3 - April - 2014

Alan Aragons Research Review April 2014 [Back to Contents] Page 1

Copyright April 1st, 2014 by Alan Aragon

Home: www.alanaragon.com/researchreview

Correspondence: [email protected]

2 The compelling case against 'food addiction.'

By Evelyn Kocur

6 Processed foods: contributions to nutrition.

Weaver CM, Dwyer J, Fulgoni VL 3rd, King JC, Leveille GA, Macdonald RS, Ordovas J, Schnakenberg D. Am J Clin

Nutr. 2014 Apr 23. [Epub ahead of print] [PubMed]

7 The effects of 12 weeks of beta-hydroxy-beta-

methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study. Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM,

Stout JR, Duncan N, Fuller JC, Baier SM, Naimo MA,

Rathmacher J. Eur J Appl Physiol. 2014 Mar 6. [Epub ahead

of print] [PubMed]

9 Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. BMJ. 2014 Apr 1;348:g2035. [PubMed] [Full Text]

10 Variability in muscle size and strength gain after

unilateral resistance training. Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB,

Hoffman EP, Angelopoulos TJ, Gordon PM, Moyna NM,

Pescatello LS, Visich PS, Zoeller RF, Seip RL, Clarkson

PM. Med Sci Sports Exerc. 2005 Jun;37(6):964-72.

[PubMed]

12 Protein: is it really as bad as they say it is? By Dylan Klein

17 Dr. Brad Schoenfeld gives the inside scoop on his

new study comparing hypertrophy-type and strength-type training. Interviewed by Alan Aragon

20 Response to: Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review. By Robert Hoenselaar


The compelling case against 'food addiction.'

By Evelyn Kocur

_________________________________________________________________

The concept of food addiction has been elevated from obscure conjecture to almost universally accepted scientific fact within the past two decades. That this has happened so relatively quickly is understandable given the predicament Western nations are in, with obesity rates rising year after year, seemingly unabated. Simply put, food addiction seems a rather plausible explanation for the overconsumption fueling this obesity epidemic. But does it stand up to scientific testing? I submit that the answer is a resounding No! What follows should convince you as well.

The nature of addiction: physiology or psychology?

Whenever the topic of addiction comes up, the debate ensues over whether it is physiological or psychological in nature. The proponents of the food addiction concept have made this part easy, however, as they have chosen the model put forth in the American Psychiatric Associations DSM-IV,1 and that model is predicated on physical dependence. This is important because, researchers often point to symptoms they can evoke while failing to establish the primary physical dependence. In the scientific literature, it was TG Randolph who first drew analogies between alcohol addiction and food addiction.

2 He focused on

physiological measures of addiction size of dose and frequency of dosing in his attempts to draw parallels. But these two measures have posed the same conundrum for alcohol and food. If alcohol is addictive and fairly widely used, why doesnt everyone who drinks become an addict? The reality is that it is highly likely that everyone who ingests a certain amount of alcohol frequently enough will develop a physical dependence. Psychological factors factor more in the how and why someone might come to ingest those amounts in the first place, but once physical dependence sets in are largely irrelevant to the question of why the person still partakes despite negative consequences.

An addiction model for food that is predicated on these same diagnostics must meet the criterion for physical dependence or it fails. When the first chapter of Overeaters Anonymous was founded in the 1960s, it was modeled after Gamblers Anonymous, which was in turn modeled after the 12 Step program of Alcoholics Anonymous. Researchers, like the rest of us, are no doubt influenced by the existence of OA and its focus on treating compulsive eating (addiction) considered to be the cause of overweight and obesity.

3 Obesity was still relatively

rare in those times, so these ideas didnt really catch on then as they have now. Now that a sizeable minority, or perhaps even a majority, seems to have been effected, and externally driven addiction seems to be a more acceptable explanation.

Brain images seal the deal

By the 1990s, the obesity epidemic that had begun a decade or so before, was gaining steam and researchers clamored to identify a cause. Alongside a veritable explosion of fast food restaurants and packaged convenience foods, Americans were

eating more, and drinking more in the form of sodas and coffee concoctions. Estimates vary, but it is not controversial that our average caloric intake has risen substantially since the 1970s, and this alone is sufficient to explain the obesity epidemic.4 While nutritional researchers sought to identify culprit foods from an energy standpoint, others sought to identify the reasons that prompted this uptick in intake. Food addiction came of age. The most convincing evidence of food that has emerged has to be the deluge of juxtaposed brain activity scans showing some known addictive drug alongside sugar. Who isnt convinced by the brain scans in Figure 1?

5 Similar pictures are seen

everywhere these days , offered up as scientific proof that sugar is addictive. It doesnt hurt that sugar is also a white powder that it lends itself well to creating images with white lines, mirrors and drug paraphernalia. In 2013, the biggest nutrition headline was: Rats find Oreos as addictive as cocaine.

6

Figure 1. Your Brain on Sugar

But its not just sugar, its seemingly all foods, or at least any food even the flimsiest case can be made against. Never mind that the same regions of the brain light up during sex, exercise, making silly faces at babies and petting puppies. In the 1980s and 1990s it was fatty foods and McDonalds was a favorite target. More recently, its sugary foods and carbohydrates in general, and McDonalds is still a favorite target. Documentaries and videos, be they mainstream,

7,8 lamestream,

9 or somewhere in

between,10

and countless media reports have sought to convince us that certain foods are indeed addictive and the cause of our battle with the bulge.

The common sense case against food addiction

Whenever a concept is advanced with such fervor as to be presumed fact, the part of my brain responsible for skepticism would light the heck out of one of those scans! Step back and think about this. Pick the food agent you are most convinced is addictive sugar generally fits that bill for most and draw analogies to alcohol. See if it all even makes sense. A true alcoholic is physically addicted to ethanol. Take it away and he/she will get the DTs.

11 You wouldnt serve a teetotaler light

beer because it contains just a little alcohol. You wouldnt put Metamucil

in a martini to render the ethanol benign. Yet the

mountain of literature implicating sugar sucrose and/or HFCS as an addictive agent fails the simple fruit test. One of the foremost crusaders against sugar, Dr. Robert Lustig, had this to say in a recent interview:

12


People always say to me, "What about fruit? It has sugar.

But I have nothing against fruit, because it comes with its

inherent fiber, and fiber mitigates the negative effects.

If sucrose were addictive like ethanol, then it wouldnt matter how much fiber it came packed with. Numerous similar

analogies could be drawn relating other aspects of food and

alcohol, none of which rescue the case for food addiction.

Wait a minute. This is Alan Aragons Research Review. Wheres the science?

Honestly I could have ended the article with my last section, but the scientists have brought out the big guns to convince you food addiction is real and the diet gurus have seized on it to sell you their detoxes and clean eating plans. So now Im going to turn those guns right back at them and present my case for why it is not. Yes, their own research often, and accidentally, refutes their claims. The vast majority of addiction research is carried out in our close friend and evolutionary relative, the rat. (That is a tongue in cheek reference to recent assertions by two researchers cited in this article claiming rats are very good models for human behavior!) Humans present far too many ethical issues for considerable research in this field, rats do not. Now while I dont share the researchers full enthusiasm for broad similarities between rats and humans, I rather celebrate the differences and what those differences can help elucidate. Rats eat throughout the 24 hour cycle, though more during their active periods. They dont eat at regular intervals or consume meals in a human sense. When fed chow they get balanced and complete nutrition with every bite. They dont eat out of emotional distress, diet to fit into that little black dress, or give a rats behind what the other rats think of their waistline. In other words, as imperfect as they are to mimic the totality of human behavior, they can be helpful in isolating the part we are interested in: What physiological effects do foods have on the brain, and do those effects alter energy intake and body weight?

