Category Archives: Sugar

another side of leptin

Posted on January 19, 2012 | 1 comment

Op. 56

Leptin is probably just as important as insulin WRT obesity, and this is as just as good a place as any to learn about this increasingly interesting hormone.

ABCs of Leptin in a nutshell:

A. Fed state: leptin is secreted from adipose and tells the brain to maintain food intake and energy expenditure at a body weight set point, which is likely established by diet.

B. Fasted state: leptin secretion declines, causing hunger to go up and energy expenditure to go down.

In the past, the cause and consequence of leptin resistance received a lot of my attention due to their importance in obesity.  Leptin resistance is, in brief, obesity.  Or the mouse on the right:

C. Obesity: eating a poor diet causes leptin resistance, which allows the body weight set point to rise until your fat cells stop responding to insulin (it’s kind of complicated)

But there’s another side of leptin that is mostly unknown, frequently overlooked, and poorly understood.  And I say this “is as just as good a place as any” to learn about it because while this side of leptin isn’t as popular as the energy expenditure, appetite, etc., stuff, it could very well be just as important, IMHO.

Leptin vs. the pathological hyperglycemia in diabetic state(s) (note the plural form of “state[s]”).

Leptin deficiency causes insulin resistance induced by uncontrolled diabetes (German, Morton, et al., 2011 Diabetes)

Divide and conquer

STZ is a beta-cell toxin used to induce diabetes.  STZ-treated mice have low insulin, low leptin, and lose weight despite a voracious appetite (just like type 1 diabetic humans).  Their insulin resistance is fully corrected while their marked hyperglycemia is attenuated by leptin injections.  Leptin reduces food intake but this doesn’t reduce body weight because energy expenditure paradoxically declines (discussed below).  Furthermore, diabetic mice restricted to eat only as much as leptin-treated diabetic mice (STZ-veh-PF)  lose significantly more weight because they lack the leptin-induced suppression in energy expenditure.

Summary of energy balance:

Control mice (veh-veh) eat the least but have much lower energy expenditure, causing them to weigh the most.  Energy expenditure is the more important variable driving high body weight in these animals (it goes down significantly more than food intake).  Diabetic mice (STZ-veh) eat the most food which is balanced by high energy expenditure (explained below), causing an intermediate body weight.  When the voracious appetite of diabetic mice is restrained (STZ-veh-PF), they weigh the least (they are starving).  Food intake is the more important variable driving low body weight in diabetic mice (energy expenditure is the same in diabetic and diabetic-PF mice).  STZ-leptin mice have intermediate food intake, energy expenditure, and body weight.  All is well, leptin cures the deranged energy balance of type I diabetes.

As mentioned above, diabetic mice eat more but weigh less because of drastically increased energy expenditure.  Energy expenditure is increased, in part, due to out-of-control gluconeogenesis (from hyperglucagonemia).  The paradoxical effects of leptin on energy expenditure (increases it in post-obese subjects but decreases it in diabetic mice) may be explained by leptin-induced reduction of this out-of-control gluconeogenesis, mediated via normalization of glucagon.

The authors further demonstrated that leptin restores liver, but not muscle or adipose insulin sensitivity in diabetic mice, independent of food intake.

Thus, insulin-deficiency -> dec. leptin -> inc. glucagon -> inc. hepatic glucose output -> hyperglycemia

Insulin’s primarily role might be to suppress glucagon.  STZ-induced “relative” state of starvation causes leptin to plummet; in the basal state, leptin may not have anything to do with glucagon because insulin keeps it under control.  But in diabetes, there’s no insulin to suppress glucagon; this is where exogenous leptin struts its stuff.

Collectively, these data further support the conclusion that insulin’s major function is to suppress glucagon, as opposed to other effects in skeletal muscle or adipose.  It’s been almost a year since Unger’s notorious publication which showed that glucagon receptor knockout mice were immune to type 1 diabetes (discussed here).  Diabetic hyperglycemia is partially mediated by insulin resistance, and largely mediated by hyperglucagonemia.  But why wasn’t hyperglycemia completely normalized by leptin replacement therapy?   These researchers sought simply to normalize leptin levels, but what would’ve happened if they provided a supraphysiological dose of leptin?  During physiological leptin replacement therapy, glucagon levels were normalized, but a hint of hyperglycemia remained.  Some other [leptin resistant?] member(s) of glucagon’s nefarious cohort must be responsible for the residual diabetic hyperglycemia…

Fortunately for us, the effects of supraphysiological leptin were tested in an identical experimental paradigm:

Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling (Denroche, Kieffer, et al., 2011 Diabetes)

Indeed, supraphysiological leptin therapy overcame whatever diabetic “leptin resistance” remained and totally cured hyperglycemia.

This study repeated much of what was done in the first study, but whereas the first study added that leptin’s effect on food intake was not involved, this study showed that hepatic leptin signaling was not responsible either:

In both cases, hyperglucagonemia appears to be a major cause of diabetic hyperglycemia, and this is cured by leptin.  Insulin sensitivity was only partially restored by physiological leptin replacement; this seems to be due to some sort of apparent “leptin resistance,” which is overcome by supraphysiological leptin.  Diabetic insulin resistance is most likely caused by hyperglucagonemia-induced increased hepatic glucose output, and this is cured by leptin’s [non-hepatic] effects on reducing glucagon levels.  Diabetic insulin resistance may be partially caused by a brain mechanism, but at least one brain mechanism (food intake) was ruled out by the German study.

