Measuring Nutrient Density: Calories vs Weight

The Nutrient Density Cheat Sheet considers the nutritional yield of foods per standard serving size. Serving size is a food measurement based on the weight of a given food, and is meant to reflect the food portion sizes that people typically eat. Recently the Nutrient Density Cheat Sheet was criticized by a somewhat fanatical vegan. She claimed that by considering nutrition per serving, I was unfairly biasing all of my scores toward animal foods. She doubled down and further claimed that if my scores were recalculated using calories instead of weight, leafy green vegetables would certainly be revealed as the most nutrient dense foods on the list.

We went back and forth about the correct methodology for some time. It took quite a while for her to coherently distill her objections down into something I could actually work with. Essentially, she asserts that water and fibre confound the weight and volume measurements in unacceptable ways, and that calories are a more accurate way to measure nutrient density. She suggested that I completely remove weight as a variable, and do my calculations strictly with nutrients per calorie. So, I decided to humour her and I did precisely what she asked me to do.

I spent a couple hours going back and recalculating all of the nutrient data by calories instead of serving weight. The results are still adjusted for bioavailability, nutrient absorption capacity, and metabolic conversion inefficiencies (my methods for each adjustment are detailed in an earlier blog post here). There are absolutely no weight measurements considered in the nutrition per calorie scoring calculations. Here are the results:

Animal foods seem to still come out on top. However, in order to insulate myself against criticisms regarding my nutrient yield adjustments, I also produced two other unadjusted scores. They use the same methodology— one is nutrient density per serving, and the other is nutrient density per calorie. Neither is adjusted for nutrient bioavailability, nutrient absorption capacity, or metabolic conversion inefficiencies. It's literally just each nutrient divided by its respective DRI and divided by calories. Results are summed across all nutrients per food, and the results across all foods are sorted and ranked. Here are those results:

As you can see some leafy green vegetables do get a boost, but ultimately animal foods are still dominating the top of the list. But, why is this? Leafy greens are low calorie and animal foods are higher calorie. So, it seems intuitive that leafy greens would be some of the lowest calorie foods, so why does measuring nutrient density per calorie actually produce these counter-intuitive results? It's because dividing nutrition by calories just gives you a silly little ratio. That's it. The results don't actually have to favour low calorie foods at all. The results just favour foods that have a similar ratio of nutrition to calories, which can include both high and low calorie foods.

Highly nutritious, high calorie foods (like Atlantic salmon) get similar scores as poorly nutritious, low calorie foods (like spinach). Think about it. If you divide 1000 by 100, you get 10. If you divide 10 by 1, you get 10. It's just a ratio. It tells you nothing about realistic portion sizes or caloric density. Which is why dividing nutrition by calories is a foolish and uninformative way of quantifying nutrient density. For example, black coffee can be found in both the adjusted and unadjusted scores when calculating nutrition per calorie. Which could leave one with the false impression that black coffee is a great source of nutrients, or is at least comparable to oysters or mussels. However, one would have to consume approximately 1.7 litres in order to exceed the RDA of a single essential nutrient found in coffee (riboflavin in this case). Whereas eating just 10g of either mussels or oysters yields more than the RDA of vitamin B12. 10g is barely the size of the tip of your finger. Whereas 1.7 litres is an insane amount of coffee to drink to get the RDA of riboflavin.

One of this vegan's primary arguments in support of nutrition per calorie measurements was that humans have a limited calorie budget (approximately 2000 kcal/day), so assessing nutrition per calorie is best. While it's true we all eat within a similar calorie budget, it's not true that measuring nutrition per calorie actually gives you much meaningful insight into the calorie yield of a food. It's just a ratio. The foods on the top of the list need not be low calorie foods at all.

Ultimately, my position is that calories are a subjective value-judgement. Calories are something you assess completely independently of nutrient density, and you increase or decrease calories according to your goals. On this basis alone, I suggest that factoring calories into the nutrient density score necessarily injects subjective bias into the results. Nutrition divided by calories has a number of unacceptable drawbacks. 

Firstly, considering nutrition per calorie assumes that calories are always a disadvantage. Secondly, it punishes foods for having essential nutrition. Both essential amino acids and essential fatty acids contain calories, so they actually lower the nutrient density score. Which clearly doesn't make any sense. Lastly, it just doesn't actually give you any meaningful information about calories. So, why even bother? Nutrition per serving also has significant interpretive challenges, but they are far less severe, and far less limiting, than measuring nutrition per calorie. Serving size simply gives you a better approximation of how humans interact with food, and that's what matters.

PS. If you like what you've read and want me to continue writing, consider supporting me on Patreon. Every little bit helps! Thank you for reading!

Nutritional Ketosis and Muscle Hypertrophy

A commonly misunderstood concept in the low carb world is the balance between muscle anabolism and muscle catabolism. The ketogenic diet (KD) has the capacity to perturb this balance negatively, though it is not guaranteed. This is because different macronutrients affect both lean body mass (LBM) and fat mass (FM) differently when considered in isolation. Let me explain.

• Protein is both anabolic and sparing to LBM, but catabolic to FM.
• Carbs are sparing of LBM and FM, but anabolic to neither.
• Fat is catabolic to LBM, but anabolic to FM.

