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Measuring bioactive nitric oxide during exercise could help improve fitness, and this new device provides real-time data

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Measuring bioactive nitric oxide during exercise could help improve fitness, and this new device provides real-time data

The heart is the master dispatcher for our lifeblood. It has the crucial burden of balancing physiological economics during rest, during a ride, and while recovering. If the heart can’t pump enough blood to equal demand for nutrients and oxygen, fatigue sets in, you bonk, and sometimes, you have to quit. Rest and replenishment are the only salvation. 

It is well understood that the body’s managerial mechanisms run much deeper, especially during exercise. Governing a cyclist’s overall ability to continue putting out power during any type of effort are the cellular and molecular constituents produced and delivered alongside every contraction of the restless courier in our chest. Oxygen, glucose, fatty acids, lactate, hemoglobin, bicarbonate, nitric oxide — all are important, each playing a role in how well we are able to respond to the stresses of exercise. They also dictate how well the body can adapt and repair between exercise sessions.

We make an intentional point to try and measure and understand the importance of biomarkers and vitals in athletic training and performance, with the current boom in wearable technologies making it possible to deliver insights never previously fathomed. Though no lack of data exists, is there a best measure to understanding an athlete’s exercise capacity and fitness?

Being able to measure blood flow has been a decades-long quest in sports medicine. Exercise physiologists often focus on the mitochondria, bioenergetics, and oxygen consumption (VO2) as a pathway to understanding someone’s performance capacity and upper limits. Coaches use biological outputs such as lactate and heart rate layered atop metrics like power to guide training strategy. The integration of all of these somatic informatics is rightfully based on what we know as best practice today.

But what are the true regulators and rate limiters of performance? We know that the ability to do work (ride a bike) is based on a few basic orderly factors:

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  1. Muscles need oxygen
  2. and fuel (glucose, fatty acids)
  3. to synthesize ATP
  4. which is used to output mechanical energy
  5. so that they can contract
  6. and work (exercise) can be done.

But a crucial step is missing: the regulation of delivering oxygen and fuel. The body was divinely designed to compensate and adapt to changing conditions, and at the level of muscle oxygenation and work output, here is how that concept is applied. At the onset of exercise, a shift in blood flow must occur to ensure oxygen and nutrients are delivered where they are needed most — your working skeletal muscles, the heart, and brain, primarily. The ability to measure and understand how this happens is crucial. As it turns out, one molecule is inadvertently responsible, and without it, everything else is impossible. 

Hello, SNO.

Performance regulation: There’s a new kid in town.

Nitric oxide (NO) has been hailed as one of the most important regulators of cardiovascular health, impacting blood pressure, inflammation, and overall vascular function. It is a potent vasodilator, responsible for directing and improving blood flow to areas of the body where blood flow is needed most. This happens during periods of oxygen demand and supply mismatch, like exercise, and it happens almost immediately. The supplement market is booming with products that help athletes improve NO production, such as L-arginine, to help maximize blood flow to muscles during a workout.

All of this stated, the classic understanding of how NO is produced and directs blood flow is beginning to change, which inevitably impacts how we think of performance regulation. Let’s break it down. We know that:

  1. Muscles need oxygen,
  2. and oxygen is carried by hemoglobin in red blood cells.
  3. Oxygen must be transferred from red blood cells to muscles 
  4. so work (exercise) can be done. 

Further:

  1. When exercise starts, 
  2. muscles begin consuming oxygen at a higher rate.
  3. A dip in available oxygen happens.
  4. Oxygen is increasingly offloaded from red blood cells to try and match the new demand. 

Remember: supply must match demand. 

Now what? An economic dance ensues between red blood cells (where oxygen is carried), and the oxygen tension in the muscle itself. A newer discovery has explained how this interplay impacts overall dispersion of blood during a workout so muscles can be adequately fueled and exercise can continue, and it is meticulously regulated.

During conditions where oxygen tension in muscles (and therefore red blood cells) decreases, a nitric oxide derivative called S-nitrosohemoglobin (SNO-Hb) is also produced and offloaded by hemoglobin alongside oxygen. SNO-Hb, part of a group of compounds called S-nitrosothiols, or SNOs, dilates the tiny blood vessels in the muscle tissue itself (capillaries, arterioles). Blood flow increases, and oxygen delivery can now meet the heightened demand. This goes for nutrient delivery too, like increased need for fatty acids and glucose.

