Competition for Calories

Here is a very new paper which has an interesting way of looking at nutrient partitioning (Archer Edward, Pavela Gregory, McDonald Samantha, Lavie Carl J., Hill James O. Cell-Specific “Competition for Calories” Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals. Frontiers in Physiology, v9:2018, 1053):

…we posit that the chronic positive energy balance (i.e., over-nutrition) that leads to obesity and metabolic diseases is engendered by apparent deficits (i.e., false signals) driven by the asymmetric inter-cellular competition for calories and concomitant differential partitioning of nutrient-energy to storage. These frameworks, in concert with our previous theoretic work, the Maternal Resources Hypothesis, provide a parsimonious and rigorous explanation for the rapid rise in the global prevalence of increased body and fat mass, and associated metabolic dysfunctions in humans

Ketogenic Infants

From (Settergren G, Lindblad BS, Persson B. Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in infants. Acta Paediatr Scand. 1976 May;65(3):343-53):

Mean values from 12 infants (age 11 days-12 months) were: CBF 69 ml/100 g0min-1; cerebral uptake (in mumoles/100 g-min-1): oxygen 104, glucose 27, acetoacetate 0.9, D-beta-hydroxybutyrate 2.3; cerebral release: lactate 2.4 and pyruvate 0.8. Significant uptake of amino acids was found only for histidine 0.95 and arginine 0.7. Significant correlations between arterial concentration and cerebral exchange were found for: ornithine, arginine, phenylalanine, aspartic acid, serine, glutamine and acetoacetate. CBF and substrate exchange were unrelated to age within the group.

Infants had higher mean CBF and greater uptake of ketone bodies than has been reported in adults.

Low Carb Hypothesis

Low Carb diets often result in greater weight loss than low fat diets – this BLOG has linked to many of these studies.

One explanation hypothesized for the greater weight loss on Low Carb diets is the Low Carb diet is said to have an inherent metabolic advantage. This metabolic advantage should manifest itself in a greater resting energy expenditure. The paper looked at two possible mechanisms – triglyceride cycling and glyceroneogenesis.

The critics of the Low Carb diet say that the advantage is that the comparisons aren’t done by holding protein constant. Overfeeding protein is not the same as overfeeding carbs or fat since protein stimulates 24 hour energy expenditure and fat doesn’t (Overfeeding Protein – Carnivore Diet).

Look to the Science

A short term (6 weeks) small (4 subjects) study was done on obese women to compare the Low Carb and Low Fat diets which held energy (total calories) and protein constant ( Segal-Isaacson CJ, Johnson S, Tomuta V, Cowell B, Stein DT. A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein. Obes Res. 2004 Nov;12 Suppl 2:130S-40S). The study concluded that there is no significant differences when controlling for protein.

Our results showed no significant weight loss, lipid, serum insulin, or glucose differences between the two diets. 

The study was a decently formulated study but there were weaknesses:

  • Small study – only 4 subjects
  • No control group
  • Older obese females only
  • Very short duration (6 weeks)
  • Low fat didn’t get super-low (20% of calories from fat)
  • The Low Carb diet results in more weight loss but the study was too small to have statistical power

The good parts of the study were:

  • Controlled feeding
  • Matched total calories and protein – varying carbs and protein
  • Decent protein level (30% of calories)
  • Low carb was 5% of calories – good level
  • Randomized control trial
  • Cross-over design so the subjects ate both foods in random order
  • Starches and fruit were the carbohydrate choices (not jelly beans)
  • Deficit was relatively small (200 calories below REE which is a fairly large amount below TDEE depending on activity level)

At the end of the study they gave the participants the choice to continue on for a year. They were given the choice of the two diets and three of the four participants chose the Low Carb diet. However, the Low Carb participants raised their carbohydrate amount from 5% to 23% over the rest of the study so their weight loss partially reversed. There were several distinct advantages for the Low Carb diet.

Lipids were dramatically reduced on both diets, with a trend for greater triglyceride reduction on the VLC diet. Glucose levels were also reduced on both diets, with a trend for insulin reduction on the VLC diet

This fits my own experiences with protein and Low Carb. I’ve seen people stall for a long time and then break the stall by increasing their protein (and dropping their fat). My conclusion is that the ketogenic diet advantage does come from the higher protein intake of the diet. The diet often causes people to increase their consumption of meat which a high quality food.

Just Eat More Protein?

