Category Archives: insulin

Impact of a low-carbohydrate, high-fat diet on gut microbiota.

NPR recently reported on a study where the participants ate either a meat-based, fiber-free ketogenic diet or a vegetarian diet and had their gut microflora analyzed.  The low carb diet was much higher in fat, and as such, increased the prevalence of a microbe involved in fat digestion.  “Bilophila.”  The article focused on this one and cited a 2012 study where Bilophila was associated with intestinal inflammation… however, the ketogenic diet increased the levels of Bacteroides and decreased Firmicutes.  These are the two that brought the whole gut microbe-obesity connection into the spotlight.  The microbiome in obese mice is characterized by low Bacteriodetes and high Firmicutes. Fecal transplants from obese mice to lean mice causes them to gain weight.  Little is known about Bilophila relative to Bacteriodetes & Firmicutes, and I suspect the focus was on Bilophila because the authors wanted something negative to say about a meat-based, fiber-free ketogenic diet, and that 2012 mouse study suggested Bilophila could be their answer.

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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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Dietary protein does not negatively impact blood glucose control.

“Dietary protein-derived amino acids have a purpose, and that purpose is not carbs.”

At a reasonable level of dietary intake, protein is used for the maintenance of organs & tissues.  Lean body mass.  It’s functional.  Protein isn’t stored in any appreciable capacity, and most excess is either oxidized or stored as glycogen.  Theoretically, about 50-60% of protein-derived amino acids can be converted into glucose, mathematically, but it’s not what you think…

“At a reasonable level of dietary intake.”  A recent publication took a look at this (Fromentin et al., 2013).   They set out to determine how much protein is converted to glucose under “optimal gluconeogenic conditions.”  That is, the subjects were 12 hours fasted, which is a physiologically relevant, optimal gluconeogenic condition.  They were then given 4 eggs (~23 g protein) that were labeled with two stable isotopes (15N & 13C, derived from hens fed isotope-enriched diets!).  Throughout the entire study duration, the subjects were infused with a third isotope, 2H-glucose.  By collecting and analyzing the enrichment of isotopically-labeled metabolites like expired CO2, urea, and glucose, the researchers were able to determine the fate of those 23 grams of protein.

Some of the dietary protein-derived amino acids were used for protein synthesis, others were oxidized.  But blood glucose levels did not change.  Nor did the rate of gluconeogenesis.

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Low carbohydrate diets favorably impact testosterone levels.

It is known.  Carbohydrate restriction improves (lowers) testosterone in women with PCOS.  It works for men, too… but by “works” I mean “increases.”

Decrease of serum total and free testosterone during a low-fat high fibre diet (Hamalainen et al., 1982) 

Intervention pseudo-crossover study: 30 healthy Finnish men in their 40’s were studied on their habitual high fat diet (40%  fat), then put on a low-fat (25%) high fibre diet for 6 weeks, then switched back to high fat.  The high fat diet was also higher in saturates, P:S ratio 0.15 vs. 1.25.

free T

 

Free testosterone levels declined on the low fat diet, but they recovered after 6 weeks of going back to their high [saturated] fat dieting (p < 0.01).

Some observational data: Testosterone and cortisol in relationship to dietary nutrients and resistance exercise (Volek et al., 1997)

…fat, and in particular saturated fat, is associated with increased testosterone levels [in men]:

observational

 

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Protein dilemma ~ sleepy or smart. #Gelatin

Gelatin and glycine have bounced around the blogosphere for quite some time.  Coming from a nutrition-centric place: you say gelatin, I think tryptophan (or lack thereof) and glycine.  Others think:

Jane Plain discusses positive mental effects of gelatin and pimps Pro-Stat (good source of glycine).  Chris Masterjohn discusses glycine and in typical WAP fashion seems to favor bone broth (20% off Kettle & Fire’s awesome broths HERE!).  Knox gelatin didn’t help Michael Allen Smith sleep better, and he apparently tracks sleep quality quite well.  However, Sondra Rose thinks it improves sleep harmony, and gelatin simply blows Dana Carpender’s mind.

bones

 

Tryptophan-rich proteins like those found in whey and egg whites will elevate blood levels of tryptophan relative to other large neutral amino acids (Trp:LNAA ratio), leading to higher brain uptake and subsequent serotonin synthesis.  Tryptophan-poor proteins like gelatin do the opposite, and impair memory.  But the high glycine content in gelatin improves sleep quality.*  Glycine powder might be able to get around this, it’s dirt cheap and it seems to have the opposite effect on brain serotonin, albeit at a much higher dose (and in rats).