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Why is measuring SNO helpful?

It could be hypothesized that many of the foundational benefits of exercise are due to these well-controlled increases in blood flow. There is a system-wide effect on the heart and brain, too. Further, there are adaptations to the cardiovascular system and blood profile in response to training. More exercise leads to more hemoglobin, a larger blood volume, and a greater and faster NO response. The latter specifically leads to a better blood flow response, and therefore improved oxygen and nutrient delivery. Theoretically, the same goes for bioactive NO derivative, SNO, at the tissue level. In this perspective, SNO is sitting in the driver’s seat and orchestrating it all.

Devices exist on the market today that measure oxygen saturation in muscles and other tissues (SmO2 or tissue oximeters), but that only paints a partial picture of the impact certain types and intensities of exercise have on an individual. Being able to measure someone’s SNO response to exercise would offer the first look into the gatekeeper of muscle oxygenation. Why do we care? All of this impacts the ability for mitochondria to output adenosine triphosphate (ATP). It is also an indicator of muscular damage during injury and nourishment during rehabilitation. These processes all require oxygen.

Measuring SNO is specific, and it may indicate the readiness and effectiveness of exercise on a personalized level. It can be associative to overall VO2, and oxygen consumption specific to the muscle (called mVO2) as well. It may be an indicator of power output and capacity, and could also correlate to lactate efflux. Further, and most importantly, it can stand alone as its own measurement. As with anything truly new and disruptive, a lot of research needs to be conducted, but there is evidence indicating the usefulness of SNO as a novel biomarker to gauge fitness and performance.

How can we measure SNO? NNOXX has a device

There is a device available today that non-invasively measures SNO, plus muscle oxygenation (SmO2) and muscle oxygen consumption (mVO2) from a company called NNOXX. (Full disclosure: I have consulted with NNOXX on clinical and regulatory affairs.)  It’s the only device of its kind, delivering continuously streaming data that can be accessed at any point during a ride or workout. NNOXX helps athletes understand the efficiency and effectiveness of an exercise by measuring these performance indicators directly in exercising muscle, in real time.

One differentiating thing about these biomarkers is that they are exercise “blind,” meaning you can ride or you can lift, and you will still produce SNO and use oxygen, just not in the same way (a topic for a different article). The $299 NNOXX device can be used to make individualized assessments during many types of exercise — biking, lifting, and running, as examples — and only needs to be placed on the exercising muscle during your workout. 

So how can riders use NNOXX to help improve their cycling performance?

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NNOXX provides a Performance Readiness Score

Muscle recovery can be impacted by insufficient calories, poor sleep, dehydration, overreaching, or even the onset of illness. NNOXX is differentiated because the biological assessments are measured and delivered in real-time based on rates of oxygenation and deoxygenation, plus the bioactive nitric oxide response while you’re exercising. All you have to do is a guided four-minute cycling protocol and the app will give you both a Muscle Readiness and Aerobic Readiness percentage tailored to your physiological status. You’ll be given a recommendation of how to proceed based on your score. You can also see a seven-day trend.

NNOXX can help you understand how well you performed compared to other rides or exercise sessions. 

The app provides individualized performance indicators, including a Power Index, Endurance Index, and Economy.  These indicators are based on your personal rates of muscle deoxygenation, reoxygenation and other factors, measured in real-time during your workout. After your workout is finished, you’ll receive your score for the day, your average range, and 60-day comparative trend. 

This feature is really useful if riders have regular routes or workouts, and they’re interested in seeing if they’re improving, especially when making changes to their routine (e.g. more sleep, additional interval sessions, changes in recovery or dietary habits, or longer rides). 

Further, users can potentially infer if a specific type of riding is best for them. For example, if the data shows you’re more efficient at climbing than previously thought, it may be something worth capitalizing on or integrating more often into your routine. The opposite can be a takeaway, too. If the app indicates you perform better doing power activities than long rides, you can use this to create a goal around improving your endurance.

What if I am new to mountain biking or cross-training and to improve my performance without hiring a coach or personal trainer? 

The NNOXX app provides an AI-guided coach to customize your ride or other workout to be the most effective and efficient. The output is based on the effects of your real-time SNO production. As data is aggregated, workouts can be compared and personalized to your individual physical performance to help maximize gains.

