5 - July - 2013

12 The health benefits of dairy protein. By Armi Legge

14 Bulletproof Coffee & concerning bloodwork: questions for 2 doctors who actually lift. Alan Aragon interviews Spencer & Kasey Nadolsky

Copyright © July 1st, 2013 by Alan Aragon Home: www.alanaragon.com/researchreview Correspondence: [email protected]

2

Clearing up common misunderstandings that plague the calorie debate, part 1. By Alan Aragon

6

High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity (Silver Spring). 2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of print] [PubMed]

8

Effects of a low- or a high-carbohydrate diet on performance, energy system contribution, and metabolic responses during supramaximal exercise. Lima-Silva AE, Pires FO, Bertuzzi R, Silva-Cavalcante MD, Oliveira RSF, Kiss MA, Bishop D. Appl Phys Nutr Metab. 38: 928–934 (2013) dx.doi.org/10.1139/apnm-20120467. [APNM]

9

The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study. Jenkins ND, Housh TJ, Johnson GO, Traylor DA, Bergstrom HC, Cochrane KC, Lewis RW Jr, Schmidt RJ, Cramer JT. J Int Soc Sports Nutr. 2013 Jul 22;10(1):33. [Epub ahead of print] [PubMed]

10 Blood type diets lack supporting evidence: a systematic review. Cusack L, De Buck E, Compernolle V, Vandekerckhove P. Am J Clin Nutr. 2013 Jul;98(1):99-104. [PubMed] Alan Aragon’s Research Review – July 2013

[Back to Contents]

Page 1

Clearing up common misunderstandings that plague the calorie debate, part 1. By Alan Aragon ____________________________________________________ Introduction Anyone involved with the health and fitness sphere has observed a never-ending battle between the calories-in/calories-out (CICO) camp and the calories don’t matter (CDM) camp, which might be more accurately called the calories don’t matter, hormones and other stuff do (CDMHOSD) camp. In its most pure form, CICO is a relatively well-known acronym for the philosophy that weight loss or gain is determined by a caloric deficit or surplus, regardless of diet composition. The CICO camp’s call to “eat less, move more” as a solution to obesity sends the CDM camp into a frothy rage. They believe that this is not only incorrect, but failed advice, as indicated by the nation’s high prevalence of obesity.

However, even in peer-reviewed papers, the non-capitalized term is common when referring to food energy in the general sense. With that detail out of the way, perhaps the more important problem with discussing calories as units of energy is that the manifestation of energy is rarely specified. In the context of food and nutrition, there are distinct differences between the energy liberated through combustion, and the energy that’s physiologically available.3 In other words, gross energy is what the foodstuff contains before it enters the body, and metabolizable energy is what the body is able to use for physiological processes. Oddly enough, a helpful model for understanding types of energy has been used in cattle production, which relies upon the tracking of energy in order to maintain health, growth, and reproduction.4 Obviously, humans differ from ruminants in certain aspects of digestion, among other things. However, the general framework of food-derived energy use is surprisingly similar. Here’s a graphic of the various fates of energy as it flows from the food source through the body of the animal:5

Let me state from the outset that there is a range of beliefs spanning the continuum between the two extreme ends of CICO and CDM. However, comparing these starkly different philosophies is the best way to expose which aspects of each are rooted in scientific evidence, and which are not. In the following discussion, I’ll attempt to clarify the misunderstandings perpetuated by both sides. Getting the definitions straight At the heart of the disagreement is a neglect to adequately establish operational definitions. Without doing so, it’s impossible to have clear, productive communication, so chaos inevitably continues. The first term that needs defining is the calorie itself, particularly as it pertains to the CICO mantra that “a calorie is a calorie.” I’ll first go over the smaller, more immaterial stuff, then move on to the meatier definitions that hold the more profound implications. A Calorie is the amount of heat required to raise the temperature of 1 kilogram of water by 1°C. The term Calorie is synonymous with kilocalorie (abbreviated as kcal). Less commonly, it’s referred to as a kilogram-calorie, or large calorie.1 When the term is not capitalized, it technically represents one-thousandth of the value of a kcal. In other words, it’s the amount of heat required to raise the temperature of 1 gram of water by 1°C. The non-capitalized term is less commonly called a gram-calorie.

Starting from the top of the chart above, gross energy is the starting point before ingestion; it’s the energy that the food contains, as calculated by combustion in a bomb calorimeter. What’s left after fecal loss is considered digestible energy. What remains after energy losses through feces, urine, and gas is metabolizable energy. Finally, net energy is what’s available for use (or storage) after losses through feces, urine, gas, and heat increment.

Here’s the amusing part. Neglecting to capitalize the word calorie when discussing kilocalories is so commonplace, that the non-capitalized term has replaced the capitalized term nearly everywhere it’s used – especially in the nutritional context. Kcals and calories have become interchangeable in the press, with the understanding that the term calorie is not actually referring to its original definition as a gram-calorie. There are some rare instances (usually in the academic literature) where care is taken to capitalize the term. A recent example is the title of Jakubowicz et al’s recent study reviewed in this issue.2

Regarding the heat increment, macronutrients vary in their thermic effect, which ultimately influences the net yield of energy available to the body. As reported by Jéquier, the thermic effect protein (expressed as a percentage of energy content) is 25-30%, carbohydrate is 6-8%, and fat is 2-3%.6 Take note that not all of the literature is in precise agreement. Halton and Hu reported greater variability,7 with the thermic effect of protein being 20-35%, carbohydrate at 5-15%, and fat being subject to debate since some investigators found a lower thermic effect than carbohydrate while others found no difference. In any case, protein has consistently shown a higher thermic effect than carbohydrate or fat.

Alan Aragon’s Research Review – July 2013

[Back to Contents]

Page 2

The thermic effect of food (TEF) is also called diet-induced thermogenesis (DIT). This is largely determined by the macronutrient composition of foods (or meals). However, other factors can influence DIT even when macronutrition is similar. A memorable example is by Barr and Wright, who found a DIT of 137 kcal for a ‘whole food’ meal, and 73 kcal for the processed food meal.8 The ‘whole food’ meal had 5% more protein, and 2.5 g more fiber, but these factors are too small to plausibly account for the substantial difference in postprandial energy expenditure. The authors speculated that the greater mechanized preparation of the processed food caused less peristalsis and greater loss of bioactive compounds, resulting in fewer metabolites, thus requiring less enzyme production. This would collectively result in more efficient absorption and metabolism. By the way, I’ve seen articles in the lay press use Barr and Wright’s study to support the idea that processed foods are prime enemies of weight loss compared to whole foods. While it’s understandable how the short-term outcomes would spark this assumption, chronic studies have not supported it. There’s a substantial body of controlled interventions showing the robust weight-reducing effectiveness of highly processed meal replacement products such as bars, shakes, and powders.9-15 It therefore is false to assume that the diet needs to be solely composed of whole and unprocessed foods in order to achieve weight loss. So yes, a calorie is a calorie when viewed as a unit of measurement – just like a gram is a gram or a liter is a liter. However, saying that “a calorie is a calorie” can evoke the false idea that the macronutrients all have the same energetic cost of processing within the body. It also neglects to make the distinction between gross energy and physiologically available energy. It goes without saying that the macronutrients have different physiological and morphological roles aside from their common role of providing energy. So the problem with saying “a calorie is a calorie” boils down to the ability of that catchphrase to mislead through its oversimplicity. Thermodynamics & bodyweight This oversimplification has bothered some academics enough to address it in the peer-reviewed literature. Feinman and Fine criticized “a calorie is a calorie” for being a misunderstanding of the laws of thermodynamics.16 What inspired them to write this was a paper by Bucholz and Schoeller, who maintained the position that a calorie is a calorie since energy cannot be created nor destroyed; only converted from one form to another.17 Feinman and Fine countered that this position focuses on the first law of thermodynamics, while neglecting the integral role of the second law. Specifically, the first law describes the conservation of energy, while the second law deals with the dissipation of energy.

championing the so-called metabolic advantage of lowcarbohydrate diets compared to low-fat diets.18 They propose that carbohydrate restriction per se imparts inherent weight loss benefits explainable by nonequilibrium thermodynamics.19 Ironically, while Bucholz and Schoeller were criticized for focusing on the first law of thermodynamics and neglecting the second law, Feinman and Fine are committing the error of focusing on differences in dietary carbohydrate instead of differences in dietary protein. The folly of this assumption was recently exposed in an elegant study by Soenen et al,20 who did an isocaloric comparison of four diets: 1) normal-protein, normalcarbohydrate; 2) normal-protein, low-carbohydrate; 3) highprotein, low-carbohydrate; 4) high-protein, normal-carbohydrate. The two higher protein conditions caused the greatest decreases in fat mass, while no significant relationship was seen between body composition change and the varying proportion of dietary fat and carbohydrate. The authors thus concluded: “Body-weight loss and weight-maintenance depends on the high-protein, but not on the ‘low-carb’ component of the diet.”

But humans are not bomb calorimeters (well duh...and?) For those who’ve been reading this and itching to yell out that humans are not bomb calorimeters, that’s rather obvious – no disagreement there. However, some folks claim that since humans are not static/closed systems (like bomb calorimeters), tracking of caloric intake and expenditure in order to alter bodyweight is a futile endeavor. This is a denial-based cop-out, since aside from temporary water shifts, there’s quite literally no way to lose or gain weight in the long-term except via sustained energy deficit or surplus. The aforementioned conditions of energy balance must be in place regardless of how loose or meticulous the tracking of energy is. For example, a focus on choosing ‘good/clean’ foods over ‘bad/dirty’ foods merely serves to impose a deficit by default. This typically occurs through either satiety-mediated energy intake reductions, the consumption of foods with less metabolizable energy, an increase in DIT & lean mass preservation via consuming enough protein, or a combination of those factors. The same principle applies to avoiding foods not on the ‘approved list’ of the fad diet of the moment.