This may appear to be a bit of an oversimplification, but in complete isolation this is essentially how the macronutrients behave under eucaloric conditions. The capacity for anabolism and catabolism will vary as we vary these macronutrients in proportion to each other in the diet. We would expect a high carb, high protein diet to maximally spare LBM. We'd also expect a high protein, KD to spare LBM, but perhaps not as effectively due to the lack of carbohydrate.

When we enter into nutritional ketosis, we deplete liver glycogen and must synthesize glucose by breaking down protein and liberating amino acids (AA). This can be protein in the diet or protein on our body. Eventually we can use other substrates like glycerol and aldehydes to synthesize glucose, but the contribution of AAs to gluconeogenesis (GNG) will always be substantial. This is why we sometimes hear low carb advocates claim that carbs are "non-essential". This is because when we don't eat them, we synthesize them.

However, we cannot rely entirely on dietary protein to satisfy our body's entire demand for glucose. For example, if our acute need for glucose exceeds our capacity to digest, absorb, and metabolize AAs from our diet to glucose, we will be pulling those amino acids from our skeletal muscle instead [1]. This seems to be true in the fed and fasted state while in nutritional ketosis.

Even if we could satisfy 100% of our glucose requirements with dietary AAs in the fed state, we still have to sleep at some point. During sleep, we're fasting by definition and relying on endogenous AAs to synthesize glucose. When protein and calories are matched between a KD and a non-ketogenic diet (nKD), a nKD will typically be more sparing of LBM [2][3]. On a nKD, we can rely on liver glycogen to maintain euglycemia throughout the night, and should awake with only modest ketones in the morning. This added benefit of carbohydrate is part of what serves to maximally spare LBM. The more we can rely on our liver glycogen to supply our body with glucose, the less we have to rely on AAs from skeletal muscle catabolism.

All this being said, it is certainly possible to gain muscle on a KD, despite the catabolic stimulus being very strong. It is likely that we merely need to provide adequate protein and a sufficiently robust anabolic stimulus, like resistance training [4]. It is likely that protein needs are going to be higher on a KD in order to achieve the same balance between anabolism and catabolism that can be achieved on a nKD. However, a KD will always cost us anabolic potential even if we do experience net increases in LBM. This means that even if we made gains, we probably could have made better gains (or at least we could have made the same gains with less effort) on a nKD. 

Ultimately, either we're spending dietary AAs on glucose instead of spending them to build muscle, or we're breaking down already built muscle by liberating AAs to spend on glucose. Glucose isn't free. Either way we lose anabolic potential.

Key points:

• Muscle hypertrophy occurs when anabolism outweighs catabolism. 
• We have an obligate need to catabolize lean tissue while in ketosis.
• Ketogenic diets unavoidably cost us anabolic potential by default.
• Amino acids used to make glucose cannot be used to build muscle.
• Typical gains are still achievable in ketosis, but require extra protein.

PS. If you like what you've read and want me to continue writing, consider supporting me on Patreon. Every little bit helps! Thank you for reading!

References:

[1] Claire Fromentin, et al. Dietary Proteins Contribute Little to Glucose Production, Even Under Optimal Gluconeogenic Conditions in Healthy Humans. Diabetes. May 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636601

[2] Greene, DA, et al. A Low-Carbohydrate Ketogenic Diet Reduces Body Mass Without Compromising Performance in Powerlifting and Olympic Weightlifting Athletes. J Strength Cond Res. December 2018. https://www.ncbi.nlm.nih.gov/pubmed/30335720

[3] Wood, RJ, et al. Preservation of fat-free mass after two distinct weight loss diets with and without progressive resistance exercise. Metab Syndr Relat Disord. June 2012. https://www.ncbi.nlm.nih.gov/pubmed/22283635

[4] Antonio Paoli, et al. Ketogenic Diet and Skeletal Muscle Hypertrophy: A Frenemy Relationship? J Hum Kinet. August 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724590

Why We Grow What We Grow

Chris Kresser recently appeared as a guest on the Joe Rogan Experience to discuss and challenge the credibility of the recent film, The Game Changers. During this interview, Kresser had made the statement that staple crops like corn and soy are actually nutrient poor, and that perhaps we should be moving away from our current model of industrial agriculture and focusing on a system that provided more nutrient dense foods.

We can debate the sustainability of different agricultural systems at a different time. For now I just want to discuss his claims regarding the nutritional content of our staple crops. I actually shared this sentiment about our staple crops before I created the Nutrient Density Cheat Sheet, a nutrition ranking tool that uses minimally biased metrics to score and compare over 500 different common foods. After my work on that project was done, it was absolutely clear to me why we choose the staple crops that we choose. It's because they're fucking badass, and for no other reason. It is absolutely insane just how nutrient dense these foods are before we process and refine them.

According to Wikipedia, the most popular grain crops in the world are: corn, rice, wheat, and soy. Kresser claims that these foods are nutrient poor and don't make a very meaningful contribution to the diet. So, what does Kresser recommend instead? When answering this question, Kresser often references the work of Mat Lalonde, and has used Mat's work to defend organ meats, herbs and spices, nuts and seeds, and cocoa as being among the most nutrient dense foods available. But, is this actually true? Are these foods actually the most nutrient dense options we can find? It depends on how we look at it.

