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We all know intermittent fasting and exercise are healthy, practical ways we can improve our health & performance. Is it possible to use them together?

Would you benefit more from a fasted workout vs. a "fed" workout?

In this episode of Research Roundup, Geoffrey Woo takes on this very question.

By analyzing a recent study that found fasted workouts improved the metabolic health of obese men, Geoff provides his framework for how you can utilize fasted workouts to meet your goals...or if you should at all.

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What You Need to Know First

For this week's Research Roundup, I'm going to help break down how you should exactly think about exercise and intermittent fasting together.

One of the most common questions that I get about intermittent fasting is, "How do I tie my workouts with my fasting?" We all have this intuition that if you go into a workout hungry, are you going to be light-headed, are you going to be too tired to actually have a good workout? On the other hand, we're starting to hear about more and more athletes who are using intermittent fasting and exercise to be optimizing performance.

How does that work? They seem to be sort of counter ideas that conflict with each other. A recent study published in the journal of clinical endocrinology and metabolism helps elucidate this question with some new data.

We're going to be using and describing that study as a way to anchor some of the ideas and frameworks that we have to think about how to incorporate fasting, exercise given your baseline conditions and what your goals are.

First, I'm going to introduce a framework for thinking about exercise and fasting and then go into a specific study to elucidate some of the key data points and findings from that study. I think you can really break down your baseline starting conditions into three scenarios.

In "Group 1", you have someone that's healthy and looking to optimize their health span. That's probably someone like my use case. I am metabolically healthy and I'm interested in increasing my health and lifespan.

Then there is "Group 2", which is the performance use case, and I'm going to divide that performance use case or that performance scenario into two sub-groups. People that are optimizing for power sports. So this is power lifting, short term burst sports, football, et cetera. And then you have endurance athletes. These are marathon runners, long distance runners. These are aerobic exercises that are over 60 minutes long.

Finally, "Group 3" is what one would consider metabolically impaired. Think metabolic syndrome, prediabetes, oftentimes an over-reliance on glucose as an energy substrate versus being more keto or fat adapted. This is a scenario that unfortunately a lot of us Americans are in. This is folks on a standard American diet, maybe a little bit overweight, a little bit pre-diabetic, and having all the standard conditions or signs of metabolic syndrome.

We have these three groups and it makes sense to think about how you apply the tools of exercise and fasting to optimize for the goals of these three types of people. Of course, if one is looking to optimize for longevity, that might be a little bit of a different application of exercise and fasting in conjunction versus someone that's optimizing for power lifting. That's different from someone that's trying to be a marathon champion versus someone that's trying to reduce their prediabetes.

This idea really ties into some of the themes that I've talked about with previous guests on this program, which include elite sports physiologists, coahces, and world-record breaking athletes. They all are periodizing or cycling their training, and some of the more cutting edge athletes and coaches are also cycling their nutrition against that training. I think when most fitness gurus or YouTube people talk to you, they tell you the one magic formula to get something done and unfortunately the world is not that simple. I think the real way to think about it is that you actually need to understand how these interventions work mechanistically and then you should assess where your starting point is and then understanding the levers. Figure out your own specific program to get to your own goals. That's a more honest, more comprehensive approach to get to your goals.

Now that we've defined the different buckets underneath a framework of how to think about fasting and exercise, let's look at the science. This study, titled "Lipid metabolism links nutrient-exercise timing to insulin sensitivity in men classified as overweight or obese" was done out of the Universities of Bath and Birmingham and it really looked at bucket three, metabolically impaired men and how do we look at exercise and fasting as a way to potentially improve biomarkers associated with metabolic health.

