What you will learn
#1 You cannot get much if any carbs from glycogen in muscle meat
#2 A diet high in animal foods and very low in carbs doesn’t ‘kick you out’ of ketosis
#3 The state of nutritional ketosis is not harmful to pregnant women
Macro wars: backing up to Paleo times
Lets refresh our memory by reiterating the 4 takeaways from the 7 myths in part 1.
- We are omnivorous, obligate carnivores. This means that we need to eat meat (animal sourced food) but we often eat much more than just meat
- There is no such thing as a dietary glucose deficiency because carbs are not an essential macronutrient, thanks to processes like gluconeogenesis
- It’s still an open question whether or not high-intensity (glycolytic) efforts are best fuelled by our own internally generated glucose or from dietary glucose
- Ketosis is a normal metabolic state to be in and shouldn’t be confused with the pathological state some uncontrolled diabetics experience called DKA (diabetic ketoacidosis)
Taken together these points counter the narrative woven by the Brand-Miller paper, called The importance of dietary carbohydrate in human evolution . It argues that cooked tubers were a major human staple enabling the rapid expansion of the human brain.
On to the last 4 myths!
The Brand-Miller paper paints the traditional Arctic populations as having high-protein diets. Relative to many industrial Western diets, that is in fact correct.
“The diets of traditional Arctic populations are sometimes given as examples of successful high-protein diets (Lindeberg 2009). An estimate of their dietary composition suggested that about 50% of the calories come from fat, 30–35% from protein (or around 300 g per day and lower for pregnant women; Speth 2012), and 15–20% from carbohydrate principally in the form of glycogen from the meat they consume (Ho et al. 1972)”
Even the Inuit, due to their high-protein and moderate-carb diet, aren’t really in nutritional ketosis. If ketosis didn’t happen in these conditions then it probably didn’t happen anywhere else (with even more vegetation available). Thus ketogenic diets aren’t “natural” and hence very unhealthy.
What’s wrong with it?
First, the Inuit were most likely, more often that not, in nutritional ketosis despite their protein intake. And second, the Inuit didn’t get any appreciable amounts of dietary carbs from “frozen muscle glycogen”.
A high-protein diet is a convenient shorthand for a very high animal food diet, but it’s too easily misinterpreted to be scientifically useful. It misleads people because they may know that some amino acids that make up protein have anti-ketogenic properties, and from that mistakenly assume that the net effect from eating them is to totally inhibit ketogenesis.
Not true though.
Our post on gluconeogenesis explains how eating eat large amounts of animal food does not raise blood sugars excessively, if at all. It’s also well documented scientifically and anecdotally that blood ketones (beta-hydroxybutyrate levels) don’t drop out of ‘low-grade’ ketosis (0.3 mmol/L) and can even remain quite high (> 2 mmol/L) when eating this way.
How much protein Arctic dwellers ate exactly probably depended on the cuts of meat they chose, how much oil they had stored, hunting successes and failures, need for calories (e.g. pregnancy, adolescence), the season (e.g. other calories like berries). So it likely went quite a bit higher and lower than 20% protein at times. What the diet certainly didn’t have was meaningful amounts of carbs.
High-protein = protein ceiling?
For some perspective on what “high-protein” can mean nutritionally, human livers and kidneys have been compared to those of lions and wolves. We have way lower functional hepatic nitrogen clearances (FHNC) and urea nitrogen synthesis rates (UNSR) . This means the animals can eat and metabolise way more protein per kg of body weight than we can.
In other words, their protein ceiling is way higher than ours. Ours isn’t exactly low though…
The human protein ceiling claimed by retired Paleo diet research pioneer Loren Cordain is 35 – 40% of calories, equated to 200-300g of protein of protein a day . For a weight-stable person not in a caloric deficit, those figures and percentages must be based off of a diet close to 4,000 kcals per day!
In terms of a single-meal basis, 35 – 40% percentage of calories from protein is definitely an underestimate of what our physiology can handle. Anyone with a couple of rib-eyes in front of them can verify for themselves. But long-term? We don’t know for sure, it’s probably close to a line you don’t want to cross – why would you need to go that high anyway?
To be more comprehensive, there can be reasons for moderating protein intake. If for example you’re targeting a certain level of blood ketones to manage a condition like cancer or epilepsy, a given blood GKI index (glucose-to-ketone index) might be warranted .
Carby meat? Only with naughty citations…
As for the Inuit’s low-to-moderate carb intake (15-20%) due to frozen muscle glycogen, that is nonsense. The Inuit ate high-fat diets of “80–85% fat, 15–20% protein, and, apart from a little muscle glycogen, almost no carbohydrate” .
The Brand-Miller paper cites Ho et al. to support their claim but that study does not explain how this estimate is arrived at. Should we just take it on faith? I certainly won’t. All that’s explained is that the estimate is based off of a 3,000-4,500 kcals daily diet.
