Important note! For a more up-to-date exploration of this subject, I strongly recommend my 2013 AHS presentation “What Is Metabolic Flexibility, And Why Is It Important?”
Most of us who eat a low-carbohydrate diet—Paleo, Primal, Atkins, or otherwise—experience anywhere from a couple days to a couple weeks of low energy as we adjust to it, an experience known informally as the “low carb flu”. And some people never seem to adjust.
Here’s why—and here are some ideas that might help you if you’re having trouble adjusting!
Note that low-carb isn’t an objective of a paleo diet: it’s just the usual consequence of eliminating grains and sugars.
It’s certainly possible to eat a higher-carb paleo diet—and it’s a good idea if you’re doing frequent, intense workouts like HIIT, Crossfit, or team sports after school—but you’d have to eat a lot of potatoes and bananas to get anywhere near the same amount of carbohydrate you used to get from bread, pasta, cereal, and soda.
Burning Food For Energy: Glycolysis and Beta-Oxidation
Our bodies have several ways to turn stored or ingested energy into the metabolic energy required to move around and stay alive. This is called cellular respiration.
The two main types of cellular respiration are anaerobic (which does not require oxygen) and aerobic (which requires oxygen). Anaerobic metabolism, also known as fermentation, is nineteen times less efficient—and we can only maintain it for short periods, because its waste products build up very quickly. This is why we can’t sprint for long distances.
A Short Metabolic Digression Explaining The Above (Optional)
Strictly speaking, glycolysis is the start of both the aerobic and anaerobic oxidation of glucose: it converts glucose to pyruvate.
In the aerobic oxidation of glucose, the pyruvate is transported into the mitochondria, whereupon it is converted to acetyl-CoA and fed into the TCA cycle (aka the citric acid cycle or Krebs cycle, depending on how long ago you took your biology course.) This produces 19 times more energy than the original glycolysis!
In the anaerobic oxidation of glucose (“lactic acid fermentation”), the pyruvate is instead converted to lactic acid, which produces no more energy.
In the aerobic oxidation of fat (“beta-oxidation”), the fat is transported into the mitochondria, whereupon it is sliced up into individual acetyl-CoA molecules, each of which enters the TCA cycle.
Humans have no way to anaerobically oxidize fat.
Glucose is the simple sugar all cells use for glycolysis, and it’s the most common. The other simple sugars we can digest are galactose (found primarily in milk), which we convert to glucose—and fructose (found primarily in fruit, table sugar, corn syrup, and honey), which our liver converts directly to glycogen or fat.
Starch is just a bunch of glucose molecules stuck together. In fact, “complex carbohydrates” in general are just sugars stuck together…and we can only absorb them through the intestine once they are broken down into individual simple sugars by our digestive system. In other words, all “carbohydrates” are just sugar.
There is a lot more to talk about here, including glycogen storage and retrieval, gluconeogenesis, and de novo lipogenesis…but explaining all the pathways of digestion, energy storage, and cellular respiration would be an entire book in itself!
Moving on: while it’s OK for fat to hang around in our bloodstream for a while, high blood sugar is actively toxic to our tissues. (The long-term consequences of untreated diabetes—heart, kidney, nerve, eye, and muscle damage, leading to numbness, blindness, amputations, strokes, and death—are basically just long-term glucose poisoning.) So after we eat something containing any amount of carbohydrate, insulin ensures that the glucose is immediately taken into our cells and either burned for energy, stored, or converted into palmitic acid—a saturated fat!
This is why a “low-fat, high-carb” diet is really a high-fat diet. Unless your “high-carb” diet involves an intravenous glucose drip carefully metered to keep your blood sugar constant, most of the ‘carbohydrates’ (sugars) you eat will be converted either to glycogen or to palmitic acid (again, a saturated fat) before you use them. “Soluble fiber” and other indigestible carbohydrates are fermented into short-chain saturated fats, like butyric acid, in your colon. Fructose, of course, is converted directly to liver glycogen or to palmitic acid. And if you’re losing weight by burning your own fat, keep in mind that human fat has roughly the same composition as lard—approximately 40% saturated!
You might ask yourself if it makes sense that natural selection would select us to store energy in the form of something directly harmful to us. If saturated fat is really so terrible, and polyunsaturated fat is really so healthy, why doesn’t our body store energy as linoleic acid, like grains do?