The second law describes energetic inefficiency, which in the context of diets goes right back to the varying thermic effect of macronutrients. As discussed earlier, protein metabolism the least efficient since it’s more energetically expensive (evidenced by a higher DIT) than the metabolism of carbohydrate or fat. This is well and good, but Feinman and Fine are famous for

It needs to be recognized that involuntary adaptive shifts separate humans from machines. We unconsciously ramp-up energy expenditure in the face of increased intake, and downshift energy expenditure in the face of decreased intake. These adaptations are a good thing, since the survival of our species would not be possible without it. This is the genius of Mother Nature at work. We humans differ energetically from bomb calorimeters primarily due to our dynamic nature, which is based on homeostatic drive. In other words, the body strives to protect itself against changes, which it tends to perceive as threats to survival. It attempts – at all times – to preserve the physiological status quo. So, when hypocaloric conditions are imposed, energy expenditure (EE) has a tendency to decrease. Conversely, when a caloric surplus is imposed, EE has a tendency to increase. This is why weight loss and weight gain typically fall short of what’s expected from the respective caloric deficit or surplus initially imposed.

Alan Aragon’s Research Review – July 2013

[Back to Contents]

Page 3

This observation spawned the term adaptive thermogenesis (AT), which Lowell and Spiegel defined as the regulated production of heat, influenced by environmental temperature and diet.21 Keep in mind that this is the broad/general definition. AT has another definition that pertains specifically to the ‘mystery’ of weight loss energetics, which I’ll discuss next.

between Bryner et al’s results and those of Liebel et al (who also used an 800 kcal liquid diet) can be explained by – you guessed it – better macronutrition and the implementation of resistance exercise. Bryner et al’s liquid diet was composed of 40% protein, while Liebel et al’s was 15%. Bryner’s subjects underwent full-body resistance training 3 times per week, while Liebel’s design neglected exercise programming altogether.

Adaptive thermogenesis in weight loss

While the mechanisms underlying AT resulting from weight loss are largely unknown, Dullo and Jacquet have proposed 2 control systems.26 In what they call non-specific thermogenesis, the sympathetic nervous system (SNS) responds to environmental changes and stressors, causing uncoupling proteins to influence the manifestation of AT. Adipose-specific thermogenesis is the body’s response to changes in fat mass. Refer to the Oct 2009 issue for more discussion of the potential mechanisms of AT.

The changes in EE are not always completely accounted for by changes in lean mass and fat mass. Therefore, in the context of hypocaloric dieting, AT is a term used to describe the gray area where reduced EE cannot be simply explained by losses in metabolic tissue or reductions in the energetic cost of movement. For example, tightly controlled research by Liebel et al showed that in obese subjects, a 10% or greater weight loss resulted in a 15% greater EE reduction than predicted by body composition change.22 However, bear in mind that these subjects were put on an 800 kcal liquid diet composed of 15% protein, 45% carbohydrate, and 40% fat. It should be painfully obvious that dieting hard on 30 g protein per day within an 800 kcal diet is far from optimal. Reductions in EE via the typical research protocols do not reflect what’s possible under conditions involving better macronutrient targets and proper training. Camps et al recently found that after significant weight loss, reduced EE beyond what was predicted was still present after a year.23 While some see this as evidence of the permanence of weight loss-induced AT, I would contend that the actual EE reduction was minor (79 kcal/day). Once again, optimizing macronutrition and training would very likely eliminate this impairment. As it stands, the subjects were not engaged in structured exercise at any point, and the details of their maintenance diet were not tracked or reported. The most dramatic case of AT to-date was seen in recent work by Johannsen et al,24 who examined the effects of morbidly obese subjects participating in a nationally televised 30-week weight loss contest. The caloric deficit was targeted at 30% below maintenance, but since dietary intake was not monitored, so it’s likely that subjects did not adhere to this, instead opting for more aggressive measures. Exercise was supervised 6 days per week, 90 minutes per session. An additional 3 hours per day of exercise was encouraged. Expectedly, the majority of weight lost was fat mass (47.1 kg), and the minority lost was lean mass (10.5 kg). Resting metabolic rate (RMR) at baseline was 2679 kcal, and this decreased to 1890 kcal by the end of the trial. This 789 kcal decrease represents a 29.4% drop in RMR. Significant AT was apparent since this was 504 kcal greater than what the loss of lean mass predicted, making it an 18.8% greater EE reduction than predicted. This is not too surprising. It makes sense that an extraordinarily high speed of weight loss (4.22 lb per week on average for 30 weeks) and high amount of weight loss (126.7 lb total) would correspond with a stronger physiological survival defense response than typically seen. Once again, it should be emphasized that Johanssen et al’s study had massive reporting gaps in dietary intake. Therefore, it cannot be viewed as ironclad ‘proof’ that dieters are doomed to an impaired metabolism after substantial weight loss. To illustrate this, Bryner et al observed an increased RMR by the end of 12 weeks in subjects on an 800 liquid kcal diet.25 The discrepancy Alan Aragon’s Research Review – July 2013

Adaptive thermogenesis in weight gain AT (in the broad sense) also applies to weight gain. However, it’s not clear whether or not the same ‘mysteriously unaccountable’ thermogenesis occurs in weight gain with the consistency that thermic decreases occur in substantial weight loss. In attempt to answer this, Joosen and Westerterp combed the literature and found 5 studies showing evidence of AT resulting from overfeeding.27 In other words, AT was apparent based on smaller than expected weight gain or unaccounted increases in thermogenesis that exceeded obligatory costs. However, they also found 11 studies that failed to detect AT, since weight gains corresponded with the amount of overfeeding, and the increased thermogenesis was proportional to the theoretical energy costs of increased body mass and greater dietary intake. To quote them: “These  results  show  that  in  humans,  evidence  for  adaptive  thermogenesis  is  still  inconsistent.  However,  they  do  not  rule  out  the  existence,  but  emphasize  that  if  present,  adaptive  changes  in  energy  expenditure  may  be  too  small  to  measure  considering  measurement  errors,  errors  in  assumptions  made  and small (day‐to‐day) differences in physical activity.” 

A question relevant to fitness, sports nutrition, and body composition-oriented goals is whether “hardgainers” have a legitimate metabolic impairment against weight gain, or whether this is a lack of discipline to maintain eating habits that sustain a caloric surplus. It turns out that conscious and unconscious increases in non-exercise activity thermogenesis (NEAT) in response to overfeeding can pose a significant challenge to expected weight gain. A prime illustration of this was a study by Levine et al, who fed non-obese adults 1000 kcal above their maintenance needs for 8 weeks.28 On average, 432 kcal was stored, and 531 kcal was burned. Nearly two-thirds of the latter (336 kcal) was attributable to NEAT, which on the upper end of the range was as high as 692 kcal/day. This finding explains why some folks can increase their daily intake by 500-600 kcal and still experience a lack of weight gain. Unbeknownst to them, their ramped-up NEAT gobbled up their caloric surplus. Summing up When the term calories is capitalized, it represents kilocalories. Non-capitalized calories represent gram-calories, which are [Back to Contents]

Page 4

Hargrove JL. History of the calorie in nutrition. J Nutr. 2006 Dec;136(12):2957-61. [PubMed] 2. Jakubowicz D, Barnea M, Wainstein J, Froy O. High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of print] [PubMed] 3. Buchholz AC, Schoeller DA. Is a calorie a calorie? Am J Clin Nutr. 2004 May;79(5):899S-906S. [PubMed] 4. AgroMedia, Inc. Energy Partitioning. Accessed July 2013. http://www.agromedia.ca/ADM_Articles/content/f1r1e1.pdf 5. This is my modified version of a schematic created for an animal science course at Purdue University (author not specified). The original PPT presentation is accessible here: http://www.ansc.purdue.edu/courses/ansc221v/energy.ppt 6. Jéquier E. Pathways to obesity. Int J Obes Relat Metab Disord. 2002 Sep;26 Suppl 2:S12-7. [PubMed] 7. Halton TL, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr. 2004 Oct;23(5):373-85. [PubMed] 8. Barr SB, Wright JC. Postprandial energy expenditure in wholefood and processed-food meals: implications for daily energy expenditure. Food Nutr Res. 2010 Jul 2;54. [PubMed] 9. Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond). 2012 Oct 31;9(1):98. [PubMed] 10. Davis LM, Coleman C, Kiel J, Rampolla J, Hutchisen T, Ford L, Andersen WS, Hanlon-Mitola A. Efficacy of a meal replacement diet plan compared to a food-based diet plan after a period of weight loss and weight maintenance: a randomized controlled trial. Nutr J. 2010 Mar 11;9:11. [PubMed]

