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
So the theory goes: high carb meal -> blood glucose spike -> insulin spikes a little too hard -> hypoglycemia -> hunger, so you eat to replenish blood glucose.
In the original theory of hangry, hypoglycemia was a core component, although as Jane Plain pointed out, it could be the relative, not absolute levels of blood glucose that count (&/or free fatty acids, but that’s a story for another day). This could be true, in part because:
1) symptoms of hypoglycemia rarely correlate with actual hypoglycemia;
2) many episodes of actual hypoglycemia are asymptomatic; and
3) hunger isn’t even one of the main symptoms of hypoglycemia.
Tl;dr: hangry might be a real phenomenon, but there are little/no data to support it, and much to the contrary.
The low carb brigade says “LCHF = no hangry.”
Turns out, the same can be said by the high carb brigade (in some contexts), so does it really matter? (see below)
What we know: obese insulin resistant patients undergo a spontaneous reduction in appetite upon initiating a carbohydrate-restricted diet. FACT (P<0.05). Low carb, high protein meals also induce more satiety than high carb meals in acute scenarios…
Imho, hunger and satiety are complicated biological phenomena that can’t be so easily simplified into cute concepts like “hangry.”
Posted in Advanced nutrition, diet, empty calories, Energy balance, insulin, Protein
Tagged carbohydrates, carbs, insulin, ketogenic, ketosis, nutrition, protein
This was met with much backlash from the low carb cavalry, because, well, if low is good then lower must be better…
I’m not anti-keto; but I’m not anti-science. FACT.
“…some people are not genetically equipped to thrive in prolonged nutritional ketosis.” –Peter Attia
Posted in Advanced nutrition, diet, Dietary fat, fat, Fish, insulin, Protein, TPMC
Tagged Atkins, body composition, calories, carbohydrates, carbs, energy balance, energy expenditure, insulin, ketogenic, ketones, ketosis, obesity
Insulin secretion is attenuated by sympathetic nervous system activity; eg, via exercise. Theoretically, exercising after a meal should blunt insulin secretion and I don’t think this will lessen the benefits of exercise, but rather enhance nutrient partitioning. And this isn’t about the [mythical?] post-workout “anabolic window.”
Sympathetic innervation of pancreas: norepinephrine –> adrenergic receptor activation = decreased insulin secretion & increased lipolysis (Stich et al., 1999):
note how quickly catecholamines are cleared upon exercise cessation
Posted in Advanced nutrition, Exercise, insulin, Protein, strength, Sugar, TPMC
Tagged calories, calories proper, carbohydrates, carbs, diet, energy balance, energy expenditure, exercise, insulin, nutrition
Jane Plain recently wrote a great article about the relationship between insulin, dietary fat, and calories. There are a lot of data on this topic, which collectively suggest: context matters!
Insulin and ketone responses to ingestion of MCTs and LCTs in man. (Pi-Sunyer et al., 1969)
14 healthy subjects, overnight fasted; dose: 1g/kg.
In brief, MCTs are more insulinogenic than corn oil. But it’s not a lot of insulin. Really. Enough to inhibit lipolysis, perhaps, but that’s not saying much… & certainly not enough to induce hypoglycemia.
Posted in Advanced nutrition, coconut, Dietary fat, Energy balance, fat, insulin, Protein, TPMC
Tagged calories, calories proper, carbohydrates, carbs, diet, empty calories, energy balance, fat, insulin, nutrition, protein
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.
Posted in Advanced nutrition, diet, Dietary fat, Energy balance, fat
Tagged appetite, Atkins, body composition, calories, carbohydrates, carbs, diet, fat, nutrition, obesity, satiety
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.
Posted in Advanced nutrition, diet, Dietary fat, fat, insulin
Tagged carbohydrates, carbs, diet, energy balance, fat, insulin, ketoacidosis, ketogenic, ketones, ketosis, nutrition, obesity, protein, sugar
For overall health and well-being, fermented foods like sauerkraut and kefir are great. Especially when following a low carbohydrate diet which is generally low in the types of foods which feed the gut microbiome.
For those with gastrointestinal problems, the gut microbiota is probably involved. Whether it is bacterial overgrowth or dysbiosis, gut bugs are usually the culprit. Treatment options vary widely, ranging from global extermination with vinegar & a low fibre diet (as per Jane Plain), or remodeling the microbiome with a prebiotic like galactooligosaccharides. Probiotics like bifidobacteria can help, too, if they’re administered with either prebiotics or fermented foods (they need something to nourish them in transit). Dark chocolate is also an excellent vessel. Resistant starch is another option, although the question remains as to whether or not this is compatible with a low carbohydrate diet.
Resistant starch has been around for a while, and when I was in school it received about 10 minutes of attention during the fibre lecture. But Jimmy Moore and Richard Nikolay have been talking about it a lot lately so I decided to freshen up on the topic. In brief, it can be therapeutic for GI issues, but some studies have shown mixed effects on glucose & insulin metabolism. The former is virtually unarguable, but I found the latter interesting. And the impact of resistant starch on ketosis is included as well.
Posted in Advanced nutrition, clamp, diet, fiber, Grains, insulin, Ketosis
Tagged bifidobacteria, carbohydrates, diet, energy balance, fibre, grains, insulin, ketogenic, ketosis, microbiota, nutrition, prebiotics, protein
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 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]:
Posted in Advanced nutrition, clamp, diet, Dietary fat, fertility, insulin, sex, testosterone
Tagged calories, carbohydrates, carbs, diet, fat, insulin, testosterone
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.
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).
Posted in Advanced nutrition, diet, gelatin, glycine, insulin, nicotine
Tagged carbohydrates, cognition, gelatin, glycine, memory, nicotine, sleep, tryptophan