And oh so interestingly, all of these effects were mimicked by leptin administration directly into the brain, at a dose which caused no change in peripheral leptin levels (German, Morton, et al., 2011 Endocrinology).  The “STZ-lep” in the figure below refers to diabetic mice with leptin administered directly into the brain.

Back to the plural form of diabetic “state[s]” mentioned in the intro.  All of the above studies were in insulin-deficient SKINNY type 1 diabetic mice.  The next study is in OBESE type 2 diabetic rats.

Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats (Cummings, Havel, et al., 2011 PNAS)  

N.B. the control rats in this study were pair-fed to the leptin treated animals to control for the leptin-induced satiation.  Leptin-treated mice lost less weight most likely because energy expenditure declined (just like in the first study mentioned above).

In agreement with the glucose normalization seen by leptin treatment in skinny type 1 diabetic animals, leptin reduced glucose levels in obese type 2 diabetic rats, and this too was associated with reduced glucagon levels:

In type 1 diabetic animals, there are very low insulin levels regardless of food intake, leptin treatment, and hepatic leptin signaling.  Thus, insulin has nothing to do with the effects of leptin in type 1 diabetes.  This study showed that insulin levels also have nothing to do with the effects of leptin in obese type 2 diabetes:

So while the efficacy of exogenous leptin administration in established obesity is questionable, it is capable of combating the pathological glucagon-induced hyperglycemia which is responsible for much of the damage incurred by the diabetic state[s].

Leptin, glucagon, and diabetes.

 

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Posted in Advanced nutrition, Energy balance, Leptin, pair-feeding, Sugar

Insulin, the nutrient anti-partitioner.

Posted on January 13, 2012 | 4 comments

“Insulin is a double-edged sword with a pointy tip” discussed the relationship between insulin and visceral fat.  In brief, any dietary intervention which lowered insulin concomitantly reduced visceral fat, and this was accompanied by a variety of health improvements.  Today’s post focuses more on the connection between insulin and body composition.  Current hypothesis: reducing insulin causes weight loss, and this weight is primarily adipose (muscle is spared).  IOW, insulin plays a primary [cause], as opposed to secondary [effect] role in regulating fat mass.  FYI the alternative hypothesis states that reduced insulin levels are simply one of the many beneficial effects of weight loss.

Exhibit A: lower insulin is correlated with more fat loss

1. Diet-induced reduction in insulin

A. Glycemic load 

Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial (Das et al., AJCN 2007)

In this year-long study, the low glycemic load (GL) diet reduced insulin levels to a greater degree than the high GL diet (-21.2% vs. -18%), and this resulted in more total fat loss (-26.1% vs. -23.5%), and a greater proportion of the total amount of weight lost was comprised of fat (92% vs. 81%).  The differences were small, but probably not due to chance given the consistency and specificity of this effect (see below).

B.  Calories vs. carbs

The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets (Brehm et al., 2005 JCEM)

In this 4 month-long study, the low-carb diet lowered insulin over twice as much as the low-fat diet (-36.8% vs. -13.6%), which resulted in significantly more total fat loss (-6.7% vs. -3.8%), and a greater proportion of the total weight lost was comprised of fat (92% vs. 81%).  The absolute differences between studies (comparing these results directly to the above results) are big, but this is not unexpected because each study has markedly different 1) patient populations, 2) study durations, and 3) interventions.

2. Exercise-induced reduction in insulin

Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men (Ross et al., 2000 Annals of Internal Medicine)

In this rather complicated 3 month-long study, the exercise group lost weight, and this was compared to a group who lost a similar amount of weight by diet alone.  The diet-alone group functioned as a control for the negative energy balance.  Exercise lowered insulin levels more than diet alone (-41.4% vs. -17.9%), which resulted in more fat loss (-18.4% vs. -16.9%), and a greater proportion of the total weight lost was comprised of fat compared to diet alone (81.3% vs. 64.9%).  If a greater proportion of the total weight lost was comprised of fat, then the intervention selectively spared lean mass resulting in a more favorable body composition; this occurs consistently in every study mentioned in this post.

Exhibit B: pharmacologically lowering insulin causes fat loss

1. Diazoxide

Beneficial effect of diazoxide in obese hyperinsulinemic adults (Alemzadeh et al., 1998 JCEM)

Diazoxide directly targets the pancreatic beta-cells to reduce glucose-stimulated insulin secretion.  In this 2 month-long study, diazoxide combined with a low-calorie diet reduced insulin levels more than diet alone (-35.7% vs. -14.7%), which resulted in more fat loss (-19.8% vs. -6.8%), and a significantly greater amount of the total weight lost was comprised of fat compared to diet alone (95% vs. 72%).

2. Octreotide

Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome (Gambineri et al., 2005 JCEM)

Octreotide is a somatostatin analogue which suppresses, among other things, insulin secretion.  In this 7 month-long study, octreotide combined with a low calorie diet reduced insulin levels more than diet alone, which resulted in more fat loss (-6.4% vs. -2.4%), and a greater proportion of the total weight lost was comprised of fat.

Exhibit C: insulin increases fat mass

The previous data supported the hypothesis that lowering insulin, by multiple completely different mechanisms, results in reduced fat mass.  The next evidence argues against the opposite hypothesis and supports a direct role for insulin in increasing fat mass.

Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus (Makimattila et al., 1999 Diabetologia)

In this year-long study, diabetic hyperglycemia was treated with insulin alone or insulin combined with metformin.  All subjects in this study gained weight and fat mass.  The addition of metformin to insulin therapy blunted the increase in insulin levels (30.8% vs. 45.5%), which reduced fat gain (11.6% vs. 22.1%), and only 73.7% of the weight gained was fat compared to 91.8% by insulin alone.

Administration of exogenous insulin increases fat mass.   Reducing insulin, by a variety of means, burns fat and spares lean mass.

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Posted in Advanced nutrition, Dietary fat, Energy balance, Sugar

Holiday feasts, the freshman 15, and damage control

Posted on January 8, 2012 | 7 comments

Holiday feasts, the freshman 15, and damage control, Op. 54

overeating ANYthing is a bad idea.  But as demonstrated in this recent study, WHAT you overeat has a big effect on how your body responds.  The overfeeding protocol studied was pretty intense, ~1000 excess kilocalories per day for 8 weeks.

Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating (Bray et al., 2011 JAMA) Healthy people where fed hypercaloric low, medium, or high protein diets.  It’s impossible to isocalorically change one macronutrient without inadvertently changing the others.  With regard to study design, this is always a tough decision, and in this study they exchanged protein for fat:

Divide and conquer

As seen in the monster-table above or simplified table below, the high protein group gained the most weight despite eating no more than the other groups; but this weight was comprised of significantly more lean body mass than in any other group. 

High protein dieters also expended more energy but still gained more weight!  Importantly, however, much of that weight was muscle.  The increase in energy expenditure is likely due to dietary protein-specific effects: 1) high metabolic cost of increased protein turnover, 2) elevated metabolic rate associated with more muscle, and 3) increased diet-induced thermogenesis.  The low protein group, on the other hand, lost muscle and gained more fat than any other group.

an aside: the energy expenditure measurements taken during overfeeding should be taken with a grain of salt, shot of tequila, and suck of a lemon because the accuracy of such measurements usually require weight-stable conditions; overfed subjects were gaining weight and in positive energy balance.  In other words, the assumptions required for doubly-labeled water to assess energy expenditure during weight-stable conditions are likely not met during weight gain (which is further complicated by the fact that the different groups were gaining different types of body weight [fat vs. fat-free mass]).  But the body composition data are probably OK (see below).

Furthermore, while it may seem like the Laws of Energy Balance were violated in this study, I assure you, they were not.  This study was not designed to test them, as evidenced by the author’s failure to conduct a comprehensive assessment of energy balance.

The high monetary cost of high protein foods (e.g., steak) is matched by the high energetic cost of their assimilation.  By increasing protein intake, energy expenditure rises in parallel.  This is most likely due to a combination of factors (mentioned above), and the result, at least in this study, is increased lean body mass.   The low protein diet, on the other hand, didn’t increase energy expenditure and resulted in more fat gain.  N.B. the absolute amount of protein consumed by the low protein group (47 grams) was too low to maintain muscle despite ingesting 40% more total calories.  In other words, the low protein dieters actually lost muscle mass while gaining fat!!

conclusions

1. THE media always screws up things (no thanks to Dr. Bray’s discussion).  The headlines should’ve read: “Dietary protein increases lean body mass more than total calories increase fat mass.”  That headline would’ve taken the focus away from the calorie debate by highlighting an important macronutrient effect.  This is important, IMHO, because body composition is a very important factor determining metabolic outcomes and quality of life, and is often overlooked (e.g., BMI).

2. While excess calories are necessary to increase lean body mass, excess protein has little effect on fat mass.  “Excess protein has little effect on fat mass” would’ve been another great headline.  But it wasn’t.

Most of the excess energy consumed by the low protein dieters was stored as fat, while in the high protein dieters it was invested in muscle and burned off.  Although it’s a little too late to prevent holiday feast-induced weight gain (or the freshman 15 for that matter) these data suggest that whenever possible, filling up on the highest protein foods available will cause the least fat gain.  Increased dietary protein -> increased lean body mass –> increased metabolic rate (you burn more fat in your sleep!)

Dietary protein doesn’t require a prescription and is a potent nutrition partitioning agent.  But as mentioned above, WRT energy balance, this study was not perfect.  So, why do I believe the effects of dietary protein are true despite the methodological flaws in Dr. Bray’s assessment of energy balance?  Because they are consistent in a variety of conditions.  For example, the remarkable effects of a high protein diet on body composition prevail even during underfeeding (aka going on a diet), a completely opposite paradigm.

Skov and colleagues tested hypocaloric high vs. low protein diets for 26 weeks and confirmed that even during negative energy balance, dietary protein favors lean body mass at the expense of fat mass (Skov et al., 1999 International Journal of Obesity)

And similar results, albeit less robust due to the shorter duration, were found in a study by Layman and colleagues in as few as 10 weeks (Layman et al., 2003 Journal of Nutrition)

During overfeeding, high protein diets cause greater increases in lean body mass and energy expenditure, and prevent excess fat accumulation relative to low protein diets.  During underfeeding, high protein diets lead to a greater retention of lean body mass and more fat loss.  Nutrient partitioning 101. All calories are not created equal.

or


??

 

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Posted in Advanced nutrition, Dietary fat, empty calories, Energy balance, Protein, Sugar, Uncategorized

Insulin is a double-edged sword with a pointy tip

Posted on December 22, 2011 | 3 comments

Visceral fat (VAT) is bad, more VAT is worse; believe, or do a Google on it.  And it is my contention that insulin, or more specifically diets that promote insulin spikes, hyperinsulinemia, or insulin resistance, is the primary driver of VAT accumulation.