11. Cheskin LJ, Mitchell AM, Jhaveri AD, Mitola AH, Davis LM, Lewis RA, Yep MA, Lycan TW. Efficacy of meal replacements versus a standard food-based diet for weight loss in type 2 diabetes: a controlled clinical trial. Diabetes Educ. 2008 Jan-Feb;34(1):118-27. [PubMed] 12. Ashley JM, Herzog H, Clodfelter S, Bovee V, Schrage J, Pritsos C. Nutrient adequacy during weight loss interventions: a randomized study in women comparing the dietary intake in a meal replacement group with a traditional food group. Nutr J. 2007 Jun 25;6:12. [PubMed] 13. Noakes M, Foster PR, Keogh JB, Clifton PM. Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome. J Nutr. 2004 Aug;134(8):1894-9. [PubMed] 14. Heymsfield SB, van Mierlo CA, van der Knaap HC, Heo M, Frier HI. Weight management using a meal replacement strategy: meta and pooling analysis from six studies. Int J Obes Relat Metab Disord. 2003 May;27(5):537-49. [PubMed] 15. Ditschuneit HH, Flechtner-Mors M, Johnson TD, Adler G. Metabolic and weight-loss effects of a long-term dietary intervention in obese patients. Am J Clin Nutr. 1999 Feb;69(2):198-204. [PubMed] 16. Feinman RD, Fine EJ. "A calorie is a calorie" violates the second law of thermodynamics. Nutr J. 2004 Jul 28;3:9. [PubMed] 17. Buchholz AC, Schoeller DA. Is a calorie a calorie? Am J Clin Nutr. 2004 May;79(5):899S-906S. [PubMed] 18. Feinman RD, Fine EJ. Thermodynamics and metabolic advantage of weight loss diets. Metab Syndr Relat Disord. 2003 Sep;1(3):209-19. [PubMed] 19. Feinman RD, Fine EJ. Nonequilibrium thermodynamics and energy efficiency in weight loss diets. Theor Biol Med Model. 2007 Jul 30;4:27. [PubMed] 20. Soenen S, Bonomi AG, Lemmens SG, Scholte J, Thijssen MA, van Berkum F, Westerterp-Plantenga MS. Relatively highprotein or 'low-carb' energy-restricted diets for body weight loss and body weight maintenance? Physiol Behav. 2012 Oct 10;107(3):374-80. [PubMed] 21. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature. 2000 Apr 6;404(6778):652-60. [PubMed] 22. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. [PubMed] 23. Camps SG, Verhoef SP, Westerterp KR. Weight loss, weight maintenance, and adaptive thermogenesis. Am J Clin Nutr. 2013 May;97(5):990-4. [Epub ahead of print] [PubMed] 24. Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E, Hall KD. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012 Jul;97(7):2489-96. [PubMed] 25. Bryner RW, Ullrich IH, Sauers J, Donley D, Hornsby G, Kolar M, Yeater R. Effects of resistance vs. aerobic training combined with an 800 calorie liquid diet on lean body mass and resting metabolic rate. J Am Coll Nutr. 1999 Apr;18(2):115-21. [PubMed] 26. Dulloo AG, Seydoux J, Jacquet J. Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance. Physiol Behav. 2004 Dec 30;83(4):587-602. [PubMed] 27. Joosen AM, Westerterp KR. Energy expenditure during overfeeding. Nutr Metab (Lond). 2006 Jul 12;3:25. [PubMed] 28. Levine JA, et al. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science. 1999 Jan 8;283(5399):212-4. [Pubmed] 29. Taubes G. The science of obesity: what do we really know about what makes us fat? An essay by Gary Taubes. BMJ. 2013 Apr 15;346:f1050. [PubMed]

Alan Aragon’s Research Review – July 2013

[Back to Contents]

1000th the value of kilocalories. In the broad scheme, calories can mean either one, depending on the context of how they’re presented. Is a calorie a calorie? As a static unit of energy, yes. Is a macronutrient a macronutrient? Of course not. There’s a tendency to get caught in the semantic mess of whether or not “a calorie is a calorie” is referring to a static unit of energy or the influence different macronutrients (and foods) have on the partitioning of energy. It’s therefore best to avoid using that oversimplistic catchphrase. AT can occur in both weight loss and weight gain scenarios. But just because it exists does not mean that calories don’t matter when manipulating body mass or composition. As the research evidence indicates, AT comprises only a minority of the diet-induced reductions in EE, which for the most part are either preventable or reversible by smart programming. Coming up In part 2 of this article series, I’ll examine the controversies surrounding the “eat less, move more” mantra. I’ll tie this in with Gary Taubes’ recent essay in the British Medical Journal,29 which poses several arguments against the focus on calories as opposed to hormonal response to diet. I’ll also discuss the neuroendocrine factors that influence bodyweight regulation, and how these can be reconciled with the classic caloric balance model. This might not all be covered in the next installment due to the breadth of information I’m anticipating, but I’ll be sure to cover it in as many parts as necessary. References 1.

Page 5

High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity (Silver Spring). 2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of print] [PubMed] PURPOSE: Few studies examined the association between time-of-day of nutrient intake and the metabolic syndrome. Our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner. METHODS: Overweight and obese women (BMI 32.4 ± 1.8 kg/m2 ) with metabolic syndrome were randomized into two isocaloric (‫׽‬1400 kcal) weight loss groups, a breakfast (BF) (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) group (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner) for 12 weeks. RESULTS: The BF group showed greater weight loss and waist circumference reduction. Although fasting glucose, insulin, and ghrelin were reduced in both groups, fasting glucose, insulin, and HOMA-IR decreased significantly to a greater extent in the BF group. Mean triglyceride levels decreased by 33.6% in the BF group, but increased by 14.6% in the D group. Oral glucose tolerance test led to a greater decrease of glucose and insulin in the BF group. In response to meal challenges, the overall daily glucose, insulin, ghrelin, and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the BF group.CONCLUSIONS: High-calorie breakfast with reduced intake at dinner is beneficial and might be a useful alternative for the management of obesity and metabolic syndrome. SPONSORSHIP: None specified. Study strengths This study is strong in concept since very little investigation has been done in the area of within-day meal timing on bodyweight, anthropometry, insulin sensitivity, and appetite. Even if the focus is on the smaller details rather than the big picture, it’s interesting nonetheless (especially if there happens to be something to it). A more concrete strength was the matching of total energy and macronutrition between conditions. This might seem like a “well duh” aspect of the design, but a neglect for matching these variables is common in studies aiming to compare temporal effects of nutrients or meals. 74 subjects completed the study. The authors mentioned that larger cohorts in future studies are needed, but this sample size was larger than what’s typically used in diet research. A dietitian met with the subjects on a bi-weekly basis to assess & bolster compliance. Subjects whose noncompliance exceeded 42.9% were ejected from the study.

suppressed in self-reported/self-administered diet designs. Another limitation I’d add is that the outcomes might only apply to the lifestyle profile of the subjects (obese/overweight women with the metabolic syndrome). Finally, there was no formal/structured exercise program imposed. I realize that this can introduce complexity, but programs optimized to alleviate problems associated with the metabolic syndrome include an exercise component. Exercise is known to improve a range of parameters that characterize the metabolic syndrome.1 Comment/application The primary findings of this study were a significantly greater weight and waist girth reduction in the large breakfast group (BF) compared to the large dinner group (D). Specifically, BF decreased bodyweight 8.7 kg (-11%), while D decreased bodyweight by 3.6 kg (-4%) over the course of 12 weeks. Secondary findings were significantly greater improvements in measures of glucose control in BF, as well as significantly greater satiety scores and lower hunger scores in BF. Corroborating the subjective ratings of better appetite control were the lower ghrelin levels in BF. In sum, BF outperformed D in all measures. So, this study supports the traditional recommendation to taper down caloric intake through the day. However, an important question is, how do these results compare with the existing body of evidence? I mentioned in a previous issue that there’s no such thing as a single study that closes the case on any topic; it’s the evidence as a whole that matters. Indeed, this body of research is equivocal. Let’s skip over the rodent-based, short-term, and observational research and look at the chronic human intervention trials. To my knowledge, the first to ever compare a larger evening intake with a larger daytime intake were Sensi and Capani, who found no significant differences in weight loss between a meal (684 kcal/day) consumed at 10 am vs 6 pm over either a 3-day or 18-day period.2 However, they detected significantly greater fat oxidation and lower carbohydrate oxidation in the later-meal conditions. Subsequently, Schlundt et al compared the 12-week effects of a 2-meal/day (breakfast-skipped) with a 3-meal/day regimen.3 Despite the isocaloric conditions, no significant differences were seen in fat loss or weight loss the end of the 12-week trial or the 6-month follow-up.

The authors acknowledge that this 12-week trial was “a short period of time, which diminishes the power to detect follow-up differences between the groups.” Importantly, they also conceded that lab supervision (and provision) of the dietary intake would have made for tighter control. Confounders such over-reporting and under-reporting intake are never completely

Next we have Keim et al, who compared the 6-week effects of eating 70% of daily calories in the morning versus the evening.4 Unlike the lesser control of the present study, Subjects lived in the research center’s metabolic suite throughout the length of the study. Unlike the present study, physical activity (including resistance & aerobic training) was standardized. The larger evening intake condition retained more lean mass, without any remarkable difference in fat mass reduction (there was actually a slight advantage to the larger evening intake). Furthermore, the present study did not measure body composition, which leaves an important question unanswered, although one could argue that the greater waist girth reduction in BF indicates greater body fat decrease.

Alan Aragon’s Research Review – July 2013

[Back to Contents]

Study limitations

Page 6

Since Keim et al’s work in 1997, this area of study stayed dormant until almost a decade and a half later when Sofer et al dropped a ‘bombshell’ on everyone with a 6-month study finding that all of the anthropometric improvements (weight loss, waist girth reduction, & body fat reduction) were greater in the treatment with most of the day’s carbohydrates eaten at dinner.5 The control diet where carbs were evenly spread through each meal was also outperformed for improving glucose control, inflammation reduction, lipid profile, and satiety ratings. Interestingly, satiety was rated higher than baseline in the experimental group by the end of the trial. These results are almost across-the-board contrary to what was seen in the present study. Keim et al’s inclusion of a structured exercise program could potentially explain the discrepant outcomes compared to those of the present study (although that still doesn’t account for all of the differences). But what could explain the diametrically discrepant outcomes between the present study and Sofer et al? The present study’s subjects had the metabolic syndrome whereas Sofer et al’s did not. Total kcals were similar, but macronutrient composition between diets differed mainly in that Sofer et al used a higher proportion of carbohydrate & fat, and lower proportion of protein. Design strengths Sofer et al had over the present study were the longer duration (6 months vs 12 weeks) and also the measurement of body composition instead of merely bodyweight and waist circumference. Sofer et al hypothesized that the superior outcomes from scooting the majority of the day’s carbs at dinner were due to a better manipulation of the body’s leptin-mediated appetite control, ultimately leading to more favorable body composition:3 “It  is  proposed  that  the  smaller  reduction  in  averaged  12‐h  leptin concentration, induced by the experimental diet, may be  an  important  factor  in  the  higher  levels  of  satiety  reported  during  the  day.  [...]  Thus,  dietary  manipulations  that  will  maintain  higher  daytime  leptin  concentrations  during  daylight  hours  in  weight  loss  process  may  be  beneficial.  Our  experimental  diet  might  manipulate  daily  leptin  secretion,  leading  to  higher  relative  concentrations  throughout  the  day.  We propose that this modification of hormone secretion helped  participants  experience  greater  satiety  during  waking  hours,  enhance  diet  maintenance  over  time  and  have  better  anthropometric outcomes.” 

