Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...Tell Me More
Even having finished and printed The Keto Reset, the quest for deeper understanding continues. I keep researching, thinking, revisiting, and discussing the science and practice of ketosis. My writing partner, Brad Kearns, and I maintain a running dialogue on all things keto. The latest conversation revolved around two very common questions or “problems” that keep coming up in the ketogenic community.
Why do some people on a keto diet blow high numbers of ketones while others eating the same way blow low numbers?
and this one…
Is ketosis glycogen-sparing or glycogen-inhibiting?
I won’t offer definitive answers fit to etch into stone. I will offer my exploration of the research, some educated speculation, and actionable advice you can ruminate on. And by all means get back to me with your take on the questions and my explorations, please. Dialogue is essential to understanding.
One theory is that some keto-adapted people are so adapted to producing and burning ketones that they don’t leave any extra to spill into the urine and breath. They make only as many as they can use and their cells gobble up almost every ketone they produce. Under this argument, low ketone numbers on a ketogenic diet are a reliable sign of full ketone adaptation.
This sounds plausible, but I haven’t seen any empirical evidence that it’s the case.
Another theory is that the keto-adapted have built so much fat-burning metabolic machinery in their muscles that they can burn free fatty acids directly and don’t require much additional fuel from ketones. They make enough ketones to fuel the brain, since our brain can’t run on fatty acids directly, but your muscles no longer require as many. Many people who have been in long term ketosis can get by quite nicely on 20-30 net grams of carbs a day and might only show .4 or .7 millimolar ketones on a blood test, but they have plenty of energy from burning free fatty acids and maintain muscle mass on relatively fewer calories than when they were dependent on carbs.
Keto pioneers Stephen Phinney and Jeff Volek found that keto dieters blew higher readings early on in the diet when they were still burning ketones in the muscle. As they grew adapted to free fatty acids as a source of fuel and produced ketones primarily for the brain, ketone levels dropped. It was totally normal. If anything, they were more fat/keto-adapted at lower ketone readings.
Consider the energy requirements of the brain. Whether it’s running on glucose (most of the population) or mostly on ketones, the brain is a steady state organ that never spikes energy demand. It’s a slow-burn 24/7 at nearly the same output whether you are sleeping, exercising hard, or concentrating hard. While the brain has a substantial caloric requirement (at roughly 2% of our body weight, it uses 20% of our resting metabolic rate), you don’t need a ton of glucose or ketones at any one time to power your brain gracefully all day long. That’s why people can “get away” with lower ketone production and still reap the benefits we expect from eating this way.
There’s almost certainly a genetic component to ketone production, too. Take the Inuit, who were rarely in ketosis despite traditionally eating a very low-carb diet. It takes several days of deep fasting for them to produce measurable ketones. Yet, they are adept at burning free fatty acids, almost as if they “skip” keto-adaptation and proceed directly to burning fat. Other variants that affect ketone production have yet to be discovered, but they’re out there.
What about people on long term ketogenic diets who still get astronomical readings? What’s going on?
A major factor not often mentioned in whether someone on a keto diet blows high or low ketones is overall calorie intake. How much food are you eating?
Ketones are generated when the amount of dietary fat available to be burned exceeds the supply of oxaloacetate (provided by protein or carbohydrates). It’s not that the body thinks, “This woman needs some ketones, stat.” It’s more like, “I’ve got too much acetyl-COA from all this fat, and I can’t find any oxaloacetate. Guess it’s ketones!” If you’re the type to use keto to justify chugging olive oil, you’ll generate lots of ketones simply because your fat intake is outpacing the supply of oxaloacetate. Keto athletes eating tons of calories will probably produce more ketones simply because they’re eating so much fat.
If you’ve attained the much-desired “caloric efficiency” I espouse and eating fewer calories overall, you’ll generate fewer ketones but still be “keto.”
Above all else, focus on the symptoms.
Can you go without a meal and maintain steady, even energy and concentration?
Are you thinking more clearly?
Has the keto flu come and gone?
Are aerobic activities easier than ever?
If any of those are happening to you, there’s no need to fret over some numbers on a device. The numbers can’t negate your real world experience.
A 1983 study by Steven Phinney gives us a few hints. He put people on a typical high-carb diet for 4 days, ran a 65% VO2 max endurance test, then switched them over to a ketogenic diet with 20 grams of carbs and about 80-85% of calories from fat for 3 weeks and ran the test again. There was no difference in time to exhaustion after either dietary arm, but glycogen storage and usage changed a ton. During the high-carb arm, the group began the workout with 150 grams of glycogen and ended it with 50 grams. While eating ketogenic, the group began the workout with 75 grams and also ended it with 50 grams.
In a modern setting, the high-carb guy could just squeeze some glucose goo in his mouth, replenish the lost glycogen, and be ready for the next race. But in a setting where glucose goo isn’t available, the keto guy has the advantage. He’s still got 50 grams of glycogen left in the tank—enough for two more races—while the high-carb guy’s 50 grams of carbs will only last him half a race. And the low-carb guy doesn’t have to eat. That’s pretty cool.
It is the modern world. You can grab some glucose goo and win the race. But there’s something special about utilizing the metabolic machinery developed over hundreds of thousands of grueling, blood-and-sweat soaked years.
Sparing glycogen is one thing. Does keto inhibit our ability to utilize the muscle glycogen we’ve spared?
Free fatty acids sure don’t, according to this study. Healthy young males spent a couple hours depleting their muscle glycogen through exercise, after which they were split into two groups. One group got a high-fat breakfast, giving them elevated free fatty acids. One group got a low-fat breakfast, giving them low free fatty acids. They measured glycogen before and after exercise in both groups, as well as markers of the pathway responsible for burning glycogen. Normally, free fatty acids impair glycogen burning. Not this time. Exercise was sufficient to overcome the inhibitory effects of FFA on glycogen-burning.
Semantics enters the fray here. One man’s spared glycogen is another’s inhibited glycogen. We spare glycogen by using less of it—by inhibiting its metabolism. That doesn’t mean the ketogenic athlete can’t burn glycogen when required. It means there’s less to go around, and that’s probably okay because, once again, the ketogenic athlete can do more with fat and ketones and doesn’t need as much glycogen.
Confusing, isn’t it? That’s biology for you.
Still, we know a fair bit. The sparing/inhibiting effect keto has on glycogen metabolism doesn’t impair endurance performance and probably even bolsters it. Long-term elite keto athletes can burn up to 2.3 times more fat at peak oxidation and 59% more fat overall than non-keto athletes, and they do it at higher intensities.
We know fat-adapted athletes beat sugar-burning athletes at high-intensity intervals due to their increased ability to burn fat and retain glycogen. These aren’t 100 m sprints—they’re 4-minute intervals on an incline treadmill—but they’re still glycogen-intensive.
We know low volume, high intensity strength training doesn’t suffer on keto.
What we don’t know is how the delicate balance between glycogen sparing and inhibiting affects high volume, high intensity glycolytic work. I suspect you’re going to lose some performance at the upper echelons of intensity. I also suspect you can regain most, if not all of it by incorporating well-placed carb refeeds.
Anyway, folks, that’s what’s been on my mind these past few days. I wanted to get it out there on the blog so you folks can mull it over and kick it around, and hopefully come back with some good feedback and insight of your own.
Thanks for reading, everybody!