Study Structure

All right, let's dive into the experiment structure and take a look at how this study was organized. This study involved two different arms. An acute arm, meaning only one exercise session was performed and a chronic training intervention that lasted six weeks. For the acute study arm, 12 obese men completed two different conditions in a randomized order. In one of the conditions, the men consumed a high carbohydrate breakfast of cornflakes, skim milk, toast, sunflower spread, and strawberry jam. Take a 90 minute break and then they did a 60 minute bout of aerobic cycling exercise. This is the fed exercise condition. On the other hand, of course we have the fasted exercise condition. These men essentially did the same 60 minute cycling exercise and then consumed the same breakfast immediately afterwards. This is a fasted exercise condition.

In the chronic training study, 30 men were randomized into one of two groups. The first group was randomized into a fasted exercise training group and they completed six weeks of cycling exercise with each exercise session completed in the morning before eating, fasted. And after exercise the group was given a carbohydrate containing recovery drink. And for the non-fasting or fed exercise group, they were provided with a carbohydrate containing beverage two hours before exercise. Each of these groups completed three sessions of cycling per week for six weeks.

Now, what were the end points and outcomes that were measured? In the acute study the researchers were mainly interested in how fuel sources were being used during exercise and the immediate effects of fasted and fed exercise on various important biomarkers. For example, the researchers analyzed breath gas samples during exercise in order to determine substrate utilization. The researchers did this by analyzing the respiratory exchange ratio, the RER, which can be used to determine whether the body's burning primarily fat or carbohydrate. Blood samples were also taken before and after exercise and they were analyzed for glucose, glycerol, fatty acids, and insulin to determine the metabolic response to exercise in the fed or fasted exercise state.

Some of the research participants also had a muscle biopsy done before and after exercise to help determine the triglyceride content of skeletal muscles, their glycogen content and mRNA expression for 34 different proteins involved in metabolism. The main outcome for this acute study was lipid or fat utilization during exercise in the fasted compared to the fed state. Now in the six week training study, blood samples, muscle biopsies and an oral glucose tolerance test were performed prior to and after the training intervention. Along with the OGTT blood samples in the chronic exercise groups were analyzed for muscle lipid composition, activity of metabolic enzymes, and proteins involved in glucose transport and insulin signaling. Body comp and aerobic capacity, which is measured by VO2 max, were also tested pre and post-training to see if fasted or fed exercise had any influence on these measures.

Study Results

Now let's cut to the chase. What did the study find? The first major finding comes from the acute study which showed that exercise before nutrient ingestion increased whole body fat utilization during exercise. In the group who consumed breakfast before exercise, results show that they had an increased utilization of carbohydrates and a reduced utilization of fat. Interestingly, glycogen levels between fed and fasted exercises weren't any different following the exercise bout.

When looking at the actual muscles, it was revealed that in both type one, slow twitch, and type two, fast twitch fibers, triglyceride content was lower and the fasted exercise group only, and this aligns with the finding that they utilize a greater amount of lipids or fat during the exercise bout. These results indicate that exercising in the morning before breakfast promotes an increased reliance on the oxidation of fat during exercise, an effect that was lost when the exercisers had a high-carb breakfast right before exercise.

The second major finding comes from the chronic study arm which showed that exercise training in a fasted state promotes increase in sustained utilization of fat during exercise. The group who trained fasted also showed lower utilization of carbohydrate during exercise versus the fed group. Now energy expenditure during the exercise didn't change between the two groups. This means that the groups were burning the same amount of energy or the same amount of calories, but the energy was just coming from different fuel sources, fats versus carbohydrates.

The third major finding found that exercise training in the fasted state improved oral glucose insulin sensitivity. Improved glucose tolerance was evidenced by the fact that the fastest training group had a lower insulin response to the oral glucose tolerance test, meaning that they needed less insulin to take up the same amount of glucose being infused. In other words, insulin was more efficient, more effective when people did fasted exercise versus those that ate before their exercise.