If youre going to try propose food addiction as a concept, youll need to model it after established addictions. So off to the DSM went the researchers for the list of substance dependence criteria. The first three are (i) tolerance, (ii) withdrawal, and (iii) overconsumption. This is important, because merely overconsuming something does not an addiction make. Researchers have been invariably successful in getting rats addicted to alcohol. If you put it in their water supply, they become addicted with ad libitum access. It takes a while, but it will happen. Pretty soon researchers discovered that they could shorten that time by employing an intermittent access protocol.

13,14 Such protocols promote binges resulting in larger

doses of alcohol at one time. If they can get rats hooked on alcohol (and other drugs) in this fashion, then they should be able to replicate this with food. Just force them to consume the addictive food. Right?

Your standard rat feeding protocol is to allow ad libitum access to a species appropriate chow, usually 10-15% fat, 15-20% protein, and the balance consisting of grains for carbohydrate in the 60-70% of energy range. This is used as the control in most every rat nutritional study out there. So they fed rats sugar (in their drinking water or in their chow), and they fed them fats, and they fed them combinations thereof, with and without the flavors of human foods added. They even fed them the actual

junky human snack foods! Care to guess what happened? Here is a summary.

Ad libitum chows: Rats fed chows enriched in refined carbohydrate (35% sucrose/30% cornstarch) or a sweet-fat chow (45% fat/17% sucrose) in ad libitum fashion consumed the same or even fewer calories vs. controls, but gained more weight due to food efficiency.

15 It is difficult

to find high fat diets that do not contain sucrose, but in a study where sucrose was controlled between a low and high fat diet, the rats fed the high fat diet consumed more and became obese.

16

Ad Libitum junk food diets: Rats fed standard chow but offered a rotating selection of human snack foods, ranging from jelly beans to pepperoni to cheese doodles, reduced their consumption of chow considerably yet consumed almost one-third more in total calories than their chow-fed counterparts. Needless to say, they became very obese.

15 In

another study, rats fed a modified chow (powdered chow and sweetened condensed milk) along with several human snack foods also consumed significantly more calories and became obese.

17

There is no mention in any of these various studies of rats engaging in binge-like behaviors associated with addiction. Next, here are a couple of studies where chronic ad libitum diets have been switched after prolonged periods:

Study One:18 Rats were fed either a cafeteria diet (like ref. 17) or a standard chow ad libitum for 16 weeks. Half of each diet group was then switched to the other diet for 9 days. This one is worth including the graphs in Figure 2. The long term intake for Caf rats was roughly double that of Chow rats. Rats switched from Caf to Chow dropped intake below that of the long term intake of the Chow rats. Rats that had been accustomed to bland Chow? They appear to have gone a bit wild, roughly tripling their intake and exceeding habitual Caf intake by around 50% of what the Caf rats consumed long term!

Figure 2. Effect of switching diet on weight and intake.


Study Two:19 These rats were given the same diet as the low fat (refined carbohydrate, REF) diet in reference 15 or standard chow (CON) ad libitum for 6 months. The REF

rats gained roughly 20% more body weight CONs. At 6

months the rats were subjected to a lever pressing test to

ascertain motivation. After training to press a lever to

dispense sugar water, the number of lever presses required

for dispensing was progressively increased. The REF rats

demonstrated less motivation by taking longer between

attempts. This was repeated with plain water to the same

result. Nine days after the diet switch, the motivation test

was again conducted. The REF rats remained less motivated

despite consuming the CON diet, and vice versa with the

CON rats suffering no impaired motivation from the REF

diet.

To me, Study Two is one of those accidental gems where the researchers set out to prove some other beliefs, and never even

realized their results undercut another premise they appear to

hold dear. The REF diet is described as a human junk food diet

(when at such low fat levels it simply is not!) and junk foods are

described as addictive and obesogenic in the discussion of the

paper. Study One employed a more obesogenic human junk

food diet, yet there was no mention of addictive-like withdrawal behavior. It is conceivable that this was simply overlooked or not noted in that study, but in Study Two, the test

for motivation involved sugar, a purported addictive agent, as

reward for completing the task. If long term exposure to a 35% sucrose diet caused addiction, one would expect the rats to

be more highly motivated to obtain still more sugar, not less.

Further, when they were withdrawn for a period, one might

expect them to chew through the apparatus to get at the sugar, or

at least try! Instead, they showed less enthusiasm than the

presumably non-addicted rats, could care less if the reward was

water or sugar-water, and demonstrated the same lack of

motivation for the sugar water even after having been deprived

of their fix. This is very compelling evidence against sugar

addiction per se, straight from a study that would otherwise seem

to favor the food addiction paradigm.

So... What exactly does one have to do to evoke addiction-like behaviors in rats? Intermittent restriction of sugar, fat, or

combinations thereof. These are summarized nicely in a review

article by Avena et.al. entitled Sugar and fat bingeing have

notable differences in addictive-like behavior 20

Intermittent Sugar Water: By alternating access to sugar water to 12 hours on/off and delaying sugar access several

hours into the circadian feeding cycle, rats increase sugar

intake. They also binge the most in the first hour of access

and engage in larger meals during the access period than ad libitum fed rats. The rats compensate for the caloric

intake by decreasing chow intake (available ad libitum).

Thus total 24 hour intake remained the same as ad libitum

access rats and they remain normal weight.

Intermittent Fat Access: Rats will binge on shortening made available for only two hours a day. Interestingly,

restricting access to only 3 times per week leads to a greater

effect. Again, however, the rats compensate with reduced

chow intake and remain normal weight.

Sweet-fat intermittent restriction:21 Rats were provided only 2 hours of access per day to a sweet-fat chow with ad

libitum access to a standard (bland low fat) chow. After

three weeks, some rats were consuming almost 60% of their

total daily calories within those 2 hours. Although they

reduced chow intake during the other 22 hours, this was not

sufficient to offset binge intake completely, thus total intake

was greater, and these rats gained weight.

I find it amazing that Avena has co-authored a mass media diet

book entitled Why Diets Fail: Because Youre Addicted to Sugar, given her unique involvement in developing the methods

to elicit bingeing in rats.

Summary of the research

Taken together, these rat studies paint a picture that is rather

more simple that you might think, especially if youve ever found yourself stuck in the PubMed rat maze on this topic.

1. Sugar supplied in water or substituted for other carbohydrate in a standard rodent chow does not induce

overconsumption, but may lead to weight gain due to

food efficiency.

2. Fat replacing carbohydrate in substantial proportion in a standard rodent chow does not induce

overconsumption, but predictably leads to weight gain

due to food efficiency.

3. Sugar and fat together generally lead to modest weight gain due to food efficiency and/or mild increases in

intake due to increased palatability.

4. Sugar + fat + flavor = high palatability. This leads to considerable overeating and weight gain due to excess

consumption (food efficiency may be a factor as well).

General feeding behavior remains normal, however.

