Tag Archives: obesity

Paleo Plants and Carnivory

From what I gather, it’s been difficult to pinpoint the role of plants in the diet of our ancestors for a variety of reasons.  For example, evidence of plants on cooking tools and dental remains is suggestive but doesn’t disprove the possibility that said evidence came from preparing the plants for some other purpose (eg, tools, weapons, or medicine), or that the stomach contents of an herbivore was ingested (which gets partial credit).

That said, after reviewing a few studies on the topic (see below), it’s safe to say that plants were eaten, probably frequently, and the types & quantities varied seasonally & geographically.  Collectively, the data suggest we aren’t carnivores.

…you had to have something to hold you over until the next fish fell prey to your deadly hunting spear…

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Lipid Hypothesis 2.0: Eat Butter

The original lipid hypothesis stated, more or less, that lowering blood cholesterol would reduce premature mortality from heart disease.  At the time, it was thought that dietary cholesterol and saturated fat increased the ‘bad’ type of blood cholesterol, so the advice was to restrict those foods.  All of that was wrong.

Time

Lipid Hypothesis 2.0: Eat Butter

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Fasting, circadian biology, and epigenetics

From the best I can gather, one of the more immediate players in circadian biology is the coenzyme nicotinamide adenine dinucleotide (NAD), which participates in a variety of redox reactions.  Fasting increases the intracellular NAD/NADH ratio, setting off a cascade of events involving epigenetics and the regulation of metabolism.

NAD activates sirtuins, a family of deacetylase enzymes.  This is epigenetics.

SIRT1

 

SIRT1 regulates the activity of BMAL1 and CLOCK, two circadian transcription factors, which target NAMPT, an enzyme that synthesizes NAD.  And in a curious feed-forward mechanism, CLOCK and BMAL1 enhance SIRT1 expression… genetic deletion of any of these players induces insulin resistance (Zhou et al., 2014), and this can be recapitulated with constant darkness: reduced BMAL1 and SIRT1, hepatic insulin resistance; the latter can be reversed with resveratrol (which may or may not be acting through SIRT1; this is controversial).  While alcohol does no great favors for circadian biology, if you’re going to imbibe, perhaps a resveratrol-rich Argentinian malbec served, and this might be the important part, at night, when all of this stuff is going on… coincidentally [fortunately], that’s precisely when most choose to imbibe.

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Advanced glycation end products (AGEs)

About a decade ago, Michael Brownlee posited that AGEs were one of The Four Horsemen responsible for the microvascular complications of diabetes.

Kill ‘em all

Thereafter, the image below (or a closely related one) appeared in at least one talk at every major diabetes conference for about 5 years.  Then it faded – maybe not because it is wrong, but rather just too simplistic to be useful (similar to CICO & ELMM).

Brownlee

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Skipping meals, intermittent fasting, grazing, etc.

or… Circadian Meal Timing!

They say if you’re going to [intentionally] skip a meal, it should be breakfast – and hey, that’s probably the easiest meal to skip.  However, a recent study showed skipping dinner FTW (well, not exactly).  I’ve never seen a proper study directly comparing the effects of skipping different meals, but here are a few that come close.  The findings may surprise you.

omelette

note: with the exception of Fernemark (Exhibit B), these studies are mostly macronutrient-controlled. That is, protein, fat, and carbs are similar between the groups; the only thing that differs is when they were ingested.  This can be tricky and/or very nuanced in some instances, like if dinner was smaller (fewer calories) but more protein-rich, for example… but in order to include 5 relevant studies and not bore you to death, you’ll have to check the full texts for those details.

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Diet study: American Diabetes Association vs. Low Carb Ketogenic

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes (Saslow et al., 2014)

Disclaimer: this study was not ground-breaking; it was confirmation of a phenomenon that is starting to become well-known, and soon to be the status quo. That is, advising an obese diabetic patient to reduce their carb intake consistently produces better results than advising them to follow a low fat, calorie restricted diet.

The two diets:

Moderate carbohydrate diet: 45-50% carbs; 45 grams per meal + three 15 gram snacks = 165 grams per day; low fat, calorie restricted (500 Calorie deficit).  Otherwise known as a “low fat diet (LFD).”

In their words: “Active Comparator: American Diabetes Association Diet.  Participants in the American Diabetes Association (ADA) diet group will receive standard ADA advice. The diet includes high-fiber foods (such as vegetables, fruits, whole grains, and legumes), low-fat dairy products, fresh fish, and foods low in saturated fat.

Very low carbohydrate diet: Ketogenic; <50 grams of carb per day, no calorie restriction, just a goal of blood ketones 0.5 – 3 mM.