 

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The incredible camping experiment, circadian proper

Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle (Wright et al., 2013)

Abstract (edited): The electric light is one of the most important human inventions. Sleep and other daily rhythms in physiology and behavior, however, evolved in the natural light-dark cycle, and electrical lighting is thought to have disrupted these rhythms. Yet how much the age of electrical lighting has altered the human circadian clock is unknown. Here we show that electrical lighting and the constructed environment is associated with reduced exposure to sunlight during the day, increased light exposure after sunset, and a delayed timing of the circadian clock as compared to a summer natural 14 hr 40 min:9 hr 20 min light-dark cycle camping. Furthermore, we find that after exposure to only natural light, the internal circadian clock synchronizes to solar time such that the beginning of the internal biological night occurs at sunset and the end of the internal biological night occurs before wake time just after sunrise

In other words, they compared circadian events during 2 weeks of normal life to 2 weeks of 100% camping.  And camping won.

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Summer is fattening. Don’t do it in winter.

Seasonal eating proper

More on seasonal eating in what appears to be the primary model for its justification for use in humans – hibernating mammals.

How it goes, or so they say: in summer, hibernators massively overeat, including carb-rich foods, in order to generate muscle and liver insulin resistance, so as to promote body fat growth.  The long light cycle reduces evening melatonin, which pushes back the usual nighttime peak in prolactin, which causes an abnormal resistance to leptin, which induces hypothalamic NPY and subsequent carbohydrate craving.  Ergo, summer is fattening.  In today’s day, increased artificial lights guarantee year-round pseudo-summer; and we no longer experience the benefits of the short light cycle: longer sleep times (akin to hibernation) and fasting – either complete fasting as in hibernation, or pseudo-fasting, ie, a ketogenic diet.

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Nutrition Disinformation III

but they actually get it right this time.   Big HT to George Henderson for bringing this ms to my attention.

In Nutrition Disinformation, Part I, the Mediterranean diets employed by Estruch & colleagues were discussed.  The study subjects’ need for antidiabetic drugs, insulin, and anti-platelets all increased over the course of 5 years.  The media and even the authors themselves reported the opposite, touting the benefits of Mediterranean diets.  Thus begat the Nutrition Disinformation series.

Nutrition Disinformation 2.0 was a follow-up to an older post on the Look AHEAD study, when the results were finally published.  The intensive lifestyle intervention consisted of a pharmaceutical-grade low fat diet (ie, LFD + a little bit of Orlistat), and exercise.  By the end of 10 years, medication use was modestly lower in the intensive lifestyle group compared to controls, but it was markedly increased from baseline.  Therefore, I deemed it egregious to say their intervention was “healthy.”  In the context of Nutrition Disinformation, “healthy” means you’re getting better.  The need for insulin, statins, and anti-hypertensives should decline if you’re getting better.

In part 3 of the series, Yancy must’ve been following the Nutrition Disinformation series 🙂 and decided to conduct a subgroup analysis on the patients in his previous low carb vs. low fat + Orlistat study.  Weight loss was roughly similar, but all other biomarkers improved more on low carb.  In the new publication, Yancy analyzed data selectively from the diabetic patients in his original study to generate a “Medication Effect Score (MES).”  MES is based on what percentage of  the maximum dose was a patient given, and adjusted for the median decline in HbA1c experienced by patients on said drug.  A bit convoluted, but I’m on board (at least tentatively).

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Physiological Insulin Resistance in Circadia

If you haven’t read Petro Dobromylskyj’s posts about Physiological Insulin Resistance, then just go do it.  Highly recommended.
I’ve written about it as well, albeit in a slightly different context:
What is our proper “natural” diet?
40 years ago a group of researchers turned ketosis into poetry.

But now on to more pressing matters.  In the food deprived state, Physiological Insulin Resistance develops, in part, to spare muscle (yea yea yeah and glucose for the brain).  But how much of this is due to ‘food deprivation’ per se as opposed to something else… like circadian rhythms.

Exhibit A. Hat tip to Dr Kruse for writing about this TED talk.  In it, Jessa describes a crab that lives on the beach; scurries up the beach when the tide comes in and back down when it goes out.  Scientists captured a few, flew them halfway around the world and put them in little tilted cages.  The crabs still scurried up & down, in time with the tides.

Exhibit B. Evidence that the lunar cycle affects human sleep.  People tend to sleep a little less during the full moon.  Subjects were recruited to a windowless sleep lab and had no exposure to sun/moon/anything outside – they maintained this circadian rhythm for 3 days  (Cajochen et al., 2013).  Different from the crabs, but similar (in a way).

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Dopamine

“When we block the D2 receptor in humans, it is expected they will develop glucose intolerance, obesity, and sedentary behavior.” -Jane Plain, in her series on The physiology of body fat regulation.  It’s probably true.

Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults (Gibson et al., 2012)

Cabergoline is primarily used to treat prolinactinoma, or prolactin-secreting tumors.  In women (& men apparently), prolactin stimulates milk production; in men, it is associated with the refractory period after orgasm.  In both genders, dopamine inhibits prolactin secretion.  Cabergoline targets the D2 receptor, but it’s a dirty drug.  It’s used off-label for gyno and to improve sexy times (Kruger et al., 2003 <– yes, that was actually tested).

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