Ketosis the metabolic state
We go in and out of ketosis. You’re said to be in ketosis, vaguely, when you have ≥ 0.5 mmol/L of beta-hydroxybutyrate (BhB) in your blood. If you eat a lot more food than you need (hypercaloric) or just what you need to maintain your physique (eucaloric), you can do so in and out of ketosis. After 2 days of fasting most people will be in ketosis. Newborns reared on breast-milk are also ketogenic .
By exercising long and hard enough you’ll deplete your muscle and liver glycogen to the point of needing to rely much more on fatty acids and thus enter ketosis . Supplementing with ketones, usually in the form of esters or salts, can get you into this metabolic state through non-dietary means .
Except for this last example, getting insulin low enough is key to have more circulating ketones (and thus be in ketosis).
Ketones and muscle mass
Researchers observed that ketones correlated positively with fasting and soon after experimented by infusing BhB into fasting patients, showing decreased oxidation of the amino acid leucine, thus promoting protein synthesis  – this anti-catabolic effect is ‘muscle sparing’ in a fasted context.
But what about fed contexts? Diets can be made ketogenic after all, primarily by lowering the amount of carbohydrates or total calories in the diet, and people have wondered if they’re suited to improving body composition. Could both the obese and bodybuilders benefit from ketogenic diets?
The researchers Wilson, Lowery, Volek and their colleagues did a study asking how ketogenic diets affects the physique of athletic individuals, more specifically resistance-trained men following a resistance-training program. The study is called “The Effects of Ketogenic Dieting on Body Composition, Strength, Power, and Hormonal Profiles in Resistance Training Males”.
Resistance-training + (Keto vs Western Diet)
The study was designed as follows.
25 men aged 25-years old with about 5 years of resistance training experience, as shown by their ability to back-squat x1.56 their body-weight, were randomly assigned to either a 75% fat ketogenic diet (KD) or a 55% carbohydrate western diet (WD) matched for calories (~ 2,600 kcals/day) and percentage calories from protein (20%).
In the first 2 weeks both groups adapted to the diet and in the last 2 weeks the KD group had a ‘carb refeed’ where they replaced fat with carbohydrate without changing total calories.
Diet compliance was estimated by a questionnaire, blood ketone readings, and support was offered through expert advice. 3 series of lab tests were given to assess body composition, strength, power and their lipid profile at Week 1 (baseline), Week 10 and 11.
This was their 3-day a week resistance training program they did for 8 weeks after adapting to the diet, from Week 3 to 10.
Both groups ate an average of 2,600 kcals/day throughout the entire study. We can’t be super confident about the accuracy of their caloric intake balance (intake and expenditure) because we only have food questionnaires to rely on.
We can be confident about body composition data thanks to DEXA scans. And we can be confident about the KD and WD showing a presence and absence of ketones, respectively, thanks to subjects reporting their Precision Xtra ketone meter readings. Notice the KD group being out of ketosis (< 0.5mmol/L BhB) at week 11 following the carb refeed at week 10.
What did the study show?
In the graphs below the KD group is black and WD is white.
The KD and WD groups increased lean body mass from week 1 to 11 (7.3% and 3.6%, p < 0.0002) and from week 1 to 10 (2.4% and 4.4%, p < 0.01). KD gained more from week 1 to 11 but gained less than WD from week 1 to 10. Why? It could be due to the carb-refeed at week 10 and/or subsequent week of rest.
Fat mass was significantly decreased in both groups. From week 1 to 10 the KD group lost 22.4% or 2.2 kg ± 1.2 kg and the WD group lost 13.0% or 1.5 ± 1.6 kg (p < 0.0001). But once again from Week 1 to 11 the tables turned, the WD group lost more fat (6.2% vs 5.4%) (p < 0.002).
The only time during this study when a group gained fat mass was in the KD group from weeks 10 to 11, after replacing fats with carbs at 1, 2 and then 3g of carbs a day in 2 day intervals. The food questionnaire says this was an isocaloric switch of carbs for fat – how sure can we be of that given it’s self-reported?
In any case, from week 1 to 11 both groups lost decent amounts of fat mass despite statistically negligible changes in the (self-reported) caloric intake estimate: 2,652.9 kcals ±205.6 vs 2,619.5 ±192.1 in the KD group and 2,528.1 ±200.4 vs 2513.1 ±236.8 in the WD group. So if we’re to believe the KD group gained fat mass without eating more calories then the next suspect is a uniquely fattening effect of whatever those carby foods were.
The reason I emphasize food here is, beyond its macronutrient composition, the extent to which the carby food is processed or not can significantly change metabolic and hormonal response to it when compared to an equivalent glucose load from an unprocessed form (e.g. potato starch versus a baked potato).
