How to train your metabolism Your guide to metabolic flexibility

Meal timing strategies to improve metabolic health

You'd like to have some off-the-shelf strategies and tools that you can use, right? Well, what you need to understand is that the perfect approach isn't perfect if you can't stick with it.

Look at it this way: fasting could be optimal for every person on the planet and if there wasn't a fast food joint or a supermarket on every corner, it might even be doable. The fact is that some people who start fasting in the morning will end up stuffing themselves with everything that's not up to three in the evening, which makes their situation even worse.

I have four approaches that I think best address metabolic flexibility and I've listed them from beginner to expert status. It's useful to remember that metabolically inflexible people are often the people at highest risk for problems with sleep, hunger, mood, energy and cravings. A person with such problems is usually a metabolically inflexible person and such people should start slowly and work their way from simple nutritional interventions to more advanced ones.

1. how can regular consumption of protein and fiber improve metabolic health?

Remember that ultimately we want to try to clear a metabolic logjam at the mitochondrial level. Fat and carbohydrate approaches are not necessarily the best idea for beginners with metabolic inflexibility. These people tend not to be able to burn fat and carbohydrates adequately and also often suffer from insatiable hunger, low energy and cravings.

Take a look at a chart from a study in the American Journal of Clinical Nutrition titled "Fat and Carbohydrate Balance During Adaptations to a High-Fat Diet". In this chart, RQ is a measure of fat vs. carbohydrate utilization. The higher the value, the more carbohydrates are burned and the lower the value, the more fats are burned.

As you can see, there is an extreme variance here, which probably has something to do (at least in part) with the differences in metabolic flexibility between subjects. This is the reason that an off-the-shelf approach will not work for everyone. It's also the reason that cold turkey keto diets and intermittent fasting won't work for beginners. Their metabolism is simply not flexible enough to handle it and the first week of transition is too miserable for most people to get through.

For this type of person, smaller, more regular meals can help combat bingeing. A focus on protein and fiber over fat and starch/sugar clears the mitochondrial highways and allows for repair. This is an old bodybuilding approach that works well for dieting beginners and for people where skipping meals can result in severe bingeing.

This approach has the added benefit of more "food interaction". It teaches a lot about the amount of calories in foods, macronutrient content and food preparation. In my experience, the most successful people who have made the transition from fat to fit have gone through this stage. I now see this step as a necessary part of the journey for many.

Once metabolic flexibility has been restored to a certain degree, it is feasible and sensible to continue with less regular dietary strategies such as fasting or macronutrient manipulations such as a keto diet.

It is useful to look at the science at this point. The three large meals a day approach is significantly inferior to more frequent smaller meals when it comes to metabolic control and flexibility. Remember that we are trying to break up the metabolic logjam. Smaller meals avoid the metabolic congestion that larger meals can cause (PMID:22587351 & PMID:21981968)

2. how can diets that focus on certain macronutrients (keto and others) improve metabolic health?

After you have regained some metabolic flexibility, you can begin to focus on one type of food or the other, but not both. Mitochondrial overload occurs when you eat all foods in large quantities.

This could be the reason why ketogenic diets and vegan diets both show benefits in metabolic parameters such as insulin resistance. One consists mainly of carbohydrates and less fat and the other consists mainly of fat and less carbohydrates. Both diets eliminate the need for the metabolism to multitask and allow it to focus on and optimize one pathway. This is the metabolic equivalent of trying to drive on congested city streets versus clear highways. By separating the energy sources in this way, we can wake up the metabolic pathways.

This could be the real benefit of a keto diet. A hidden, often neglected aspect of the keto diet is that it is a "one flavor" diet - savory and creamy. Diets that are more one-flavored (boring) have been shown to be more effective at satisfying hunger due to neural feedback mechanisms in the brain that reduce hedonistic food-seeking behaviors.

3. how can intermittent fasting improve metabolic health?

Another approach is to spend a lot of time not eating. A more enjoyable way is to spend as much time eating as not eating. 12 hours with food and 12 hours without food is the minimum.