In contrast, the authors of the present study offer the following speculations involving the greater diet-induced thermogenesis of the morning meal associated with the circadian clock: “Our  findings  also  support  a  strong  correlation  between  the  timing  of  food  intake  and  body  weight.  The  association  with  feeding time has been shown in various organisms as a strong  time  giver  for  the  circadian  clock  (6,16).  As  the  circadian  clock  and  metabolism  are  tightly  linked  (12),  and  disruption  of  circadian  rhythms  leads  to  obesity  (13),  it  is  plausible  that  energy intake and content at different times, i.e., breakfast vs.  dinner,  may  affect  the  clock  differently.  Indeed,  morning  diet‐ induced  thermogenesis  (DIT)  was  significantly  higher  than  afternoon  and  night  DIT  and  afternoon  DIT  was  higher  than  night  DIT,  suggesting  that  the  time  when  a  meal  is  consumed  Alan Aragon’s Research Review – July 2013

affects  the  thermogenic  response  and  must  be  considered  in  the energy balance (40).” 

The present study is at least partially supported by a recent study led by the same author. In a trial immediately preceding this one, Jakubowicz et al found that a high-carbohydrate breakfast resulted in the prevention of weight regain in overweight but otherwise healthy subjects, while a low-carbohydrate, proteinmatched breakfast did not.6 In fact, the latter group regained 11.6 kg in the 16-week uncontrolled follow-up phase, while the highcarb breakfast group lost additional 6.9 kg. However, unlike the present study, there were no significant differences in weight loss or waist girth reduction between conditions during the 16week controlled hypocaloric phase. In the most recent study in this vein, Garaulet et al found that 20 weeks on a regimen with a later lunch resulted in less weight loss than an earlier lunch.7 However, the latter study’s results were not nearly as robust as those of the present study, which are perhaps the most dramatic to-date in terms of weight loss differences between conditions. So, in summing up the 7 chronic human intervention studies (including the present study), 1 shows a fat oxidation advantage of eating later in the day,2 1 shows no significant difference in weight or fat loss,3 1 shows a greater preservation of lean mass mass from eating more calories later in the day,4 1 shows a greater weight loss, fat loss, and waist reduction from eating more carbs later in the day.5 3 studies show essentially the opposite (a favorable effect of front-loading caloric intake), but none of the latter measured body composition.6-8 Another notable detail is that only 1 of these 7 studies included a structured training program (and it happened to show a slight body composition advantage to eating more later in the day).4 The overall body of evidence is clearly equivocal, so it’s not prudent at this time to latch on to a “you must eat breakfast” or a “breakfast is bad” approach to weight or fat loss. Let me reiterate a conclusion I drew in the December 2012 issue of AARR, which closely applies here: “As I see it, there’s a hierarchy of importance for carbohydrate  timing through the day. First off, make sure the total for the day  is consumed. Secondly, time the constituent doses so that they  maximize,  and  do  not  hinder  training  performance.  Tied  for  second,  on  non‐training  days,  position  carb  intake  to  suit  your  personally  preferred  distribution  pattern  (regardless  of  what  opposing lines of research might suggest). Third and lowest on  the  hierarchy  of  importance  is  the  option  to  experiment  with  hypothetical  optimization  techniques  currently  under  scientific  investigation.”  

Adding to that, I’d say that the individual’s personal preference should ultimately dictate the distribution of calories through the day. If someone simply prefers having a larger evening meal (or the converse of that), then this should be honored, since constantly fighting this preference can compromise long-term adherence. The evidence simply isn’t compelling enough to recommend an attempt at battling personal preference for the purpose of adopting a particular meal pattern. The focus instead should be on total daily targets. Individual preference and training schedule should dictate how these totals are configured. [Back to Contents]

Page 7

Effects of a low- or a high-carbohydrate diet on performance, energy system contribution, and metabolic responses during supramaximal exercise. Lima-Silva AE, Pires FO, Bertuzzi R, Silva-Cavalcante MD, Oliveira RSF, Kiss MA, Bishop D. Appl Phys Nutr Metab. 38: 928–934 (2013) dx.doi.org/10.1139/apnm-2012-0467. [APNM] PURPOSE: The purpose of the present study was to examine the effects of a high- or low-carbohydrate (CHO) diet on performance, aerobic and anaerobic contribution, and metabolic responses during supramaximal exercise. METHODS: Six physically-active men first performed a cycling exercise bout at 115% maximal oxygen uptake to exhaustion after following their normal diet for 48 h ( 50% of CHO, control test). Seventy-two hours after, participants performed a muscle glycogen depletion exercise protocol, followed by either a high- or low-CHO diet ( 70 and 25% of CHO, respectively) for 48 h, in a random, counterbalanced order. After the assigned diet period (48 h), the supramaximal cycling exercise bout (115% maximal oxygen consumption) to exhaustion was repeated. RESULTS: The low-CHO diet reduced time to exhaustion when compared with both the control and the high-CHO diet (−19 and −32%, respectively, p < 0.05). The reduced time to exhaustion following the low-CHO diet was accompanied by a lower total aerobic energy contribution (−39%) compared with the high-CHO diet (p < 0.05). However, the aerobic and anaerobic energy contribution at the shortest time to exhaustion (isotime) was similar among conditions (p > 0.05). The low-CHO diet was associated with a lower blood lactate concentration (p < 0.05), with no effect on the plasma concentration of insulin, glucose and K+ (p > 0.05). CONCLUSION: In conclusion, a low-CHO diet reduces both performance and total aerobic energy provision during supramaximal exercise. As peak K+ concentration was similar, but time to exhaustion shorter, the low-CHO diet was associated with an earlier attainment of peak plasma K+ concentration. SPONSORSHIP: None specified.

Study strengths This study is innovative since it’s the first to ever examine the effects of a high-carbohydrate (HC) versus a low-carbohydrate (LC) diet on time-to-exhaustion (TTE), as well as compare the aerobic versus anaerobic contributions of these diets during supramaximal-intensity exercise. The subjects were described as physically active, and they happened to be relatively lean (13% body fat). This reduces the confounding potential of newbie status, which can often mask treatment effects. A third condition (moderate-carb control) was included, as opposed to merely testing the two extremes. A crossover was implemented, which helped alleviate the low statistical power of the small sample (6 subjects). Study limitations It’s possible that the outcomes of this study are confined to the protocol used. A TTE model was used, as opposed to a time trial which either measured the work done over a fixed time period or the time it took to complete a fixed amount of work. TTE models are not necessarily reflective of real-world race conditions, and have been found to have greater variability than time trials,9,10 although this idea has been recently challenged.11 To add an important disclaimer, the present study’s TTE test was done at supramaximal intensity (115% of VO2max), as opposed Alan Aragon’s Research Review – July 2013

to submaximal intensity taken to exhaustion, so the traditional criticisms might not apply. Another limitation was the length of time that the diets were imposed (48 hours prior to testing). Although this was enough to establish a steady state of glycogen storage prior to testing, some might argue that it was not enough time to allow the subjects to adapt to the LC condition. A counterpoint to this would be that the testing was not conducive to a critical reliance on fat oxidation due to its supramaximal intensity. Comment/application

The primary finding was that the LC diet (25% carb, 30% prot, 45% fat) caused significantly lower supramaximal exercise endurance compared to the HC diet (70% carb, 10% prot, 20% fat), resulting in a TTE of 3.0 & 3.7 minutes, respectively. No significant performance difference was seen between the HC diet and the moderate (50% carb) control diet. As seen above, the LC diet had a lower aerobic energy contribution than HC. The control diet trended toward a lower aerobic contribution than HC (p = 0.08), but higher aerobic contribution than LC (p = 0.09). Blood lactate was significantly higher in the HC than LC, but there were no differences between HC and control or between LC and control. The lower TTE in the LC condition is perhaps not too surprising, given that LC diets have a generally poor track record for optimizing performance that involves sustained high-intensity exercise above the lactate threshold.12 Even the noted low-carb advocate Steven Phinney (who is typically mentioned in the same breath as Jeff Volek) admitted to observing “constrained” sprinting capability in cyclists on a ketogenic diet.13 The problem with compromised supramaximal performance – even in endurance events – is eloquently put by Burke & Kiens:14 “It is tempting to classify endurance and ultraendurance sports  as submaximal exercise, which might benefit from increased fat  utilization  and  a  conservation  of  limited  endogenous  carbohydrate  stores.  However,  the  strategic  activities  that  occur in such sports, the breakaway, the surge during an uphill  stage, or the sprint to the finish line, are all dependent on the  athlete's  ability  to  work  at  high  intensities.  With  growing  evidence  that  this  critical  ability  is  impaired  by  dietary  fat  adaptation  strategies  and  a  failure  to  find  clear  evidence  of  benefits  to  prolonged  exercise  involving  self‐pacing,  it  seems  that we are near to closing the door on one application of this  dietary protocol.” 

[Back to Contents]

Page 8

Study limitations The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebocontrolled, crossover study. Jenkins ND, Housh TJ, Johnson GO, Traylor DA, Bergstrom HC, Cochrane KC, Lewis RW Jr, Schmidt RJ, Cramer JT. J Int Soc Sports Nutr. 2013 Jul 22;10(1):33. [Epub ahead of print] [PubMed] BACKGROUND: Anatabine (ANA), a minor tobacco alkaloid found in the Solanaceae family of plants, may exhibit antiinflammatory activity, which may be useful to aid in recovery from exercise-induced muscle damage. The purpose of this study, therefore, was to examine the effects of ANA supplementation on the recovery of isometric strength and selected non-invasive indicators of muscle damage. METHODS: A double-blinded, placebo-controlled, crossover design was used to study eighteen men (mean +/- SD age = 22.2 +/- 3.1 yrs; body mass = 80.3 +/- 15.7 kg) who participated in two randomly-ordered conditions separated by a washout period. The ANA condition consisted of consuming 6--12 mg anatabine per day for 10 days, while testing took place during days 7--10. The placebo (PLA) condition was identical except that the PLA supplement contained no ANA. Maximal voluntary isometric peak torque (PT) of the forearm flexors, arm circumference, hanging joint angle, and subjective pain ratings were measured before (PRE), immediately after (POST), and 24, 48, and 72 h after six sets of 10 maximal, eccentric isokinetic forearm flexion muscle actions. Resting heart rate and blood pressure were measured at PRE and 72 h in each condition. RESULTS: For PT, hanging joint angle, arm circumference, and subjective pain ratings, there were no condition x time (p > 0.05) interactions, there were no main effects for condition (p > 0.05), but there were main effects for time (p < 0.001). There were no condition x time (p > 0.05) interactions and no main effects for condition (p > 0.05) or time (p > 0.05) for blood pressure or resting heart rate. CONCLUSIONS: ANA supplementation had no effect on the recovery of muscle strength, hanging joint angle, arm swelling, or subjective pain ratings after a bout of maximal eccentric exercise in the forearm flexors. Therefore, ANA may not be beneficial for those seeking to improve recovery from heavy eccentric exercise. Future studies should examine the effects of ANA on the pro-inflammatory cytokine responses to exercise-induced muscle damage and the chronic low-grade inflammation observed in obese and elderly individuals. SPONSORSHIP: This study was funded by a research grant from Rock Creek Pharmaceuticals, Inc.