Let's break it down. Firstly, Mat's scale only considers essential nutrition per 100g of food, and does not include essential amino acids or essential fatty acids. The scale also does not adjust for bioavailability, nutrient absorption capacity, or nutrient conversion inefficiencies. Needless to say, it is very incomplete. However, as it turns out, my scale does take those things into consideration, or at least it tries to approximate those things based on the best available literature. The Cheat Sheet also includes essential amino acids and essential fatty acids. Lastly, it considers the nutrient density per serving, because serving size better reflects how we interact with different foods. Here are the results when we use my scale to compare our staple crops to Kresser's top picks:

When considered in their whole food state, our staple crops are actually incredibly nutrient dense per serving and can likely contribute a great deal to our diet. Some of Kresser's picks are great, and others are not so good when considering nutrient density per serving. Because he cited food categories instead of individual foods, I was generous and actually took the best food from within each category he listed instead of taking an average. That way we're only looking at the champions of each group.

As we can see, organs are incredibly nutrient dense and can make an incredible addition to the diet. I've written about that before. Herbs and spices are actually pretty nutrient poor per serving, coming in dead last out of everything on the list. They're really not anything to write home about. Nuts and seeds are great, but actually not as good as wheat or soy. Cocoa isn't that great by comparison, either. Keep in mind that I'm considering our staple crops in the cooked state, as well. These numbers aren't confounded by things like dehydration. If we take an average of the total nutrition of each group, we see that our staple crops have an average score of 66, whereas Kresser's picks have an average score of 50. 

I guess the take-home message is, don't make claims before you're in full possession of the relevant facts. While it actually is true that Kresser's top selection of nutrient dense foods actually ranks higher when we consider nutrition per 100g, it is also true that nobody actually eats 100g of dried clove. Virtually nobody eats 100g of nuts or cocoa either. When we consider these foods as people typically consume them, it's obvious why we choose the staple crops that we choose. Provided we're considering these foods in their whole state, they're awesome. 

PS. If you like what you've read and want me to continue writing, consider supporting me on Patreon. Every little bit helps! Thank you for reading!

Sugar Doesn't Cause Diabetes, and Ketosis Doesn't Reverse It

One of the only clinical diagnostic criteria for type II diabetes mellitus (T2DM) is a persistently elevated blood glucose (BG) level. Chasing down the cause of this BG elevation has been the subject of an enormous investigation for many decades. Many researchers disagree about the ultimate pathogenesis and pathophysiology of the disease state, and in the 21st century we have the fortune of being able to see these disagreements play out in real time online. Actual PhDs doing actual pivotal research have taken to using social media platforms like Twitter and publicly accessible academic platforms like Research Gate to debate the merits and consistency of the available data. In these places you will find an enormous breadth of opinions— some plausible, some preposterous, and some that surely reflect reality quite accurately.

Some people argue that sugar causes the disease. Others blame fat and animal products. Some even say it is merely an inescapable consequence of aging. People have many conflicting opinions about T2DM. I'm not a researcher. I'm not an expert. But for what it's worth, I'd like to share my thoughts on this subject. To do this, I want to use a bit of a different format with this post. I'm going to state my position in point form, and then I'm going to defend it by breaking each point down. So let's get to it.

1. Fatty acids cause insulin resistance, but glucose shows it to you.
2. Diabetes is a disease of excess calories.
3. Carbohydrate restriction is therapeutic, not curative.
4. Ketosis is functional diabetes, therefore also therapeutic.

Before we dive into dissecting each one of these points, we need a little crash course in cellular physiology. It won't be painful, I promise. We're just going to briefly review the Randle cycle. 

The Randle cycle is basically a series of biochemical pathways inside of your cells that signal which fuel substrates are to be burned. In one arrangement, a cell will preferentially burn glucose. In the other arrangement, a cell will preferentially burn fatty acids (FA). Under normal conditions, the arrangement is dependent on the relative proportions of each available substrate. For example, after a carbohydrate rich meal, the cycle will favour burning carbohydrates. After a fat rich meal, the cycle will favour burning FAs. Here we see a diagram of these mechanisms in action. 

On the left and right we see glucose and long-chain fatty acids (LCFA) being transported into the cytosol of an adipocyte. Here we see how the availability of either substrate dictates which substrate is to be burned as fuel. Let's start with glucose.

When glucose enters through glucose transporter type 4 (GLUT4), it is driven through an enzymatic pathway known as glycolysis and cleaved in half. This gives us two three-carbon units of pyruvate, which enter the mitochondria. Not seen here, one pyruvate goes on to participate in the Citric Acid (TCA) cycle, and the other pyruvate gets converted to a two-carbon unit called Acetyl-CoA by the pyruvate dehydrogenase complex (PDH). The extra carbon is lost as CO2. If there is too much pyruvate, this drives up Acetyl-CoA and inhibts PDH. This is a form of negative feedback. When the PDH complex is inhibited by Acetyl-CoA, excess pyruvate is shunted out of the cell as lactate.

