Category Archives: Energy balance

USDA vs. nutrition, round II

Posted on January 26, 2012 | 2 comments

The school lunch program is screwed.

First the USDA modifies the definition of a vegetable to include pizza.  Now they significantly altered their standards for school lunches to include fewer healthy foods and more USDA-approved ones (see report at the USDA’s website).  In brief, this move further reduces the nutrition of school lunches and will likely do more harm than good.  Here’s why:

In this cross-sectional Swedish study, parents recorded 7-day food diaries for their 4-year old children who then went in for a regular checkup.

Metabolic markers in relation to nutrition and growth in healthy 4-y-old children in Sweden (Garemo et al., 2006 AJCN)

On a 1,400 kcalorie diet, these children were consuming roughly 15% protein, 33% fat, and 52% carbs (about 20% of which came from sucrose).  That seems like a lot of calories, but besides playing all day, 4 year old children are also growing at an incredible rate.

Interesting finding numbers 1 & 2:  Children who got most of their calories from fat had the lowest BMI (i.e., they were the leanest), and the opposite was observed for carbs.

When divided into groups of normal weight vs. overweight and obese, some interesting and non-intuitive patterns emerged.  For example, lean kids don’t eat less food; but they do eat fewer carbs and less sucrose (and make up the difference by eating more fat and saturated fat).

Some of the weaker correlations showed:
-total calorie intake was associated with growth (logical)
-total carbohydrate intake was associated with increased fat mass (unfortunate yet also logical)
-total fat intake was associated with decreased fat mass (interesting)

And those who ate the most saturated fat had the least amount of excess body fat. (more on this below)

Fortunately, in a young child, a poor diet hasn’t had enough time to significantly impact their metabolic health; as such no macronutrient was associated, either positively or negatively, with insulin resistance [yet].

In a more appropriately titled follow-up, Swedish pre-school children eat too much junk food and sucrose (Garemo et al., 2007 Acta Paediatrica), Garemo reported that most of their carbs came from bread, cakes, and cookies, while most of the sucrose came from fruit, juices, jam, soft drinks, and sweets.  And WOW, go figure- most of the fat came from meat, chicken, sausage, liver, eggs, and dairy; NOT vegetable oils.

And in a mammoth dissertation, Eriksson (2009) confirmed many of these findings in a larger cohort of 8-year old Swedish children and had this to say about dairy fat:

The open boxes represent overweight kids, the closed boxes are lean kids.  Going from left to right, in either the open or closed boxes, BMI declines with increasing intake of full fat milk (perhaps parents should reconsider skim milk?).  Eriksson also confirmed that saturated fat intake was strongly associated with reduced body weight.  Interestingly, she mentioned that food intake patterns are established early in life, so it might be prudent to remove sugars and other nutrient poor carb-rich foods, and introduce nutritious whole foods as early as possible.  I’m not exactly sure how she assessed patterns of food intake establishment, but it seems logical.  Especially in light of the following study… we’ve seen 4 year olds, 8 year olds, and now we have 12-19 year olds.  The relationship between diet and health is consistent across all age groups.

Virtually all of the above data in Swedish children seem to suggest dietary saturated fat, whether it’s from beef, sausage, eggs, whole fat dairy, or liver (i.e., WHOLE food sources; NOT hydrogenated vegetable oils), is associated with reduced fat mass.  Metabolic abnormalities were not present, probably because the children were simply too young (although body weight seems to respond relatively quickly, other downstream effects of poor nutrition take years to accumulate before symptoms develop).

An American study about nutrient density and metabolic syndrome was recently published.  These kids were exposed to poor nutrition for just long enough to experience some of those malevolent effects.

Dietary fiber and nutrient density are inversely associated with the metabolic syndrome in US adolescents (Carlson et al., 2011 Journal of the American Dietetic Association)

The figure below divides fiber (a proxy for good nutrition; i.e., leafy vegetables, beans, etc.) and saturated fat into groups of least and most amounts comsumed. The lowest fiber intake was 2.9 grams for every 1,000 kcal, and 9.3% of these kids already had metabolic syndrome; the highest fiber intake was 10.7 grams / 1,000 kcal and 3.2% had metabolic syndrome.  Thus, consuming a fiber-rich [nutrient dense] diet is associated with a significantly reduced risk of metabolic syndrome.

The next rows are saturated fat.  The lowest saturated fat intake was 6.9 grams / 1,000 kcal and 7.2% had metabolic syndrome; the highest saturated fat intake was 18 grams / 1,000 kcal and 6.7% had metabolic syndrome…. huh?  While it didn’t reach statistical significance, the trend for saturated fat paralleled that of a “nutrient dense” diet.  Is it possible that saturated fat might be part of a nutrient dense diet?   if saturated fat comes in the form of red meat, liver, eggs, etc., then yes, it is part of a nutrient dense diet.  This conclusion evaded both the study authors and the media.

In 4 and 8 year old Swedish children, those who ate the most saturated fat had the least excess fat mass.  In 12 – 19 year old American adolescents, those who ate the most saturated fat had the lowest risk for metabolic syndrome.

