cognitive test performed on a laptop or other device. In the Stroop test, you are shown the written name of a color (such as BLUE), and the font color is either congruous or incongruous with the word’s real color. But you must decide quickly in order for the assessment to actually work. It’s pretty clever because if you are fatigued, you’ll make more mistakes when trying to correctly identify whether or not what is shown is congruous.

The fatigue biomarker index is not the only way to measure fatigue. We compared the fatigue biomarker index to two commonly used methods to measure fatigue: a survey and a cognitive ability test.

Surveys are still the most common method of measuring fatigue, and they work by asking people questions related to how they feel and how tired they are. The answers to the questions are then compiled and a score is provided that indicates the person’s level of fatigue. However, surveys are subjective and people may answer differently. On top of that, depending on the scenario, people may not answer the survey questions honestly.

Another method is to measure how people think. As people grow tired, their ability to perform simple tasks declines. This type of test can be done on a mobile device and only takes a few minutes to complete. Like the survey, a single score can be produced and is associated with fatigue. But the big problem with this is that performance on the test may be affected by many things (not just fatigue).


A Comparison of the Three Methods

We compared fatigue that was measured by these three methods. The comparison is shown in the graph below.

The first thing to notice is that the survey data is clustered in a way that shows a difference between the sleep-deprived group and the non-sleep-deprived group. However, there is a lot of overlap between the groups. The cognitive test shows a similar outcome, though there is a much smaller amount of overlap between groups. Lastly, the fatigue biomarker index shows that the groups are very much separated when compared to the other methods.

The exception is that there are two individuals in the control group that have levels of the fatigue biomarker index that are suggestive of fatigue. Maybe these two individuals were very fatigued going into the study. Or perhaps they’re afflicted with a sleep disorder or other issue that prevents them from obtaining adequate sleep. Although we did not evaluate these possibilities systematically, it’s certainly possible these two participants may have other issues that caused them to enter the study already fatigued.

The important overall message here is that the fatigue biomarker index accurately identifies people that are fatigued, and it does the best job of measuring fatigue (at least from a statistical perspective).


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References

 

Haythornthwaite, J. A., & Edwards, R. R. (n.d.). Profile of Mood States (POMS). Immpact. Retrieved from http://www.immpact.org/meetings/Immpact12/background12.html

 

Salivary Biomarkers of Physical Fatigue as Markers of Sleep Deprivation – PMC. (n.d.). PubMed Central (PMC). Retrieved April 25, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836344/

 

The Stroop Color and Word Test – PMC. (n.d.). PubMed Central (PMC). Retrieved April 25, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388755/

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