Newsletter #222

You're probably already well aware that prolonged sitting is linked to greater risk of cardiovascular disease. For instance, a meta-analysis of 18 studies found that the highest levels of sedentary behavior were associated with 147% higher risk of cardiovascular disease and 90% higher risk of dying from heart disease. But why exactly?

Well, one major reason has to do with blood flow in the legs. Extended sitting reduces blood flow in the arteries in your legs, particularly the popliteal artery, which runs behind the knee and is the primary vascular supply to the knee and lower leg. Less blood flow results in impaired endothelial function. The endothelium is a membrane that lines the walls inside of your blood vessels, and endothelial dysfunction is considered to be an important contributor to the initiation and progression of atherosclerotic lesions.

We have known since the 1960s that atherosclerosis tends to develop in regions of arteries with low shear stress, meaning less outward pressure due to blood flow, and the legs seem to be uniquely prone to developing these lesions, perhaps due to the effects of sitting. It has since been well established that prolonged leg bending (like when sitting in a chair) impairs endothelial function in the arteries of the leg due to lower blood flow and shear stress, and even young children experience profound reductions in vascular function after hours of sitting.

This kind of sucks, since a lot of us make our living through sedentary jobs, which basically require you to spend long periods of time in relative inactivity. Fortunately, there are some things that we can do about it. Endothelial dysfunction due to sitting is mediated by reductions in nitric oxide (NO) production, and broadly speaking there are two ways we can counteract this:

The first is kind of obvious: increase blood flow through some form of movement. Shear stress from blood pressing on the endothelial walls of blood vessels results in rapid rises in NO, which improves endothelial function. But here’s the cool part: even really small intermittent leg movements, while you are sitting, could make a big difference here, as you’ll see.

Another way is to increase nitric oxide bioavailability. This can be achieved either by consuming large amounts of dietary nitrates, which can boost NO through the nitrate-nitrite-nitric oxide pathway, or through regular physical activity, which over time leads to boosted production of nitric oxide even at rest.

Researchers at the University of Missouri recruited 15 young healthy subjects and put them through three different experimental trials: 1) sitting for 3 hours without prior exercise; 2) sitting for 3 hours after 45 min of cycling on a stationary bike; and 3) standing for 3 hours without prior exercise. To assess how their arterial function responded to the experiments, the researchers measured flow-mediated dilation (FMD) in the popliteal arteries before and after each trial. As you’d probably expect, 3 hours of sitting without exercise resulted in a major impairment in popliteal artery FMD (baseline: 3.8±0.5%, post-sitting: 1.5±0.5%). However, when the participants performed exercise prior to sitting, or when they stood, their popliteal artery FMD remained steady. This study is particularly nice because it offers two different potential paths to prevent vascular dysfunction: either stand up instead, or do a workout beforehand.

The same research team at Missouri recruited 11 young healthy subjects and had them sit, with both feet on the floor, for three hours. They were instructed to jiggle one leg up and down every four minutes (using a timer to remind them at each interval), but to keep the other leg completely still throughout (basically a control). The popliteal artery of the leg that remained still exhibited a reduction in blood flow and shear rate throughout the sitting period, which was accompanied by an impairment in flow-mediated dilation (presit: 4.5 ± 0.3%; postsit: 1.6 ± 1.1%). In contrast, every bout of fidgeting resulted in a pronounced increase in arterial blood flow and shear rate, and FMD in that legsignificantly improved after the sitting period (presit: 3.7 ± 0.6%; postsit: 6.6 ± 1.2%).

Researchers at Chukyo University in Japan recruited eleven healthy young subjects and randomly assigned them to consume either 140 mL of beetroot juice (containing ~12.8 mmol of nitrate) or a placebo that tastes and looks the same but is devoid of nitrate. The subjects were then situated in a comfortable chair, where they sat for three uninterrupted hours and either read or played on their smartphone without moving their legs. At a later date, all participants were switched to the opposite condition (either supplement or placebo) so that every participant could effectively serve as their own control. When they drank the control beverage, they showed a 65% relative reduction in popliteal FMD (basically, inducing a state of endothelial dysfunction). But when they drank the beetroot juice prior to the sitting bout, their FMD remained unaffected.

Researchers in Tokyo recruited two groups of men: 10 male collegiate cyclists, and nine men with no regular endurance training. They measured their aerobic fitness through an incremental exercise test (unsurprisingly the cyclists were way fitter), and assessed their popliteal artery FMD. Similar to the other trials, the guys sat for 3 uninterrupted hours, and the researchers gauged the effect of this sitting bout on their endothelial function. In the untrained group, popliteal artery FMD fell considerably after sitting, much like we've seen in these other studies. However, the prolonged sitting did not seem to affect the cyclists. This is pretty impressive because it suggests that chronic physical exercise, not just an acute bout of activity, can protect vascular function while sitting. The researchers attribute this finding to greater nitric oxide synthesis and bioavailability. Previous studies suggest that endurance training boosts NO synthesis at rest, which would help protect FMD through a mechanism similar to supplementation of dietary nitrates.

Sedentary behavior is clearly deleterious to your cardiovascular health, which is one reason why we recommend integrating movement breaks into your day. But emerging research also suggests that physical activity, including just standing and walking, may influence aspects of your cognitive performance. This is due, in part, to changes in blood flow to the brain, as well as through a long-term rise in levels of growth factors in the brain. Pretty cool!

In this course, we review:

🧠 Effects of exercise on the mind

💡 How physical activity within the day can improve your thinking

🏋️ Strategies to integrate more movement into your day

Thanks for reading, enjoy the weekend, and we'll see y'all next week!

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