5. Intermittent access to sugar or fat can result in binge behavior, but rats compensate for the calories consumed

during binges. Thus, total intake remains the same and

the rats remain a normal weight.

6. Intermittent access to a more palatable sugar-fat chow, with free access to regular chow, leads to severe

binging in such a way that rats cannot completely

compensate for the caloric excesses by limiting intake

of regular chow. This leads to weight gain.

Similar observations to these have been made by various

researchers using various protocols. Although often

accompanied by impressive neurobiological and neurochemical

changes, as well as brain scans lit up like the sky on the Fourth

of July, the behaviors simply do not support a substance

dependence addiction model like that developed for alcohol and

cocaine, or even caffeine.

In the real world humans become addicted to such substances with a predictable pattern, though on differing timescales and/or

prevented limited exposure. The person engages in optional intake of a non-life sustaining, mind altering compound. With repeated exposure a tolerance develops thus requiring more of

the agent over time to produce the same effect. As intake

increases to compensate for the tolerance, a physical dependence


develops as the body/brain becomes accustomed to this new normal. If the substance is then removed, withdrawal symptoms ensue, sometimes quite severe, and even life-threatening,

producing strong cravings for the substance. Since withdrawal

symptoms are alleviated with consumption of the substance, this

drives the cycle of addiction. The evidence is simply not there to

support this mechanism for foods or their particular components

to result in physical dependence.

The take-away message

Im often asked what negative results such as those Ive laid out, provide people with in terms of actionable information. In this

current environment of pseudoscience and guru-speak gushing

from every corner of the media, I believe that there is benefit to

just presenting it at all. Consider it a deprogramming of sorts.

There is a lesson to be learned from these rats in terms of what

actually causes the addiction-like behaviors. It is restriction that triggers the physiological addiction cycle, such as it exists, with food. At least that is the conclusion that the research,

conducted by the proponents of the alternative concept, leads us

to.

____________________________________________________

Evelyn Kocur holds a B.S. in Biology from Rensselaer Polytechnic Institute and an M.S. in Materials Science (Metallurgy) from The University of Connecticut where she studied corrosion phenomenon. She is a former research scientist in the pharmaceutical and electronic materials industries and currently teaches college math and science. Following her personal interests in nutritional science, Evelyn

began blogging as CarbSane at The Carb-Sane Asylum in 2010 focusing on nutrition and diabetes research. Her first book, Restriction Addiction: Why the "cure" for food addiction may just be the cause, and how to break the cycle, is available at: http://carbsanity.blogspot.com/p/restriction-addiction.html

____________________________________________________

References

1. DSM-IV Alcohol Abuse and Dependence. Office of the Surgeon General (US); National Institute on Alcohol Abuse

and Alcoholism (US); Substance Abuse and Mental Health

Services Administration (US). Rockville (MD): Office of

the Surgeon General (US); 2007.

http://www.ncbi.nlm.nih.gov/books/NBK44358/

2. Randolph, TG. The descriptive features of food addiction; addictive eating and drinking. Q J Stud Alcohol. 1956 Jun;

17(2):198-224. [PubMed]

3. Overeaters Anonymous 4. Swinburn, B et.al. Increased food energy supply is more

than sufcient to explain the US epidemic of obesity. Am J Clin Nutr. 2009 Dec;90(6):1453-6. [PubMed] [Full PDF]

5. What Happens to Your Brain on Sugar, Explained by Science

6. Rats find Oreos as addictive as cocaine 7. Supersize Me 8. The Men Who Made Us Fat

9. Fat Head Movie 10. The Skinny on Obesity 11. http://en.wikipedia.org/wiki/Delirium_tremens 12. Feb. 2014 NYT Interview called Learning to Cut the Sugar

with Dr. Lustig, by Anahad OConnor. http://well.blogs.nytimes.com/2014/02/19/learning-to-cut-

the-sugar

13. Hopf, FW et.al. Motivation for alcohol becomes resistant to quinine adulteration after 3-4 months of intermittent alcohol

self-administration. Alcohol Clin Exp Res. Sep 1, 2010;

34(9): 15651573. [PubMed] 14. Loi, B et.al. Increase in alcohol intake, reduced flexibility

of alcohol drinking, and evidence of signs of alcohol

intoxication in Sardinian alcohol-preferring rats exposed to

intermittent access to 20% alcohol. Alcohol Clin Exp Res.

2010 Dec; 34(12):2147-54. [PubMed]

15. Sampey, BP et.al. Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose

Inflammation: Comparison to High-Fat Diet. Obesity.

2011 June;19(6): 11091117. [PubMed] 16. Woods, SC et.al. A Controlled High-Fat Diet Induces an

Obese Syndrome in Rats. J. Nutr. 2003 April; 133(4):

1081-1087. [PubMed]

17. Hansen, MJ et.al. Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high-fat feeding in

the rat. J. Neurochem. 2003 Dec; 88(4): 909-916.

[PubMed]

18. South, T et.al. Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean

rats from chow to a palatable diet. Physiol Behav. 2012 Feb

28;105(4):1052-7. [PubMed]

19. Blaisdell, A et.al. Food quality and motivation: A refined low-fat diet induces obesity and impairs performance on a

progressive ratio schedule of instrumental lever pressing in

rats. Physiol Behav. 2014 Apr 10;128:220-5. [PubMed]

20. Avena, NM et.al. Sugar and Fat Bingeing Have Notable Differences in Addictive-like Behavior. J Nutr. 2009

Mar;139(3): 623628. [PubMed] 21. Berner, LA et.al. Bingeing, Self-restriction, and Increased

Body Weight in Rats With Limited Access to a Sweet-fat

Diet. Obesity. 2008 Sept; 16(9): 19982002. [PubMed]


Processed foods: contributions to nutrition.

Weaver CM, Dwyer J, Fulgoni VL 3rd, King JC, Leveille GA,

Macdonald RS, Ordovas J, Schnakenberg D. Am J Clin Nutr.

2014 Apr 23. [Epub ahead of print] [PubMed]

My commentary

As a scientific statement by the American Society for Nutrition (ASN), this paper is not conducive to the typical critique of strengths and limitations inherent in experimental studies. Its essentially an updated review of the state of the science. The reason it jumped out at me when choosing literature to review is because the term processed foods carries strongly negative connotations, and much of this vilification is simply not warranted. Its true that food processing in certain cases has indeed created problems, particularly in cases of overconsumption of highly refined food products displacing whole & less-refined foods. However, processing has also contributed significantly to the improvement of human health. The latter is widely overlooked, especially with the constant barrage of sensationalistic media messages that are universally against food processing. The chart below (Table 5 in the text) summarizes the wide array of consumer benefits of current and developing food processing technologies. Notice that a recurring benefit is the enhancement of well-being and quality of life.

One aspect that rings loudly with me personally is the ability of food processing technology to optimize nutrition for populations such as infants, pregnant mothers, and the elderly. Also, through the isolation of various compounds, food processing technology has played a tremendous role in not just the enhancement of athletic performance through supplementation, but for populations at risk for essential nutrient deficiencies. A recent review by van Boekel et al list the most important benefits of food processing as follows:

1

Food safety (pathogens): The main benefit of food processing is inactivation of food-borne pathogens, as is normally required by Food Safety Legislation.

Food safety (other aspects): inactivation of natural toxins and enzymes, prolongation of shelf-life.