In their words: “Experimental: Low Carbohydrate Diet.  Participants will be instructed to follow a low carbohydrate diet: carbohydrate intake 10-50 grams a day not including fiber. Foods permitted include: meats, poultry, fish, eggs, cheese, cream, some nuts and seeds, green leafy vegetables, and most other non-starchy vegetables. Because most individuals self-limit caloric intake, no calorie restriction will be recommended.

Both groups were advised to maintain their usual protein intake.

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Carbohydrates, calories, appetite, and body weight.

The Optimal Diet, Atkins, South Beach, Paleo, Zone… all have one thing in common: some degree of carbohydrate restriction.

Low, lower, lowest: does it matter?

There are 4 relatively large, randomized ‘diet-induced weight loss’ studies that all reported fairly comprehensive food intake and body composition data. The studies ranged in duration from 24 weeks to one year and included anywhere between 50 and ~300 overweight and obese participants.

In general, participants assigned to the low fat intervention were advised to restrict calories and fat whereas those assigned to low carb were told they could eat as much as they wanted as long as it wasn’t carbs.

Your mileage may vary – but these studies cover a large number of subjects from a wide range of backgrounds, suggesting the results might be applicable across the board.  Conclusion?  the amount of body fat lost was much more strongly associated with the reduction in carbohydrates than calories.  The only modestly surprising aspect was the magnitude… (see the figures below).

The four studies, in chronological order:

Brehm 2003: over the course of 6 months, those who consumed an average of 163 grams of carbohydrate per day lost 8.6 pounds of body weight while those who consumed 97 grams lost 18.7 pounds.

McAuley 2005: 24 weeks; those who ate 171 grams lost 10.3 pounds, while those who ate 133 grams lost 15.2 pounds, and those who ate 107 grams lost 15.6 pounds.

Maki 2007: 36 weeks; those who ate 186 grams lost 5.7 pounds, those who ate 131 grams lost 9.9 pounds.

Gardner 2007: 1 year – those who ate 138 grams lost 10.3 pounds, 181 grams lost 3.5 pounds, 195 grams lost 4.8 pounds, and 197 grams lost 5.7 pounds.

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Ketoacidosis

Nutritional ketosis is a normal, physiological response to carbohydrate and energy restriction.  A ketogenic diet is an effective weight loss strategy for many.  Ketoacidosis, on the other hand, is a pathological condition caused by insulin deficiency.  The common theme is low insulin; however, in ketoacidosis, blood glucose levels are very high.  Ketone levels are elevated in both states, although are 10-20x higher in ketoacidosis (~0.5-2 vs. > 20 mM).  Nutritional ketosis and ketoacidosis should not be confused with one another, and a ketogenic diet doesn’t cause ketoacidosis.

In ketoacidosis, gluconeogenesis occurs at a very high rate and the lack of insulin prevents glucose disposal in peripheral tissues.  Skeletal muscle protein breakdown contributes gluconeogenic substrates, exacerbating the problem.  This can cause blood glucose to reach pathological levels, exceeding 250 mg/dL.

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Dietary protein, ketosis, and appetite control.

Dietary protein has a purpose, and that purpose is not carbs.”  Nor is it to break ketosis or stall weight loss.  

Drastically increasing protein intake may reduce the degree of ketosis in the context of a large energy surplus, but this is likely due more specifically to the large energy surplus than the protein.  This would explain why Warrior dieters (1 meal meal per day) often report reduced ketones if they eat too much protein.  It’s more likely that the 2000 kcal bolus is exerting it’s anti-ketotic effect by being a large energy surplus, such that anything other than 90% fat would blunt ketosis.  It’s not the proteins… Want proof?  Here’s an n=1 to try: give up Warrior dieting for a few days and try 3 squares.  My bet is that you’ll be able to increase protein intake and still register ketones as high or higher than before.  There are data to support this and reasons why it may not matter (below).

disclaimer: I don’t think “deep ketosis” is necessary to reap the benefits of carbohydrate-restriction.  But if you love high ketone meter readings, then this might be a better strategy to maintain deep ketosis while getting adequate protein. win-win.

if I hear: “oh no, I was kicked out of ketosis!” one more time… 

All of the studies below are confounded one way or another, but so are we humans.

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Lights Out! Get your melatonin.

From T.S. Wiley’s website:
“People spent summers, before electric lights, sleeping less & eating heavily in preparation for winter because the light triggered the hunger for carbohydrates. Now, light is available 24 hours a day. Heating and air-conditioning climate control our hormonal responses to consume carbohydrates now available year round. This is the scenario for obesity, Type II diabetes, and depression… In Wiley’s opinion, sleep is the best medicine.”