Protein alone doesn’t produce the same advantage that protein and Low Carb have together. This is shown in studies which substitute carbohydrates for protein (Blatt AD, Roe LS, Rolls BJ. Increasing the protein content of meals and its effect on daily energy intake. Journal of the American Dietetic Association. 2011;111(2):290-294).

This study showed that varying the protein content of several entrées consumed ad libitum did not differentially influence energy intake or affect ratings of satiety over a day. When the appearance, taste, fat content, and energy density were controlled, simply adding meat to lunch and dinner entrées to increase the protein content within commonly consumed amounts was not an effective strategy to reduce daily energy intake.

Sigma Nutrition Radio

Here’s a good program on this subject (SNR #64: Are Low-Carb Diets More Effective For Fat Loss?). tl/dl – Low Carb probably has better adherence than Low Fat diets.

Evidence for the Role of Insulin in Weight Gain

Here’s an interesting study which provides evidence for the role of Insulin in Weight Gain (Velasquez-Mieyer P, Cowan P, Arheart K, et al. Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2003;27(2):219-226).

For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased.

When grouped by BMI response, high responders (HR; ΔBMI < −3 kg/m2) and low responders (LR; ΔBMI between −3 and −0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; ΔBMI > −0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR.

Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, ΔBMI correlated with ΔCISI, Δfat mass, and Δleptin. ΔFat mass also correlated with ΔIAUC and ΔCISI.

In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

From the body of the study:

The role of increased carbohydrate craving and intake has been previously suggested to play a contributory role in the development of obesity. However, the connection between insulin and carbohydrate craving and intake is less clear. The frequent intake of highly refined carbohydrates may induce weight gain by initiating and sustaining a chronic state of hyperinsulinemia. Carbohydrate intake stimulates insulin secretion, raising circulating insulin levels, which in turn favors increased fatty acid uptake, lipid biosynthesis, and inhibition of lipolysis, leading to energy storage.

Conversely, it had been suggested that insulin stimulates hyperphagia and fosters carbohydrate cravings, producing increased levels of insulin that promote insulin resistance and exacerbation of the hyperinsulinemic condition. This suggests that a vicious cycle is set in motion that perpetuates hyperinsulinemia and weight gain, and that breaking this cycle can promote weight loss.

Interesting.

Carbs are Fat Sparing

Our bodies burn carbs in preference to fats. That is because we only have a limited amount of storage for carbs and we have a very high capacity for fat storage. 

We are typically burning some mixture of both fat and carbs (except at extremes). The amount of carbs we are burning is strongly influenced by the amount of carbs we have eaten. If you ate nothing but carbs and ate them at an amount matching your total energy expenditure you will pretty much just burn carbs. 

Since most people don’t eat in their sleep there’s some point where the carbs go down and the body starts to draw from the carb stores, aka, glycogen. That can last as long as a day or so but as the glycogen stores draw down the body starts to shift to fat burning. This is known as glycogen sparing.

On a low carb diet our fuel mixture shifts to largely fat based. At very low levels of Insulin that come with a reduction in carbohydrates, our peripheral cells resist the small amount of glucose we produce and we spare the glucose for the parts of our body which rely on glucose for fuel. This is how the low carbohydrate diet is glucose/glycogen sparing.

A high carb diet is fat sparing since it spares our body fat from being burned and reduces the amount of time that glycogen stores are being drawn down. 

Blood Sugar Rises

It is common and well documented by Cahill in his landmark studies on starvation that at the start of carbohydrate restriction blood sugar often goes up in the first few days before it starts to drop.

I’ve seen this myself with long fasts (greater than 4 days). The first few days result in your body making a lot of glucose in spite of low carbs in your diet.

It takes several days for your ketone production to kick in. That’s why the body dumps glucose.

I’ve also noticed an association between weight loss and blood sugar. My blood sugar is often up on the day before I drop in weight. In reverse, my blood sugar is lower when my weight goes up.

Satiety Index

There’s a study that was done of food satiety (Holt SH, Miller JC, Petocz P, Farmakalidis E. A satiety index of common foods. Eur J Clin Nutr. 1995 Sep;49(9):675-90) (PDF).

Isoenergetic 1000 kJ (240 kcal) servings of 38 foods separated into six food categories (fruits, bakery products, snack foods, carbohydrate-rich foods, protein-rich foods, breakfast cereals) were fed to groups of 11-13 subjects. Satiety ratings were obtained every 15 min over 120 min after which subjects were free to eat ad libitum from a standard range of foods and drinks.

A satiety index (SI) score was calculated by dividing the area under the satiety response curve (AUC) for the test food by the group mean satiety AUC for white bread and multiplying by 100.