The balance between fat accumulation and fat loss is regulated by four distinct mechanisms, which are similar in myriad biological systems:

1)      Enhanced fat accumulation

2)      Reduced fat accumulation

3)      Enhanced fat loss

4)      Reduced fat loss

They are not mutually exclusive, but small shifts in any of them can cause big changes in fat mass with vast implications for metabolic outcomes.  And to complicate matters further, we are talking about two distinct fat depots which are independently regulated by those mechanisms… there are a lot of possibilities.

Subcutaneous fat (SCAT), the kind associated with a “pear” body shape, is a relatively safe place to store excess energy; i.e., safer than VAT or other ectopic depots such as liver or muscle.  And in lean healthy individuals, SCAT is more sensitive than VAT to the anti-lipolytic effects of insulin.  In other words, insulin favors the storage of excess energy in the relatively safer SCAT.  But when insulin levels spike, insulin resistance and hyperinsulinemia develop.  This causes the reverse to occur- fat mass accumulates in VAT.  Fortunately, this is completely reversible by weight loss or adopting a low-insulin diet.

Evaluation of two dietary treatments in obese hyperinsulinemic adolescents (Armeno et al., 2011 Journal of Pediatric Endocrinology and Metabolism)

This study examined the effects of two isocaloric hypoenergetic diets of identical macronutrient composition that differed markedly in their ability to spike insulin levels for 16 weeks in 86 obese Argentinian children.

CD = control diet; LIR = low insulin response diet.

Divide and conquer

After 16 weeks, the LIR group lost more weight than CD, and waist circumference declined to a greater extent.

And of particular relevance to my current thesis, the decline in waist circumference was disproportionately greater (relative to the body weight loss) in the LIR group compared to CD.

Importantly, this correlated well with a greater reduction in fasting insulin levels in LIR relative to CD.

Waist circumference is a good indicator of VAT.  Reduced insulin levels improved insulin sensitivity, which promoted a shift away from VAT- an example of how small shifts can have a big impact on the abundance of fat mass stored in one depot relative to another one.  And this also had a functional impact on metabolic outcomes- AST, a marker of liver dysfunction, was reduced to a greater extent in the LIR group relative to CD.

Why do I attribute these effects to reduced insulin levels?  Aside from the sound (IMO) biological rationale mentioned above, it occurs consistently regardless of how insulin levels are reduced.

Greater weight loss and hormonal changes after 6 months diet with carbohydrates eaten mostly at dinner (Sofer et al., Nature Obesity)

While the Armeno study in obese children (above) reduced insulin levels with a diet that didn’t spike insulin levels ever, this study did so by restricting the insulin spike to once per day, at dinner time.  This was a longer study (6 months) in an older population (39 Israeli adult police officers).

Interestingly, and similar to the Armeno study, the experimental group (dinner carbs) lost more body weight and experienced a greater reduction in waist circumference than the control group.

As in the Armeno study, the reduction in waist circumference was disproportionately greater in the experimental group than in controls, and this also correlated with a greater reduction in fasting insulin.

This was accompanied by functional improvements as well- the experimental group experienced a greater increase in HDL and a bigger decline in the inflammatory insulin-desensitizing cytokine TNF-alpha.

The similarities between these two studies is eery, especially given the markedly different patient populations (obese Argentinian children vs. obese Israeli cops) and study duration (4 months vs. 6 months).

Why do I attribute these effects to reduced insulin levels?  Aside from the sound (IMO) biological rationale mentioned above, it occurs consistently regardless of how insulin levels are reduced.

The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women (Harvie et al., 2011 International Journal of Obesity)

This study compared the effects of a chronic 25% energy restricted diet (CER) to an intermittent energy restriction (IER) which reduced food intake only on Monday and Tuesday while allowing ad lib food intake for the rest of the week in 89 overweight young British women for 6 months.

Similar to both of the above studies, the experimental group (IER) lost more body weight and experienced a greater reduction in waist circumference than controls.

And this too was accompanied by a greater reduction in fasting insulin levels.

Function improvements occurred as well- the experimental group experienced a greater increase in insulin sensitivity and the insulin-sensitizing hormone adiponectin.

These findings further contribute to the phenomenally similar effects of reducing insulin levels, in three markedly different experimental paradigms (obese Argentinian children vs. obese Israeli police officers vs. overweight British women):

Why do I attribute these effects to reduced insulin levels?  Aside from the sound (IMO) biological rationale mentioned above, it occurs consistently regardless of how insulin levels are reduced.

Could greater VAT loss be due to weight loss and not reduced insulin levels per se?  It’s possible, but given the effects of pharmacologically reducing insulin levels (see HERE) it seems like insulin, not body weight, is the main driver.

You just gotta get those insulin levels down

  1. Eat fewer foods that spike insulin
  2. Restrict carbs to one meal per day
  3. Intermittent energy restriction

 

calories proper

 

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Posted in Advanced nutrition, Dietary fat, Energy balance, Sugar, Uncategorized

Fructose vs. The Laws of Energy Balance

Posted on December 13, 2011 | Leave a comment

Exclusively from literature featured in past blog posts, e.g. HERE and HERE, excessive fructose consumption seriously deranges metabolism.  Furthermore, fructose pre-disposes to and exacerbates leptin resistance, which is one of the most proximal causes of obesity viz. overeating.  However, this doesn’t exonerate processed foods, modern grain-based diets, or trans-fats because they frequently co-exist.  Many popular breakfast cereals contain all three, and IMO a fructose-free breakfast cereal wouldn’t do much in the treatment and/or prevention of obesity.  Just eat better.  And we might even get “low-fructose” foods on grocery store shelves in the near future (but don’t hold your breath, food companies LOVE their fructose).

