I’ve been following the links between blood pressure modulatory hormones and circadian rhythms for a while now — and while it’s a fascinating overall picture, this nut hasn’t been cracked [yet]. A paper published in Science may have brought us one step closer. (And some potential biohacks.)
Background reading (probably important, because my thoughts on this aren’t very coherent [yet]):
LIGHT, Leptin, and Environmental Mismatch (skip down to Part 2)
Circadian phase delays and metabolism
Circadian biology: jet lag, mood, & potential role of BP regulatory peptides
The new study: Changes in the composition of brain interstitial ions control the sleep-wake cycle (Ding et al., 2016)
It was a study on mouse brain, but the #context is very relevant here.
Tl;dr: they showed that changes in extracellular ions, independent from neuronal activity, can induce sleep or wakefulness. “Independent from neuronal activity” was accomplished by silencing the neurons with tetrodotoxin.
…but it isn’t dead, imo, because that would be really hard to do. Like, seriously.
side note: please consider the modern views of Taubes, Lustig, Gardner, Attia, and others on Carbs™. They’re less “Carbs-cause-obesity, keto-for-all, etc.,” and more thinking it might not be Carbs™ per se, but rather processed and refined foods. And #context… And I tend to agree at the moment (nuances and caveats are subject to change, as more evidence accumulates).
disclaimer: I haven’t seen the full text of Hall’s recent study, but that’s not really relevant to what I want to discuss. In other words, I don’t think the full text will provide any additional details on this particular point.
Tl;dr: this study was not designed to prove or disprove metabolic advantage or the insulin-obesity hypothesis.
It’s in the study design: four weeks of low fat followed by four weeks of low carb. We KNOW that weight loss slows over time (especially if calories are controlled, as they were in this study). It has to do with the order of treatments.
Weight loss-slowing over time in the Minnesota Experiment:
Posted in Advanced nutrition, diabetes, diet, Dietary fat, empty calories, Grains, insulin, Ketosis, Leptin, Protein, sleep, Sun, TPMC
Tagged calories, carbs, diet, empty calories, energy balance, fiber, grains, insulin, ketogenic, ketones, ketosis, leptin, nutrition, obesity, Paleo, processed food, protein, sugar, trans fat
Social jet lag is basically a general term that refers to circadian arrhythmia. Sort of like insulin resistance, it’s rampantly abundant — some have estimated a prevalence of up to 75%! Social jet lag can be induced by shift work, East/West travel, late meal timing, artificial light at night, sleeping late, not enough sunlight in the morning, etc., etc. And while any of the above insults, by themselves, may not really screw up your circadian rhythms, you can see how easy it is for one person to fall prey to nearly of them:
Eat a late dinner, stay up late using artificial light (eg, computer, smart phone, etc.), sleep late the following day so you skip breakfast and don’t get any sunlight in the morning.
CIRCADIAN MISMATCH ACCOMPLISHED
This increases your risk for a wide variety of ailments, ranging from cancer to diabetes to bipolar disorder: no bueno.
One key mediator of the effects of LIGHT is melatonin. Artificial light at night suppresses melatonin. Sunlight in the morning can blunt the impact of this! It all ties in together. Gravitas.
Great review article here.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, diabetes, diet, Dopamine, Energy balance, Ketosis, Leptin, melatonin, resveratrol, Sun
Tagged calories proper, carbs, circadian rhythm, energy balance, ketosis, melatonin, sleep
The history of low fat diets is riddled with crappy low fat food-like products.
Food quality matters.
Insulin resistance is a spectrum
Take a group of obese people and assess insulin sensitivity however you like: some researchers demand nothing less than a hyperinsulinemic-euglycemic clamp (Gold Standard), others are OK with insulin levels during an oral glucose tolerance test.
Next, divide the people up based on this — there are a few ways you can do it. You can: take the top half vs. the bottom half (a method which includes everyone); take the top third vs. bottom third (excluding the middle third); take the top quarter vs. bottom quarter (excluding the middle 50%), etc.
THIS MATTERS because in referencing this topic, many people claim most obese are insulin resistant. They may be more insulin resistant than lean people, but even within obese people, there’s a spectrum, and the spectrum matters in this #context.
Posted in Advanced nutrition, diabetes, diet, Dietary fat, empty calories, Energy balance, fat, fiber, insulin, Ketosis, Protein, Sugar
Tagged Atkins, body composition, calories proper, carbs, diet, energy balance, fat, insulin, ketogenic, nutrition, processed food, protein, sugar
Bear with me here… this could be very important (or just all in my imagination haha)
Fact: melatonin secretion happens at night (or at least that’s when it’s supposed to happen):
And it’s important to adopt healthy circadian behaviors early on to prevent or minimize the age-related decline in melatonin secretion:
Posted in Advanced nutrition, chronopharmacology, circadian, Dopamine, Leptin, melatonin, muscle, sleep, TPMC
Tagged calories proper, circadian rhythm, insulin, ketosis, nutrition
Next time someone says VLC/keto is harmful or at least not helpful for fat loss because of a new rodent study, they’ll probably be wrong.
BOOKMARK THIS ONE GUYS.
Rodent studies on ketogenic diets or exogenous ketones are valuable and interesting in a variety of #contexts, although I’d argue that regulation of fat mass isn’t really one of ’em.
For starters, rodents aren’t particularly ketogenic – it’s rare to see ketones >1 after an overnight fast even in long-term ketoadapted mice. Also, many rodents gain weight until they die, whereas humans plateau and stay relatively weight-stable for their entire lives (at least historically, and I’m not talking about yo-yo dieting).