Thus, white bread had an SI score of 100% and the SI scores of the other foods were expressed as a percentage of white bread.

The results were:

There were significant differences in satiety both within and between the six food categories. The highest SI score was produced by boiled potatoes (323 +/- 51%) which was seven-fold higher than the lowest SI score of the croissant (47 +/- 17%).

Most foods (76%) had an SI score greater than or equal to white bread.

The amount of energy eaten immediately after 120 min correlated negatively with the mean satiety AUC responses (r = -0.37, P < 0.05, n = 43) thereby supporting the subjective satiety ratings. SI scores correlated positively with the serving weight of the foods (r = 0.66, P < 0.001, n = 38) and negatively with palatability ratings (r = -0.64, P < 0.001, n = 38).

Protein, fibre, and water contents of the test foods correlated positively with SI scores (r = 0.37, P < 0.05, n = 38; r = 0.46, P < 0.01; and r = 0.64, P < 0.001; respectively) whereas fat content was negatively associated (r = -0.43, P < 0.01).

This goes a long way to explain the Kitavan diet which is largely sweet potatoes. Can you imagine eating sweet potatoes every day as a main staple? Even though they are high carbohydrates it would be tough to over eat them.

Added: Gary Taubes takes on the palatable foods cause obesity theory (CATCHING UP ON LOST TIME – THE ANCESTRAL HEALTH SYMPOSIUM, FOOD REWARD, PALATABILITY, INSULIN SIGNALING AND CARBOHYDRATES… PART II(E, AS IN “END” AND “ENOUGH ALREADY”). Gary has some good points about the usefulness of this idea.

Carb-Insulin Theory

There’s a lot of contention about the carbohydrate-insulin-obesity (C-I-O) hypothesis to explain obesity. In my opinion, some of this can be traced to Gary Taubes’ abrasive personality. Gary is someone that a lot of people love to hate and he seems to like to help them hate him (Gary Taubes BLOG on this subject).

One of the leading voices against C-I-O is Stephan Guyenet. His BLOG frequently takes on Gary Taubes and the C-I-O hypothesis. In this post he takes on one of the more reputable proponents of C-I-O (Testing the Insulin Model: A Response to Dr. Ludwig. Saturday, January 30, 2016).

Gary Taubes’ main objection is to the Calories-In-Calories-Out (CICO) model. Stephen Guyenet isn’t a supporter of CICO but he sees Taubes’ objections as against a caricatured strawman. Guyenet recognizes the weakness of the CICO model. One of his more salient points is:

This [CICO] model seems to exist mostly to make lean people feel smug, since it attributes their leanness entirely to wise voluntary decisions and a strong character.

Stephen provides a critique of the Carb-Insulin hypothesis that lists a large number of studies that provide evidence against the predictions that the C-I-O hypothesis generates.

I will take some time in the future to look at his lines of evidence against C-I-O but my own interest in Low Carb was from the effect on T2 diabetes and not so much in obesity. Weight loss is just a nice side effect of Low Carb. I have struggled more with Low Carb to reach maintenance than I have with weight loss. I have no doubt that Low Carb works well for Type 2 diabetes. Whether or not the issue is the hormone Insulin or some other cause matters less to me than the effect. I think the evidence is that Low Carb does a better job at managing T2D without medications than either the Zone or Paleo diets.

Stephen’s Model of Obesity

Stephen goes on to presents a third model to answer the basic questions.

This model centers around Leptin and Insulin and places the brain at the center of weight control. Stephen presents his view in this paper (Stephan J. Guyenet and Michael W. Schwartz. Clinical Review. Regulation of Food Intake, Energy Balance, and Body Fat Mass: Implications for the Pathogenesis and Treatment of Obesity. J Clin Endocrinol Metab. 2012 Mar; 97(3): 745–755). From the paper:

The increase of energy intake that has fueled the U.S. obesity epidemic is linked to greater availability of highly rewarding/palatable and energy-dense food.

Obesity occurs in genetically susceptible individuals and involves the biological defense of an elevated body fat mass, which may result in part from interactions between brain reward and homeostatic circuits.

Inflammatory signaling, accumulation of lipid metabolites, or other mechanisms that impair hypothalamic neurons may also contribute to the development of obesity and offer a plausible mechanism to explain the biological defense of elevated body fat mass.

This is where Low Carb can work well since it eliminates these highly palatable food. However, Stephen doesn’t see a particular advantage to Low Carbohydrate diets.