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans (Stanhope et al., 2009 Journal of Clinical Intervention)

Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women (Cox et al., 2011 European Journal of Clinical Nutrition)

Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-h glucose and insulin excursions (Stanhope et al., 2011 American Journal of Clinical Nutrition)

These studies came out in a few separate publications, were ultra-high budget, and used very advanced techniques to quantify energy expenditure and body composition.  AND much care was taken to ensure the subjects were truly weight stable when appropriate (inpatients for two weeks in the beginning and end of the study so all of their food intake and anthropological measurements could be assessed accurately).  The experiment consisted of feeding subjects a sugar-sweetened beverage, either glucose or fructose, equivalent to 25% of their daily energy requirements.

During the inpatient portions, subjects were fed a standardized diet of 15% protein, 20% fat, and 55% carb:

Note the differences in GI & GL (bottom two rows).   Fructose has a negligible impact on glycemia because, well, it’s fructose (not glucose), and it doesn’t magically transform into glucose after ingestion.

When left to their own free will, the patients pretty much ate the same:

In general, after a period of adaptation, their intake of other foods should have declined by 25% to compensate for the additional calories from the sugar drinks, but sugar seems to hijack the appetite set point – first row in the table above; calories were 20-25% higher, almost the exact amount of calories in their sugar drinks – therefore all subjects gained a few pounds (1% of initial body weight) (and then they went back on good behavior when they were being observed in the metabolic ward):

Herein we have the first unexpected pearl: the fructose group gained visceral fat (VAT) whereas the glucose group gained subcutaneous fat (SCAT) (eerily similar to what is seen with trans-fats!).

Exhibit A:

The glucose group actually gained slightly more fat mass than the fructose group, but most of the excess weight was deposited in the relatively inert SCAT, or “extraabdominal” regions.  The fructose group, on the other hand, gained it all in VAT (apple, not pear).  Abdominal fat and waist circumference increased significantly in the fructose drinkers.  FYI that is very interesting.  And it wasn’t caused by individual differences- it’s not like some people were more predisposed to gain more VAT than SCAT; these subjects were randomized.  Diet, or more specifically, dietary sugars caused this differential fat storage.  Amazing.

Exhibit B:

This figure shows the differences in fat gain.  The glucose group gained less VAT than SCAT, while the fructose group did the opposite.  Genetics had nothing to do with this.  It is diet.  It is nutrition.  For the love of God people, it is nutrition.

In lieu of the recent publication by Dr. Bray, it is interesting to note the second pearl: an example of the irrelevance of the laws of thermodynamics (universal) with respect to the Laws of Energy Balance (conjured up by yours truly).  Namely, energy expenditure is affected by the diet… IOW, the laws of thermodynamics are not violated, but all calories are not equal (THERE. I said it… on the record, in cyberspace, for all of eternity).

This nuance is introduced in figure 2:

Divide and conquer

On the left, fat oxidation is slightly lower in the glucose group.  This is expected, because carb oxidation should have increased due to the increased carb consumption (in the form of the glucose drink).  But as seen in the right panel, fat oxidation declined significantly in the fructose group.  From this, we would expect fat gain to be greater in the fructose group compared to the glucose group … but it wasn’t.  Artefact?  Error in measurement?  I don’t know how, but this appears to be a violation of the Laws of Energy Balance (which is impossible).  UNLESS energy expenditure declined more in the fructose group than in the glucose group.

Exhibit C:

And it did!  Both groups increased their sugar consumption (by design), and energy expenditure declined in both groups (they all gained weight).  The fructose group gained about a pound less than the glucose group, but consumed slightly fewer calories on average.  So the reduced fat oxidation didn’t enhance fat gain in the fructose group because food intake declined proportionately; and they maintained energy balance relative to the glucose group because energy expenditure was slightly lower (this is complicated).

To be clear, the fructose-induced VAT deposition is not explained by reduced fat oxidation as that would imply less fat gain overall, relative to the glucose group (which didn’t happen).

Fructose-induced VAT deposition is a product of the deranged nutrient partitioning caused by fructose itself.  It’s a dangerous lil’ bugger.  How does fructose conspire with the metabolic machinery to selectively enhance visceral adiposity?  Not sure, but it might have something to do with insulin.  Glucose but not fructose stimulates insulin secretion, and SCAT is more sensitive to the anti-lipolytic effects of insulin than VAT.  The overall fat gain was similar in both groups, in accord with the Laws of Energy Balance.   But insulin tends to drive fat into metabolically safer SCAT.  An example of this concept in practice can be seen by looking at obese insulin resistant people.  In this population, SCAT is less responsive to insulin, relativeto lean people, and indeed, they have significantly greater visceral fat mass.  So fructose doesn’t trigger an insulin response, which means excess calories are less likely to be stored in SCAT, but since this can’t violate the Laws of Energy Balance the calories must go somewhere…  deposited into the notorious VAT bank where they not only still make you fat but also initiate a storm of metabolic abnormalities.