Metabolic Flexibility and the Respiratory Exchange Ratio
If we have excess glucose in our bloodstream, our muscles will burn it first, because it’s toxic. But eventually we run out of glucose, and that’s when our bodies need to switch over to beta-oxidation—burning fat. The ability to switch back and forth between the two processes is called “metabolic flexibility” in the scientific literature.
Metabolic flexibility varies dramatically from individual to individual, which we would expect based on the widely varying experiences people report with low-carb diets. So how do scientists figure out what fuel our bodies are burning?
It turns out that beta-oxidation (fat-burning) produces less carbon dioxide than glycolysis (sugar-burning)—and we can measure that in our breath. The ratio of CO2 to O2 is 0.7 for beta-oxidation and 1.0 for glycolysis…so an RER (Respiratory Exchange Ratio) of 0.7 indicates pure fat-burning, and 1.0 and above indicates pure sugar burning. (You can read more about the RER here.)
Typical healthy people have a resting, fasting RER of approximately 0.8. Therefore, we can easily see that the frequent vegetarian and vegan claims of “Nothing else can provide any energy without first being converted to carbs” and “You can get plenty of energy from fat, but you have to go into ketosis to do it” are—like most nutritional claims made by veg*ans—complete bunk.
Metabolic Flexibility: The “Low Carb Flu” Is Not Your Imagination
It shouldn’t be a surprise that the obese and diabetic tend to have higher resting RERs, and that higher RER is a significant predictor of future obesity. If our ability to burn fat for energy is impaired, we’re going to have a hard time losing weight, and we’ll become ravenously hungry when our blood sugar runs out no matter how much fat we have available to burn.
Is this sounding familiar to anyone?
Sounds like the “low carb flu”, doesn’t it? When we talk about our metabolic “set point”, part of what we’re talking about is metabolic flexibility. It does no good to have a huge store of fat if we can’t burn it for energy!
Int J Obes Relat Metab Disord. 1992 Sep;16(9):667-74.
Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore Longitudinal Study on Aging.
Seidell JC, Muller DC, Sorkin JD, Andres R.
“…The adjusted relative risk of gaining 5 kg or more in initially non-obese men with a fasting RER of 0.85 or more was calculated to be 2.42 (95% confidence interval: 1.10-5.32) compared to men with a fasting RER less than 0.76.”
Furthermore, it turns out that people with a family history of type II diabetes, but who don’t yet have it themselves, have higher RERs and impaired metabolic flexibility.
Diabetes August 2007 vol. 56 no. 8 2046-2053
Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes
Leonie K. Heilbronn1, Søren Gregersen2, Deepali Shirkhedkar1, Dachun Hu1, Lesley V. Campbell1
“…An impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals.”
AJP – Endo November 1990 vol. 259 no. 5 E650-E657
Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ
F. Zurlo, S. Lillioja, A. Esposito-Del Puente, B. L. Nyomba, I. Raz, M. F. Saad, B. A. Swinburn, W. C. Knowler, C. Bogardus, and E. Ravussin
This is very important: we can see that impaired fat oxidation must be related to the causes, not the consequences, of obesity and diabetes. So we’ve struck another blow to “calories in, calories out”, and the idea that you’re fat just because you’re lazy.
In support of this theory, I note this paper, which contains the following graph of several individuals’ RER in response to a high-fat diet vs. a moderate-fat diet. Keep in mind that the change was only from 37% to 50% fat, which is relatively minor, and the paper doesn’t tell us what fats were being consumed…but this graph is still instructive:
The top graph is the average, the bottom graph is for each individual. Note that some adapted right away, some took several days, and some were still not adapted on day 4!
Higher RER isn’t all bad. It’s associated with having more fast-twitch muscle fibers, which are associated with a greater ability to build muscle mass. This fits the anecdotal evidence that people who gain fat easily also tend to gain muscle easily, whereas skinny people have a much harder time bulking up.
So maybe you’re lucky, or already in good health, and you adapt relatively quickly to a low-carb diet. But what if you’re not? What if you’re stuck with the “low carb flu”?
