Newsletter #282: Sleep, Mitochondria, and Metabolism
Sleep is kind of an evolutionary enigma. At least on the surface.
On the one hand, it is a highly vulnerable state, leaving us at the mercy of our environment and unable to defend ourselves. It’s also time-consuming and unproductive, which is why people throughout history have aspired to get less of it. On the other hand, it appears to be nearly universal in the animal kingdom. And no person or creature can forego sleep without suffering physiological consequences.
So, sleep must be super important. But oddly enough, we have yet to settle on a “true purpose” for sleep, though a number of hypotheses have been proposed. One older idea, which has regained some traction lately, is the free radical flux theory of sleep. The basic idea is that while we are awake and active, reactive oxygen species accumulate, due to high metabolic demands (especially from the brain). Then, when we sleep, our metabolism drops to its lowest level, and endogenous antioxidant systems are able to efficiently mop up free radicals. However, when sleep is truncated, this restorative process is disrupted, leading to oxidative stress.
Mitochondria, being “the powerhouse of the cell,” are actually responsible for most of these free radicals being generated as a byproduct of normal metabolism. But ironically, the mitochondria are also one of the primary victims, as they are highly vulnerable to oxidative damage. As a result, animal models suggest that sleep deprivation leads both to accumulation of reactive oxygen species and mitochondrial dysfunction.
Deteriorating mitochondrial function is bad news for multiple systems, but it’s perhaps most obvious when viewed through the lens of metabolic health. Mitochondrial abnormalities are much more prevalent in individuals with insulin resistance and type 2 diabetes, and there’s good reason to think that mitochondrial dysfunction could partially mediate the well-established link between sleep and blood sugar regulation.
So, I thought I would zero in here on two key studies — one old study and one newer one — that have examined how sleep loss influences mitochondrial function, and in turn affects glycemic control. Even better, one of these trials managed to identify a potential solution to this problem.
This Week’s Research Highlights
Total sleep loss reduces markers of mitochondrial function, which is accompanied by worse glycemic control.
To examine how sleep loss affects energy metabolism, researchers in Prague recruited seven healthy young students and monitored them for a 3-day control period. They drew blood samples and extracted muscle biopsies from each individual after this control period, then completely deprived them of sleep for 120 hours, or five whole days. (This study was conducted more than forty years ago, when it was probably a little easier to subject people to this level of sleep deprivation). Afterwards, the researchers repeated the blood samples and muscle biopsies.
The skeletal muscle samples were analyzed before and after the intervention for activity of various key mitochondrial enzymes. For example, citrate synthase activity is frequently used as a biomarker of mitochondrial content and function. For three of these enzymes, decreased activity was highly significant, including activity of citrate synthase (–24%), malate dehydrogenase (–35%), and glycerol-3-phosphate dehydrogenase (–17%) in human skeletal muscle.
Taken together, this suggests decreased functional capacity of the mitochondria in response to sleep loss, and this appears to have led to metabolic derangement in these young men.
The subjects showed a significant increase in free fatty acid (FFA) concentrations, going from a healthy level, on average, to what would now be considered in the typical prediabetic range. This was also reflected in their blood sugar, as the subjects experienced a rise in blood glucose (increased by ~10.6 mg/dl).
These authors, in 1981, stated, "The observed elevated glycaemia, elevated and protracted glycaemia during the oral glucose tolerance test...suggest the presence of a pre-diabetic type of metabolism during sleep deprivation."
Sleep loss results in reduced mitochondrial function and insulin sensitivity — but performing high-intensity interval training mitigates this effect.
Experiments using total sleep loss can be very helpful for clearly illuminating the importance of sleep. But most of us are not routinely foregoing sleep for more than 24 hours.
To examine how partial sleep restriction influences mitochondria and metabolic health, and how physical activity might interact with this phenomenon, Australian researchers recruited 24 healthy young men and had them spend eight nights in a temperature controlled sleep laboratory. The men were allocated into three groups:
- Normal sleep (8 hours in bed for five nights)
- Sleep restriction (4 hours in bed for five nights)
- Sleep restriction + HIIT (4 hours in bed for five nights and three high-intensity interval exercise sessions)
At the beginning and end of the trial, all subjects got blood work done, as well as muscle biopsies to assess mitochondrial respiratory function.
So what happened? Well, let’s start by taking a look at the sleep restriction group (without exercise). When they were given an oral glucose tolerance test, they showed a 22% increase in plasma glucose area under the curve (AUC), as well as a 29% increase in mean insulin AUC, indicating that their glycemic control had deteriorated. And much like what was reported in the prior study, they showed a reduction in mitochondrial respiratory function, as well as decreased mitochondrial protein synthesis.
However, in the group that was subjected to the exact same degree of sleep restriction but who also performed HIIT, these effects were totally abolished. Both their mitochondrial respiratory function and their blood sugar control remained healthy in the face of five nights of serious sleep loss.
This reinforces the beneficial impact of intense physical activity on mitochondrial function, and suggests that exercise could be key for fighting the negative effects of sleep loss.
Random Trivia & Weird News
There are many examples throughout history of attempts at biological control going awry. People take an exotic species and introduce it to a new habitat, hoping that it will prey upon local pests, but the interloper creates unforeseen issues, and sometimes winds up even making things worse!
One such example is the Asian mongoose. Sugar cane farmers brought this creature to Hawaii, hoping that it would control rats in sugarcane fields.
Herein lies the problem – the mongoose is diurnal, like us, meaning that they are active during the day and sleep at night. Meanwhile, rats are primarily nocturnal. This meant that the mongoose and the rat, while living in the same space, did not interact with one another.
Instead, the mongoose has had a serious negative impact on native bird populations, as well as endangered sea turtles. It has been reported that the mongoose is responsible for ~$50 million in damages, due to their ecological toll.
Podcasts We Loved This Week
- Erik Richter: Interactions between exercise and insulin. Via Inside Exercise.
- Larry Reagan: Pondering the effects of insulin resistance and bad stress on the brain. Via Brain Ponderings with Mark Mattson.
Products We Like
Supplemental melatonin can help a lot with falling asleep at the right time, and realigning your circadian rhythm. Furthermore, it has been suggested that taking melatonin may protect mitochondria from the ravages of oxidative stress.
But it’s important to source melatonin carefully, because quality control for over-the-counter supplements can be really questionable. A recent chemical analysis of the melatonin gummies found that almost all brands failed to match the claims on the labels. The actual per-serving dose of melatonin ranged anywhere from 74% to 347% of the labels’ stated amount.
That’s why you want to make sure to get a supplement that is independently lab-tested, like Nature Made. As an added bonus, this brand is super easy to find in grocery stores and drug stores all over.
humanOS Catalog Feature of the Week
This week, we’d like to highlight our How-to Guide for Smart Daily Light. We evolved in the presence of natural daily cycles of light and darkness. But obviously, the invention of artificial lighting means that we can now fully control when and how much light we’re exposed to, which has altered this relationship. Today, most of us spend the majority of the day indoors, under comparatively dim artificial lights. Then, after sundown, we are exposed to more bright light, and importantly more blue light due to our digital devices. Consequently, we are getting less bright light during the day and less darkness at night.
This is important because light sends crucial signals to the body, and the intensity and timing of this light matters for your health as well as your performance. But fortunately, there is a lot you can do about it. In this guide, we discuss how you can achieve a pattern of natural light and darkness in the modern world by adjusting behavior, modifying your indoor spaces, configuring your devices, and more.