 

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Posted in Advanced nutrition, empty calories, Energy balance, Fructose, Sugar, Trans fat

pizza on the docket

Posted on November 22, 2011 | Leave a comment

they’re all crooks!

or

a slice of pizza does not count as a serving of vegetables. Period.

not the worst thing for you, really just a bunch of empty calories.  definitely NOT a serving of vegetables.

The government-sponsored school lunch program is designed to provide nutrition and improve the health of our children.  And they get around 11 billion dollars (i.e., $11,000,000,000) every year to do so.  Due to the recent surge in obesity, Congress acted fast!  School lunch programs do not closely follow the dietary guidelines.  To us taxpaying voters, $11,000,000,000 of our taxes are being wasted AND our kids are suffering.   Therefore, Congress quickly changed the status of pizza to “vegetable.”  Many schools serve pizza, and thus are now more closely in line with the dietary guidelines; so our taxes are being less-wasted and our children are healthier because they are eating more vegetables! To be clear: now that pizza is a vegetable, your children are healthier.

You can’t make this shit up – it is what happens when government gets involved in nutrition.  Please, ignore the Dietary Guidelines, they are horribly misguided.  And be extremely wary of electing anyone who wants to control nutrition; or vote with your dollars, don’t buy processed food!  The message is almost always wrong and both our bank accounts and our health suffer the consequences.  I would suggest supporting nutrition education programs, but NOT IF THEY SAY PIZZA IS A VEGETABLE.  If anything, a slice of pizza should count as dessert plus 3 servings of grains :/

Isn’t it bad enough that French fries, or crisps, count as vegetables?

Admittedly, claiming “the Dietary Guidelines are horribly misguided” is a strong statement, especially when said guidelines direct how a portion of our taxes are spent AND which foods are made available to our children.  This is important.

 

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Glycemic index revisited, again, etc.

Posted on October 12, 2011 | 1 comment

The glycemic index (GI) ranks foods based on how high 100 grams (~3.5 oz.) of them make go your blood sugar.  Dietary simple sugars like sucrose (table sugar) and glucose (e.g., Gatorade) have high GI’s because they are quickly digested and absorbed.  Fats and proteins register low on the GI because, well, they don’t provide any glucose.  Complex carbohydrates and fibres are intermediate.  And most important, mixed meals have a low to intermediate GI.  It was once dogma that only high GI foods caused weight gain, but a plethora of somewhat disappointing studies have shown that 1) a low GI diet doesn’t protect lean people from weight gain, and 2) switching from a high to a low GI diet doesn’t facilitate weight loss.  Glycemic load (GL) was then introduced which incorporates the amount of the food consumed, such that low GI foods could have a high GL if enough was eaten at once.  This fared slightly better than GI, but in the end, the total amount of carbohydrates turned out to be more important than the type of carbohydrates. IOW, WRT glycemia and body weight, quantity outweighs quality.  But that doesn’t stop the researchers from testing it … over and over again (on the taxpayers dime!).  In their defense, epidemiological studies have demonstrated a very modest relationship between GI/GL and disease risk, just not with body weight, adiposity, etc.

For example,

Substituting white rice with brown rice for 16 weeks does not substantially affect metabolic risk factors in middle-aged Chinese men and women with diabetes or a high risk for diabetes (Zhang et al., 2011 Journal of Nutrition)

I like this study for its practicality.  It is a real-life, highly “do-able” intervention, which is usually a critical concept in interpreting and applying the results from dietary intervention studies.  Switching out white rice for brown rice, easy enough!  The entire population was Chinese, who ingest phenomenal amounts of rice anyway (>30% of total calories… daily!), so attrition was not a problem.  And as wonderfully illustrated in the chart below, making the switch for 4 months had no effect whatsoever (see the P-values in the far right column).

 

 

LDL cholesterol went down slightly more in the white rice group, but this is biologically insignificant.  All other metabolic parameters were unchanged.  For those who like to nit-pick, BMI went down slightly more in the brown rice group while waist circumference went down slightly more in the white rice group, meaning that body composition may have been more favorably affected by white rice :/

This study is reminiscent of a much larger and more important one by none other than Willett and his Harvard cronies in a population of Brazilian women:

An 18-mo randomized trial of a low-glycemic-index diet and weight change in Brazilian women (Sichieri, Hu, Willett et al., 2001 AJCN)

This study was of a similar design; although they targeted both GI and GL.  The intervention was more robust; there were much bigger dietary differences between the groups, probably because Willet’s crew has virtually unlimited resources, but this didn’t change the outcome.  Total carbohydrate (60% of kcal), fat (27%), and protein (13%) intakes were the same but GI and GL were almost 3 times greater in the high GI (HGI) group compared to the low GI (LGI) group.  FTR, “3 times” is a really big difference… IOW, if GI or GL had any effect whatsoever, they would have detected it from a mile away.

For those who were wondering what exactly comprises a low or high GI diet, a sample menu was provided:

As seen in the table below, there were no dietary differences other than GI & GL between the groups (meaning it was a well-controlled intervention; kudos):

And as illustrated in the figure below, GI and GL had no effect on body weight:

N.B. the scale of the abscissa- it encompasses one kilogram (2.2 pounds); thus, it should look more like this:

Anyway, it looks like both groups lost a LOT of weight, but really their body weight declined very slightly by about 1-2 pounds, then slowly creeped back up (over the course of 18 months).  AND for those nit-pickers, it looks like the low GI group ended up slightly heavier! (not really, as the difference was very small and statistically insignificant). IMHO, WRT GI & GL, the Willet study is compelling.  It was of the highest quality study design: a randomized, controlled, intervention (as opposed to less conclusive or meaningful epidemiological, observational, cross-sectional, etc., studies).  So what was the rationale to re-test GI & GL in a much smaller study with a weaker intervention (brown vs. white rice)?  Beats me!  But the notion that a low GI or GL favorably affects body weight will not go away.  Carbohydrate quantity not quality is the major determining factor.