Among various scientific rationales that have been advanced for such diets is that excessive insulin secretion induced by rapidly digested carbohydrate foods causes a subsequent, transient fall of plasma glucose levels; this, in turn, triggers excess feeding and ultimately causes obesity. …. Although clinical trials have established that reduced carbohydrate diets can safely induce modest long-term weight loss, the mechanisms typically advanced to explain this benefit have little in the way of experimental support and are not informative with respect to the control of food intake.

I think there’s something to the fall of blood sugar stimulating hunger. The reason I think that’s true is that it is my experience. I get hungry a few hours after eating a protein meal. Stephen’s explanation is that it is because my stomach is emptying and sending a signal to the brain. It would be interesting to note the difference in someone with a different reaction to protein meals. This theory is old and is presented here (Jean Mayer. Glucostatic Mechanism of Regulation of Food Intake. N Engl J Med 1953; 249:13-16).

Protein Dilution Theory

An alternate explanation of the data is the Protein Leverage Hypothesis. The increase in obesity is explained by an increase in food consumption since 1980 which matched a relatively stable absolute level of protein in the diet. If the total calories are going up but the protein calories are constant it means that the protein is being diluted. The theory is that we seek out a constant level of protein which means we need to eat more food to get our protein if the protein content of food is decreasing. Ted Naiman states this as (Diet 2.0 – Homo sapiens diet):

Today, modern agricultural practices and modern food processing have dumped a massive quantity of refined carbohydrates (sugar and flour) and refined fats (oils) into the food supply, creating protein and nutrient dilution. Because humans eat to a tightly regulated protein and micronutrient satiety drive, we frequently overeat empty calorie carbs and fats just to get adequate protein and micronutrients.

Ludwig’s Latest Paper

Ludwig produced a paper recently ( Ludwig David S, et.al. The Carbohydrate-Insulin Model of Obesity: Beyond “Calories In, Calories Out”
JAMA Intern Med. 2018 Aug 1;178(8):1098-1103).

See Ludwig’s earlier response to Guyunet (Defense of the Carbohydrate-Insulin Model Redux: A Response to Kevin Hall).

“But Kitavas Eat Sweet Potatoes”

One of the common rebuttals to the Carbohydrates + Insulin => Obesity hypothesis is the case of the Kitavans (Lindeberg S, Nilsson-Ehle P, Terént A, Vessby B, Scherstén B. Cardiovascular risk factors in a Melanesian population apparently free from stroke and ischaemic heart disease: the Kitava study. J Intern Med. 1994 Sep;236(3):331-40). The Kitavans eat ancestral diets with huge amounts of carbohydrates, mainly sweet potatoes.

Low Caloric Density

Part of the answer may be found in the caloric density of Sweet Potatoes. Turns out not it takes a whole lot of potatoes to get in your daily calories. 

One pound of Sweet Potatoes provides 340 calories. The typical Kitavan’s energy expenditure was measured at 2200 calories. To get in 2200 calories in a day that would be more than 6 lbs of Sweet Potatoes. That’s a lot of Sweet Potatoes.

Plus, if you could manage to eat 6 lbs of Sweet Potatoes a day it would only be ~40g of protein over the whole day.

Low Fat Choice

It is also a very low fat choice with 4.4g of fat in the 7 lbs of Sweet Potatoes. It is theoretically possible to be lean on very high carbohydrates but you have to be very low fat at the same time.

This diet isn’t the typical hyper-palatable diet of the west. 

Serum Fasting Insulin Differences

As noted, the Kitavan diet is a common rebuttal to the Carbohydrate Insulin Obesity hypothesis. However, the insulin levels of the Kitavans show that they have much lower fasting insulin levels than Europeans (Lindeberg, Staffan et al. Low serum insulin in traditional pacific islanders—The Kitava study.  Metabolism – Clinical and Experimental , Volume 48 , Issue 10 , 1216 – 1219).

Serum fasting insulin levels were lower in Kitava than in Sweden for all ages (P < .001). For example, the mean insulin concentration in 50- to 74-year-old Kitavans was only 50% of that in Swedish subjects. Furthermore, serum insulin decreased with age in Kitava, while it increased in Sweden in subjects over 50 years of age. Moreover, the age, BMI, and, in females, waist circumference predicted Kitavan insulin levels at age 50 to 74 years remarkably well when applied to multiple linear regression equations defined to predict the levels in Sweden. The low serum insulin that decreases with age in Kitavans adds to the evidence that a Western lifestyle is a primary cause of insulin resistance. 