Nutritional value: improved digestibility, bioavailability of nutrients.

Sensory quality: taste, texture and flavor. Functional health benefits: e.g. probiotics, prebiotics,

Maillard reaction products (MRPs), flavonoids, other food constituents and their reaction products.

Convenience: availability of ready-to-eat and semiprepared foods, e.g. microwavable frozen meals.

Cost: economy of scale Diversity: independence from the seasonal availability of

foods, and introduction of global food supply chain. Quality of life: improved because less time required for food

supply and preparation.


The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study.

Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM,

Stout JR, Duncan N, Fuller JC, Baier SM, Naimo MA,

Rathmacher J. Eur J Appl Physiol. 2014 Mar 6. [Epub ahead of

print] [PubMed]

INTRODUCTION: Studies utilizing beta-hydroxy-beta-

methylbutyrate (HMB) supplementation in trained populations

are limited. No long-term studies utilizing HMB free acid

(HMB-FA) have been conducted. Therefore, we investigated the

effects of 12 weeks of HMB-FA supplementation on skeletal

muscle hypertrophy, body composition, strength, and power in

trained individuals. We also determined the effects of HMB-FA

on muscle damage and performance during an overreaching

cycle. DESIGN: A three-phase double-blind, placebo- and diet-

controlled randomized intervention study was conducted. Phase

1 was an 8-week-periodized resistance-training program; Phase

2 was a 2-week overreaching cycle; and Phase 3 was a 2-week

taper. Muscle mass, strength, and power were examined at

weeks 0, 4, 8, and 12 to assess the chronic effects of HMB-FA;

and assessment of these, as well as cortisol, testosterone, and

creatine kinase (CK) was performed at weeks 9 and 10 of the

overreaching cycle. RESULTS: HMB-FA resulted in increased

total strength (bench press, squat, and deadlift combined) over

the 12-week training (77.1 18.4 vs. 25.3 22.0 kg, p < 0.001);

a greater increase in vertical jump power (991 168 vs.

630 167 W, p < 0.001); and increased lean body mass gain

(7.4 4.2 vs. 2.1 6.1 kg, p < 0.001) in HMB-FA- and placebo-

supplemented groups, respectively. During the overreaching

cycle, HMB-FA attenuated increases in CK (-6 91 vs.

277 229 IU/l, p < 0.001) and cortisol (-0.2 2.9 vs.

4.5 1.7 g/dl, p < 0.003) in the HMB-FA- and placebo-supplemented groups, respectively. CONCLUSION: These

results suggest that HMB-FA enhances hypertrophy, strength,

and power following chronic resistance training, and prevents

decrements in performance following the overreaching.

SPONSORSHIP: this research was funded in part through a

grant from Metabolic technologies Inc. JMW, rPl, JMJ, JcA, and

SMcW declare no competing interests. Jr, JF, and SB are

employed by Metabolic technologies, Inc.

Study strengths

This study is innovative since its the first to ever examine the chronic effects of the free acid form of HMB (HMB-FA) in

trained subjects on a monitored, periodized resistance training

program. Blinding was meticulous on both sides of the

experiment. The design was also unique since its the first to include an over-reaching period (in addition to the other novel

conditions). The authors provided the details of the training

program in a supplemental document (downloadable here, full

study PDF here). Diet was standardized and designed by a

registered dietitian who counseled the subjects throughout the

study. Compliance with supplementation was over 98%.

Study limitations

The authors did not specifically acknowledge any limitations of

their study. This is odd, since its pretty much standard practice to do so, even if the limitations are disclaimed in the same breath

(which is common as well). A limitation that is not noted in the

text but is noted by the lead author in this video (starting from 17

inutes in) is the following:

These [subjects] were very unique individuals. What we did was put them through the most brutal protocol you can imagine possible. I cant even describe how brutal this protocol is. And so what we did was for an entire semester, we filtered through individuals we felt that were mentally and physically able to withstand this brutal bout of training. [...] All these guys were genetically outstanding, you could tell they had full muscle bellies, they were essentially jacked. You could tell that they were extreme responders to training. Now, in most studies you just recruit anybody, and you could have non-responders, moderate responders, high-responders. We filtered so we had purely high-responders to training.

This highly selective recruitment process places severe

limitations on the extrapolability of the outcomes to other

subjects who arent necessarily genetically gifted for size and strength gains. Its possible that the results seen in this study are only achievable in a very narrow segment of the trained

population with extraordinarily high mental fortitude and

physiological responsiveness to extremely rigorous training. One

population of relevance could be the military (especially elite

forces on prolonged missions), who are subjected to extreme

conditions and constant over-reaching.

The next limitation I want to point out involves the reporting of

the data. As seen in the data tables (full study here), the standard

deviations are identical at all time points between the control and

intervention group in every variable at multiple testing sessions.

Ive personally never seen anything like it, and Ive seen plenty of data tables in the sports nutrition literature. When questioned

about this on the ISSNs Facebook page, lead author Jacob Wilson responded that, ...we used a covariant analysis and reported the adjusted means as was requested by the reviewers.

This is very very common in the scientific papers. I asked James Krieger (the stats wiz behind the recent protein timing

meta-analysis I did with him & Brad Schoenfeld) for his

feedback, and heres what he said:

It looks like they are reporting the pooled standard deviation, which is unusual to report but does not indicate their statistical analysis is flawed. I dont see anything wrong with the stats that they ran. There are ways to get variance data at each time point (rather than a pooled variance) using SAS (which is what they used) even if you report adjusted means. Im surprised the reviewers let them just go with the pooled SD, which is not very meaningful when examining the outcomes.

A final limitation Id like to point out is the omission of testosterone data from the manuscript. This is unfortunate since

the dramatic results of the subjects raised questions about

anabolic steroid use. The manuscript states that there were no


significant changes in free or total testosterone, but no data are

listed in support. Luckily, in a heated Facebook debate where

this data was demanded, Wilson graciously provided it:

As seen above, all subjects total testosterone levels were all within normal range throughout the trial.

Comment/application

The main findings were that HMB-FA increased strength by

more than threefold that of placebo (vertical jump increased

markedly as well), both groups gained LBM (although

insignificantly in the placebo group), and both lost fat (although

insignificantly in the placebo group). Below are the numbers:

The HMB group had a remarkable LBM gain of 7.4 kg (16.28

lb) while dropping 3.5 kg (7.7 lb) body fat. In contrast, the

placebo group gained 2.1 kg (4.62 lb) LBM while losing 1.7 kg

(3.74 lb) body fat. These are both favorable scenarios, but

clearly the HMB groups results especially the LBM gain is nothing short of astounding. What makes it particularly

impressive was that these subjects were resistance-trained; they

were not novices primed for huge leaps in muscle size and

strength.

The LBM gains seen in the present study have been met with

severe skepticism since theyre superior to what has been observed by Bhasin et al,

2 whose subjects were on a

supraphysiological dose of testosterone (600 mg/week).

However, its important to note that dramatic results from HMB are not completely anomalous. What Wilson et al saw is

essentially a replication of Kraemer et als 2009 study,3 which also reported spectacular changes in body composition,

including similar gains in LBM to those seen in the present

study. However, their subjects were not trained, so dramatic

results are less surprising (as opposed to the present study, where

the trained subjects were closer to their potential for muscle

mass). Furthermore, Kraemer et al used calcium HMB, whereas

the free acid form was used in the present study.