Skeletal muscle, on the other hand, seems more similarly regulated: keto isn’t muscle-sparing in either specie… most people, perhaps unwittingly, increase protein intake on keto, and THIS spares muscle (N.B. this is simply to spare muscle, whereas in non-keto dieters, it’s not uncommon to see increased muscle in the #context of high protein). That’s because carbs are more anabolic than fat. QED.
There’s just a fundamental difference in the way fat mass and appetite is regulated between the species. There are many similarities, which is why these studies are still valuable, but fat mass isn’t one of ‘em.
Posted in Advanced nutrition, diet, Dietary fat, Energy balance, fat, insulin, Ketosis, muscle, pair-feeding, Protein, TPMC
Tagged Atkins, body composition, calories, calories proper, carbs, diet, energy balance, energy expenditure, insulin, ketogenic, ketones, ketosis, nutrition, obesity, protein
Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight and obese adults: a randomized pilot trial (Gardner et al., 2015)
Low carb diet: participants went from 230 grams/d to less than 50 for the first 3 months, then creeped up to ~80 over the next 3 months.
Will the critics say “the carbz weren’t low enough!”? REALLY?
Posted in diet, Dietary fat, Energy balance, fat, insulin, Protein, TPMC
Tagged carbs, diet, energy balance, insulin, ketosis, obesity, protein
Brief background reading: amylin (according to Wikipedia)
In a study by Hollander on type II diabetics, the synthetic amylin analog pramlintide was tested (Hollander et al., 2003). In this year-long RCT, over 600 patients were treated with placebo or up to 120 ug pramlintide BID (twice per day). On average, these subjects were obese (BMI 34), diabetic for ~12 years, and had an HbA1c of 9.1%. After one year, HbA1c declined 0.62% and they lost about 1.4 kg… not very impressive.
But it’s not all bad news; after viewing those relatively negative results (3 lb weight loss over the course of 1 year), another group of researchers led by Louis Aronne and Christian Weyer believed amylin had yet to be tested proper. So they designed a better study; it was shorter, used higher doses of pramlintide, and they enrolled obese yet non-diabetic patients (Aronne et al., 2007). They opted for higher doses of pramlintide (240 ug TID [three times per day]) because in dose-escalation studies, the incidence and severity of adverse drug reactions was consistently low at all doses tested.
They chose to study obese-er subjects (BMI 38, compared to 34 in the Hollander study) because obese subjects lose fat more readily than lean people, so if the study is designed to measure fat loss, then it is better to select a population of subjects where more fat loss is predicted. They selected non-diabetic subjects for a similar reason; diabetics must regularly inject insulin which promotes the accumulation of fat mass — this could counteract any fat reducing effects of pramlintide.
In other words, it was a more powerful and better designed study.
After 16 weeks, pramlintide-treated subjects lost an average of 3.6 kg (~8 lbs), or about half a pound per week. 30% of patients lost over 15 pounds (1 lb/wk)! Importantly, the weight loss didn’t appear to have reached a plateau by week 16, so it would have most likely continued along a similar trajectory had the study been longer. There were no side effects, and a battery of psychological evaluations showed that the patients receiving pramlintide felt it was easier to control their appetite and BW, they didn’t mind the daily injections, and overall well-being increased. At the very least, these evaluations meant the subjects weren’t losing weight because of nausea or malaise. In fact, it was quite the opposite.
Posted in Advanced nutrition, diet, Dietary fat, Energy balance, fat, insulin, Ketosis, Leptin, liver, microbiome, muscle, pair-feeding, Protein, TPMC
Tagged body composition, calories proper, carbohydrates, carbs, diet, energy balance, energy expenditure, insulin, ketogenic, ketosis, nutrition, obesity, protein
1st Generation: ketone salts. Only problem is the huge dose of salt limits how much you can take without adverse effects… but these are the ones on the market.
2nd Generation: ketone esters.
Advantage: no salt, and probably “slow-release.”
Disadvantage: gonna be WAY more expensive than the salts (which are still pretty expensive).
~40 grams of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (a ketone ester) (from Clarke et al., 2013):
They did this thrice daily, so some people were getting up to 170 grams.
ONE HUNDRED SEVENTY GRAMS
[keep that number in mind]
Posted in Advanced nutrition, circadian, coconut, diet, Dietary fat, Energy balance, fiber, insulin, Ketosis, Leptin, microbiota, muscle, TPMC
Tagged Atkins, carbs, insulin, ketogenic, ketones, ketosis, leptin, microbiota, muscle, nutrition, protein
Does it matter where fatty acids are oxidized, liver or skeletal muscle? Of course, they’re oxidized in both tissues (quantitatively much more in the latter), but relative increases in one or the other show interesting effects on appetite and the regulation of fat mass [in rodents].
Warning: a lot of speculation in this post.
It’s known that LC diets induce a spontaneous decline in appetite in obese insulin resistant patients. Precisely HOW this happens isn’t exactly known: the Taubes model? improved leptin signaling? probably a little bit of both, other mechanisms, and possibly this one:
Exhibit A. Oxfenicine
Posted in coconut, diet, Dietary fat, Energy balance, insulin, Ketosis, Leptin, liver, muscle, TPMC
Tagged Atkins, body composition, calories proper, carbs, diet, energy expenditure, insulin, ketosis, obesity