At best, then, it could be claimed that it is possible to have a low fasting insulin and a relatively high carbohydrate diet and the link of carbohydrates to fasting insulin levels is a central claim of the carbohydrate insulin obesity hypothesis.

Other Dietary Differences

Kitavans also eat a significant amount of fish. There are quite a few other interesting facts about the Kitavan diet (See: Interview with a Kitavan).

The Kitavans eat no grains. Their diet has a lot of tubers.

Seasonality

The Kitavans eat different starchy carbohydrate sources throughout the year. From the Interview above:

In the beginning of the year, we eat sweet potato, cassava and mostly tuna for protein. During mid year, before yam comes in to replace sweet potato and cassava, taro is then ready for harvest. And then yams are ready for harvesting so the food supply is continued on.

Lot of Smokers

An interesting tidbit is that 75% of the Kitavans are smokers and yet they have little to no heart disease. Does that mean we should take up smoking?

More Speculation and Differences

Interesting paper on the subject (Ian Spreadbury. Comparison with ancestral diets suggests dense acellular carbohydrates promote an inflammatory microbiota, and may be the primary dietary cause of leptin resistance and obesity. Diabetes Metab Syndr Obes. 2012; 5: 175–189).

A diet of grain-free whole foods with carbohydrate from cellular tubers, leaves, and fruits may produce a gastrointestinal microbiota consistent with our evolutionary condition, potentially explaining the exceptional macronutrient-independent metabolic health of non-Westernized populations, and the apparent efficacy of the modern “Paleolithic” diet on satiety and metabolism.

How Much Protein on Low Carb Diets?

The DRI (Dietary Reference Intake) is 0.8 grams of protein per kilogram of body weight, or 0.36 grams per pound.  This amounts to:

* 56 grams per day for the average sedentary man.
* 46 grams per day for the average sedentary woman.

As I noted in a prior post (Overfeeding Studies) minimum protein requirements are determined by nitrogen studies which typically give standard diets with adjusted protein contents until excess nitrogen is produced in the urine. This indicates that the person is in a positive protein intake since the excess protein is being expelled as urea (nitrogen).

The problem is the standard diet is used for the baseline which includes carbohydrates. In the standard diet glucose needs are completely met from carbohydrates. In a Low Carb diet glucose needs come from fat and protein in the diet (via GNG).

It is important to determine if the Dietary Recommended Intake (DRI) for protein is adequate for people on a Low Carb Diet (Protein Intake – How Much Protein Should You Eat Per Day?).

So how should we determine if those are adequate levels for a person on a low carb diet? Protein Sparing Modified Fasts (PSMF) are low carb diets which also are low fat. They are typically higher levels of protein with the intent of preserving Lean Body Mass (LBM) in the face of a high caloric deficit. There is a study which determined the Protein needs via nitrogen balance on the PSMF diet (Bruce R Bistrian, George L Blackburn, Jean-Pierre Flatt, Jack Sizer, Nevin S Scrimshaw, Mindy Sherman. Nitrogen Metabolism and Insulin Requirements in Obese Diabetic Adults on a Protein-Sparing Modified Fast. Diabetes Jun 1976, 25 (6) 494-504).

 In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. 

This seems like a reasonable approximation for the minimal protein needs on a Low Carbohydrate Diet. The number 1.3g/kg of body weight is significantly more than 0.8g/kg of body weight. A 200 lb (100kg) person would need to eat a minimum of 130g of protein a day.

Here is a similar view from Dr Donald Layman (Donald K. Layman; The Role of Leucine in Weight Loss Diets and Glucose Homeostasis, The Journal of Nutrition, Volume 133, Issue 1, 1 January 2003, Pages 261S–267S).

More recently, the overall contribution of dietary amino acids to glucose homeostasis received further support on the basis of quantitative evaluations of hepatic glucose production. Jungas et al. provided an elegant argument that amino acids serve as a primary fuel for the liver and the primary carbon source for hepatic GNG. Other investigators extended this thinking with the findings that endogenous glucose production in the liver is a critical factor in maintenance of blood glucose. After an overnight fast, GNG provides 70% of hepatic glucose release, with amino acids serving as the principal carbon source. These studies provide further evidence for a linkage between dietary protein and glucose homeostasis.

Continuing…

…a diet with low carbohydrates and increased protein would reduce the role of insulin in managing acute changes in blood glucose and maximize the liver’s role in regulating blood glucose through hepatic GNG.

We need additional protein in a low carb diet to provide the substrate for GNG.