The present study has been referred to as an example of one that

defies the rule that only overweight novices can experience a

significant degree of simpultaneous fat loss and muscle gain

(A.K.A. recomposition or recomp). However, despite the subjects being trained, Im not surprised that recomp occurred in both groups. Both the HMB and placebo groups began the trial

at approximately 21% body fat, which is not particularly lean.

On a final note, HMB has an equivocal track record of

effectiveness, as shown in a recent review by Zanchi et al (their

table of studies shows considerable hit & miss).4 Wilson et al

would probably argue that theres a scarcity of studies examining the effect of HMB within the context of sufficiently

rigorous, periodized training program of sufficient length.


Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. BMJ. 2014

Apr 1;348:g2035. [PubMed] [Full Text]

OBJECTIVE: To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. DESIGN: Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. DATA SOURCES: Medline, Embase, and screening of citations and references. ELIGIBILITY CRITERIA: Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). RESULTS: 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. CONCLUSIONS: Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. SPONSORSHIP: The authors did not receive funding.

Study strengths

This is the largest analysis of vitamin Ds clinical outcomes ever done: 107 systematic literature reviews, 74 meta-analyses of

observational studies, and 87 meta-analyses of randomized

controlled trials (RCTs). Its rare to see analyses of this breadth since, frankly, its a hell of a lot of work. This analysis provides a relatively comprehensive summary of the existing literature. It

also attempted to account for the extent of bias and

heterogeneity in the observational vitamin D literature.

Study limitations

As acknowledged by the authors, the analysis was unable to

assess the relationship between vitamin D supplementation dose

and effect size in RCTs. Furthermore, the effect of different

choices of comparison groups or of varying vitamin D

distributions and median differences of the observational studies

could not be assessed either. Importantly and as a general

principle of pooled study data the quality of the analysis is dependent on the quality of the studies comprising it. Quoting

the authors, ...some health related outcomes were poorly covered, and we have flagged this gap.

Comment/application

The salient finding of this umbrella analysis was a lack of support for the effectiveness of vitamin D supplementation on its

own to do what its most commonly touted for increasing bone mineral density & reducing risk of fractures. The essence of the

general findings are well-captured in this excerpt of the

discussion:

Vitamin D might not be as essential as previously thought in maintaining bone mineral density. [...] The lack of convincing associations and the relative dearth of probable associations (table 6) suggest that evidence for benefits that may be reaped from population-wide vitamin D supplementation is weak. Probable associations, where highly significant effects appear in randomised trials, hold the most promise for clinical translation, but they pertain to specific populations (children, pregnant women, patients with chronic kidney disease), and even in these cases the evidence is not sufficient to make universal recommendations about daily intake.

Seeing that this conclusion is at odds with a sizable body of

literature suggesting of the benefits of vitamin D

supplementation,5-10

I contacted Dr. Michael F. Holick, who is

perhaps the most prolific and renowned vitamin D researcher in

the world. Heres his emailed response to me regarding the umbrella review by Theodoratou et al:

There continues to be a lot of misinformation written by people who have little or no experience in the field of vitamin D but somehow believe that they can write about it. Please see the enclosed letter I recently wrote regarding another meta-analysis that was flawed.

Holick attached a letter of dissent (full text here),11

which

includes the following primary counterpoints:

The medical model of evidence was used to assess the evidence of the health benefits of vitamin D, which is not

necessarily appropriate for natural compounds.

The more appropriate way to establish causality is through application of Hill's criteria for causality in a biological

system.

Most RCTs were poorly designed and had poor compliance, thus compromising the detection of a beneficial effect.

By claiming that, the hypothesis that variations in 25(OH)D concentrations would essentially be a result, and

not a cause, of ill health and inflammation, the authors would also have to pre-suppose inverse correlations between

solar UVB doses and cancer incidence and mortality rates

noted in ecological studies were due to confounding factors.

Their hypothesis connecting ill health and inflammation as the cause for reduction in blood concentrations of 25(OH)D

is flawed and lacking supporting literature, which the

authors misrepresented in attempt to substantiate this claim.


Variability in muscle size and strength gain after unilateral resistance training.

Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB, Hoffman EP, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Clarkson PM. Med Sci Sports Exerc. 2005 Jun;37(6):964-72. [PubMed]

PURPOSE: This study assessed variability in muscle size and strength changes in a large cohort of men and women after a unilateral resistance training program in the elbow flexors. A secondary purpose was to assess sex differences in size and strength changes after training. METHODS: Five hundred eighty-five subjects (342 women, 243 men) were tested at one of eight study centers. Isometric (MVC) and dynamic strength (one-repetition maximum (1RM)) of the elbow flexor muscles of each arm and magnetic resonance imaging (MRI) of the biceps brachii (to determine cross-sectional area (CSA)) were assessed before and after 12 wk of progressive dynamic resistance training of the nondominant arm. RESULTS: Size changes ranged from -2 to +59% (-0.4 to +13.6 cm), 1RM strength gains ranged from 0 to +250% (0 to +10.2 kg), and MVC changes ranged from -32 to +149% (-15.9 to +52.6 kg). Coefficients of variation were 0.48 and 0.51 for changes in CSA (P = 0.44), 1.07 and 0.89 for changes in MVC (P < 0.01), and 0.55 and 0.59 for changes in CSA (P < 0.01) in men and women, respectively. Men experienced 2.5% greater gains for CSA (P < 0.01) compared with women. Despite greater absolute gains in men, relative increases in strength measures were greater in women versus men (P < 0.05). CONCLUSION: Men and women exhibit wide ranges of response to resistance training, with some subjects showing little to no gain, and others showing profound changes, increasing size by over 10 cm and doubling their strength. Men had only a slight advantage in relative size gains compared with women, whereas women outpaced men considerably in relative gains in strength. SPONSORSHIP: National Institutes of Health Grant no. 5R01NS040606-03.

Study strengths

The large number of subjects (585 total) heightened statistical power and allowed a comparison of gender differences. Cross-sectional area (CSA) of the upper arm musculature was measured via magnetic resonance imaging (MRI), as opposed to merely circumference, which cannot distinguish between lean and fat tissue. Training was periodized, with reps beginning at 12 RM and progressing to 6 RM. All of the assessment and training techniques/protocols were videotaped and shared by all the sites in order to standardize the methods as much as possible.

Study limitations

Subjects over 40 years-old were excluded from the study, leaving open questions about the applicability of these outcomes to older populations. Dietary control was minimal, aside from the instruction to maintain usual habits. It would have been helpful to analyze the macronutrient composition of subjects habitual intake, since variations especially in protein intake can significantly impact gains in muscle size and strength during resistance training programs.

12,13 Its possible that the results

could be limited to the untrained population, as well as the training protocol used on the targeted muscles (3 exercises for the biceps, 2 exercises for the triceps, 3 sets per exercise). Sessions per week were not specified which is unfortunate since that leaves us with a very vague idea of total volume.

Comment/application

As depicted above, out of the 585 subjects, 232 showed a 15-25% increase in CSA, 10 particularly high responders experienced over a 40% increase in CSA, while on the opposite end of the spectrum, 36 subjects showed less than a 5% increase in CSA. The range of size changes was notable due to an actual decrease in CSA on the low end of the range (-2 to +59%). Formal examination of individual dietary intake would likely have explained any drop in CSA, but the range of responses is strikingly broad nevertheless. Men had 2.5% greater gains in CSA than women. Next up are the strength effects.

