“Insulin Dynamics”

This one has a bit for everyone.


Relationship of Insulin Dynamics to Body Composition and Resting Energy Expenditure Following Weight Loss (Hron et al., 2015)


I think study was actually done a few years ago, originally published here (blogged about here), and re-analyzed through the eyes of Chris Gardner.  I think. (But it doesn’t really matter as the study design appears to be identical.)


Experiment: give someone an oral glucose tolerance test (75 grams glucose) and measure insulin 30 minutes later.  Some people secrete more insulin than others (a marker of insulin resistance); these people also have a lower metabolic rate after weight loss = increased propensity for weight regain.  However, if these people follow a low carbohydrate diet, then the reduction in metabolic rate is attenuated.  Some people who don’t secrete a lot of insulin after a glucose load may do better in the long-run with a lower fat diet.


Continue reading


Some nuances of Intermittent Fasting

Intermittent fasting (IF) is not a universal panacea, regardless of whether you’re not eating anything at all for a few days each week/month or just restricting your feeding window to a few hours per day.

Some protocols, eg, 20h fasting every second day, significantly improve insulin sensitivity in adipose tissue (Halberg et al., 2005). This is expected to make fat gain easier, and while this wasn’t meant to be a study on body composition per se…


body composition


After just a few weeks, things weren’t changing in a good way (NS).


Continue reading


Hall et al., THE FIRST SIX DAYS (update)

Some people say the study design was rigged to favor the Low Fat diet (LF), which is dirty business but not exactly criminal; sometimes, this happens in science.

The claims go something like this: baseline diet was so high in carbs that they were locked into making unreasonable adjustments to formulate isocaloric low fat and low carb diets; eg, fat was too low in the low fat diet and carbs weren’t low enough in the low carb diet.

The biggest finding was “Fat Imbalance,” which favored LF.  Here’s why I don’t think the baseline diet mattered very much.

Tl;dr: drastically cutting fat intake (LF diet) is much more effective than upregulating fat oxidation (LC diet) to create a large Fat Imbalance in an acute setting, ie, THE FIRST SIX DAYS.


Continue reading


A brief explanation of Hall et al., ie, THE LOW CARB WAR

“Examination of acute shifts in energy balance by selectively reducing calorie intake from one macronutrient.”

Intro (1/2): please don’t read this study with the media headlines in your mind.  Don’t even pay any attention to the study’s title, abstract, intro, and discussion.  In no way did this study put low carb proper on the chopping block, regardless of what you’ve seen online or elsewhere.  Mmmkay?


Intro (2/2): if you want a lesson (or refresher) in Advanced Nutrition, check out the Supplemental Information: in formulating his mathematical models, Dr. Hall seemingly reviewed every single biochemical pathway and physiological variable ever invented.  Read it, for science.  Really.


Continue reading


Ketosis is a hack: here’s why

There are multiple distinct flavors of diabetes/obesity, as evidenced by the fact that some people have: 1) impaired glucose tolerance (but normal fasting glucose); 2) others have impaired fasting glucose (but normal glucose tolerance); and 3) others have both.  This means there isn’t a linear relationship between these phenomena*.  There are also: 4) obese patients with normal glucose metabolism; and 5) lean patients with type 2 diabetes.

*I think the great Dr. Kraft may have missed some of the nuances here.

There is not 100% overlap among these, suggesting [confirming] distinct diabetes/obesity phenotypes (and probably causes & best treatments).





Continue reading



Many pre-diabetic, diabetic, and insulin resistant people have used the low carbohydrate diet to successfully manage their blood glucose levels.  It just plain works.  FACT (P<0.05).

However, a small subset of this population fails to achieve normal fasting glucose.  This is likely due, in part, to a type of circadian mismatch induced by aberrant meal timing and excess exposure to artificial light at night.  For an extensive list of citations supporting the former, see “Afternoon Diabetes;” stay tuned for evidence of the latter.  In brief, a combination of delaying food intake for as long as possible after waking in the morning (“skipping breakfast”) and consuming most calories at night = no bueno.  These behaviors can also promote a circadian mismatch and phase delay.  Hint: eat when the sun is up; sleep when it is down.


Continue reading



Marijuana is a very complex plant: many different strains with differing profiles of psychoactive, non-psychoactive, and peripherally-active compounds that impact metabolism.  Most have THC, which activates endogenous cannabinoid receptors and mimics many of the effects of smoked marijuana (eg, see studies by Hart, Wachtel, and Curran).

Do not underestimate the complexity of this plant.





I’m not ‘anti-pot’ as there are far worse drugs out there… however, some advocates make really bad “pro” arguments, like saying it’s actually healthy (or at least not harmful in any way)…
there are many independent lines of evidence which suggest otherwise, metabolically speaking.


MJ not crack


Rimonabant, the notorious pot-blocker, reduces appetite and is a fairly effective weight loss drug, but has the unfortunate side effect of doing the opposite of marijuana, psychologically speaking.  See any of the RIO studies, eg:


weight loss Rimonabant


All participants lost weight and experienced improved metabolic profiles, insulin sensitivity, etc., by blocking endogenous cannabinoid receptors.