In any case, raw seal meat seal contains 0 grams of carbohydrate . In fact, the Brand-Miller paper is contradicted by the the authors it chooses to cite, Varnam and Sutherland :
“if meat is frozen before ATP and glycogen levels are depleted post-mortem glycolysis is suspended. On thawing, however, the meat undergoes severe contraction with associated toughening and loss of large quantities of drip (thaw rigor)”. Simply stated “in response glycogen, the main energy store in the muscle, is converted to lactic acid by anaerobic, post-mortem glycolysis”.
Translated, this means that although flash-freezing meat momentarily and drastically slows down glycolysis right after killing the animal, this won’t stop glycolysis from depleting glycogen when the meat is finally thawed for consumption.
Lactic acid (a 3-carbon molecule) found in thawed muscle meat comes from unthawing frozen glycogen (chains of 6-carbon glucose molecules). It’s important to understand that eating lactic acid doesn’t count as eating carbs.
Frozen or flash-frozen meat contains minute quantities of glycogen because it will have broken down to lactic acid
“the regulatory enzymes which control ATP metabolism and glycolysis in the living tissue are still active in the muscle postmortem, but these enzymatic mechanisms are not able to maintain the ante-mortem levels of ATP and glycogen because the oxygen supply of the cell is stopped as soon as the blood circulation is interrupted by death of the animal. The lack of the aerobic ATP synthesis from ADP in the muscle mitochondria results in an anaerobic depletion of glycogen and consequently in a disappearance of ATP within a few hours p.m.”
Glycogen converts to lactic acid over time as a function of temperature (°C). Mr.Sharp explained this in 1936, saying
“1. In fish-muscle in the frozen state the maximum rate of glycogenolysis
occurs in the interval -3.2° to -3.7°.
2. Freezing at -2° and lower temperatures for a period of 4 hours causes
injury to the muscle, resulting in very rapid lactic acid formation on thawing.
Freezing at – 1-60 has no such effect, and on thawing the normal rate of lactic
acid formation is resumed. Between – 1.60 and -2° a “critical” temperature
of freezing exists.”
Translated, this means meat is still #zerocarb. Rest easy dear lovers of steak.
The Brand-Miller paper suggests there is genetic evidence that nutritional ketosis is a state evolution has helped push us away from rather than towards, saying,
“the derived A-allele has been shown to associate with hypoketotic hypoglycemia and high infant mortality suggests that it is an important adaptation to high meat, low-carbohydrate diets”
Nutritional ketosis from eating a high-meat low-carb diet appears to be a very bad thing: about ¾ of the Inuit population have a genetic mutation stopping the carriers from entering nutritional ketosis who otherwise would be on such a diet, and pregnant mothers with detectable blood or urine ketones have higher infant mortality.
What’s wrong with it?
On the big picture levels, it fails to recognize that evolution can have more than 1 strategy for humans to use fatty acids in the Arctic’s crazy cold environment. This is not evidence of nutritional ketosis being unhealthy so much as it is evidence evolution used fatty acid metabolism in more ways than we’ve been able to imagine.
Specifically, the studies used to support the claims of adverse events of ketogenesis simply do not support that.
So what do we know about this mutation? ¾ of the Inuit who eat a high-meat low-carb diet have a gene (CPT1A) that’s mutated (P479L) causing the protein product (carnitine palmitoyltransferase I) to no longer normally regulate the oxidation of long-chain fats within mitochondria. This mutated protein notably stops the people who have it from entering ketosis, amongst other things .
If nature strongly selected for this mutation over time then it must be good (helps survival and reproduction). But does this mean that not having it is bad? No, at least not necessarily. To assume ‘yes’ is logical error called the transposed conditional. In fact, we’re confronted with the empirical fact that the other ¼ of the Inuit don’t have the mutation! They do enter ketosis and are fine.
So why might this mutation have been selected for?
It may have a lot to do with the cold temperatures characterizing life in the Arctic. One explanation is that the inhibition of ketogenesis enables supraphysiological concentrations of fatty acids to accumulate and force something called decoupling. Decoupling produces heat. You want heat in the Arctic.
Petro Dobromylskyj from the Royal Veterinary College explains how that is supported by a further piece of evidence, saying that:
“there is also evidence that the mutation decreases the inhibitory effect of malonyl-CoA on fatty-acid β-oxidation in mitochondria, thereby partially compensating for the drop in ketogenesis associated with reduced CPT1A activity”
So this mutation diverts fats away from ketogenesis and into the mitochondria, wherein it will be oxidized for energy (ATP). But the fatty acid oxidation ‘brake’ (malonyl-CoA) has now disabled. So for the cell to protect itself from an excess of ATP it must use the fat to produce heat rather than more ATP.
The takeaway here is that this mutation is not evidence of ketosis being ‘selected out’ of humans because it’s bad for us, it’s simply evidence of a non-ketogenic way of using a lot dietary fat in a particularly cold environment.
Brand-Miller suggests the following
“high levels of ketones in the blood, which can compromise reproductive function (Kim and Felig 1972) larger infants are born to women with higher blood glucose (Butte 2000), while a link has been made between maternal gestational ketonemia and a reduced off-spring IQ (Rizzo et al. 1991)”
Having ketones in the blood is deleterious for women’s reproductive systems, so much so that their infant will be metabolically damaged and suffer a drop in IQ.