Out of the 585 subjects, 232 subjects 232 showed a 40-60% increase in 1 RM, 36 high responders showed over 100%, and 12 unfortunate subjects had less than a 5% increase in 1 RM. Men had greater variability in isometric strength gains, while womens gains varied more greatly in dynamic strength. Women experienced greater gains in strength, while men had slightly greater gains in size. It would be interesting to see this experiment done on trained subjects. Testosterone levels were not associated with CSA variability. The authors attribute this to the subjects 40-year age cutoff, citing a review by Matsumoto14

suggesting that functionally significant age-related decreases in testosterone levels do not occur until roughly age 60 and up.


1. van Boekel M1, Fogliano V, Pellegrini N, Stanton C, Scholz

G, Lalljie S, Somoza V, Knorr D, Jasti PR, Eisenbrand G. A review on the beneficial aspects of food processing. Mol Nutr Food Res. 2010 Sep;54(9):1215-47. [PubMed]

2. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul 4;335(1):1-7. [PubMed]

3. Kraemer WJ1, Hatfield DL, Volek JS, Fragala MS, Vingren JL, Anderson JM, Spiering BA, Thomas GA, Ho JY, Quann EE, Izquierdo M, Hkkinen K, Maresh CM. Effects of amino acids supplement on physiological adaptations to resistance training. Med Sci Sports Exerc. 2009 May;41(5):1111-21. [PubMed]

4. Zanchi NE1, Gerlinger-Romero F, Guimares-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH Jr. HMB supplementation: clinical and athletic performance-related effects and mechanisms of action.Amino Acids. 2011 Apr;40(4):1015-25. [PubMed]

5. Grber U, Spitz J, Reichrath J, Kisters K, Holick MF. Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermatoendocrinol. 2013 Jun 1;5(3):331-347. [PubMed]

6. Wacker M, Holick MF. Vitamin D - effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013 Jan 10;5(1):111-48. [PubMed]

7. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108. [PubMed]

8. Holick MF. Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets. 2011 Jan;12(1):4-18. [PubMed]

9. Cranney A1, Weiler HA, O'Donnell S, Puil L. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. [PubMed]

10. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71. [PubMed]

11. Holick MF, Grant WB. Correspondence: Vitamin D status and ill health. The Lancet Diabetes & Endocrinology, Volume 2, Issue 4, Pages 273 - 274, April 2014 [Lancet]

12. Schoenfeld BJ, Aragon AA, Krieger JW. The effect of protein timing on muscle strength and hypertrophy: a meta-analysis. J Int Soc Sports Nutr. 2013 Dec 3;10(1):53. [PubMed]

13. Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Dec;96(6):1454-64. [PubMed]

14. Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A Biol Sci Med Sci. 2002 Feb;57(2):M76-99. [PubMed]


Protein: is it really as bad as they say it is?

By Dylan Klein

____________________________________________________

Introduction & background

Early last March a provocative study published by Levine et al1

in the prestigious Cell Metabolism has really shaken up the

nutritional science world ever since one of the authors of the

study suggested that eating a diet higher in protein is potentially

more harmful than smoking cigarettes. Talk about rustling some

jimmies!

Now, before we go any farther, lets keep one thing in mind: this was not a randomized controlled trial wherein participants were

randomly assigned to either high or low protein groups and

followed for a period of time at which point various health

outcomes could be tallied and assessed. No, instead this study

was part epidemiological and part rodent research, each of which

has their own serious limitations when extrapolating to health

policy and human physiology. That being said, Levine et al

reported that in people aged 50-years and over, moderate and

high protein intakes were associated with increased type 2

diabetes mortality, but not cardiovascular disease (CVD),

cancer, or all-cause mortality. However, when the study

population was split into persons aged 50-65 and those 66 and

over, high and moderate protein intakes were associated with

increased mortality from cancer and all-causes in the 50-65 age

group, but not the latter. In addition, when animal protein was

accounted for, the harmful associations between protein intake

and mortality risks disappeared, suggesting that animal proteins,

and not plant-based proteins, are potentially harmful at higher

intakes during middle-age. With respect to those over 65, it

appears that higher protein intake had a protective effect and was

not associated with increased disease mortality risk, save type 2

diabetes. But wait, theres more!

In subsequent analysis the investigators looked at insulin-like

growth factor-1 (IGF-1) and its association with protein intake

and mortality risks. In recent years insulin and IGF-1 have been

suggested to contribute to the pathogenesis of cancer, due to

their similar intracellular signaling pathways and downstream

effects on various targets that favor cell survival rather than

death.2 Therefore, cells which should probably die are instead

salvaged and are at an increased likelihood of becoming

cancerous through various metabolic reprogramming mechanisms. This has prompted a recent interest in examining

the potential therapeutic effects of low-carbohydrate and/or

ketogenic diets in treating cancer due to their ability to

drastically reduce serum levels of glucose and insulin3 two

factors that are predictive of future cancer risk and cancer-

related mortality.4-6

The current study, however, chose to focus

only on protein and IGF-1. So, what did the researchers find?

They found that IGF-1 levels were positively associated with

protein intakes and that for every 10ng/mL increase in IGF-1 for

those ages 50-65, mortality risk of cancer increased by about

9%. No association was observed in those over 65. But thats not all!

Next, the investigators used a mouse model to confirm that their

associations were more than just associations. In doing so, a

relatively standard mouse strain (C57BL/6) was split into two

groups that were given isocaloric diets, either high or low in

calories from protein. Next, these mice were artificially given

cancer via a subcutaneous injection of murine melanoma cells.

The researchers then tracked tumor growth/progression in the

high and low protein groups. At the end of study period, it was

shown that the tumors from the mice on the high protein diet

grew much faster and were much larger than the tumors from the

mice consuming the low protein diet. Moreover, mice in the low

protein group had significantly lower serum IGF-1 and

significantly higher levels of IGF-binding protein-1 (IGFBP-1; a

binding protein that doesnt allow IGF-1 to bind to its receptor and exert its effects). In addition, using a second genetically-

modified mouse model (GHRKO) that lacked both the growth

hormone receptor and IGF-1, tumor progression was strongly

inhibited compared to control mice that did have both the

receptor and the normal levels of the hormone. In aggregate,

these rodent models suggest that IGF-1 and its downstream

signaling pathways are likely contributing to tumor progression

and the increase in cancer mortality. Moreover, by reducing

protein intake one can potentially limit the growth of cancerous

tumors.

While there was even more going on in the recent study (you

never get off easy with a Cell paper) Im not going to bore you to tears with the rest of the article. The bottom line is, to quote

the concluding remarks of the authors:

Overall, our human and animal studies indicate that a low protein diet during middle age is likely to be beneficial for the

prevention of cancer, overall mortality, and possibly diabetes

through a process that may involve, at least in part, regulation

of circulating IGF-1.