This is not a very difficult change for most people, considering the normal phase without food during sleep. As you regain your metabolic flexibility, this will become easier. A metabolically flexible person should be able to go through longer periods without food. As you adapt, you can experiment with longer periods without food (16 to 24 hours).

This is probably the quickest and most natural way to restore your metabolic flexibility. It is also the way that will cause the most negative reactions in someone who is not metabolically flexible.

Our ancestors couldn't have eaten 4000 kcal in one meal if they tried. However, a meal with dessert at a buffet restaurant can easily provide this amount of calories. The drive to eat is one of the strongest drives of all (the sex drive would be another). Even worse, a metabolically inflexible person is much more likely to not be able to handle all that food. Therefore, for most people, this approach will simply not work as a starting point.

4. how can cyclical nutrition and exercise improve metabolic health?

In metabolic research, there is a measure known as the Respiratory Exchange Ratio (RER or RQ for short). We have already seen this in the chart above. This is the amount of CO2 you breathe out in relation to the amount of oxygen (O2) you breathe in. This is a way to measure the amount of carbohydrates vs. the amount of fat you burn. More CO2 means more carbohydrates, more oxygen means more fat. This value ranges from 1.0 (only carbohydrates are burned) to 0.7 (only fat is burned).

The food you eat roughly corresponds to the RER at rest. The energy you burn during exercise correlates mainly with the opposite energy you burn when you are not exercising. Simply put, this means that if you eat fat, you will burn more fat at rest and if you burn fat during exercise, you will burn more carbohydrates at rest.

It's important to remember this when thinking about combining diet and exercise strategies. If you want to be a better fat burner, then you should perform a workout that utilizes more of the sugar pathways and provide energy for that workout through more sugar. So if you're doing a high-intensity workout, you should consume more carbohydrates during that time.

Or look at it from the opposite direction: if you eat more carbohydrates, then you should do a more intense workout. I call this the "Eat More, Exercise More" (EMEM) approach.

Accordingly, if you eat more fat, you should train at a much lower intensity. Apart from the most fat-adapted athletes, very low-carb ketogenic diets are better suited to lower intensity exercise like walking. I refer to this as the "Eat Less, Exercise Less" (ELEL) approach.

Of course, calories also play a role, which is why the EMEM and ELEL approaches apply regardless of whether you use a dietary approach with only certain macronutrients or a mixed low-calorie dietary approach. The difference is that EMEM generates the calorie deficit through exercise, and ELEL generates the deficit through food. Both approaches work because they force the body to be more flexible and confront it with a less extreme calorie deficit, which means less stress.

An "Eating More and Exercising Less" (EMEL) or couch potato approach can easily overwhelm the mitochondrial pathways through a top-down or bottom-up effect. An "Eating Less and Exercising More" (ELEM) or diet approach can often generate too much stress and lead to compensatory eating responses and stress-induced insulin resistance.

The best approach to flexibility involves looking at all the different metabolic switches you can flip:

• ELEL (eat less, exercise less) is the winter switch.
• EMEM (eat more, exercise more) is the switch for late spring and early fall.
• ELEM (eat less, exercise more) is the switch for early spring (for a few weeks).
• EMEL (eat more, exercise less) is the switch for late fall (for a few weeks).

What do sleep, exercise, training, stress and temperature have to do with metabolic flexibility?

The metabolism is nothing more than a big stress barometer. Its job is to determine what's going on out there in the world, measure the amount of stress present at any given moment and relay this to the cells in the body.

It does this using hormones and this hormonal system can be affected by the top-down and bottom-up mechanisms of metabolic inflexibility. Sleep, exercise, training, stress and temperature are largely under our control.

What effects does stress have on metabolism?

You can achieve metabolic inflexibility through your diet or you can do so through stress.