And Wikipedia:
“Wiley’s main thesis in Lights Out is that light is a physiological trigger that controls dopamine and hormones like cortisol. Wiley posits that with the extension of the natural day through artificial lighting, rest at the hormonal level is rarely adequate for optimum biological needs of the body. In her view, this results in both fatigue and unnatural appetite, which leads to weight gain, exhaustion, and disease. Wiley theorizes that the body’s responses are cyclical, reflecting the seasons of the year, and that the body’s needs vary seasonally. According to Wiley, during the winter months the body needs more sleep, and carbohydrates should be restricted as they would have been naturally during hunter-gatherer times.”

melatonin

Most of the first third of Wiley’s book “Lights Out: Sleep, Sugar, and Survival” centers around light exposure, melatonin, and the many, many effects of a screwed up circadian cycle.  Jane Plain and Jack Kruse have written volumes on the subject, please see their websites for more in-depth analyses and practical applications…

Much of this blog post is my take on that first third (I couldn’t wait to finish it before writing about it), plus a little input from Google, Pubmed, et al; some commentary & pseudo-fact-checking as well.  I’m going to finish the book, and hopefully it will inspire a few more blog posts as opposed to a tin foil hat.  Most of the stuff in Lights Out makes incredibly good sense, but: 1) that doesn’t mean it’s true; and 2) the strings of logic are far too long to do a proper fact-check.  But really it’s how well it makes sense (mostly) that has me intrigued.

divide and conquer

Melatonin is a sleep-inducing hormone controlled by the light-dark cycle.  It is known.  On the day-to-day, melatonin increases at night and decreases during the daytime.  From Wiley: on a seasonal level, longer days during the summer meant less melatonin overall during these months.  Since melatonin suppresses sex hormones (inconsistent? Eg, Smith et al., 2013), summer is supposed to be breeding time, so the baby is born in spring when food is plenty (I’m OK with this now, but will certainly disagree come December).  Melatonin also suppresses metabolic rate, so the decreased daylight and thus increased melatonin during the winter months helped to survive on less food (supported by Marrin et al., 2013).

Disruptions in circadian rhythms royally screws us up.  According to Wikipedia, fireplaces/candles and incandescent bulbs produce less of the melatonin-suppressive blue lights… use these at night in winter?


Antidepressant and circadian phase-shifting effects of light. (Lewy et al., 1987)
Abstract: Bright light can suppress nighttime melatonin production in humans, but ordinary indoor light does not have this effect. This finding suggested that bright light may have other chronobiologic effects in humans as well. Eight patients who regularly became depressed in the winter (as day length shortens) significantly improved after 1 week of exposure to bright light in the morning (but not after 1 week of bright light in the evening). The antidepressant response to morning light was accompanied by an advance (shift to an earlier time) in the onset of nighttime melatonin production. These results suggest that timing may be critical for the antidepressant effects of bright light.

Next:  Prolactin inhibits sex hormones, and melatonin stimulates prolactin (supported by Gill-Sharma 2009Campino et al., 2008).  Thus, less melatonin in summer means less prolactin = more sex & fertility.  She also says day sex is more likely to result in conception compared to night sex for this reason (couldn’t find a reference for or against this).

Dopamine inhibits prolactin, whereas TRH & melatonin stimulate it.  Melatonin also blunts ACTH-induced cortisol secretion (supported by Torres-Farfan 2003Campino 2008).  Winter = high melatonin, prolactin, and low cortisol & dopamine.  Summer = high dopamine & cortisol, and low melatonin & prolactin.  Prolactin is supposed to be high in winter, during pregnancy; low dopamine would support this.

Circadian rhythm

Dopamine is a summer hormone?  Lu et al. (2006) showed high dopaminergic activity was associated with light and wakefulness (ie, summertime).  However, Venero (2002) showed melatonin stimulated dopamine synthesis in specific brain regions, and Eisenberg (2010) showed increased dopamine synthesis in fall & winter relative to spring and summer.  Two  possible confounding factors come to mind: 1) Location, location, location!  Some of these discrepancies may be due to brain region-specific dopamine metabolism… actually, Lu is the only odd-man out, so perhaps dopamine is a winter hormone?  And 2) Wiley’s main premise is that we pwned the light… epigenetics and the like mean that we, including the people in those studies, have deeply screwed up light/dark summer/winter metabolic programs on an epigenetic level, so it’s possible those studies are riddles with artefacts.  However, Wiley also says that people get sick because they live in perpetual summer (lights on all the time = high dopamine), and Markianos (2013) showed elevated dopamine metabolites in overweight patients; in my experience these studies usually continuously enroll patients, year-round.


I’m really just blazing through abstracts here – this is why I call it “pseudo-fact-checking;” not to be confused with any degree of academic rigor.

To be continued… (no tin foil hats, I promise) (not yet at least)

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calories proper