My take on the matter First off, and I know Im preaching to the choir, correlation does not equal causation. While epidemiological data may show

interesting associations as well as lay the groundwork for future

research, it does not show cause and effect. Second, speaking of

cause and effect, there are absolutely no well-controlled,

randomized trials looking at protein intake and either cancer

mortality, type 2 diabetes mortality, or overall mortality in any

aged population, regardless of health status. Lastly, rodent

research needs to be taken with a grain of salt. While rodents do

serve a vital role in medical and nutrition research, the data

should not be blindly extrapolated to humans and formulated


into health policy until a substantial body of evidence has

accrued. This, however, is not the case. Therefore, if we are to

evaluate this study based on the aforementioned criteria, I see

nothing to convincingly sway my mind that protein is in any way

shape or form harmful to health and I havent even gotten to the substantial methodological weaknesses contained within the

paper itself; which is exactly what we will get to next!

I'm not upset that you lied to me, I'm upset that from now on I can't believe you.

Perhaps the greatest short-coming of the recent paper (and

believe me, there is plenty), is the investigators reliance on NHANES food recall data. To help illustrate the absolute futility

of the NHANES survey, a press release last October regarding a

recent study looking at the validity of NHANES food intake data

reads, 40 years of federal nutrition research fatally flawed. And while it might seem like a bit of an over exaggeration, I

think I can convince you that it most certainly is not.

First off, for those unaware, NHANES stands for National

Health and Nutrition Examination Survey and, to quote the CDC

directly:

[It is] designed to assess the health and nutritional status of adults and children in the United States [] The NHANES interview includes demographic, socioeconomic, dietary, and

health-related questions. The examination component consists of

medical, dental, and physiological measurements, as well as

laboratory tests administered by highly trained medical

personnel. Findings from this survey [are] [] used in epidemiological studies and health sciences research, which

help develop sound public health policy, direct and design

health programs and services, and expand the health knowledge

for the Nation.

The key thing to know here is that all dietary information is

recorded as part of a one-time, 24-hour dietary recall. During

this process participants try to accurately recall their previous

days dietary intake under the supervision of a trained dietitian. From this survey total calories, protein, carbohydrate, and fat are

calculated, as well as a whole host of other dietary estimations.

Thus, the entire validity of the NHANES survey rests upon the

respondents ability to accurately and truthfully recall their previous days nutrition. Yeah, you can see where this is headed

The reason why NHANES is fatally flawed

In an effort to see just how valid NHANES diet recall data really

is, Archer et al7 analyzed the 39-year history of the multiple

NHANES surveys (from 1971 through 2010) and compared

those intakes to what they estimated to be realistic total daily

energy expenditures for men and women based on the Schofield

predictive equations plus an additional activity factor of 1.35.

Anything reported below this value was deemed not physiologically credible. So, what did Archer and company find?

What they found was that during the almost four decades-long

history of the NHANES, the mean reported energy intakes for

women were below physiologically plausible in every single one

of the nine NHANES studies. Men, however, did manage to

provide mean energy intakes that were plausible in three of the

nine studies unfortunately Levine et al used recall data from one of the six that didnt. Furthermore, at no point during those 39 years did more than 43% of overweight and obese women

and 49% of overweight and obese men report realistic energy

intakes. The mean amount of caloric underreporting for women

was about -365kcals while men underreported by about -

281kcals.

This, however, should come to no surprise. Studies comparing

24-hour dietary recalls to doubly-labeled water have shown time

and time again that respondents, especially overweight and

obese subjects, underreport their energy intakes.8 Moreover,

studies using metabolic biomarkers have also shown that

compared to urinary nitrogen measurements, respondents also

misreport their protein intakes (i.e. over- or under-report);9-11

which brings me back to the Cell Metabolism study.

By using NHANES dietary recall data, the researchers were

assuming that a single, 24-hour dietary recall which has been shown to be highly inaccurate with regards to both energy and

protein intakes was 1) accurate, and 2) representative of the respondents diets for the next 18 years! Thats right, mortality data was accessed for subjects at 18 years post interview with

not a single follow-up measurement of dietary intake in between.

I dont know about you, but I dont possess that kind of faith nor would I try to suggest that protein is more harmful that

smoking cigarettes when the only data Im using to compare diet and mortality is completely laughable. Therefore, in my eyes,

this study does a horrible job at trying to pin mortality risk on a

single macronutrient which by itself is just outright ridiculous.

"There are three kinds of lies: lies, damned lies, and

statistics."

Moving on to Levine et als analysis of the mortality data, I will simply quote the remarks from a scathing unpublished (read:

rejected) letter-to-the-editor, written by an all-star team of

protein researchers, namely Donald Layman, Arne Astrup, Peter

Clifton, Heather Leidy, Douglas Paddon-Jones, and Stuart

Phillips. Their critique reads:

[Levine et al.] used Hazard Ratio (HR) analysis and concluded that the [high protein] group had a 73-fold increased risk of

dying from diabetes. The HR and confidence interval (CI) were

reported as 73.52 (4.47 1,209.70). To our knowledge, that is the highest HR ever reported for any dietary component and

certainly for one within dietary guidelines of the [Institutes of

Medicine]. The CI with a 400-fold range and an upper value of

1,209.70 with 6-significant figures of accuracy is not credible.

Hazard Ratio analysis is a standard method for clinical studies

with equal treatment groups and survival as a primary outcome,

but have important a priori criteria for their use: 1) equal size

groups, 2) no evidence of selection or group bias, and 3) linear

outcomes over time. The present study fails to meet all three

criteria.

Indeed, with respect to a priori 1, there were 436 persons in the

low protein group, 4,800 persons in the moderate protein group,


and 1,145 persons in the high protein group when comparing

protein intakes to mortality risk. Not quite equal size groups by

any stretch of the imagination. Thus, coupled with laughable

dietary recall data we have highly biased and inappropriate

statistical analysis leading to misleading results about diet and

mortality. It appears that Mark Twain was right after all.

A brief break from reality

Now that weve established that NHANES is basically useless when it comes to drawing any meaningful relationships between

diet and disease mortality, along with the authors untenable statistical analysis that would make anyone wonder how this

paper got published in the first place, lets for a moment suspend reality and take at face value the findings of Levine et al If we

are to take such a huge leap of faith, then the next obvious

question to ask is, what does the rest of the literature say on the subject? That is to say, what are the associations between protein and overall, cancer, and type 2 diabetes mortality? Well,

folks, youre in luck, because thats exactly where Im going next!

Protein and all-cause mortality

First, lets start with protein and all-cause mortality. In a recent 2013 systematic review and meta-analysis of the available

observational research looking at low-carbohydrate as well as

low-carbohydrate, high-protein diets (LCHP),12

it was shown

that both types of diets are associated with an increased risk of

overall death. While you may be spitting out your bullet-coffee

right now, keep in mind that this isnt to condemn protein, per se. Due to the nature of a LCHP diet, or any diet wherein you

manipulate macronutrient content, you cant simply say that its the increase in protein thats leading to increased mortality and neglect the fact that you also reduced carbohydrate intake as

well. Moreover, this was a meta-analysis of observational

studies only; there is absolutely no well-controlled randomized

data to support the contention that higher protein intakes lead to

increased mortality. Thus, as it stands now, there is no

convincing data to suggest lowering your protein intake to

increase your chances of living a longer and healthier life. In

fact, a good case can be made for many different populations to

consume more protein than what is suggested by the RDA13

a topic that Ive covered previously on my site.