See podcast episodes 8 and 7 where Gabor Erodsi and I go over this. It’d be great to see future studies control for the degree of food processing across the different diets and I’d start with starchy/sugary foods first. Anyways….
Muscle thickness changes between weeks 1 and 11 were increased in both groups, however KD saw a significantly greater increase than their WD counterparts (p < 0.02). It’s key to understand when the greater increase occurred, which is from week 10 to 11 after KD’s carb refeed.
Turning to performance now. At no point during the 11 weeks were there significant differences between the group means with regards to peak power. No blood markers changed significantly in either group at week 10 compared baseline measurements from week 0.
Only triglycerides and testosterone shot up, and only in the KD group when measured at week 11 after carbs were replaced with fat. It’s pretty likely the higher triglycerides are due to an increase in carbs (not necessarily because they ate more more calories).
It’s less clear why testosterone shot up. Could it be that glycogen supercompensation signals energy abundance and increases testosterone in preparation of things usually following a good energy budget? Ultimately introducing carbs confounds the interpretation of why both markers increased. That’s OK because it wasn’t the main aim of the study anyways.
What can we conclude from it?
Sure, give keto a try
The authors says “the KD can be used in combination with resistance training to cause favorable changes in body composition…” and I agree. We can have a good degree of confidence in the study. But the authors add “…performance and hormonal profiles in resistance-trained males” to that statement, and although I share that opinion I prefer to leave performance and hormones out of it for now since the study doesn’t show that as clearly and wasn’t designed to anyways.
I would add that favorable body composition changes seen in the KD group suggests the diet may help increase an athlete’s power-to-weight ratio, something of great importance when hitting peak wattage (power) during a highly anaerobic effort.
The study controlled for protein (…but didn’t measure intake, only estimated it). Contorlling for protein is something too few nutrition studies even attempt to do – so kudos. It looked at macronutrient effects on body composition changes, trying to always eat the same amount of calories throughout the study.
The study chose a trained population who can be expected to show lower intervention effect size (i.e. smaller changes in the parameters) given their tendency to already have improved their physique (‘noob gainz’ acquired).
Yet the effect we see is actually pretty good, like for example the 22% and 13% loss of total fat mass for KD and WD, respectively. The study lends (indirect) support to the literature showing that body composition improves with a well-formulated diet and resistance-training program.
It uses food questionnaires to assess dietary data. At least ketone monitoring made up for it somewhat by ensuring KD subjects were indeed ketogenic. As discussed before, we know nothing about the quality of the food either group was eating.
Furthermore on quality, we don’t know if their estimate of total grams of protein eaten accounts for protein quality (bioavailability and amino acid completeness score). Put simply, were their protein sources of animal, plant or supplemental origins? This matters and we do not know.
Why the KD group increased muscle mass from week 1 to 10 but did so lagging a little behind the WD group? Only to quickly overtake the WD group by week 11…one theory is that that WD muscle thickness was overestimated from week 1 to 10 because this diet super compensates muscle glycogen.
By extension this suggests KD muscle thickness was underestimated. Maybe. If it’s the case, we could further argue the carb-refeed, providing 1g of glycogen with 3g of water, was directed into muscle tissue and thus effectively levelled the playing field in terms glycogen availability for lean body mass increase. But a quick bit of math from the authors says that only 20% to 30% of the lean body mass gain could be from glycogen supercompensation secondary to KD’s carb-refeed.
Beyond the carb refeed
What if it has little or nothing to do with the carb refeed? Athletes with depleted glycogen replenish their glycogen levels just as well as higher-carb athletes do . This is true in the untrained and a more consistent finding in this population; carb-loading to replenish glycogen faster doesn’t work [6, 7].
It’s interesting to consider that “under conditions expected to be highly unfavourable to glycogen synthesis following high intensity exercise, such as food absence or active recovery, the rates of muscle glycogen synthesis in humans and rats are among the highest reported in the literature (Pascoe and Gladden, 1996; Nikolovski et al, 1996; Fairchild et al., 2003) [my emphasis] .
Indeed, it appears humans can artfully recycle lactic acid resulting from glycolysis, getting it to the liver and turning it into glucose through the Cori cycle. It’s then ready for export into the bloodstream and will eventually enter the muscle to be joined together as muscle glycogen. Turns out, shovelling more carbs down your gullet won’t top up your muscle glycogen any faster – it’s not quite how we work.
If you look at the abundance of ketogenic foods available throughout human evolution and how normal it is for humans to enter and exit this metabolic state, I posit the safe bet was always on well-formulated ketogenic diets being a good way to maintain or improve one’s physique. Evidence for this has been accumulating [9, 10, 11, 12]. And this study adds to the evidence base.