Insulin sensitivity is a major topic on our podcast. The improved insulin sensitivity in the fasted training group was accompanied by a number of changes in gene expressions that explain this finding. For example, the fasted trading group had a threefold increase in AMPK. AMPK is a nutrient sensor known to be involved in fat metabolism, mitochondrial biogenesis, and glucose uptake, and it's activated during conditions of low energy or low glucose availability. And of course this makes sense considering the above mechanisms. Alongside the increase in AMPK activity, researchers also found that there was a twofold increase in the amount of glucose transporter protein GLUT 4 in the skeletal muscle of the fasted exercise group. GLUT 4 is a protein involved in transporting glucose across cell membranes and this likely helps explain why there was some improved insulin sensitivity observed in this group.

One last aspect to discuss in light of these findings is the fact that many of the benefits accrued in the fasted training group compared to the fed training group occurred independently of changes in body composition or fitness. While the fasted exercise group experienced greater changes in metabolic markers compared to the fed exercise group, both groups actually improved their body comp and aerobic fitness during the training. This eliminates a potentially confounding aspect of the study. So the performance improvements were the same, but the underlying metabolic health was different. That's an interesting, subtle insight.

Key Takeaways

One thing I really liked about this study was the comprehensiveness of the endpoints studied in this research. Not only did the researchers look at performance endpoints like VO2 max and body composition, they also looked and did the work that explains the mechanisms. They did the muscle biopsies to see how the substrates were utilized. Glucose versus fatty acids. They looked at the glycogen levels. They also took it one step further, looking at the underlying metabolic pathways, things like AMPK, things like GLUT 4 upregulation or downregulation. This study wasn't just a cursory understanding of what's happening. It gives you the metabolic and biological and biochemical explanation of why these things were happening.

The key takeaway for this study really is relevant for group three in our overall framework here. So for folks that are metabolically impaired, folks that are obese or overweight, fasted exercise is really potentially effective for you. So again, where we have group one which is healthy, looking to optimize for longevity and health span. Group two was performance athletes and with subgroups of power lifting or power sport versus endurance sport. And then group three are folks that are metabolically impaired. This study essentially tested in randomized controlled trial of fed exercise versus fasted exercise for folks that are metabolically impaired. So essentially a perfect study describing the pros and cons of training fasted versus fed.

I think the takeaways here are quite clear. Fasted exercise is really beneficial to target a couple of the key major things that you want to be focused on if your metabolically impaired. Your insulin sensitivity and increased fat oxidation, those are two major things that you want to be looking at. And the study is also very nice to understand why this was happening. And the reason is that you have an increase in AMPK, an increase in GLUT 4. So not only do you have a recommendation, you also have a biochemical explanation of why you should consider this recommendation. Really nice takeaway here.

Does that mean that everyone, including folks from group one or group two, should everyone only be doing fasted exercise? So what are really the pros and cons here? So when you have a fasted exercise, you're really challenging your body's energetics, meaning that you're really using low energy availability as a way to stress your body into optimal adaptations to counteract those stresses. When you're looking at folks in group one, and this is folks like myself, I'm metabolically healthy and my goals are primarily for health span and lifespan, I need to think about a couple end points to focus on. Of course fat oxidation is important for me. Of course insulin sensitivity is important for me, but I also do care about functional strength and gaining lean muscle tissue.

One of the longer term things that are correlated with mortality is sarcopenia or muscle loss. So you don't want to be so fasted that you're very frail and you get injury and that will cause me to die earlier. So you need to find the balance between muscle building and anabolic type exercises or routines that increase anabolic muscle building, and while also taking advantage of things like training on AMPK in which we also know is optimal for longevity.

The way I think about my routine or folks in group one is that you want to periodize or make cycles of fasted and fed exercises. So for example, I might think about having a few days of my week to really do maximal exercise. If I'm really trying to push up my weight on the squat or the bench press, then I'll probably have a little bit of a carbohydrate and amino acids before that workout. But on other days of the week, if I'm doing more lighter weight or more endurance based exercises, I'll use no food at all or a lot less food or even do the exercise fasted. So think about as a balance and not as a one size fits all solution. And I think this is where science translates into art and where coaching and personal experience really starts mattering, right? Work with really, really smart physiologists and coaches to really fine tune the science, which is done on a population level and how that translates to the individual, which is yourself.