The stress hormones (cortisol and adrenaline) are all about releasing energy. When you are at work and under stress, you release sugar and fats into the bloodstream. In a perfect world you would burn all this stuff off by fighting or fleeing, but in our modern world all these energy sources are released but they are not burned off. This can have top-down and bottom-up consequences for metabolism.

Cortisol in particular seems to have some annoying side effects. It reduces the activity of the motivational centers of the brain and activates the reward centers. It could also play a role in making us eat larger meals.

What effects does sleep have on metabolism?

Sleep problems can exacerbate insulin resistance and have all the negative effects of stress described above.

What effects does exercise have on metabolism?

This is different from exercise. We know this because metabolic research distinguishes between Exercise Associated Energy (EAT) and Non-Exercise Associated Energy (NEAT).

EAT accounts for only 5% of the changeable metabolism, while NEAT accounts for 15 to 20%. NEAT (walking and other activities of daily living) have multiple top-down and bottom-up effects by clearing fat-burning pathways, increasing glucose receptors without a need for insulin, and lowering cortisol levels.

What effects does exercise have on metabolism?

Exercise is a great tool, but it is overrated and cannot overcome metabolic flexibility issues on its own.

At best, exercise generates a temporary state of metabolic flexibility. In our traffic analogy, training is like an ambulance that can clear the way for you to get through. If you are lucky enough to be driving directly behind this vehicle, then it will also clear the way for you. For most people, however, the traffic backs up as soon as this vehicle has passed.

This is why the old mantra "you can't make up for a bad diet with exercise" is very true. "Training snacks" - the idea of performing short, intense workouts before or after a meal - can help. A 2008 study review by Thyfault et al. was able to show that one session of intense exercise can dramatically increase muscle insulin sensitivity for the next 24 hours.

What effect does temperature have on metabolism?

It makes a difference and we know that adaptations to cold or hot temperatures can increase metabolic flexibility.

When our metabolism is forced to respond to temperature challenges, energy is expended and metabolic pathways are exercised. This is the reason why you should adjust your thermostat in your home and train at natural temperatures in the gym.

Cold sleeping temperatures, hot workout temperatures and hot-cold cycling therapies all have their role in the development of metabolically more flexible brown adipose tissue.

Which supplements can restore mitochondrial flexibility?

You can think of mitochondria as little engines or power plants. They absorb energy sources and burn them. Mitochondria that are overloaded and damaged are like old overloaded engines that misfire, emit black smoke and sputter along.

In this analogy, the black smoke is hydrogen peroxide damaging the cellular machinery (and one of the reasons your beard is turning gray) and the sputtering is your constant irritability, hunger and inconsistent energy.

Clean-burning, efficient mitochondria are like those brand new electric Teslas you can barely hear that can make a sports car look old in terms of speed and power. This is an analogy for predictable stable energy, reduced hunger, optimal performance in the gym and optimal recovery after exercise.

Turning your old clunker into a Tesla is something you could use some help with and there are a few supplements that can make a difference.

Glutathione

Part of the long-term changes in mitochondrial dysfunction and metabolic flexibility come from mitochondrial DNA adaptations such as acetylation and other chemical reactions that affect mitochondrial function through feedback.

Glutathione is like a cold wet sponge that neutralizes the hot, sticky mass of mitochondrial radicals. The best and cheapest place to get this supplement is not glutathione itself - this is not well absorbed by the body. Whey protein, however, is a rich source of glutathione precursors and has been shown to be a good glutathione booster. Whey protein is cheap insurance that your cellular machinery will not be destroyed by free radicals.

Alpha lipoic acid

Another important multitasking nutrient is alpha-lipoic acid. This acts as both a water-soluble and fat-soluble antioxidant, which means that it can reduce metabolic damage from free radicals both in the cytosol of cells (water-soluble) and in the inner mitochondrial membranes where metabolic actions take place (fat-soluble). It also ensures that glutathione remains active for longer.