When LCFA enter the cell, they're broken apart into two-carbon units called long chain fatty Acyl-CoA (LC-FAC) by long chain fatty Acyl-CoA synthetase (LC-FACS). These enter the mitochondria through carnitine palmitoyltransferase 1 (CPT1). From there, each LC-FAC is converted to Acetyl-CoA through beta-oxidation (β-ox). Notice how excess Acetyl-CoA does not have a negative feedback system inside the mitochondria. Instead, excess Acetyl-CoA drives up mitochondrial citrate, and thus drives up cytosolic citrate. Cytosolic citrate is the signal to inhibit GLUT4 and phosphofructokinase 1 (PFK-1). This means that if enough citrate is generated, glucose is both inhibited from entering the cell and inhibited from entering glycolysis.

Further downstream we discover that FAs do in fact have their own negative feedback system. The consequence of continuing to drive up cytosolic citrate is to eventually produce Malonyl-CoA. Which stimulates fatty acid synthase (FAS) for the purposes of storing excess fatty acids through the synthesis of new triglycerides (TG). Malonyl-CoA also inhibits CPT-1, preventing LC-FAC from being transported into the mitochondria.

There we go. We now understand the basics of the Randle cycle. Now let's talk about how this is fundamentally relevant for understanding my position on T2DM.

1. Fatty acids cause insulin resistance, but glucose shows it to you.

Let's refer back to the graphic above. We know that FAs in the cell uniquely inhibit GLUT4. It all depends on the relative proportions of FAs to glucose that are available to the cell. The more FAs you have in the cell, the more resistant that cell will be to translocating GLUT4 to the cell surface to take up glucose. Thus, the activity of the PDH complex will be impaired as the cell begins to preferentially burn FAs as fuel [1]. This impairs oxidative glucose disposal and increases non-oxidative glucose disposal [2]. Essentially, when you eat a high-fat diet, you lose glycogen in your liver, your cells will make the switch to FA-burning, and oxidative disposal of glucose will go down. When you finally do get a bolus of glucose, it will serve to replete glycogen stores and will be disposed of through non-oxidative pathways. More astute individuals in the low-carb community will recognize this whole situation as "physiological insulin resistance", which they rightly state is a non-pathological state.

However, since merely increasing the availability of FAs to a cell will powerfully reduce its sensitivity to insulin [3], we can surmise that the relative insulin sensitivity of a cell is dictated by its FA burden. As such, if one's cells are overburdened with FAs, glucose concentrations in the blood will be higher due to the Randle cycle's effects on insulin sensitivity and glucose disposal [4]. When you challenge the body with glucose while the body is attempting to burn through a surplus of FAs, glucose is going to have to wait outside the cell in the blood until those FAs are burned. When we see this happen in T2DM, it is very tempting to blame the carbs in the diet as being the ultimate cause of the persistently elevated glucose we see in the blood. But the glucose isn't actually to blame. The elevated BG is merely reflecting the competition between energy substrates based on the relative availability of each substrate to the body's cells, particularly the adipocytes. When there is too much fat, glucose cannot be burned.

Am I attempting to imply that a high-fat diet causes T2DM? No, not at all. But the effects of high-fat feeding on glucose metabolism gives us insight into the roles of carbs and fats in T2DM. Which leads me to my next point.

2. Diabetes is a disease of excess calories.

We can confidently say that the symptoms of T2DM are made uniquely worse by carbohydrates, as removing them has profound utility with regards to symptom management [5]. Nobody can really dispute this credibly at this point. However, there is a massive amount of evidence indicating that the primary source of insulin resistance in T2DM at the cellular level is the FA burden of the actual cell [6]. So, what determines the FA burden of a cell? By and large, the answer is every Taubesian acolyte's least favourite word—calories. Calories, calories, calories. 

But isn't insulin a fat storage hormone? Aren't the carbohydrates responsible for sequestering fat into our fat tissue? Yes and no. Insulin stores fat and displaces lipolysis proportionate to the energy provided by the carbohydrates that stimulated the insulin. So yes, if you were somehow able to learn the history of each TG in your adipose tissue, you'd discover that the vast majority of those TGs originated as FAs consumed in the diet. However, insulin wasn't really required to store any of them. If we refer back to the diagram of the Randle cycle for a moment, we discover that merely overburdening an adipocyte with FAs will stimulate TG synthesis. Whether those TGs were stored in the adipocyte through insulin or stored passively by merely consuming fat, it is the total calorie balance of the diet that determines the TG content of the adipocyte at the end of the day [7].

There is a growing body of evidence that suggests that sufficient caloric restriction leads to the remission and perhaps the reversal of T2DM in a manner that is entirely predicted by fat mass loss [8][9]. Fat mass loss is dictated by caloric intake. No more, no less. 

So, to recap. If you overeat carbohydrates, you will indeed store every ounce of fat you consume. However, calorie for calorie, if you overconsume fat, you will drive up TG synthesis and store every ounce of excess fat you consume as well. At the end of the day, total calorie intake minus your total energy expenditure determines fat loss or fat gain. If you overeat enough calories chronically, eventually your adipocytes become so overloaded with FAs that they're indefinitely stuck in the FA-burning position. It is similar to only being able to turn one handle on a faucet, when you should be able to turn both.