Now let's talk about group two, which is performance athletes. If you're looking to win an Olympic gold medal for example, you actually don't want to be stressing and allowing your body to compete in a fasted or a constrained state. You actually want to give it as much substrate as available as possible to perform at its optimal and maximal peak. And I think you need to really think about performance into two buckets. You've got the power burst sports and then the endurance group, and intuitively you can see that these are two very different types of athletes. Two different types of goals. I'm going to think about it in two different dimensions. Are your goals power or anaerobic performance or are your goals aerobic performance? That is one dimension. And the other dimension that you need to think about is are you training and building up adaptation or are you competing where you're trying to win that gold medal that specific day.

You need to think about your fasting versus fed and the types of exercises specific to each of the quadrants that we just described. Now for folks that are really focused on power, bodybuilding, gaining mass, again you probably want to be having more of your exercise lean towards fed exercise because it makes sense, and the literature actually does show that for building power you're going to be mainly glucose driven and having availability of glucose readily available. It's going to be a dominant driver for availability of power and ATP. So for anaerobic exercises you're going to lean towards fed. Now of course when you're actually competing, went it's at a gold medal competition, absolutely go into that competition fed. You're going to need as much availability of substrate as possible. You want to maximize everything. While that might not be good for optimal longevity to pound a hundred grams of sugar, it's going to be probably helpful for your one specific bout.

But for the training you might want to consider adding some bouts of fasted exercise. Again, this is where your specific training protocols, you should consult a coach or really dive down into exactly what goal you're looking at, but getting the adaptation, triggering AMPK, getting up your insulin sensitivity is probably helpful to incorporate in somewhat, I would say on a lower bound, as you're doing an exercise routine to build up towards competition.

Now let's talk about aerobic performance. Oftentimes these are cyclists, marathoners, triathletes, and these exercises or bouts go for 60 minutes upwards of eight hours. Oftentimes when we talk to athletes that are these types of athletes, they do a lot more fasted exercise. Oftentimes when you're transitioning from off season to on season, they might do a lot of fasted exercise to really jumpstart their training season, and I think the subtle, interesting point here is that as these endurance activities rely more and more on fat oxidation as a primary fuel substrate, because you just run out of glycogen, run out of glucose, you do want to be training that fat utilization, that fat oxidation rates. So I would say for group two, for aerobic training, you probably want to do a little bit more fasted workouts than folks that are anaerobic or power sport athletes. But absolutely for competition day, all the hard training you did fasted makes your body a lot more efficient on its substrate utilization. But on competition day, give it as much substrate as possible.

And to talk a little bit about one of our own key products, H.V.M.N. Ketone Ester, it gives you additional substrate that doesn't normally occur in your food supply. We're all familiar with carbohydrates, we're all familiar with fat, but what if you have ketones, a third substrate in your system at the same time, and usually you don't have all three going at the same time. So that's where maximal performance and why on competition day, ketones are so helpful for a lot of athletes that we work with.

In Conclusion

To conclude and give you a holistic sense of the framework, we all have different starting positions or metabolic health and we all have different possible goals that we want to reach. And it just makes sense that we need to apply the tools of exercise and tools of fasting in the right ways for the specific person and for the specific goal. I think this whole notion of this framework really just ends up at a biological, fundamental truth, which is that there is no free lunch here. There's always going to be some trade off. If you're optimizing for one thing, it oftentimes comes at the expense of another thing and that decision is going to be different for each and every one of us and that's great.

That's human individuality and that's why I'm excited about teaching people and giving people frameworks to think about this. Because again, it's not really useful if someone just tells you a one rule, one size fits all solution because my goals might be different from your goals. It's not useful for you. But if you understand the frameworks, you understand the biological mechanisms, you can actually reason yourself into the exercise routines, the fasting routines that actually works for your own specific use case.

That's it for this week's Research Roundup. Let me know what you think about the study and our framework below!

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