Adverse effects?  Wellll, there’s a drug called Marinol (pure THC) that’s technically an anti-emetic (reduces the urge to vomit); it improves appetite in patients with conditions associated with anorexia or wasting.  It’s a cannabinoid agonist.  Blocking CB1 with Rimonabant induces nausea in some patients: no bueno, but not unexpected given the known effects of Marinol.  Rimonabant is also associated with depression and anxiety (in some patients); also not unexpected.

So, it’s not a good idea to block this receptor pharmacologically (for psychological reasons) or activate it recreationally (for metabolic reasons).  Obesity researchers (and big pharma no doubt) are still looking for a pot-blocker that doesn’t penetrate the brain  to avoid the negative psychological side effects (eg, Klumpers et al., 2013).



Best. Graph. Ever.  The effect of Rimonabant on how stoned participants felt after smoking pot.  Yes, “Stoned” was published in the Journal of the American Medical Association (Huestis et al., 2001).




Indeed, Rimonabant effectively treats “cannabis intoxication” (Crippa et al., 2012).  Antagonist versus agonist 101.


Part II: the biological effects of cannabis, THC, marijuana, and antagonists, etc.


THC acts like insulin on adipocytes: increased adipogenesis, fatty acid uptake, and decreased lipolysis (eg, see studies by Teixeira and Cota).   Munchies, anyone?

Cannabinoids and mimetics/agonists induce hunger and repress satiety; cannabinoid blockers induce satiety and weight loss.  However, I actually don’t think marijuana is obesogenic aside from its anti-anorexic effects.  Cannabis use is not always associated with obesity, possibly due to confounding and/or the lack of good crossover studies (you can’t really do a proper study in healthy humans with MJ for ethical reasons).  But most rodent studies agree that cannabinoids, acting via cannabinoid receptors, induce metabolic syndrome-like effects in nearly every single tissue and on the whole-body level.



CB1 cannabinoid receptor deletion in mice leads to leanness, resistance to diet-induced obesity, and enhanced leptin sensitivity (Trillou et al., 2003).  For context, mice lacking CB1 is somewhat analogous to humans not smoking marijuana.

In liver, cannabinoid signaling induces fat accumulation and insulin resistance (Osei-Hyiaman et al., 2008).  This is absent in CB1 and liver-specific CB1 knockout models.   Mice overexpressing this receptor in liver exhibit increased insulin resistance (Liu et al., 2012).

Activating cannabinoid receptor-2 (CB2) causes insulin resistance and adipose tissue inflammation, and this is blunted in mice lacking CB2 (Deveaux et al., 2009).




The knockouts & over-expressing rodent models, and pharmacological agonist & antagonist studies are all consistent.  That said, I still don’t think this is the worst recreational drug out there, even among “legal” ones.


calories proper



Sunlight and the circadian rhythms in your skin

SUNLIGHT entrains circadian rhythms.  It gives us vitamin D and melanin; it can give us a sunburn, but some evidence suggests that it does NOT cause skin cancer.

“lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma” (Kennedy et al., 2003)

Anecdotally (or so I’ve heard), skin cancer frequently develops in places not regularly exposed to sunlight.  If true, this flies in the face of the dogma which goes something like this (Tl;dr): ultraviolet light from the sun penetrates into the nuclei of skin cells and damages DNA; if the right [wrong] genes are altered/mutated and the mutated cells proliferate, it can develop into a tumor (gross oversimplification).

So, what might explain the discord?

LIGHT entrains the circadian clock; this includes regulating cell cycle genes.  Aberrant cell cycling may lead to out-of-control proliferation in the wrong context, aka cancer.  Interestingly, some evidence suggests that part of the circadian regulation of cell cycle genes includes turning down proliferation when exposure to UV light is expected to be high (daytime); so DNA repair machinery has more time to fix any cell cycle genes that are mutated by UV light before the cell proliferates (Geyfman and Andersen, 2009) = lower chance of creating and propagating a potentially cancerous skin cell.

Continue reading


Saturated fat, cholesterol, and carbohydrates

“You catch more flies with honey…”

^^^good policy in general, but especially for debating in the realm of nutritional sciences.


A short while back, Nina Teicholz discussed low carb ketogenic diets and plant-based diets with John Mackey.  Although I disagree with the dichotomy (keto vs. plant-based), it’s well-worth a watch:



Three topics that could not be avoided in such a discussion: saturated fat, cholesterol, and carbohydrates.



Continue reading


Artificial light regulates fat mass: no bueno.

“despite not eating more or moving less”

We’ve seen this time and time again: LIGHT IS A DRUG.


above quote is extrapolated from this rodent study: “Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity.”


Artificial light impacts nearly every biological system, and it doesn’t even take very much to have an appreciable effect (think: checking your smart phone or watching a television show on your iPad in bed at night).  In this study, adding 4 hours to the usual 12 hours of light slammed the autonomic nervous system, disrupting sympathetic input into brown adipose leading to a significant increase in body fat  “despite not eating more or moving less.”


Continue reading