3. Carbohydrate restriction is therapeutic, not curative.

Let's go back to BG for a moment. Why is carbohydrate restriction beneficial for T2DM? If it's the fat inside the cell that's causing the problem, why should there be benefits to restricting carbohydrates at all? The short answer is that consuming excess fat carries fewer short-term negative symptoms when compared to glucose in the context of T2DM. When we consume excess fat, it may be readily stored in a number of places. Even though some of these storage depots are problematic, like the liver or even the blood, fat stored in these places causes very few noticeable symptoms under certain conditions. Don't get me wrong, though. It's still not a good thing to store ectopic fat, or to store fat in the blood. However, when you consume glucose while adipocytes and visceral fat stores are experiencing an overload of fat (as with T2DM), all hell breaks loose.

The body does not prefer to store glucose as fat [10]. It never has, and it never will. Glucose that can't be burned is shunted out of cells as lactate. Once the lactate is in the blood it goes to the liver and participates in the Cori cycle to be recycled into glucose. It is then sent back into the blood [11]. Typically, lactate is returned to the liver to be converted to glucose to replete hepatic glycogen. The body knows that while you're burning FAs as fuel, the liver needs extra glucose. But T2DM typically presents with a scenario wherein both subcutaneous fat stores as well as hepatic fat stores are maxed. This impairs the liver's ability to store glycogen. The liver and the adipose are both paddles in a game of Pong, with glucose and lactate as the ball. This is confirmed by the higher levels of plasma and urinary lactate associated with T2DM [12]. As one would expect, this effect can be observed in people with certain glycogen storage disorders as well [13]. In T2DM, this merry-go-round repeats itself indefinitely, until the FA burden on the adipocytes can be resolved. 

But, at this point you might be wondering why this merry-go-round is damaging. Personally, I don't actually think the glucose itself is damaging, but what inevitably results from that glucose is damaging. In this state, you cannot have a glut of BG without a glut of blood lactate, and that is problematic. Lactate can cause anything from hypoxia to tissue necrosis, and pretty much any of the comorbidities associated with T2DM. In fact, some people with T2DM have experienced acute lactic acidosis from taking metformin, a drug that inhibits the Cori cycle [14]. Inhibiting the Cori cycle increases lactate levels in the blood [15][16]. I'm not trying to scare diabetics out of taking metformin. Not at all. In fact, one of the reasons metformin is beneficial is because it opens the loop. If the lactate can't go to the liver to be converted to glucose, it may be redirected to the kidney to be excreted in the urine. This is because the liver and the kidney are two of the body's largest lactate disposal sites. If you take the liver out of the equation, you may very well urinate the excess lactate more easily, or even metabolize it in the kidney more easily. 

I suspect that a combination of metformin and a low-carbohydrate diet could be a powerful tool for reducing many of the comorbidities associated with T2DM. In my estimation, the lactate probably has more to do with these comorbidities than does the glucose itself. But removing the glucose removes the lactate. So, removing the glucose has tremendous utility in T2DM symptom management. Until the FA burden on the adipocytes can be rectified, one cannot expect to be able to tolerate a glucose challenge. It is for this reason that I'm willing to say that the reduction in diabetic symptoms associated with carbohydrate-restriction may very well constitute T2DM remission. However, this is not T2DM reversal. Reversal would imply that one has restored glucose tolerance. Mechanistically, the only durable path toward genuine T2DM reversal would be rigorous calorie restriction, regardless of the macronutrient ratio of the diet. Though, a low carbohydrate diet would likely be less rocky along the way. 

Additionally, as a consequence of the body not preferring to store glucose as fat, you have an innate preference to dispose of glucose through oxidative pathways. This generates a lot of metabolites and byproducts of metabolism that are inherently damaging, and even more damaging in the context of T2DM. Substances like methylglyoxal, reactive oxygen species, and other breakdown products. These products disrupt metabolism and can damage a number of tissues. They can also further disrupt insulin signalling through oxidative damage of the insulin receptor substrate proteins. When you swap the carbohydrates for fat in the diet, there is a greater opportunity to safely store the energy you've consumed. Because the body can safely store this energy, and there is no pressing need to burn it immediately, there is considerably greater leeway with carbohydrate-restrictive diets when we're considering T2DM and its associated comorbidities. 

4. Ketosis is functional diabetes, therefore also therapeutic.

This statement may seem provocative and hyperbolic, but I'm absolutely serious. If you compare ketotic metabolism to diabetic metabolism, there are some spooky similarities.

Pretty much all of the hallmarks of T2DM overlap with the hallmarks of nutritional ketosis, with the exception of glucose, insulin, and lactic acid. This is why ketosis is therapeutic for T2DM. Ketosis removes the primary source of the bulk of the comorbidities associated with T2DM, but the underlying pathology still remains. The insulin resistance persists. The high energy status, and many of its long-term consequences, likely persists as well. In short, ketosis is T2DM without the hyperglycemia. Ketosis takes a dysfunctional state, and makes it more functional by removing the challenge to the glucose disposal system while it is impaired. It doesn't reverse the dysfunctional state. It merely improves the situation by masking some of the associated symptoms.

PS. If you like what you've read and want me to continue writing, consider supporting me on Patreon. Every little bit helps! Thank you for reading!