Is it too much of a stretch to connect these ideas by saying that in the short run, a low saturated fat (nutrient poor, carb-rich) diet predisposes to obesity; and in the long run it predisposes to metabolic syndrome  ???

Collectively, these data suggest a diet based on whole foods like meat and eggs, including animal fats, with nutrient dense sources of fiber (e.g., leafy vegetables) but without a lot of nutrient poor carb-rich or high sugar foods, may be the healthiest diet for children.  

Flashback: recap of “USDA vs. nutrition, round I”
USDA: 1
Nutrition: 0
They made pizza a vegetable and insiders suspect that next they’ll try to make it a vitamin.

USDA vs. nutrition, round II

USDA: replacing normal milk with low fat milk
nutrition: full-fat milk was associated with lower BMI in both lean and obese children (see the Eriksson figure above)

USDA: increasing nutrient poor carb-rich options
nutrition: this was associated with increased fat mass in children (Garumen et al., see figures above)

USDA: reducing saturated fat as much as possible
nutrition: reduced saturated fat was associated with excess fat mass in children and metabolic syndrome in adolescents.

Such changes will have an immeasurable long-term impact if children grow up thinking these are healthy options.  Finally, this blog post does not contain a comprehensive analysis of saturated fat intake and health outcomes in children, but the USDA’s new regulations should have been accompanied by one.  In other words, these regulations should not have been based on the studies discussed above, but the studies discussed above should have been considered when the USDA was crafting their recommendations.  Obviously, they weren’t.

calories proper

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

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.

 

calories proper

1 Comment

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

sucrose, visceral fat, et al.

Posted on January 3, 2012 | 2 comments

Sugar-containing beverages vs. visceral fat

or

The malevolence of regular (non-diet) soda

 

Background: visceral fat is an ectopic lipid storage site which is associated with a host of problems.  The amount of visceral, but not subcutaneous fat correlates very well with insulin sensitivity.  The figure below is from a classic paper which showed just that (Banerji, Lebovitz, et al., 1997 AJP).  On the left is a plot of subcutaneous fat vs. glucose disposal (a measurement of insulin sensitivity), and there is no clear relationship.  On the right, however, shows a strong negative correlation of visceral fat and insulin sensitivity.

Visceral fat is associated with insulin resistance, which is a precursor to type II diabetes.  So, what causes fat storage in visceral adipose tissue (besides hyperinsulinemia)?

Sucrose-sweetened beverages increase fat storage in the liver, muscle and visceral fat depot: a 6-mo randomized intervention study (Maersk, Richelsen, et al., 2011 AJCN)

If you just started drinking a few cans of soda per day without intentionally changing anything else, this is what would happen.  The control groups got milk (isocaloric), diet soda, or water.  Food intake and physical activity was similar at baseline and during the intervention.

Figure 1 takes the cake:

Visceral fat, the most unhealthy fat depot, increased markedly in the group consuming regular cola, while it decreased in those drinking milk.  Diet soda or water had no effect.  A similar trend occurred with liver fat, probably the second-most unhealthy fat depot.  Same thing for muscle fat.

And from what we can infer, these effects were independent from energy balance (similar food intake and physical activity before and during the intervention).  Food intake data weren’t presented, but we’re told it was similar in all four groups.  Given these food intake-independent changes in body weight, energy expenditure data would have been a great addition to this manuscript.

The exoneration of diet soda?  In this study, the diet soda group seemed to win, with the best overall changes in body composition as per percent body fat.

And while those consuming milk gained the most weight, they gained muscle (possibly due to the higher protein content of milk).  AND the diet soda group gained the second highest amount of muscle (possibly due to the nutrient partitioning effects of caffeine, although that explanation is admittedly a bit of a reach).  The only differences in macronutrient intake were due to the beverages in question.

Food intake data should’ve been presented and measurements of energy expenditure would’ve added a lot.  The composition of the beverages and resulting changes in body weight/composition suggest no major deviations in the Laws of Energy Balance, and the changes in muscle mass make sense with what we know about dietary protein and sugar.  Furthermore, there is good reason to believe the observed malevolent effects of regular non-diet soda are true.

Similar results were seen in a well-controlled study where isocaloric glucose or fructose-containing beverages were given to overweight/obese humans for 10 weeks (Stanhope, Havel, et al., 2009 JCI):

Also similar to 3 weeks of 80 grams sucrose per day given to healthy young men (Aeberli, Berneis, et al., 2011 AJCN):

(waist circumference is a reasonably good marker for visceral fat)

The former studies have been of the [stronger] intervention type, but the same thing is seen in observational studies (Pollock, Dong, et al., 2011 AJCN).  This next study is of particular importance because it is in children.  The major sources of fructose were fruit juice and regular soda.  Elevated visceral fat is observed as early as 14-18 years of age!

What is most relevant about this study is that kids who drank the most fruit juice and soda were beginning to show signs of pre-diabetes and elevated inflammatory markers.  In kids.

there’s nothing redeeming about sucrose or its partner in crime fructose.

 

calories proper

 

 

 

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Posted in Advanced nutrition, Energy balance, Fructose

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.

 

calories proper

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