Acetyl-L-carnitine

The next active ingredient is carnitine - and acetyl-L-carnitine in particular. The attached acetyl group allows the molecule to exert a more direct influence on the mitochondria, where it is needed to channel fats into the internal fat-burning machinery. Carnitine, like alpha lipoic acid, is also a wonderful buffer against some of the metabolic smoke (i.e. damaging free radicals) produced by metabolic inflexibility.

NAD+

This compound plays a dual role as an energy precursor and as a signaling molecule within the mitochondria. It is an integral part of energy production in the mitochondria by acting as a precursor to NADH, which is the key molecule that shuttles electrons from one part of the mitochondria to another.

When NAD+ levels drop due to metabolic stasis, NADH levels are also affected and mitochondrial efficiency decreases. Adding NAD+ to this mix stimulates the mitochondrial machinery. It also acts as a signaling molecule that relays important information to the DNA.

NAD+ helps protect DNA from damage in several ways, including stimulating SIRT function. For those who are not biochemists, SIRT is the abbreviation for sirtuin and sirtuins are among the most important anti-ageing compounds. They keep the metabolism flexible as we age. You can think of NAD+ as an upgrade for your car's engine, while giving you the best tires and a more durable body.

The practical application: Challenge your metabolism!

The best way to develop a flexible metabolism is to eat and exercise in different ways. If you're a fat eater, eat some carbs. If you're a runner, spend some time training with weights. And vice versa. To train your metabolism, you need to challenge your metabolism. This is the real benefit of fasting, keto, intervals, refeeds and the rest. Those who always do the same thing will not progress.

A simple summary

• It's not about having a fast metabolism, it's about having a more flexible metabolism.
• Metabolic flexibility refers to the ability of the metabolism to switch quickly and efficiently between different energy sources based on availability (i.e. what you eat) and demands (what your activity requires).
• The two primary energy sources your body burns are fat and sugar/glucose. However, it can also burn protein, ketones and alcohol.
• Alcohol is like a KLW on our metabolic highway - it impedes the flow of traffic. Sugar is like an SUV - they are a bit of a pain on the highway - but only because there are too many of them. (In other words, most people eat too much sugar. Fat is like a midsize car.
• Protein is like an Uber, a bicycle, a motorcycle or an e-scooter. Focus on eating protein and you'll reduce some of the metabolic burdens on the highways. Protein is satiating, which means you eat fewer calories overall, and it has many different places apart from acetyl-CoA where it can enter the body's energy pathways.
• Ketones are very similar to public transportation. It's not easy for most people to get into the state of ketosis, but when they do, their metabolic highway gets unclogged from a lot of congestion.
• Metabolic inflexibility comes from top-down (food or stress causing insulin resistance) or bottom-up (an overload of mitochondria leading to insulin resistance) effects.
• Fasting, eating small, regular meals that are lower in carbohydrates and fat or a keto diet can help to restore metabolic flexibility, although the specific approach should be chosen based on individual preferences and tolerance.
• Cyclical changes in diet and control of stress and sleep are important.
• Training, exercise and temperature need to be understood and utilized.
• Supplements such as whey protein, alpha lipoic acid, carnitine and NAD+ can support metabolic flexibility.

Wow, that was complex

Okay, I know that was a lot to take in. It's a complex topic that could fill several books. It's also an area that needs a lot more research. What I did above was to try to give you an overview and open your eyes. For those who are more interested in the biochemical details, I recommend reading the four articles in the references.

References:

1. Smith RL et al. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocrine Reviews. 2018 Aug 1;39(4):489-517.
2. Galgani JE et al. Metabolic flexibility and insulin resistance. American Journal of Physioliogy Endocrinology & Metabolism. 2008 Nov;295(5):E1009-17.
3. Goodpasture BH et al. Metabolic Flexibility in Health and Disease. Cell Metabolism. 2017 May 2;25(5):1027-1036.
4. Muoio DM. Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock. Cell. 2014 Dec 4;159(6):1253-62.

Source: https://www.t-nation.com/lean-built-eating/how-to-train-your-metabolism/

By Dr. Jade Teta