For a new-to-market device and a new biomarker, the metrics provided by the device do seem to be physiologically reliable and accurate. Because the data is provided continuously with relatively no lag, the information can easily be compared to other performance indicators. Users can see how their body is compensating for increases in cadence or terrain grade, as examples.

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NNOXX recently released a feature that allows users to import their Strava and Peloton data into the High Performance Platform on their website. Comparisons between SNO and SmO2 can be made alongside work, power, heart rate, and others on a single platform. 

Again, the SNO biomarker and associated performance indicators are new. Like most things in science and medicine, it takes time to build up a bank of clinical evidence that is trustworthy, and the data on SNO as a performance biometric promises to evolve as discoveries are made and information is added. The digital technology boom is allowing researchers and developers to change the landscape at an unmatched speed, and NNOXX is a great example of what I believe is a positive outcome of the race.

Sources

Premont, R. T., Reynolds, J. D., Zhang, R., & Stamler, J. S. (2020). Role of nitric oxide carried by hemoglobin in cardiovascular physiology: developments on a three-gas respiratory cycle. Circulation research, 126(1), 129-158.

Reynolds, J. D., Posina, K., Zhu, L., Jenkins, T., Matto, F., Hausladen, A., … & Stamler, J. S. (2023). Control of tissue oxygenation by S-nitrosohemoglobin in human subjects. Proceedings of the National Academy of Sciences, 120(9), e2220769120.

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Fitness

How the 3-3-3 Rule Helped Me Stick to an Exercise Routine

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How the 3-3-3 Rule Helped Me Stick to an Exercise Routine

If you’ve ever started a new workout routine with the best intentions only to find yourself skipping sessions by week two, you’re not alone. I’m the type to get trapped in the same cycle of burnout, where I go hard for a couple of weeks, feel exhausted, feel guilty, and repeat. For me, what finally broke that cycle wasn’t a new gym membership or a fancy fitness app, but a simple scheduling hack: the “3-3-3 rule.” I’d seen this rule applied it to general productivity, and all the same principles can apply to your fitness habits, too. Here’s how you can use the 3-3-3 rules to structure your workouts and create a habit that sticks.

What is the 3-3-3 rule?

The 3-3-3 “rule” (or “method,” or “gentle suggestion”) is essentially a weekly workout framework built around three types of movement, each done three times per week:

  • Three strength training sessions. This includes lifting weights, bodyweight circuits, resistance bands, whatever builds muscle and challenges your body.

  • Three cardio sessions. This includes running, cycling, swimming, jump rope, a dance class—what counts as “cardio” is up for debate, but here, I think of it as anything that gets your heart pumping.

  • Three active recovery days. This includes light walking, yoga, stretching, foam rolling, and so on.

And yes, I realize this math adds up to nine intentional days of movement across a seven-day week. Here’s the thing: You do double duty some days, or skip workouts here and there, or adjust to a nine-day cycle, because the point isn’t rigid scheduling. The point is rhythm over a strict structure. For me, the 3-3-3 rule provides a sense of momentum that’s flexible enough to fit into real life, but consistent enough to actually stick to.

Why the 3-3-3 rule works for me

Before I get into how the 3-3-3 rule helped me specifically, let’s talk about why so many workout plans fall apart in the first place. I believe most of them make two classic mistakes. The first is doing too much, too soon. You go from zero to six days a week at the gym, you get burnt out, and the whole thing unravels. The second mistake is having no real structure at all—just vague intentions, like “I’ll work out when I can,” which never materializes into anything real for a lot of people.

For me, the 3-3-3 rule solves both of those problems. It gives me enough structure to build habit and momentum, but not so much intensity that my body and brain feel overwhelmed. I personally adore running, but I struggle to motivate myself to lift weights; the 3-3-3 rhythm here helped me find a middle ground between those two workouts. When I know I have three strength sessions to hit in a week (or nine-ish day cycle), I can look at my calendar and find three slots without too much drama or dread.

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There’s also plenty of breathing room built into the plan, which was the biggest game changer for me. I used to have the (toxic) thought that my rest days were wasted days, which is a mentality that led to either overtraining or complete inactivity with pretty much no middle ground.

Plus, there’s something psychologically satisfying about the number three. I know and love the rule of threes in photography, comedy, survival tips, and all over the place.

How to make a 3-3-3 workout schedule work for you

The 3-3-3 rule has a ton of wiggle room for customization. Here are some ideas for how you can approach it:


What do you think so far?