The supplementation period was 10 days, with days 7-10 involving testing. It’s possible that a longer supplementation period and/or a higher antabine dose than 6-12 g was required to be effective. Another potential limitation was the inclusion of other nutrients in both treatments (834 IU vitamin A, and 66 IU vitamin D3). Although it’s not likely, the possibility of confounding/masking effects from these nutrients can’t be completely dismissed. Although the subjects were instructed to maintain their habitual dietary intake, there was no reporting or analysis of it. Average compliance was high, at 95.3%, but it ranged between 74% and 104%, which is unexpected for a small number of subjects and a short supplementation period. A final limitation was that non-invasive means of measuring muscle damage (with the exception of strength testing) are more subjective than direct measurement of serum biomarkers such as creatine kinase, myoglobin, or 3-methylhistidine. Comment/application The main findings were a lack of significant effects on peak torque, hanging joint angle, subjective pain ratings, and arm circumference. These findings were contrary to the authors’ hypothesis that antabine would “attenuate losses in muscular strength and improve the recovery of the hanging joint angle, relaxed arm circumference, and subjective pain ratings due to its potential anti-inflammatory properties.” They additionally hypothesized antabine would also decrease blood pressure and increase heart rate due to its similar chemical structure (see the charts here & here) – yet this didn’t happen either. The authors speculate that despite their null findings, it’s still possible that antabine could be useful for counteracting the baseline systemic inflammation associated with obesity and aging. Previous research in mice showed its ability to inhibit the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa-B (NFkB).15,16 This in addition to its reduction of inflammatory cytokines render antabine subject to further research seeking to mitigate conditions of chronic, low-grade inflammation. What I found particularly interesting was the apparent lack of sponsor bias. Rock Creek Pharmaceuticals, Inc. funded the study, and they happen to sell Antabloc, which was the same formula tested in this study. The supplement’s failure to show significant effects on any of the tested parameters lends confidence in the authors’ statement that, “Rock Creek Pharmaceuticals, Inc. had no involvement in the data collection, analysis and interpretation of the data, writing of the manuscript, or in the decision to submit the manuscript for publication.”

This was the first study to test the ergogenic effects of antabine in human subjects. Previous research has either been in mice, or in vitro, measuring inflammatory effects or preventive potential against alzheimer’s disease.15,16 The present study has specific relevance to competitive and recreational athletes. Subjects were blinded as to the placebo versus antabine supplementation via delivery through mint-flavored lozenges in both groups. A crossover was implemented in order to alleviate the lowered statistical power of the small sample (18 subjects total).

Bourgeois et al examined safety and efficacy trials of drugs registered in ClinicalTrials.gov,17 and found that industry-funded drug trials reported positive outcomes in 85.4% of the publications, which contrasted most strongly with governmentfunded trials reporting positive outcomes in 50.0% of the publications. Interestingly, a systematic review by Golder and Loke did not find any significant bias against the reporting of adverse effects in pharmaceutical industry-funded studies.18 However, they did find that authors with industry funding were more likely to interpret the data as supportive of the drug’s safety, despite the presence of adverse outcomes.

Alan Aragon’s Research Review – July 2013

[Back to Contents]

Study strengths

Page 9

Blood type diets systematic review.

lack

supporting

evidence:

a

Cusack L, De Buck E, Compernolle V, Vandekerckhove P. Am J Clin Nutr. 2013 Jul;98(1):99-104. [PubMed] BACKGROUND: Diets that are based on the ABO blood group system have been promoted over the past decade and claim to improve health and decrease risk of disease. To our knowledge, the evidence to support the effectiveness of blood type diets has not previously been assessed in the scientific literature. OBJECTIVE: In this current systematic review, published studies that presented data related to blood type diets were identified and critically appraised by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). DESIGN: A systematic search was performed to answer the following question: In humans grouped according to blood type, does adherence to a specific diet improve health and/or decrease risk of disease compared with nonadherence to the diet? The Cochrane Library, MEDLINE, and Embase were systematically searched by using sensitive search strategies. RESULTS: Sixteen articles were identified from a total of 1415 screened references, with only one article that was considered eligible according to the selection criteria. The identified article studied the variation between LDL-cholesterol responses of different MNS blood types to a low-fat diet. However, the study did not directly answer the current question. No studies that showed the health effects of ABO blood type diets were identified. CONCLUSIONS: No evidence currently exists to validate the purported health benefits of blood type diets. To validate these claims, studies are required that compare the health outcomes between participants adhering to a particular blood type diet (experimental group) and participants continuing a standard diet (control group) within a particular blood type population. SPONSORSHIP: There was no funding source for this project. Study strengths This is analysis is conceptually strong because the practice of blood typing has received widespread popularity since the 1996 publication of naturopath Peter D'Adamo’s best-selling book Eat Right 4 Your Type. There’s even a Blood Type Diet Certification headed by Peter Malia, a naturopath who was trained by D'Adamo. The far reach of this diet paradigm makes the present analysis particularly relevant, especially since a wide range of allied health practitioners have either dabbled in it, practice it, or have been confronted with client/patient questions about its evidence basis. As for the technical strengths of the meta-analysis, all languages were included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used to judge the quality of the studies. Study limitations Observational as well as controlled studies were included. While this relatively loose allowance might be construed as a flaw in the design, in this case it didn’t end up mattering due to the lack of data – not to mention lack of support for the diet to begin with. The single study that fulfilled all of the inclusion criteria Alan Aragon’s Research Review – July 2013

was somewhat of a mess. It was a controlled interruption time series, with participants drawn from another study. There was a lack of participant blinding and an incomplete accounting of subject outcomes (Only 254 out of the 315 randomly assigned patients were analyzed). Furthermore, the study did not provide a direct answer to the PICO (population, intervention, comparison, and outcome) question. The study thus received a C grade based on the GRADE standards (C = low, D = very low evidence quality). Comment/application

As seen above, out of 1415 studies initially considered for the analysis, only 1 fulfilled all of the inclusion criteria. This solitary study did not directly answer the question of whether or not adherence to a specific diet based on blood type improves health or lowers disease risk compared to nonadherence. Specifically, Birley et al compared the variation in LDL-c levels between different MNS blood types in response to a low-fat diet.18 As pointed out by the authors, aside from the PICO question not directly answered, MNS blood types are “functionally discinct” from ABO blood types, which comprise the basis of D'Adamo’s hypotheses. Furthermore, a systematic review by Masson et al (published after Birley et al’s study) which analyzed 74 studies concluded that in terms of lipid response to dietary intervention, “...the effects of genetic variation are not consistently seen and are sometimes conflicting.”19 Back to the present study, the authors concluded that based on their meta-analysis, no evidence currently exists to support the validity of blood type diets. To quote them: “However, there is currently no evidence that an adherence to  blood  type  diets  will  provide  health  benefits,  despite  the  substantial  presence  and  perseverance  of  blood  type  diets  within the health industry. Until the health effects of blood type  diets have been substantiated, the widespread claims should be  clarified  so  that  consumers  are  aware  that  the  advertised  health  benefits  are  theoretical  and  not  supported  by  scientific  evidence.” 

[Back to Contents]

Page 10

\ 1.

2. 3.

4.

5.

6.

7.

8.

9. 10. 11.

12. 13. 14. 15.

Pattyn N, Cornelissen VA, Eshghi SR, Vanhees L. The effect of exercise on the cardiovascular risk factors constituting the metabolic syndrome: a meta-analysis of controlled trials. Sports Med. 2013 Feb;43(2):121-33. [PubMed] Sensi S, Capani F. Chronobiological aspects of weight loss in obesity: effects of different meal timing regimens. Chronobiol Int. 1987;4(2):251-61. [PubMed] Schlundt DG, Hill JO, Sbrocco T, Pope-Cordle J, Sharp T. The role of breakfast in the treatment of obesity: a randomized clinical trial. Am J Clin Nutr. 1992 Mar;55(3):645-51. [PubMed] Keim NL, Van Loan MD, Horn WF, Barbieri TF, Mayclin PL. Weight loss is greater with consumption of large morning meals and fat-free mass is preserved with large evening meals in women on a controlled weight reduction regimen. J Nutr. 1997 Jan;127(1):75-82. [PubMed] Sofer S, Eliraz A, Kaplan S, Voet H, Fink G, Kima T, Madar Z. Greater weight loss and hormonal changes after 6 months diet with carbohydrates eaten mostly at dinner. Obesity (Silver Spring). 2011 Oct;19(10):2006-14. [PubMed] Jakubowicz D, Froy O, Wainstein J, Boaz M. Meal timing and composition influence ghrelin levels, appetite scores and weight loss maintenance in overweight and obese adults. Steroids. 2012 Mar 10;77(4):323-31. [PubMed] Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Apr;37(4):604-11. [PubMed] Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity (Silver Spring). High Caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. 2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of print] [PubMed] Jeukendrup A, Saris WH, Brouns F, Kester AD. A new validated endurance performance test. Med Sci Sports Exerc. 1996 Feb;28(2):266-70. [PubMed] Hopkins WG, Schabort EJ, Hawley JA. Reliability of power in physical performance tests. Sports Med. 2001;31(3):21134. [PubMed] Laursen PB, Francis GT, Abbiss CR, Newton MJ, Nosaka K. Reliability of time-to-exhaustion versus time-trial running tests in runners.Med Sci Sports Exerc. 2007 Aug;39(8):1374-9. [PubMed] Cook CM, Haub MD. Low-carbohydrate diets and performance. Curr Sports Med Rep. 2007 Jul;6(4):225-9. [PubMed] Phinney SD. Ketogenic diets and physical performance. Nutr Metab (Lond). 2004 Aug 17;1(1):2. [PubMed] Burke LM, Kiens B. "Fat adaptation" for athletic performance: the nail in the coffin? J Appl Physiol. 2006 Jan;100(1):7-8. [PubMed] Paris D, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C, Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M. Anti-inflammatory activity of anatabine via inhibition of STAT3 phosphorylation. Eur J Pharmacol. 2013 Jan 5;698(1-3):145-53. [PubMed]