Regaining Your Metabolic Flexibility
Obviously we’d like to regain our metabolic flexibility. But how? Here’s one way:
Journal of Applied Physiology September 2008 vol. 105 no. 3 825-831
Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation
Francesca Amati,1 John J. Dubé,2 Chris Shay,3 and Bret H. Goodpaster1,2
“…Exercise training, either alone or in combination with weight loss, increases both exercise efficiency and the utilization of fat during moderate physical activity in previously sedentary, obese older adults. Weight loss alone, however, significantly improves neither efficiency nor utilization of fat during exercise.”
Diabetes September 2003 vol. 52 no. 9 2191-2197
Enhanced Fat Oxidation Through Physical Activity Is Associated With Improvements in Insulin Sensitivity in Obesity
Bret H. Goodpaster, Andreas Katsiaras and David E. Kelley
“Rates of fat oxidation following an overnight fast increased (1.16 ± 0.06 to 1.36 ± 0.05 mg · min−1 · kg FFM−1; P < 0.05), and the proportion of energy derived from fat increased from 38 to 52%." October 15, 2009 The Journal of Physiology, 587, 4949-4961. Improved insulin sensitivity after weight loss and exercise training is mediated by a reduction in plasma fatty acid mobilization, not enhanced oxidative capacity
Simon Schenk1, Matthew P. Harber1, Cara R. Shrivastava1, Charles F. Burant1,2 and Jeffrey F. Horowitz1
“…Resting fatty acid oxidation was unchanged after the intervention in WL [weight loss]. Consistent with an increase in maximal oxidative capacity, resting whole-body fatty acid oxidation was increased more than 20% after WL + EX [weight loss + exercise].”
In other words, despite the title, weight loss plus exercise increased resting fat oxidation…but just losing weight did not!
AJP – Endo April 2008 vol. 294 no. 4 E726-E732
Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise
Jason R. Berggren,1,2 Kristen E. Boyle,1,2 William H. Chapman,4 and Joseph A. Houmard1,2,3
“10 consecutive days of exercise training increased (P ≤ 0.05) FAO [fatty acid oxidation] in the skeletal muscle of lean (+1.7-fold), obese (+1.8-fold), and previously extremely obese subjects after weight loss (+2.6-fold)…These data indicate that a defect in the ability to oxidize lipid in skeletal muscle is evident with obesity, which is corrected with exercise training but persists after weight loss.”
How about that? It turns out that exercise is important after all…not because of the calories you burn by exercising, which you usually replace right away because you’re hungry, but because it helps you regain metabolic flexibility. Exercise stimulates your body to burn more fat, both during exercise and at rest.
And that’s what health is about: we’re not interested in losing weight if it just means losing muscle. We’re interested in losing fat.
There are other benefits beyond fat loss, too: exercise tends to normalize broken metabolisms.
Diabetes March 2010 vol. 59 no. 3 572-579
Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity
Ruth C.R. Meex1, Vera B. Schrauwen-Hinderling2,3, Esther Moonen-Kornips1,2, Gert Schaart1, Marco Mensink4, Esther Phielix2, Tineke van de Weijer2, Jean-Pierre Sels5, Patrick Schrauwen2 and Matthijs K.C. Hesselink1
“Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P < 0.01). Insulin sensitivity tended to improve in control subjects (delta Rd 8% increase; P = 0.08) and improved significantly in type 2 diabetic subjects (delta Rd 63% increase; P < 0.01). Suppression of insulin-stimulated endogenous glucose production improved in both groups (−64%; P < 0.01 in control subjects and −52% in diabetic subjects; P < 0.01). After training, metabolic flexibility in type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22).”
Did you catch that? “Metabolic flexibility in type 2 diabetic subjects was restored”?
Unfortunately, this study didn’t measure resting fat oxidation, like the others—but it does suggest that there’s no need to kill yourself with “Biggest Loser”-style misery. 30 minutes of cycling at 55% of maximum effort twice a week, and one session of weight training once a week, was enough to restore metabolic flexibility. That doesn’t sound very intimidating, does it? (And there are many better and more entertaining ways to get half an hour of moderate aerobic exercise than sitting on a stationary bike.)
“Aerobic exercise was carried out on a cycling ergometer twice a week for 30 min at 55% of a previously determined maximal work load (Wmax). Resistance exercise was performed once a week and comprised one series of eight repetitions at 55% of subjects’ previously determined maximal voluntary contraction (MVC) and two series of eight repetitions at 75% MVC and focused on large muscle groups (Chest press, leg extension, lat pull down, leg press, triceps curls, biceps curls, abdominal crunches, and horizontal row).”