Levine et al also caution the intake of animal-based proteins in

favor of plant-based proteins due to the fact that they observed

no apparent mortality risk when animal protein was controlled

for. While some research may suggest that vegetarian and/or

vegan diets may confer additional health benefits, such as a

longer lifespan, the fact of the matter is that vegans and

vegetarians also take part in a whole host of other healthful

things, such as not smoking, not drinking, actually eating fruits

and vegetables, and most importantly, exercising.14-16

The fact

that they eat less animal products has nothing to do with their

supposed increased longevity and better health. Indeed, when

health-conscious meat-eating individuals are compared to vegans and vegetarians, there is absolutely no difference in

overall mortality rates.17

Therefore, its not the meat that is detrimental to health; rather, its the lifestyle that meat-eaters tend to follow (in general) that imposes negative health

outcomes. As a matter of fact, some research suggests that

vegetarians are actually less healthy in terms of cancer, allergies,

and mental health disorders, as well as experiencing a poorer

overall quality of life compared to individuals who do eat

animal-based protein.18

Thus, when other healthful

characteristics are controlled for, there is absolutely no benefit to

eating plant-based proteins in terms of overall mortality or

general health.

Protein and cancer mortality

Not surprisingly, the literature here is considerably lacking well-

controlled randomized research. Nevertheless, in a recent 2013

systematic review19

the authors examined five different cohorts from five different observational studies and concluded that the

research looking at protein and cancer mortality is, so far,

inconclusive. Similar conclusions were made about protein

intakes and risk of developing various types of cancers. So

again, there is absolutely no convincing evidence to suggest

lowering ones intake of protein in order to reduce the risk of dying from disease.

Regarding Levine et als rodent model that showed a high-protein diet increases tumor size and growth, it should be noted that there is contradictory rodent evidence to suggest that increasing protein intake along with decreasing carbohydrate intake can actually significantly inhibit tumor size and growth, contrary to what was shown in the current study. Indeed, in 2007 a group of Canadian researchers

20 showed that, in mice injected

with human prostate cancer cells, a diet higher in protein (45% of total calories) and lower in carbohydrate (10% of total calories) led to significantly lower tumor volume and tumor volume-to-bodyweight ratios after 9-weeks compared to a diet high in carbohydrate (40% of total calories) and lower in protein (10% of total calories). Moreover, the high-protein diet also had significantly lower levels of plasma insulin/IGF-1, as well as protein levels of phosphorylated Akt (an indicator of insulin/IGF-1 signaling) in tumor cell lysates. This is diametrically opposite of what Levine et al propose.

More recently, in 2011 Ho et al21

showed that tumor progression is significantly inhibited by a high-protein (58% of total calories) low-carbohydrate (15% of total calories) diet compared to a more Westernized diet with ~23% of calories from protein. Based on these studies it would seem that high intakes of protein do not necessarily promote tumor progression but can actually be part of a diet that slows tumor growth granted that carbohydrate intake is also reduced. It should be noted, however, that these studies did differ in methodology, in both the strains of mice used, as well as the types of cancerous cells that were injected; therefore, it is hard to accurately compare study outcomes. Nonetheless, the assertion that high protein intakes increase cancer mortality risk or promote tumor progression is far from settled science.

Protein and type 2 diabetes

Lastly, lets take a look at the literature surrounding protein intake and type 2 diabetes. In clinical trials, increasing the protein to carbohydrate ratio during a weight loss diet has been shown to improve glucose regulation in both obese

22 and type 2

diabetic subjects,23-26

sometimes even better than traditional


weight loss diets that impose similar weight reductions.27,28

Moreover, it has even been shown that higher protein diets improve glucose homeostasis in type 2 diabetics without weight loss.

29,30 When a structured exercise program is thrown into the

mix something considerably lacking in the conversation about health and disease overall higher protein lower carbohydrate diets can be equally, if not more, effective at improving blood glucose levels after 12 weeks.

31 Finally, in a 2012 meta-analysis

it was shown that LCHP diets were no worse than lower protein higher carbohydrate diets at reducing HbA1c, fasting blood glucose, and fasting plasma insulin levels,

32 while a 2013 meta-

analysis showed that there was a significant decrease in HbA1c in persons who consumed higher protein diets.

33 Thus, it appears

that, compared to lower protein intakes, higher protein diets can be just as effective, if not more so, at controlling and/or improving type 2 diabetes.

As far as contradictory evidence that suggests that low-carbohydrate and/or high total/animal protein diets might increase the risk of type 2 diabetes, all such studies are observational in methodology and do not indicate cause and effect.

34-38 We do know, however, that diets higher in

total/animal protein tend to be associated with lower fruit and vegetable intake and higher intakes of processed foods and sugars (i.e. all the makings of a crappy diet). Indeed, in a recent meta-analysis looking that the link between dietary patterns and type 2 diabetes risk,

39 it was shown that diets that conformed

more to what would be considered a healthy diet (i.e. less processed grains and more fruits and vegetables) was associated with reduced risk of type 2 diabetes while diets that were considered unhealthy (i.e. higher in processed grains/meats and refined sugars) were associated with increased risk of type 2 diabetes. What this goes to show is that having a well-balanced diet is probably more important than limiting or increasing a single macronutrient without regard to the rest of your daily intake. In the end, a crappy diet is a crappy diet. I dont care how much protein you are or arent eating.

Wrapping up

In the end, it doesnt look like the recent Cell Metabolism study is anything to lose sleep over. Horrible study methodology paired with biased statistics and a body of shabby inconclusive and/or contradictory observational research suggests that reducing your protein intake should be the last thing on your list of dietary amendments (no comment about Alans PAP!).

And with that I will leave you with the concluding remarks from the aforementioned unpublished letter-to-the-editor, written by Layman et al:

Our overall assessment of [the Cell Metabolism] paper is that the conclusions and analyses are biased and flawed. While there is growing consensus that a moderate protein intake between 1.0 and 1.5 g/kg/d may confer health benefits beyond those afforded by the current RDA for protein, we also recognize there are gaps in the current knowledge base and encourage discussion of important contradictory evidence/data. Future research must be well designed, rigorously reviewed, and credibility communicated. Unfortunately, the article by Levine et al. presents conclusions not supported by their own analyses or the greater literature.

________________________________________________________________________________________________________

Dylan earned his BSc in nutritional sciences and dietetics from Rutgers University where he is currently pursuing his PhD in nutritional biochemistry and physiology. Dylan writes regularly on his blog/website, Calories in Context, where he covers a wide range of nutrition and performance-related topics. Dylan has experience as a sport nutritionist for the Rutgers Football and Ranger Army Challenge teams and also works with the lay public, both in-person and via e-mail correspondence, where he

specializes in fat loss, muscle gain, and body re-composition. For more information, you can visit his site at nutridylan.com or e-mail him at [email protected]. ________________________________________________________________________________________________________

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Dr. Brad Schoenfeld gives the inside scoop on his new study comparing hypertrophy-type and strength-type training. Interviewed by Alan Aragon

____________________________________________________

What follows is an interview with my colleague and personal

friend, Dr. Brad Schoenfeld about his recent publication* thats been generating lots of discussion. My questions are in bold.

Enjoy the discussion, and big thanks to Brad for the insight &

expertise!

*Schoenfeld BJ, Ratamess NA, Peterson MD, Contreras B, Tiryaki-Sonmez G,

Alvar BA. Effects of different volume-equated resist

3 - April - 2014

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