Alan Aragon’s Research Review – July 2013

16. Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, AitGhezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M. Anatabine lowers Alzheimer's Aβ production in vitro and in vivo. Eur J Pharmacol. 2011 Nov 30;670(23):384-91. [PubMed] 17. Bourgeois FT, Murthy S, Mandl KD. Outcome reporting among drug trials registered in ClinicalTrials.gov. Ann Intern Med. 2010 Aug 3;153(3):158-66. [PubMed] 18. Birley AJ, MacLennan R, Wahlqvist M, Gerns L, Pangan T, Martin NG. MN blood group affects response of serum LDL cholesterol level to a low fat diet. Clin Genet. 1997 May;51(5):291-5. [PubMed] 19. Masson LF, McNeill G, Avenell A. Genetic variation and the lipid response to dietary intervention: a systematic review. Am J Clin Nutr. 2003 May;77(5):1098-111. [PubMed]

[Back to Contents]

Page 11

The health benefits of dairy protein. By Armi Legge ____________________________________________________

wasn’t focused on getting “big and freaky,” just maintaining overall health and decent body composition which is what most people are after. The researchers identified several potential health problems dairy protein may be able to combat: 1. The cluster of symptoms called metabolic syndrome which includes imbalanced blood lipids, poor glucose control, hypertension, impaired endothelial function, inflammation, overweight, and obesity is a growing problem around the world. 2. “Sarcobesity” is another growing problem where people are gaining body fat and losing muscle mass, especially as they age. Poor eating habits, aging, and physical inactivity are considered the main culprits of these problems.

Editor’s note: I thought this piece might serve as a refreshing, science-based contrast to all of the silly anti-dairy alarmism that perpetually pervades the lay media. ____________________________________________________ Introduction It’s funny to think there’s something that vegans and paleos agree on. It’s even funnier to think they’re both wrong. Dairy has been getting a pretty bad rep for a while. It’s blamed for causing cancer, inflammation, acne, and pretty much everything else you can think of. Granted, many health authorities get a little too worked up about the benefits of dairy. It’s easy to think that if you don’t drink it at every meal, you’re basically guaranteed to get osteoporosis. Others are a little more conservative, and simply claim that there’s no need to eat dairy. That’s true, but you generally don’t need to eat any specific food as long as you’re able to hit your macro- and micronutrient targets. Some take things even further and claim that consuming dairy has no benefit and thus should be avoided. If you ignore the fact that dairy is delicious, this argument might seem to hold some water (or whey) at first. However, a new review published in The Journal of Nutrition and Metabolism (free full text here) gives a nice summary of the potential benefits of consuming dairy protein.1 Alan already debunked the idea that dairy isn’t helpful in terms of bone growth in the November 2008 issue of AARR.2 While going through all of the claims against dairy would be fun, it would also take a while (and I have some cookies in the oven, so time is an issue).Toady, we’re going to take a look at the other side of the equation — some of the benefits of dairy. More specifically, dairy protein. The review The review, “Milk protein for improved metabolic health: a review of the evidence,” mainly focused on how consuming dairy protein could improve glucose control and muscle mass. It Alan Aragon’s Research Review – July 2013

Eating less and exercising more to correct energy imbalance is the best way to correct or prevent obesity. When people lose weight, however, about 25% of the weight they lose is often lean mass, much of which is muscle. (Don’t worry, this number can be much lower if you consume adequate protein, lift weights, and don’t diet too aggressively. See AARR January 2011, April 2008, and April/May 2013 for more on this). Luckily, some researchers think our bovine friends can help with this. The dairy solution People who consume dairy tend to have a lower risk of metabolic disorders and cardiovascular disease. Virtually all of the proteins in dairy have the potential to improve metabolic health. Dairy also tends to be high in minerals and micronutrients. This seems like a good argument for consuming whole protein sources rather than just supplements. Whey and casein, the two primary proteins in dairy, are both extremely high quality protein sources, thanks to their wide range of essential amino acids and ease of digestion. There’s evidence that whey and casein can help improve insulin action, increase satiety, reduce blood pressure, and increase muscle protein synthesis. They may also improve immune function. Let’s start by looking at how dairy affects metabolic health. Glucose control Several studies have shown that dairy protein can help reduce post-meal glucose levels. It doesn’t seem to take much dairy to cause these effects — somewhere around 10-40 grams, depending on the study. These effects occur in healthy people and those with type-2 diabetes. Whey seems to be superior to casein in this regard, though there’s still some evidence casein may also improve glucose control as well. While dairy protein seems to reduce post-meal glucose, it’s not clear if this is true for fasting glucose levels. The only study thus far that’s tested this found that dairy did reduce fasting insulin levels, but not glucose levels. (Another hit to the “dairy raises insulin which makes you fat,” theory). Blood lipids & blood pressure Dairy tends to reduce the level of triglycerides and other fats in [Back to Contents]

Page 12

the blood after a meal, though not all studies have found this to be the case. It’s also not clear if these results are maintained over the long-term, if they have any real impact on health over time, or if they’re generalizable to everyone. One study found that consuming 15 grams per day of a whey protein supplement helped reduce fasting triglycerides, but only in people with a high risk of metabolic syndrome. There is also some animal evidence that dairy protein might help reduce fatty liver disease in rodents. Most trials have found that whey protein can reduce blood pressure in people with hypertension and improve arterial function, although not all have found this to be the case. The reason for this discrepancy isn’t clear. Based on the totality of evidence, the authors believe that people with poor blood lipids and/or high blood pressure may benefit from consuming a moderate amount of dairy.

cases (got milk?). Incidentally, there is an emerging body of evidence pointing to the superiority of protein blends over single sources (even whey alone).3,4 Consuming both casein and whey protein post-exercise tends to increase myofibrillar muscle protein synthesis. Short-term studies have generally shown that dairy protein supplements have little effect on muscle growth, while longer term studies have generally shown positive trends. Many of these studies didn’t include exercise of any kind. When they did, it wasn’t always progressive, so we don’t know what effect it might have on muscle growth or weight loss with a reasonable strength training program. Once again, there was little dietary control in most of these studies which throws a huge monkey wrench into the results. As always, we need more research.

Inflammation and immune function

The bottom line

In-vitro studies have shown that whey protein can suppress immune activation and lower inflammation, but in-vivo studies have not all found this to be the case. At this point, there isn’t enough evidence to say for sure that dairy proteins help reduce inflammation or improve immune function, but the research is promising.

While consuming dairy is far from a guarantee of health, the claims that it offers no additional benefit over other protein sources are also dubious. There’s some evidence that dairy protein may improve insulin action and glucose control, lower blood lipids and blood pressure, aid fat loss, and assist in muscle growth. Of course, other protein sources also have benefits over dairy protein, so it seems wise to have a balance of both.

Appetite control Dairy proteins generally enhance satiety and reduce food intake more than other foods, and in some cases more than other proteins such as soy. One study also found that whey suppressed food intake more than casein, at least in the short-term. Dairy proteins do alter levels of satiety-related gut hormones, but at this point we’re mostly in the dark as to how dairy proteins suppress appetite more than other protein sources. Weight loss Some data indicates that adding whey protein to the diet under ad libitum conditions can reduce food intake and cause weight loss, while others have not. Interestingly, in one study where people did not lose weight after eating more dairy protein, they still had lower blood lipids and insulin levels. Controlled weight loss studies where people eat more dairy protein have generally found mixed results in terms of body composition. Some have found adding dairy protein improves fat loss and spares muscle mass while others have not. These inconsistent results are largely due to poor overall dietary control — especially not matching total protein intake between groups. At this point, it’s not clear if whey or casein is better for sparing muscle mass during weight loss. Muscle growth

Both whey and casein have pros and cons, so a mixture of both is probably a wise choice – like most whole dairy sources. You also have to consider that whole dairy foods are high in micronutrients and fairly cheap – much cheaper than most protein supplements. If you don’t like dairy, avoiding it won’t kill you. If you like dairy, adding it to your diet in moderate amounts may give you some small benefits over other protein sources. The key here is that you have options, and there’s no reason to restrict your intake to one protein source. Of course, all of this evidence pales in comparison to the simple fact that avoiding dairy means giving up ice cream — which is simply unacceptable. References 1. 2. 3.

4.

McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a review of the evidence. Nutr Metab (Lond). 2013 Jul 3;10(1):46. [PubMed] Aragon AA. Milk-bashing: a sport for the ignorant. The Alan Aragon Research Review. Nov 2008:12. [AARR] Reidy PT, Walker DK, Dickinson JM, Gundermann DM, Drummond MJ, Timmerman KL, Fry CS, Borack MS, Cope MB, Mukherjea R, Jennings K, Volpi E, Rasmussen BB. Protein blend ingestion following resistance exercise promotes human muscle protein synthesis. J Nutr. 2013 Apr;143(4):410-6. [PubMed] Paul GL. The rationale for consuming protein blends in sports nutrition. J Am Coll Nutr. 2009 Aug;28 Suppl:464S-472S. [PubMed]

____________________________________________________

Whey protein seems to stimulate protein synthesis, while casein seems to be more effective at preventing muscle protein breakdown. Casein seems to cause a more sustained release of amino acids with a lower spike in amino acids levels, while whey protein has a more immediate spike with a shorter duration. It seems like a mix of both would be optimal in most

Armi Legge is the editor and founder of Imprüvism.com, a website that uses science to help people become more awesome. He is also the cofounder and product manager of Imprüvr, an app that helps people track their workouts with as little effort as possible.... He also likes ice cream and cookies.