…Yet You Must Take Advantage Of Your Newfound Metabolic Flexibility
Of course, our newly-regained flexibility won’t help if we stuff ourselves with the government-recommended 7-11 servings of “heart-healthy whole grains” (= “carbs”, = sugar) per day, because we will be constantly burning sugar. Only when we’re done burning glucose can we use our newfound flexibility to burn some fat.
A Short Digression: Please Stay Off The “Faileo Diet”
Some ‘paleo’ books still insist that saturated fat is bad for you and paleolithic people didn’t eat much of it, which is absolute nonsense. But your calories have to come from somewhere…if not fat, then from protein or carbohydrates. And since those same books also usually disallow potatoes and other convenient sources of starch, you’re basically stuck eating lots of lean protein.
As a result, you’ll eat very few calories, because of the satiating effect of protein—which is fine if you’re just trying to lose weight, but disastrous if you’re physically active, because you’ll be perpetually exhausted. This is why fat-phobic ‘paleo’ is sometimes called the “Faileo Diet”.
The Difference Between Beta-Oxidation and Ketosis
Here’s where I say something that might be controversial: I think going cold-turkey VLC (very low carb) or zero-carb makes the transition much harder, particularly for people who are already physically active.
Beta-oxidation (fat-burning) occurs nearly continually, and produces much of our energy at rest once insulin has cleared any sugar spike out of our system. However, our body does have some requirement for glucose, which it satisfies in the short-term primarily by having the liver make it—a process called gluconeogenesis.
If we eat zero carbs, or very few, over a period of time, our body enters a state called ketosis, in which some of our tissues that used to require glucose shift over to burning ketone bodies, which are alternative products of fat metabolism. And while it is true that our brains and hearts actually run more efficiently on ketones, it takes several weeks for our bodies to fully adapt. Meanwhile, we lack energy for high-effort activities, because our muscles are depleted of glycogen, which is made from glucose.
So you might not have the “low-carb flu”—you might be stuck in an unnecessary multi-week rut of keto-adaptation.
Interested in learning more about ketosis? Read Stephen Phinney’s “Ketogenic Diets and Physical Performance” (Nut Metab 2004, 1:2) for more information about ketosis and the process of keto-adaptation. Once you’ve read that, if you’re deeply interested in the ketotic state, try ketotic.org…and if you’re interested in a ketogenic diet that isn’t nutrient-deficient or disgusting, try these articles from the Drs. Jaminet (Ketogenic Diets I, Ketogenic Diets II).
There is a persistent myth that ketosis is dangerous: it’s not. People (including some doctors) commonly confuse it with ketoacidosis, a pathological state usually only found in uncontrolled diabetics and (rarely) raging alcoholics.
Even worse, you might be stuck in the state informally known as “Low Carb Limbo”—in which you’re eating too few carbohydrates to fuel high-effort, glycolytic activity, but too many carbohydrates to ever keto-adapt.
If you’re active and determined to keto-adapt, read this excellent article from Primal North, “Keto-Adaptation vs. Low Carb Limbo”.
Conclusion: Stay Out Of The Muddy Middle
In summary, it’s much easier and quicker to burn fat via beta-oxidation than it is to adapt to ketosis…so unless ketosis is your goal, you might be making your transition to a healthy diet much harder by keeping your carb intake too low.
I think that if we keep our carbohydrate intake near our body’s requirement while not in ketosis, which is perhaps 15-20% of total calories—and only eat those carbohydrates with meals involving complete protein and fat, not by themselves—most of us should be able to gain the fat-burning benefits of metabolic flexibility without suffering the pain of trying to adapt to ketosis. So if you’re new to Paleo or low-carb eating, you’re stuck with long-term “low-carb flu”, and especially if you’re already physically active, try adding some root starches like potatoes or sweet potatoes to your meals. (Or white rice, if you’re following the Perfect Health Diet.)
(And if you’re determined to keto-adapt, go fully ketogenic, as per “Keto-Adaptation vs. Low Carb Limbo.”)
Live in freedom, live in beauty.
For more information, continue reading my 2013 AHS presentation “What Is Metabolic Flexibility, And Why Is It Important?”
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