For strength days, pick a format you actually enjoy. That might be a full-body circuit, a push/pull/legs split, or a class at your gym. (Boxing, anyone?) Your focus on these days should be a progressive challenge—push yourself, yes, but don’t obliterate yourself.

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For cardio days, variety helps. Mix a longer, easier effort with a shorter, more intense session (like a 20-minute interval run). I know I’m biased, but cardio really shouldn’t feel like punishment.

For recovery days, resist the urge to “make them count” by sneaking in extra work. The whole point is to let your body consolidate the gains from your harder days. Walk, stretch, breathe, and trust the process.

Another practical tip: Pick a night to map out your 3-3-3 week ahead of time. You’ll probably find that the week arranges itself pretty naturally once you’re looking for those nine windows.

The bottom line

As always, consistency should always be your priority in fitness. If you’ve been struggling to find a rhythm, if your past workout plans have always fizzled out around week three, give the 3-3-3 rule an honest four-week try. Maybe start with a 1-1-1 month! After all, the 3-3-3 rule isn’t a hack to totally transform your physique, but I do think it can provide something way more valuable. Finding a routine that works for you—like the 3-3-3 rule works for me—is the first step to make exercise a reliable, sustainable part of your life.

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I’m a running coach — I’ve just tested shoes actually designed for women’s feet, and they’re a total game changer

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I’m a running coach — I’ve just tested shoes actually designed for women’s feet, and they’re a total game changer

Why you can trust TechRadar


We spend hours testing every product or service we review, so you can be sure you’re buying the best. Find out more about how we test.

QLVR ENDVR: Two minute review

Most running shoes feel familiar for a reason: the formula has barely changed in millennia. We have archaeological evidence of shoes being fastened with “shoelaces” as far back as around 3,500 BC, yet the basic lace-up running trainer remains the default.

QLVR (pronounced “clever”) set out to challenge that. Its debut shoe, the ENDVR, is a laceless “running slipper” built around a women-specific mechanical structure, with a slip-on Wing Fit system inspired by the way a bird’s wing opens and closes around movement.

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Mere minutes of daily vigorous exercise can cut your risk of 8 diseases | CNN

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Mere minutes of daily vigorous exercise can cut your risk of 8 diseases | CNN

Move more. Sit less. For many years, that’s been accepted guidance for people wanting to get healthier.

Now that message is getting refined, with a growing body of research suggesting that certain types of movements may be more beneficial than others when it comes to health benefits.

The intensity of your exercise may matter as well. A new study published in the European Heart Journal found that a small amount of vigorous activity may be linked to lower risk of eight different chronic diseases.

The findings raise questions about why intensity matters and how people can incorporate more intense exercise routines into everyday life. To better understand the study’s implications, I spoke with CNN wellness expert Dr. Leana Wen, an emergency physician and clinical associate professor at George Washington University. She previously served as Baltimore’s health commissioner.

Before beginning any new exercise program, consult your doctor. Stop immediately if you experience pain.

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CNN: What did this study examine about exercise and its relationship to chronic disease?

Dr. Leana Wen: This investigation looked at how the intensity of physical activity is related to the risk of developing a range of chronic diseases. Researchers analyzed data from two very large groups in the UK Biobank, which is a long-term health study in the United Kingdom that tracks medical and lifestyle information from hundreds of thousands of participants. One group included about 96,000 people who wore wrist activity trackers that objectively measured their movement, and the other included more than 375,000 people who self-reported their activity.

The researchers followed participants over an average of about nine years and examined the development of eight conditions: major cardiovascular events, atrial fibrillation, type 2 diabetes, immune-related inflammatory diseases, fatty liver disease, chronic respiratory disease, chronic kidney disease and dementia, as well as overall mortality.

The key finding was that the proportion of activity done at vigorous intensity mattered. People who had more than about 4% of their total activity classified as vigorous had substantially lower risks of developing these conditions compared with people who had no vigorous activity at all. The numbers were stunning, with the participants having the following results:


  • 63% lower risk of dementia,

  • 60% lower risk of type 2 diabetes,

  • 48% lower risk of fatty liver disease,

  • 44% lower risk of chronic respiratory disease,

  • 41% lower risk of chronic kidney disease,

  • 39% lower risk of immune-mediated inflammatory diseases,

  • 31% lower risk of major cardiovascular events,

  • 29% lower risk of atrial fibrillation, and

  • 46% lower risk of death from any cause.