Alan Aragon’s Research Review – July 2013

[Back to Contents]

Page 13

Bulletproof Coffee & concerning bloodwork: questions for 2 doctors who actually lift. Kasey & Spencer Nadolsky interviewed by alan Aragon ____________________________________________________ First off, I want to thank you both for doing this interview. Let’s get right to it. Some of your patients with concerning bloodwork happened to be consuming Dave Asprey's recipe (“special” coffee with generous helpings of butter and MCT oil). Can you please elaborate on this? SN: Yep definitely. I am currently listed as a healthcare provider in the Primaldocs.com and Paleophysiciansnetwork.com directories. I've listed myself in these because you tend to get more compliant patients this way. I am also a provider for WellnessFx.com where you can get your blood drawn without having to see a doctor and then you can consult over the phone with me as I look over the lab report. Many of the people who sign up for WellnessFx.com are Paleo followers as well. Well, I started noticing a trend with the blood work. Many of these "super healthy" folks had sky high numbers on their cholesterol panels! When doing the dietary recalls for the patients with these high numbers, the most consistent variable I found was that they were drinking this "Bulletproof Coffee." My brother in law had actually told me about this special coffee/fat mixture so I was slightly familiar. It didn't make too much sense to me why Paleo people would be drinking large quantities of fat in their coffee but they are always down for some self-experimentation so I am okay with that as long as it isn't dangerous. Now most of these guys are well educated in the context of Paleo bloggers so when I told them to cut out their BP coffee they were reluctant. They told me, "but cholesterol doesn't matter!" The only problem was that I didn't check just "Total Cholesterol," which we now understand not to be that great of a risk factor for heart disease. I checked the most advanced lipid testing available with LDL particle numbers and also apolipoprotein B. KN: This situation became apparent to me after I had a few patients specifically referred to me in order to evaluate their advanced lipid tests (VAP or NMR) which they requested upon their primary care physicians explaining to them that their LDL cholesterol had risen and was now high enough to warrant medication. There turned out to be one significant thing in common for all these patients, which I will explain after I give just one case presentation of an otherwise healthy adult male who had very normal lipid levels in previous years but suddenly reasonably elevated levels. Case: The most recent case I had was a consult for a 39 year old male without any known past medical history but was sent to me for further evaluation of his lipids after screening showed significantly elevated total and LDL-c compared to previous Alan Aragon’s Research Review – July 2013

screening. He had no complaints, felt well and was without any history chest pain, dyspnea(shortness of breath), fatigue, hair/skin changes, goiter (enlarged thyroid), weight changes, libido change, sexual dysfunction, GI (abdominal pain/nausea/diarrhea) complaints nor urinary changes. He states he has exercised regularly for most of his life and includes resistance training without any problems. No concerning family history of coronary artery disease (heart disease), diabetes, or other significant problems. His only change in lifestyle over the past couple of years was going from a "moderately low carb diet" to a "Paleo diet" and recently started "Bulletproof Coffee" just a few months ago. His diet has otherwise been high in meats including poultry/beef/fish and some veggies but rare fruit. He denied any changes in weight or body composition during this time frame, does not use tobacco, and sleeps 8 hours nightly. Exam was without any concerning findings, reasonable blood pressure, no thyroid enlargement and waist circumference 34". The important components from his recent labs included total cholesterol of 282, directly measured LDL-c 198, HDL-c 66, non-HDL 216, and most importantly an apoB 136. He also had a low-normal hsCRP, normal Lp(a) and pattern "A" with his VAP test. For comparison, here are his previous basic lab results: 3 months prior: total cholesterol 248, HDL 59, non-HDL 189, LDL 181, trig 41; normal thyroid function tests; normal fasting glucose and electrolytes. 2010 (3 years ago): TC 203, HDL-c 48, non-HDL 155, LDL-c 143, trigs 58 2005 (8 years ago): TC 219, HDL-c 43, non-HDL 176, LDL-c 139, trigs 185 (this was prior to his "moderately low carb diet" consisting of basic changes such as increasing veggies, decreasing processed carbohydrates). My assessment was that this is an otherwise very healthy adult male with no known atherosclerotic disease and no concerning family history or other risk factors for heart disease but now with newly elevated non-HDL and apoB which are both well above goals for a low risk patient even though the pattern is nonatherogenic. The interesting part, of course, is the that they recently increased now statistically putting him at increased atherosclerotic risk. I advised him to cut out the excessive butter and medium-chain triglyceride oil, increase his veggies, consume more of his fat from nuts and "Mediterranean" type fats and recheck his lipids in 6-8 weeks. This case was actually not as extreme as a case I had previously, and there was a similar case reported with impeccable timing published in the Journal of Clinical Lipidology for which to compare: They reported a case about a 52 year old female who recently started supplementing with daily coconut oil and was found to have significantly elevated TC (303), LDL-c (178), HDL-c (106), trigs (94), and non-HDL (197) before stopping and rechecking 6 weeks later showing TC of 201, LDL-c of 127, HDL-c 58, trigs 77, and non-HDL 143. [i] [i] J Clin Lipid 2013;7(3)151 [Back to Contents]

Page 14

As discussed in the AARR from April, 2011, the evidence demonizing SFAs directly in regards to cardiovascular disease has turned out to be weak, specifically when comparing to processed trans-fatty acids and processed carbohydrates. But there is still evidence suggesting adding excessive amounts of SFAs may be detrimental and certainly so when compared to other fatty acids such as omega-3 & omega-6 PUFAs from fish, nuts, seeds, etc and MUFAs from olives/avocados, and nuts/seeds. Obviously those sources of fatty acids have other beneficial components like fiber, lignans, and anti-oxidant properties which may contribute to the observed cardiovascular benefits shown in their studies vs SFAs. We’ve also seen the body of evidence grow revealing benefits from cocoa, which is high in SFA, but perhaps is also confounded by the other components similar to those mentioned above. The problem I have seen, as witnessed by evaluating patients similar to the one I presented above, is that consuming what I would consider excessive amounts of SFAs from items such as butter and coconut oil (which, by the way, are processed to some degree and extracted from their whole food sources) has adverse effects on increasing atherogenic lipoproteins which are directly involved in the process of forming atherosclerotic plaques within coronary arteries (otherwise known as coronary artery disease) and the rest of our vasculature. That said, SFA intake is associated with increased apoB1 even though systematic reviews have questioned the pure association of SFA consumption and CVD.23 Dairy as a whole has evidence to support its beneficial role in dietary health including risk of heart disease and diabetes4 but not necessarily the high-fat forms such as butter and cream.5 The effects or benefits of MCT oil in regards to lipids is more convoluted. A review of MCT studies in 2002 concluded that there may be a mild improved energy expenditure plus a potential caloric deficit from improved satiety when MCT isocalorically replace LCTs.6 i.

ii. iii.

iv.

Study of MLCT vs LCT (25-30gm/d) showed better weight, waist, and triglyceride lowering in hypertriglyceridemic patients with bmi 24-28 but not in other bmi categories.7 30ml of coconut oil vs soybean oil in viscerally obese women during hypocaloric diet appeared superior for lipoprotein patterns and decreased waist circumference.8 It has been mentioned that MCTs or coconut oil do not contribute to hypertriglyceridemia due to ability to forego chylomicron transfer to lymphatic system and deliver directly to portal system but coconut oil has been shown to cause increased post-prandial hypertriglyceridemia in diabetics compared to normal controls.9 Study comparing coconut oil, butter, and safflower oil showed butter leading to elevated TC, LDL-c, and apoB compared to the others while safflower oil had lowest LDL-c and apoB while coconut oil group was intermediate.10

Can you please explain the significance of measuring LDL-c, non-HDL, LDL-p & apo B? KN: We like to look beyond the tradition LDL-c (the amount of measured cholesterol in low-density lipoproteins) because there are now ways to more accurately measure the risk associated Alan Aragon’s Research Review – July 2013

with more specific lipoproteins. The easiest way to measure “atherogenic” lipoproteins is something called “non-HDL,” which is just total cholesterol minus the HDL-c (giving you just measurement of atherogenic cholesterol lipoproteins), and is much stronger at predicting cardiovascular events than LDL-c as shown in multiple studies11 because it accounts for the increased risk due to other atherogenic lipoproteins12 including VLDL-c, apoB, and apoCIII. It additionally showed superiority even in statin treatment trials as revealed in the Emerging Risk Factor Collaboration meta-analysis.13 The Framingham Offspring Cohort14 and Multi-Ethnic Study15 of Atherosclerosis have clearly shown a stronger correlation of LDL-p16 (low-density lipid particle number) and apoB (the specific protein attached to atherogenic lipoproteins), respectively, to incident of coronary artery disease and subsequent heart attacks and the like than measurement of LDL-c (though incidence of bad events is closely related17). This becomes even more important when correlations may be discordant (one measure high while the other is low) which is prevalent specifically in insulin resistance (metabolic syndrome) or diabetes.18 The body of evidence has grown considerably to include the Copenhagen study,19 Health Professionals Study,20 and EPIC-NORFOLK.21 While using advanced lipid testing in the general population is not universally agreed upon at this time, non-HDL may serve as a nearly optimal test with the option for checking apoB or LDL-p when concern for discordance is high.22 Many of the “Paleo” and “Bulletproof Coffee” disciples claim that even having significantly elevated levels of these strong correlating lipoproteins don’t matter without the inflammation associated with metabolic syndrome. But in addition to the evidence mentioned above (especially Framingham which showed LDL-p to outperform even non-HDL in metabolic syndrome and diabetes), other studies (Nurses Health23 and Cardiovascular Health Study24 have shown even stronger correlation of apoB and LDL-p compared to LDL-c while adjusting for diabetes, hypertension, hsCRP (marker of inflammation and cardiovascular risk), smoking, physical inactivity, and weight thus essentially accounting for “inflammation.” SN: Here’s an overview of the difference between the standard lipid panel and advanced lipid testing and why it matters. Cholesterol cannot travel through the blood stream by itself so it attaches to these proteins called apolipoproteins to form what are called lipoproteins. It's almost like cholesterol is the cargo and the apolipoprotein is the boat - together they make a cargo ship traveling through your arteries like a river. This is important to understand because it is an apolipoprotein (in particular, apolipoprotein B or apo B) and not the cholesterol that gets "stuck" in the inside of blood vessels and starts the atherosclerosis cascade. So you see it isn't the cargo that is the problem, it is the ship that crashes into the sides of the river (the inner walls of your arteries) and causes damage. This is a super simplified version, but hopefully you get the gist. Standard lipid panels look at cholesterol concentrations in the various lipoproteins (e.g. low density lipoproteins or LDL-C). [Back to Contents]