AND as blogged extensively on HERE, potato chips were the most obesogenic foods in one hyooge study.  potato chips have a relatively low GI, around 55.

 

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Posted in Advanced nutrition, Dietary fat, empty calories, Sugar

Nutrition under attack

Posted on October 4, 2011 | 1 comment

Global nutrition is in a state of emergency

Tax this:

Not this:

 

If you catch a whiff of anyone talking about a dietary fat tax here in the states, attack!  Hold no bars.

Passage of the Danish saturated fat tax confirms the shit hit the fan.  They should’ve taxed people for being fat (to offset the increased medical and healthcare costs associated with obesity), or sugars (for making people fat).  Instead, the food companies, famous for crafting thousands of varieties of Danish pastries, lobbied for the taxes to be levied against dietary fat.  This “inadvertently” encourages people to consume more Danish pastries with only 7 grams of saturated fat yet 39 grams of sugar!  The tax will favor Pop Tarts over eggs, and this is supposed to make people healthier?

A dietary fat tax is particularly troublesome because it strikes an expensive blow against real whole foods like eggs, butter, and meat, while leaving unscathed processed foods like doughnuts, refined grains, and SUGAR.  This disproportionately affects healthy foods that are in no way responsible for the obesity epidemic.

My suggestions:

1)      Leave people alone.

2)      A better target, which would entail markedly less collateral damage, is “added” sugars.  Taxing “added” sugars would hit soda, processed food-like products, snacks, and junk food… lots of bad guys, few good guys

3)      Make a tax based on empty calories: foods with a higher ratio of calories to nutrients get taxed more than nutrient-dense foods… thus, people would be eating fewer calories but more nutrients!  That wasn’t too hard?

4)      Tax food in direct proportion to its shelf-life.

5)      The revenue from any of these alternative options should be put toward nutrition education programs in elementary schools.  And a portion of the money saved in healthcare costs should be redirected into funding research in the nutritional sciences.  And the rest can be used to pay off the National debt.

 

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Posted in Advanced nutrition, Dietary fat, empty calories, Fructose, Grains, Sugar, Trans fat

Empty calories V

Posted on September 27, 2011 | Leave a comment

The final horcrux!  Empty calories induce a feed-forward loop that promotes  over-consumption. … the following evidence is indirect, of course, but very compelling.

Food intake measured by an automated food-selection system: relationship to energy expenditure (Rising, Ravussin, et al., 1992 AJCN)

This study was designed to validate a new technique for measuring food intake; it had nothing at all to do with “empty calories.”

10 lean, healthy young men.  During a 4-day run-in period, the amount of calories required to maintain energy balance was measured with extreme precision.  Then for 7 whole days, they lived in a metabolic ward and dined from … wait for it … “vending machines.”

 

The vending machines were loaded with entrees, snacks, and beverages, [sic]: “familiar and preferred foods,” aka a “cafeteria diet.”  And I was delighted to see they also published the menu:

 

This study fit so perfectly because the Empty Calories series’ singular major thesis is: empty calories promote over-consumption.  And this can be tested by examining the two logical extremes: 1) a diet devoid of empty calories is inherently healthier, and any increase in the amount of empty calories consumed is accompanied with a decrease in health outcomes; and 2) eating more empty calories will not be balanced by eating less of something else, because empty calories are nutritionally bankrupt and do not affect satiety proper.  And this menu, oh yes, is almost entirely empty calories.

The researchers purposely filled the vending machine with individually packaged processed foods because of their convenience; it’s a very easy way to measure food intake, which was the focus of their study.

The following figure is absolutely nuts; you couldn’t make this stuff up.  like it was mathematically designed to support the Empty Calories credo.

 

It started immediately on day 1 of “ad libitum intake;” food intake doubled- the food was so nutrient poor that twice as many calories were necessary to satisfy their appetite.

Where did all those excess “empty calories” go?  Some (~17%) were spontaneously burned off (increased 24h EE) but most were invested in the infamous negative-yield* calorie savings banks (i.e., adipose).  [*you don’t get back more than you invested].

 

Side note: check the numbers, an overconsumption of 10975 kJ/d = 2622 kcal.  For 7 days = 18,353 kcal; which is approximately the amount of energy in 5.2 pounds (2.4 kg) of fat tissue.  They gained 2.3 kg, just a hair less than mathematically predicted (so much for spontaneously burning off 17% of the excess).  Body composition was not measured, but given the huge increase in carbohydrate intake, I imagine insulin levels were through the roof driving all of the excess energy into fat mass.

This has been confirmed numerous times.  For example, Larsen et al. (1995):

 

When fed the “cafeteria diet” from vending machines, these women almost doubled their food intake and gained a full pound of fat in under a week.  But I digresss.

“And this can be tested by examining the two logical extremes: 1) a diet devoid of empty calories is inherently healthier, and any increase in the amount of empty calories consumed is accompanied with a decrease in health outcomes; and 2) eating more empty calories will not be balanced by eating less of something else, because empty calories are nutritionally bankrupt and do not affect satiety proper.”