References:

[1] Chokkalingam K., et al. High-fat/low-carbohydrate diet reduces insulin-stimulated carbohydrate oxidation but stimulates nonoxidative glucose disposal in humans: An important role for skeletal muscle pyruvate dehydrogenase kinase 4. J Clin Endocrinol Metab. January 2007. https://www.ncbi.nlm.nih.gov/pubmed/17062764

[2] Bisschop P.H., et al. Dietary fat content alters insulin-mediated glucose metabolism in healthy men. Am J Clin Nutr. March 2001. https://www.ncbi.nlm.nih.gov/pubmed/11237931

[3] Stephen F. Burns, Sheryl F. Kelsey, and Silva A. Arslanian. Effects of an Intravenous Lipid Challenge and Free Fatty Acid Elevation on In Vivo Insulin Sensitivity in African American Versus Caucasian Adolescents. Diabetes Care. February 2009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628707

[4] Siôn A. Parry, Rachel M. Woods, Leanne Hodson, and Carl J. Hulston. A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin Sensitivity: The Metabolic Consequence of Binge Eating. Nutrients. August 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579612/

[5] Sarah J. Hallberg, et al. Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Ther. April 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104272/

[6] Taylor R., et al. Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for β Cell Recovery. Cell Metab. October 2018. https://www.ncbi.nlm.nih.gov/pubmed/30078554

[7] Kevin D. Hall and Juen Guo. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. May 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568065/

[8] Lean M.E., et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. February 2018. https://www.ncbi.nlm.nih.gov/pubmed/29221645

[9] Roy Taylor. Calorie restriction for long-term remission of type 2 diabetes. Clin Med (Lond). January 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399621/

[10] Acheson K.J., Schutz Y., Bessard T., Anantharaman K., Flatt J.P., Jéquier E. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr. August 1988. https://www.ncbi.nlm.nih.gov/pubmed/3165600

[11] Chen Y.D., Varasteh B.B., and Reaven G.M. Plasma lactate concentration in obesity and type 2 diabetes. Diabetes Metab. August 1993. https://www.ncbi.nlm.nih.gov/pubmed/8293860

[12] Jean L. J. M. Scheijen, et al. L(+) and D(−) Lactate Are Increased in Plasma and Urine Samples of Type 2 Diabetes as Measured by a Simultaneous Quantification of L(+) and D(−) Lactate by Reversed-Phase Liquid Chromatography Tandem Mass Spectrometry. Exp Diabetes Res. March 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310144/

[13] Hagen T., Korson M.S., and Wolfsdorf J.I. Urinary lactate excretion to monitor the efficacy of treatment of type I glycogen storage disease. Mol Genet Metab. July 2000. https://www.ncbi.nlm.nih.gov/pubmed/10924273

[14] E. Fitzgerald. Metformin associated lactic acidosis. BMJ. September 2009. https://www.bmj.com/content/339/bmj.b3660

[15] Huang W., Castelino R.L., and Peterson G.M. Lactate Levels with Chronic Metformin Use: A Narrative Review. Clin Drug Investig. November 2017. https://www.ncbi.nlm.nih.gov/pubmed/28836132

[16] DeFronzo R., Fleming G.A., Chen K., and Bicsak T.A. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. February 2016. https://www.ncbi.nlm.nih.gov/pubmed/26773926

The Sapien Diet: Peak Human or Food Lies?

I am a fan of Brian Sanders' podcast, Peak Human. I don't agree with much of his particular outlook on food and nutrition, but I do enjoy most of the guests that he interviews. It wasn't until recently that I gave his website a look. It was a bizarre experience to say the least. His site builds a case for something he calls the Sapien Diet. In addition to advocating for carbohydrate-restriction and time-restricted feeding, the diet is oddly focused on minimizing conditions that can negatively affect nutrient absorption and bioavailability. However, despite claiming that his perspective is evidence-based and non-biased, his personal biases toward food are quite transparent. I didn't have to look far.

This image is one such example, which implies that healthy foods like apples and bananas are both toxic and nutrient poor, or at least that they have diminished nutrient bioavailability.

While it is true that plant foods contain natural toxins like insect antifeedants, there is no clear evidence that nutritional doses of these toxins from whole foods pose a health risk to humans sufficient enough to justify specific food avoidance as a general recommendation. It is particularly odd to use this speculation to buttress something as pretentious as the "Sapien Diet", which he asserts is the optimal human diet. Profound claims require profound evidence. 

Using plant foods like bananas, apples, bell peppers, strawberries, and even butternut squash to demonstrate the dangers of anti-nutrients is very bizarre, as those plant foods are typically extremely low in anti-nutrients. Not only that, but edible plant ovaries like fruit contain some of the lowest concentrations of plant toxins specifically because they evolved to be eaten by animals like humans. Whereas foods like broccoli actually can contain high amounts of these toxins. However, on balance these plant toxins seem to exert a net positive effect on human health, not negative. The dangers of broccoli to human health are not clearly born out in any prospective, epidemiological, or experimental data. So it makes absolutely no sense to me to scare people away from plants, or suggest that general plant avoidance is supposedly a hallmark of the optimal human diet. It's antithetical to the vast majority of our evolutionary history.