What’s wrong with it?
The study to support compromised reproductive function from blood ketones was done in pregnant women fasting between 84 and 90 hours by authors Felig et al.; it really has nothing to do with a eucaloric ketogenic diet, let alone a high-quality one based on animal foods .
In fact, the authors highlight the role of gluconeogenesis in pregnancy, saying,
“maternal hepatic gluconeogenic mechanisms are capable of responding to increased substrate delivery during starvation in pregnancy”.
Nowhere in their paper are ketones suggested to compromise reproductive function.
The same authors are quoted again but for another paper of theirs with pregnant women. They didn’t report negative results with regards to a ketogenic metabolic state but did report encouraging ones, saying,
“starvation resulted in significant hypoglycemia and hyperketonemia and in an elevation of free fatty acid and glycerol concentrations. In 13 of 18 fasted subjects, blood glucose levels fell below 50 mg/100 mL. No specific symptoms or signs of hypoglycemia were noted ketones may become an important fetal fuel during maternal caloric deprivation”
Furthermore, a study from the 1980s found that diabetic mothers who were restricting calories and had ketones in their urine as measured by Ketostix didn’t have dangerous levels of ketones in their urine nor did their infants seem negatively affected (e.g. fetal distress or asphyxia neonatorum).
If only the Brand-Miller paper had heeded the advice in the paper by Rizzo et al. that they themselves cite about the IQ drop:
“the associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women”.
It seems that the only reasonable explanation for why the Brand-Miller paper contends that ketosis is unnatural or unhealthy, is that they must be confusing ketosis with ketoacidosis. This is a common mistake lay people make.
Ketoacidosis is a simultaneous and excessive rise in the blood of both glucose and ketones which occurs in type 1 diabetics. Or in late-stage type 2 diabetics who’ve ‘burned out’ their ability to retain normal insulin signaling (largely due to a loss of beta-cell function).
Nutritional ketosis, on the other hand, naturally arises as a result of restricting carbohydrates (e.g. eating salmon and salad for a week) or fasting. Just like drinking shouldn’t be confused with drowning, nutritional ketosis shouldn’t be confused with ketoacidosis.
Lastly, a study by Nancy Butte looking at women with gestational diabetes is cited in the Brand-Miller paper to support the notion that ketosis is not good for one’s metabolism, when in fact the study reached no such conclusion, stating that:
“the ADA states that the percentage of carbohydrate in the diet is dependent on individual eating habits and that the effect on blood glucose and percentage fat depends on assessment and treatment goals the lower percentage of carbohydrate blunts the postprandial hyperglycemia”
The paper warns diabetic mothers to be mindful about how many carbs (and fat) they’re eating. Sensible. It also emphasizes that fewer carbs means fewer blood sugar spikes after a meal. Clearly not an anti-low-carb message.
The Brand-Miller paper makes makes a point about not needing to rely on animal foods so much for a good ratio of the essential dietary omega-3 and omega-6 fats, saying that they
“can also be obtained directly from other dietary sources, or it can be synthesized from other fatty acids such as α-linolenic acid (ALA), which is present in oils from ocean fish, eggs, seed oils, and various leafy plant foods”.
Ancestral humans didn’t rely on animal foods as much as once thought because we evolved ways to transform the unusable form of plant fatty acids into the essential animal forms.
What’s wrong with it?
First, they get the essential fatty acid wrong. They say α-linoleic acid (ALA) is the essential omega-6 fatty acid but it’s more likely to be arachidonic acid (AA) for humans .
Second, they say that the plant forms of fatty acids will get the job done since we can convert them from the non-usable (plant) form into the usable (animal) form. Although different people can convert more or less ALA (plant omega-3) into EPA and DHA (animal omega-3s), such as women who can do more of that than men on average , it’s not true that the conversion is good enough to rely on plant foods alone (or even mainly).
Back in 1998 radioisotope studies showed this in adults
“with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%”.
Western diets are excessively rich in omega-6 polyunsaturated fatty acids, which further reduces our conversion ability. So pointing to our limited conversion ability as evidence of human reliance on plants rather than animal foods for the evolution of our large brains is not a good argument.
Our modern ‘plant-based’ diets are high in omega-6 seed oils, a likely cause of the epidemic of diseases of civilization. Targeting plant foods as meaningful sources of EPA and DHA is thus not recommended, especially in light of the 2006 estimate where Westernized diets contain a 15:1 to >16:1 ratio of omega-6 to omega-3 fatty acids .
#1 You cannot rely on plants to have adequate amounts of omega-3 and omega-6 fats nor a good omega-3 to omega-6 ratio. To achieve both, you must first limit plant omega-6 fats by ditching seed oils, and second, eat generous amounts of animal foods (e.g. fish).
#2 The mutation in the Inuit population that stops them from going into nutritional ketosis is not evidence suggesting nutritional ketosis is bad; it is evidence that there is more than one way to use fatty acid metabolism to survive and reproduce in the Arctic environment.
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