These results are amazing. Imagine if someone invented a medication that could reduce the risks of all these diseases at once — it would be very popular! Crucially, even people who exercised a lot still benefited if the proportion of time they spent doing vigorous physical activity was increased. Conversely, people who were relatively inactive also benefited from adding just a little bit of higher-intensity exercise to their daily routines.

CNN: What counts as “vigorous” physical activity?

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Wen: Vigorous activity is generally defined as exercise that substantially raises your heart rate and breathing. A simple way to gauge it is the “talk test.” If you can speak comfortably in full sentences while exercising, you are likely in the low to moderate range. If you are so out of breath that you can only say a few words at a time, that is vigorous.

Running, cycling, lap swimming or climbing stairs quickly could count. But this also depends on people’s baseline fitness. For some individuals, taking longer strides with walking can be vigorous exercise. Others who are already fairly fit would need to do more. It’s also important to remember that vigorous activity doesn’t have to be in the context of a structured exercise plan. Short bursts of effort in daily life, such as rushing to catch a bus or carrying heavy groceries upstairs, can also qualify if they raise your heart rate and make you breathless.

CNN: Why might higher intensity exercise provide additional health benefits?

Wen: Higher intensity activity places greater demands on the body in a shorter period. This type of movement can improve cardiovascular fitness, increase insulin sensitivity and support metabolic health more efficiently than lower-intensity activity alone. Some studies have also linked vigorous activity with cognitive benefits.

Greater intensity may have distinct benefits across different organ systems. The researchers found that some conditions, such as immune-mediated inflammatory diseases, appeared to be more strongly linked to the intensity of activity than to the total amount. On the other hand, type 2 diabetes and kidney disease were influenced by both how much activity people did and how intense it was. Why this is the case is not yet known, but intensity appears to have a significant impact across diseases affecting multiple organs.

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CNN: How much vigorous activity do people need?

Wen: The threshold for people seeing a benefit appears to be relatively low. The researchers found that once people reached more than about 4% of their total activity as vigorous, their risk of developing chronic diseases dropped substantially.

To put that into practical terms, we are not talking about professional athletes dedicating their lives to hours of high-intensity training. Everyday people may see benefits from just doing a few minutes of vigorous effort daily.

CNN: How can people realistically incorporate vigorous activity into their daily routines?

Wen: One helpful way to think practically is that vigorous activity does not have to happen all at once. It can be accumulated in short bursts throughout the day.

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People can take the stairs instead of the elevator and do so at a faster pace than usual. When they are heading to work, they can add some speed walking. They can park farther away when grocery shopping and walk briskly while carrying groceries.

Structured exercise also can incorporate intervals where people alternate between moderate and more intense effort. If you’re swimming laps, you can warm up at a more leisurely pace, then do a few laps at a faster pace, then again at a leisurely pace and repeat. This suggestion applies to any other aerobic exercise: Aim for multiple intervals of at least 30 seconds to a minute each where your body is working hard enough that you feel noticeably out of breath.

CNN: What about someone who is older or has mobility issues?

Wen: Not everyone can or should engage in high-intensity activity in the same way. Vigorous activity is relative to that person’s baseline. For someone who is not used to exercise, even a short period of slightly faster walking or standing up repeatedly from a chair could be considered high intensity. And not everyone may be able to walk. In that case, some exercises from the chair can have aerobic benefits.

Individuals who have specific medical conditions should consult with their primary care clinicians before embarking on a new exercise routine. People with mobility issues also may benefit from working with a physical therapist who can help to tailor exercises appropriate to their specific situation.

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CNN: What is the key takeaway for people trying to improve their health?

Wen: To me, the main takeaway from this study is that it’s not only how much total exercise you get but also how hard you push yourself that matters. And you don’t have to have a lot of high-intensity exercise: Adding just a little has substantial health benefits across a wide range of chronic health conditions.

At the same time, exercise needs be practical. People should look for opportunities to safely increase intensity in ways that fit their daily lives. The most effective approach to physical activity is a balanced one: Exercise regularly, incorporate more challenging activities when you can and build habits that are sustainable over time.

Get inspired by a weekly roundup on living well, made simple. Sign up for CNN’s Life, But Better newsletter for information and tools designed to improve your well-being.

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