Some of the only evidence cited for the acute dangers of anti-nutrients is a paper wherein a 65-year old woman drank nothing but smoothies containing an enormous amount of leafy green vegetables for ten days straight. The total oxalate content of the smoothie was 1.3g. This is 940% more oxalate than the average person consumes on a typical Western diet. This is not a nutritional dose. She used her blender to turn healthy leafy green vegetables into a drug that had a pharmacological effect on her body. Not only this, but this woman was also dosing relatively high amounts of calcium citrate (1200mg) and vitamin D (1000 IU). The authors of the paper also remark that it was likely the recent gastric bypass surgery she'd undergone in addition to a regimen of antibiotics she was taking at the time that predisposed her to the effect. The only common whole food on the market that has been shown to generate this effect all by itself is star fruit. One star fruit can contain up to 10g of oxalate. But that is the exception. Most fruit contains less than 10mg of oxalate.

Furthermore, it is implied on the opposite side of the infographic that butter is low in toxins with high nutrient bioavailability. It's ironic, considering that one of butter's primary nutrients, saturated fat, associates more consistently with poor health outcomes than broccoli, but I suppose that's a separate discussion. The point is, at the end of the day the health implications of butter are still largely up for legitimate academic debate. However, the health-promoting aspects of broccoli and even high-sugar fruit are exceedingly consistent and well supported by multiple lines of evidence. This alone suggests that there is more to a food than merely its micronutrient bioavailability. Lastly, while it is probably true that the bioavailability of nutrients in butter is probably higher than something like carrots, it is still the case that butter is one of the most nutrient-poor foods available on the market. It is hardly more nutritious than brown sugar when matched for calories. If I had to choose between butter or chocolate chip cookies as a means of furthering my nutrition, I'd be utterly foolish to choose the butter. I invite anyone to credibly challenge this statement.

It is also not always the case that animal foods are superior sources of nutrients. It is not even true that plant foods always have poorer bioavailability of nutrients when compared to animal foods. Calcium is a good example. The bioavailability of calcium from cruciferous vegetables is around fifty percent, whereas the bioavailability of calcium from either any sort of dairy product or even edible bones is typically around thirty percent. 

Sure, someone could point out that the absolute amount of calcium in the animal foods will be so high that they're still a better choice. Yes, I agree. However, I'll refer you back to my example between butter and carrots. It is true that the bioavailability of a nutrient like vitamin A will likely be higher with butter. It is also true you'll probably never get as much vitamin A from butter as you could get from carrots, despite the poorer bioavailability and the metabolic conversion inefficiencies. 

Moving on. The Sapien diet is essentially based on three basic principles. These principles are prefaced by the statement that the Sapien Diet is "how homo sapiens should eat". So, henceforth I will be rightly assuming that these are specific and unwavering rules for optimal nutrition for all human beings. Lofty claims, but that is essentially how it is stated. Let's begin.

The first principle encourages us to consume minimally processed, nutrient dense, whole foods. I actually agree with this recommendation, and see little to argue against in general. In the details we're encouraged to embrace a number of animal foods, which I also agree with. We're further encouraged to favour low-sugar fruit, though it is not explicitly stated why at this point. I strongly disagree with this recommendation for reasons I have stated above.

The last section of the blurb goes on to state that processed foods, sugar, refined grains, and vegetable oil should be utterly avoided. At this point, it is not explained why. We're merely expected to take for granted that these foods are valueless and best excluded from our diet. I simply don't agree with that.

It is puzzling that nuts and seeds are included in the list of foods we're encouraged to embrace. Yet, these are the exact foods that are typically highest in anti-nutrients, plant toxins, and the plant oils we're encouraged to avoid. These foods actually do associate more strongly with health problems than most other plant foods (especially fruit), as they are typically more allergenic and more strongly associated with mineral deficiency syndromes due to their high phytate content and their dense polyphenol content. I'm not saying they're bad foods. I'm merely pointing out an apparent inconsistency with regards to the Sapien Diet's priorities.

The second principle first encourages us to target protein, include protein with every meal, and make sure protein adequacy is met. I agree with this. It then states that we should favour animal protein over plant protein. I agree with this, too. It's a surer bet that you'll meet your protein requirements if you're favouring animal foods. However, some of us actually can't satisfy the second principle thus far without violating the first principle, even if we're sticking to animal protein. The elderly are a good example. It is prohibitively difficult for some elderly people to meet their protein requirements due to common decrements in appetite that tend to result from old age. Highly processed foods like whey protein isolate can step in to ensure these people get what they need. As trivial of an example as that may appear, it is nonetheless one level of nuance with far-reaching implications that can easily break the Sapien Diet's core heuristics. Not everyone can do what this diet is asking them to do, which again cuts against the notion that the Sapien Diet is how homo sapiens should eat.

It is then implied that we're to favour animal protein over plant protein on the basis that animal protein is more bioavailable. Again, I agree. However, this isn't ample justification for plant protein avoidance, if that is actually what is being suggested. A diet of steak and butter will have less protein and less overall nutrition than a diet of steak and, say, lentils when matched for calories. Why would we want to avoid the lentils in this case? Lentils can not only provide added protein, but they can also augment the overall nutritional profile of the diet. A better recommendation might be to simply target protein generally, and don't be afraid of your food.