The second postulate has been addressed and sufficiently supported by Ravussin’s vending machine study (above).  Fortunately for us a study that addressed the first postulate was blogged on previously.

 

Remember now?

(Hashim and Van Itallie, circa 1965)

 

When fed a bland yet nutritionally complete diet, obese subjects spontaneously and drastically reduced their food intake, and body weight plummeted for EIGHT STRAIGHT MONTHS.  Although this was confirmed a decade later by Cabanac and Rabe (1976), it only indirectly supports the first postulate because it was not real food.  But it proves the point that nutrient sufficiency supports satiety, and this can be dissociated from total calorie intake.  IOW, if the diet provides the essential nutrition, then the remaining daily energy requirement can be met by burning excess fat mass stored in adipose tissue.

avoid ‘empty calories’ and cash out

 

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Empty calories III

Posted on September 12, 2011 | 1 comment

Empty calories.  Nutrient density.  Empty calories.  The ANDI score?

With the advent of the ANDI, it is safe to say the phrase, school of thought, and cult following to “a calorie is a calorie” is fading.  All calories were not created equal; some make you fat, others make you strong.  Cantankerous old biochemists and low-fat diet proponents will likely remain loyal, however, with the former citing heat production in a bomb calorimeter (mumbo), and the latter citing the equivalency of nutrient density and animal fat scarcity (jumbo).

But for the rest of us, there is gravitas in this concept       empty calories.

A good place to start might be a critical view of Fuhrman’s  Aggregate Nutrient Density Index (ANDI).  In brief, ANDI is an index of healthiness and is calculated by dividing the amount of nutrients in a given whole food by the calories.

Pro’s and con’s

1)      it only applies to whole foods.  This is convenient because most processed foods would score miserably low unless they’ve been industrially fortified with synthetic vitamin-like chemicals.  Perhaps Fuhrman restricted ANDI to whole foods because something like Diet Coke Plus would score about a million (lots of vitamins, few if any calories), rendering ANDI utterly meaningless to the masses and downright offensive to people like me.

 

2)       “nutrients per calorie” is a far more biologically meaningful and physiologically relevant concept than “calories per gram.”

  1. “Calories per gram” can be too easily manipulated.  E.g., one ounce (~28 grams) of soybean oil has 248 kilocalories: 248 kilocalories / 28 grams ? 9 kcal/g.  Add it to an ounce of water and you get 248 / 56 ? 4.4 kcal/g.  It’s still the same nutritionally, but the “caloric density” was halved by trickery.
  2. “Nutrients per calorie” is relatively unchangeable.  Let’s say there are 14 grams of omega-6 fatty acids in an ounce of soybean oil; that would be 14 grams per 248 kcal.  Add it to an ounce of water and it’s still true.  Drink it on the moon and it’s still true (relatively).

However,

1)      ANDI selectively quantifies only one aspect of a food’s nutritional value.  It is an important aspect, but please note that a diet based on high ANDI foods would be nutritionally inadequate.  Furthermore, there are highly relevant health parameters that ANDI completely ignores.  More questions:

  1. Shouldn’t more important nutrients be given a higher score?
  2. Shouldn’t excess amounts of a nutrient detract from the score?
  3. What about other non-nutritive health-promoting properties of a food?  E.g., foods that are healthier than indicated by their ANDI score:
    1. i.      foods that have some as-of-yet undiscovered nutrients
    2. ii.      foods that indirectly promote health (like pre- or pro-biotics)

2)      Furthermore, ANDI is fundamentally flawed in its application to foods whose value is based at least partially on the actual calories themselves.

  1. Fuhrman uses the ANDI score on fats, which score dismally low because they contain few “nutrients” and a lot of calories.  Thus, industrially-modified, partially-hydrogenated trans fat-rich soybean oil has the same ANDI score as olive oil.
  2. Animal proteins, including grass-fed beef, wild salmon, and pastured eggs, also score incredibly low.  These foods are far more healthful than many most others, essential for life (unlike kale, which is the highest-scoring ANDI food), and much of their value is contained in the quality of their calories.
    1. i.      the fatty acids in salmon are healthy in and of themselves; they don’t contain any nutrients per se; they ARE the nutrient.  But ANDI doesn’t take this into account; it views all fatty acids as empty calories, a grave mistake.
    2. ii.      the same goes for animal proteins.  Eggs, for example, are higher in protein quality than any other food on the ANDI scale yet they score quite low.  And getting a bio-equivalent amount of protein from lower quality plant proteins would require consuming many more calories.

The failure of ANDI to incorporate any measure of fat or protein quality is its demise; why it is unable to stand alone as an indicator of healthiness… a diet consisting exclusively of high ANDI foods is incompatible with life.  A protein deficiency would be vastly more severe than a low ANDI diet, and on a lighter note, the fish oil fatty acids would provide much greater benefits than a high ANDI diet.  These nutritional factors play too big a role in determining healthspan and quality of life to be ignored.

BUT, ANDI is nice in its simplicity, and it works very well for most plant-based foods.  E.g., spinach and cabbage have very high ANDI scores; rice, grains, and pasta have very low ANDI scores.

The diets of many cultures are based almost exclusively on low-ANDI foods.  This is largely because it is much easier to produce enough calories to feed a village than to produce enough nutrients.  Starvation is deadlier than dermatitis.  In the Western world, however, we are fighting a different battle: you need to eat a LOT of empty calories in order to get enough nutrients, but then you get fat.

 

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