Page 15

This more or less gives an estimate of all of those aforementioned apo B particles, which I mentioned are a large part of atherosclerosis. However, this estimation CAN be off for various reasons that is beyond the scope of this article. Either way, the LDL-C (which isn't even directly measured in a lipid panel) does a decent job at estimating the risk and is why you see it listed as "bad cholesterol." To even better estimate the apo B particles with a standard lipid panel, you can calculate what is called Non-HDL Cholesterol. High Density Lipoproteins contain apo A particles, which DO NOT cause atherosclerosis and are actually protective and anti-atherogenic. This is why HDL is called "good cholesterol." So the thinking is that anything that isn't HDL (apo A containing) cholesterol, is bad (atherogenic). With this you can calculate the Non-HDL by just subtracting HDL from Total Cholesterol. This gives you an even better estimation of the apo B containing particles. With advanced lipid testing, you can actually measure the amount of apo B and/or the lipoprotein particle number. It isn't an estimation like the standard lipid panel. So now you are looking at the true problem (apo B particles) and not the innocent bystander cholesterol (cholesterol is still involved in the process though). Any concluding thoughts? SN: After I explain to these BP coffee drinkers that it is the lipoprotein particles / apo B and not necessarily the cholesterol that matters more, they start to understand. I then go on to explain that while saturated fat is not likely dangerous in whole food sources (see AARRapril 12' I think), the highly concentrated saturated fat bomb that is BP coffee is likely the culprit for their high apo B / LDL - Particle levels. What I then find is that when these folks stop the BP coffee and then go back to their protein based breakfast (eggs, protein shake, etc) their levels come back down. While they generally don't have any weight changes or noticeable body composition changes when using the BP coffee, the common theme is these higher LDL-Particles and/or apo B levels. Maybe they are just getting extra calories but it is my feeling that they are getting unneeded extra saturated fat that is driving these high levels. KN: From a clinical perspective, I feel that excessive added calories from what is essentially processed, or at least extracted SFAs, from potentially healthful whole foods such as milk and coconuts for a significant lipemic load may be hazardous to cardiometabolic health. I would consider comparing macronutrient profiles of other basic coffee preparations and consider your options wisely. Compare macronutrient profiles: Bulletproof coffee: 456 kcal; 22g fat (42 sat); 0 carb; 0 protein 2 tbsp. ½ & ½: 40 kcal; 3g fat (2 sat); 1g carb; 1g protein 1oz whole milk: 18 kcal; 1g fat (1 sat); 2g carb; 1g protein Lean Latte* (1 serving) 150 kcal; 3.5g fat (2 sat); 9g carb (6 fiber); 21 g protein *Disclaimer for conflict of interest ☺ Alan Aragon’s Research Review – July 2013

While natural SFAs are unlikely to be problematic in reasonable amounts from their natural whole food sources and perhaps even with some benefit, our experience suggests that these disproportionately added quantities of processed fats leads to elevation in atherogenic lipoprotein levels which is consistent with the body of evidence and of concern for potentially increased cardiovascular atherosclerotic disease. Conceivably this will open the door to more research on the subject. _________________________________________________                                     Kasey  Nadolsky  (left):  BA  in  kinesiology  at  Michigan  State  University,  captain of the varsity wrestling team and 4x NCAA qualifier ranked as  high  as  #4  nationally  and  academic  all‐American.  Attended  Nova  Southeaster College of Osteopathic Medicine before residency training  in  internal  medicine  at  the  Naval  Medical  Center,  Portsmouth,  Va.  Board  certified  in  internal  medicine  and  obesity  medicine  following  residency, currently training in endocrinology fellowship at the National  Capital  Consortium,  Bethesda,  MD.  Memberships:  American  Association  of  Clinical  Endocrinology,  The  Endocrine  Society,  National  Lipid  Association,  The  Obesity  Society,  American  Society  of  Bariatric  Physicians,  and  American  Thyroid  Association.  Cofounded  www.leanerliving.com with Spencer while in medical school.    Spencer  Nadolsky  (right):  Dr.  Spencer  Nadolsky  is  an  osteopathic  physician  who  specializes  in  weight  loss  (bariatric  medicine)  and  cholesterol  (lipidology).  While  earning  a  BA  in  exercise  science  In  undergrad  he  wrestled  heavyweight  for  the  UNC  Tar  Heels  and  was  ranked  as  high  as  3rd  in  the  nation  at  one  point  while  also  garnering  Academic All‐American status. 

_________________________________________________ References 1.

2.

3.

Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, Wilson PW, D'Agostino RB. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol. 2007 Dec;1(6):583-92. [PubMed] Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr. 2010 Mar;91(3):535-46. [PubMed] Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009 Apr 13;169(7):659-69. [PubMed]

[Back to Contents]

Page 16

4.

5. 6. 7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17. 18.

Elwood PC, Pickering JE, Givens DI, Gallacher JE. The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids. 2010 Oct;45(10):925-39. [PubMed] Iggman D, Risérus U. Role of different dietary saturated fatty acids for cardiometabolic risk. April 2011; 6(2):209-23. [Future Medicine] St-Onge MP, Jones PJ. Physiological effects of medium-chain triglycerides: potential agents in the prevention of obesity. J Nutr. 2002 Mar;132(3):329-32. [PubMed] Zhang Y, Liu Y, Wang J, Zhang R, Jing H, Yu X, Zhang Y, Xu Q, Zhang J, Zheng Z, Nosaka N, Arai C, Kasai M, Aoyama T, Wu J, Xue C. Medium- and long-chain triacylglycerols reduce body fat and blood triacylglycerols in hypertriacylglycerolemic, overweight but not obese, Chinese individuals. Lipids. 2010 Jun;45(6):501-10. [PubMed] Assunção ML, Ferreira HS, dos Santos AF, Cabral CR Jr, Florêncio TM. Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity. Lipids. 2009 Jul;44(7):593-601. [PubMed] Pietraszek A, Hermansen K, Pedersen SB, Langdahl BL, Holst JJ, Gregersen S. Effects of a meal rich in medium-chain saturated fat on postprandial lipemia in relatives of type 2 diabetics. Nutrition. 2013 Jul-Aug;29(7-8):1000-6. [PubMed] Cox C, Mann J, Sutherland W, Chisholm A, Skeaff M. Effects of coconut oil, butter, and safflower oil on lipids and lipoproteins in persons with moderately elevated cholesterol levels. J Lipid Res. 1995 Aug;36(8):1787-95. [PubMed] 16. Liu J, Sempos CT, Donahue RP, Dorn J, Trevisan M, Grundy SM. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol. 2006;98:1363-68. [PubMed] Sacks FM, Alaupovic P, Moye LA, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation 2000;102:1886-92. [PubMed] Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009 Nov 11;302(18):1993-2000. [PubMed] Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, Pencina MJ, Schoonmaker C, Wilson PW, D'Agostino RB, Vasan RS. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA. 2007 Aug 15;298(7):776-85. [PubMed] Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC Jr, O'Leary DH, Saad MF, Tsai MY, Sharrett AR. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2007 May;192(1):211-7. [PubMed] Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, Wilson PW, D'Agostino RB. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol. 2007 Dec;1(6):583-92. [PubMed] Illingworth DR. Management of hypercholesterolemia. Med Clin North Am. 2000 Jan;84(1):23-42. [PubMed] vidson MH, Ballantyne CM, Jacobson TA, Bittner VA, Braun LT, Brown AS, Brown WV, Cromwell WC, Goldberg RB, McKenney JM, Remaley AT, Sniderman AD, Toth PP, Tsimikas S, Ziajka PE, Maki KC, Dicklin MR. Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol. 2011 Sep-Oct;5(5):338-67. [PubMed]

Alan Aragon’s Research Review – July 2013

19. Benn M, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B: the Copenhagen City Heart Study. Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):66170. [PubMed] 20. Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005 Nov 29;112(22):3375-83. [PubMed] 21. El Harchaoui K, van der Steeg WA, Stroes ES, Kuivenhoven JA, Otvos JD, Wareham NJ, Hutten BA, Kastelein JJ, Khaw KT, Boekholdt SM. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol. 2007 Feb 6;49(5):547-53. [PubMed] 22. Orringer CE. Non-HDL cholesterol, ApoB and LDL particle concentration in coronary heart disease risk prediction and treatment. February 2013;8(1):69-79. [Future Medicine] 23. Shai I, Rimm EB, Hankinson SE et al. Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: potential implications for clinical guidelines. Circulation 2004 November 2;110(18):2824-30. [PubMed] 24. El Hadri K, Moldes M, Mercier N, Andreani M, Pairault J, Feve B. Semicarbazide-sensitive amine oxidase in vascular smooth muscle cells: differentiation-dependent expression and role in glucose uptake. Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):89-94. [PubMed]                            

       

     

  Who doesn’t love open access to scientific research? Here’s a directory of open access journals: http://www.doaj.org/

If you have any questions, comments, suggestions, bones of contention, cheers, jeers, guest articles you’d like to submit, or any feedback at all, send it over to [email protected]. [Back to Contents]

Page 17