As we continue reading, we'll see that he plays to a dubious yet bizarrely popular low-carb trope⁠— that fat is the preferred fuel of the body and provides unique health benefits, therefore carbohydrate-restriction is both advised and optimal. I wholeheartedly disagree. I'm not going to go into all of the reasons as to why right now, but perhaps we could further explore my disagreement if I were invited onto the Peak Human podcast to discuss them verbally. Carbohydrate-deprivation could have some unique benefits, but there is no clear evidence that these benefits aren't equally offset by decrements elsewhere. Everything has a cost. Not only that, but the notion that fat is the preferred fuel for the human body is completely at odds with what is gleamed by even the most cursory evaluation of human metabolism and physiology. The whole idea is dead-on-arrival. It doesn't make sense.

I also find it very strange that we're to be guided specifically away from plant foods like bananas because they "provide a ton of energy (empty calories) and not a lot of nutrients", but also guided toward foods like coconut oil. Coconut oil is one of the most calorie-dense, nutrient-devoid foods someone could consume. One extra large Ron Jeremy-sized banana has the same calories as a single tablespoon of coconut oil, and the banana's nutritional profile absolutely crushes the coconut oil. Hands down. No contest. No argument. I'm not saying bananas are awesome or that coconut oil is bad. I'm saying the Sapien Diet contains many internal contradictions that make it seem more than just a little silly.

The last principle is time-restricted feeding. I'm actually surprised at this, since there is virtually no large scale validation of this practice as an effective modality for, well, anything. Some studies suggest that compressing your feeding window merely shortens the amount of time you have to shove food in your face during the day, and thus can induce a caloric deficit in some people. I agree that if you're looking to lose body fat, this strategy can be effective for some people, but not all. It also has a tendency to hinder muscle hypertrophy in athletes when matched against time-unrestricted feeding, and probably isn't optimal as a general recommendation. I don't have much more to say than that. 

Here's my overall perspective and response to what I've read. I view all of nutrition essentially as a great big bin-packing problem. There are many satisfactory solutions to the problem that encourage health and meet our needs, spanning a huge array of different foods and food combinations. To me, the question isn't about which foods everyone should staunchly avoid or staunchly include in their diet, because that cancels many legitimate, safe opportunities for personalized nutrition. I just don't feel that this is the best way to pack the bin. The question should be about which foods best encourage optimal health for the individual, and on top of that which foods can be enjoyed without compromising that individual's optimal health. Maybe there are some core fundamental characteristics of the bin packing that should be conserved across all possible solutions. Things like achieving nutritional adequacy, staying in calorie balance, exercising, etc. But there is likely always room for flexibility that doesn't compromise the bin itself.

The blood-boiling thing that diet zealots just can't accept about this outlook is that it literally allows for the inclusion of all foods. Even junk foods. Is there some amount of liver or egg consumption that directly promotes optimal health? For most people I think the answer would probably be yes. Most people would probably be better off consuming some amount of liver or eggs as opposed to consuming none. However, is there some amount of banana that is compatible with optimal health? For the vast majority of people, absolutely! Banana is a healthy food. Furthermore, is there some amount of chocolate cake that is also compatible with optimal health? For most people who would be consuming it against the background of a diet that already maximally satisfies their personal nutritional needs, the answer would probably be yes as well.

Say you're going on a trip and you're packing a suitcase. Chances are good that regardless of the nature of your trip you will fill your suitcase with a core assortment of indispensable items. But then, you will likely have at least some leeway to customize and personalize much of whatever else it is that you will take with you. I look at nutrition the same way. Once the fundamentals have been optimally satisfied, you have at least some liberty to enjoy yourself and enjoy your foods. For one person, they might fill their extra suitcase space with bananas and mangoes. Others might fill that space with avocados and almonds. If either of them can pack a cookie or two without perturbing the essentials, I think that is perfectly fine and can possibly even be health-promoting in and of itself.

This is a typical example of my diet:

My diet breaks down to around 55% carbs, 15% fat, and 30% protein. At this moment I consume just shy of 2300 kcal per day. I can achieve nutritional adequacy of all essential vitamins, minerals, and amino acids within the first 1500 kcal of my day. If I wanted to fill the remainder with sugary fruit, starchy plants, and refined grains, what does their relative nutrient bioavailability or sugar content matter? Are there better options? Perhaps marginally for some of those things, sure. Would it make an appreciable difference? I doubt it. I enjoy my nutrient dense diet, and I enjoy the flexibility that it grants me. I'm granted the liberty to indulge more frequently by virtue of the fact that my overall dietary pattern is profoundly nutrient dense. That is part of the advantage of a nutrient dense diet, and the indulgences need not be a detraction.

We shouldn't devalue entire foods based on one context-sensitive aspect of those foods. No matter how tempted we are to do so. Be it phytate, toxins, lectins, processed food, carbohydrates, bioavailability, etc. All foods have value. If they didn't have value, people wouldn't eat them. Likely there is a place for nearly all foods in a healthy diet. Food avoidance may be a powerful heuristic that some people can use to lose weight and keep it off. For others, not so much. Some people would likely prefer moderation, however moderation might lead some other people directly to ruin. But I don't think either heuristic reigns supreme as a default approach. Nutrition is personal. I'm not persuaded that the Sapien Diet is the diet that all homo sapiens should be eating.

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