Tag Archives: fat

The curiosities of nicotin..ic acid

Niacin vs. ketosis

Part I.  Rodents

It is thought: niacin causes red itchy face (> 100 mg/d) and acutely lowers FFAs; chronically, it raises some questionable fraction of HDL (> 1000 mg/d) and probably causes diabetes.

It is speculated: niacin binds a particular “ketone” receptor (GPR109?) (physiological relevance?).

It is known: niacin is ketogenic in rats.  Repeat: niacin is ketogenic in rats.

Niacin aka nicotinic acid and nicotamide aka niacinamide both fulfill the requirement for Vitamin B3 (ie, prevent pellagra).  But only the former causes flushing… and only the former is ketogenic (two apparently unrelated phenomena).

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How to define a “healthy” diet. Period.

Whether you’re strictly adhering to a diet or just doing your own thing, if year after year your GP is prescribing more and more medications to stave off morbidity and keep you intact, then the diet you’re following is most likely Fail.  The same is true if your body weight is creeping upward or your quality of life is creeping downward.lunchables

The glaring Fail of all 3 diets in the recent Mediterranean Diet Study for the medications criteria threw up a huge red flag.  As a brief refresher, at baseline and 5 years later, prescription medication usage was as follows:

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Paleotard, meet potatotard, Op. 132

(credit to Dylan and Woo, respectively, for introducing me to those terms)

Empty calories – the potato

While it has a decent amino acid profile, with only 3 grams of protein it’d take a diabetic amount of potatoes to fulfill your daily protein.  By “diabetic,” I mean about a thousand grams of starch.  potatoes are just as glycemic as white bread.

potato

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40 years ago a group of researchers turned ketosis into poetry.

But first, a brief primer.  In red.

“The glucose muscle-sparing effect of fat-derived fuels” 

or, the Randle Cycle 2.0.  it’s like a course in life enhancement.

Part I.  Intermediary metabolism

The glucose-fatty acid cycle
The Randle Cycle, as originally proposed, states that fatty acid oxidation inhibits glucose oxidation.  This is good because during starvation, every tissue than can survive on fatty acids instead of glucose should do so, sparing as much precious glucose as possible for the brain.

The glucose-sparing effect of fat-derived fuels
A critical vital horcrux to this is in the oh-so-humbly-disguised phrase “fat-derived fuels.”  The fat-derived fuels are ketones, and they are rescuing the brain from starvation (ie, neuroglycopenia); they do so by supplementing glucose as a fuel source.  Ketones are good at this; many tissues are happy to oxidize ketones when they are available.

The glucose muscle-sparing effect of fat-derived fuels
Ketones are derived from fat.  During prolonged starvation, glucose comes from skeletal muscle amino acids (eg, alanine).  Ketones spare glucose.  Thus, ketones spare muscle.  QED.

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Biohacking holiday weight gain

What should you eat before the big feast?  (hint: eggs.)  And don’t try to compensate in advance by eating less, this will only make you hungrier.  Furthermore, foods in your regular diet are probably healthier than holiday fare, so you definitely don’t want to eat fewer healthy foods to make room for empty calories.

Tip 1. 

Variation in the effects of three different breakfast meals on subjective satiety and subsequent intake of energy at lunch and evening meal (Fallaize et al., 2012)

Participants were served only one of these for breakfast:

And given unlimited amounts of these for lunch and dinner:

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Philosophy of the faux-low carb mouse and others like it

The Laws of Energy Balance are always maintained.  Here are some insights into how this is accomplished from a mouse perspective.  A hormonal milieu which is unfriendly for fat storage will make you lean, but not by magic.  We’ve got: 1) reduced food intake; and/or 2) increased energy expenditure.

Recall the faux-low carb mouse (Ins1+/-; Ins2-/- aka InsKO; Mehran et al., 2012).  They can’t get fat because of an inability to develop hyperinsulinemia.  Food intake isn’t reduced, so energy expenditure goes up.  Since the fat isn’t stored, it needs an “out,” so it either inhibits food intake or ramps up energy expenditure; InsKO gives us the latter.

While not hormonally-mediated, PPARg+/- mice can’t get fat because of defective adipogenesis and they handle this problem both ways; by reducing food intake and increasing energy expenditure (Kubota et al., 1999).  Similar to InsKO, PPARg+/- have lower insulin, but the primary defect in these mice is defective adipogenesis.  They can’t store fat, so this unstored fat: 1) tells the brain there’s plenty of fuel around so stop eating; and 2) ramps up energy expenditure to burn itself off:

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The faux-low carb mouse and a diatribe

The faux-low carb mouse

Hyperinsulinemia drives diet-induced obesity blah blah blah (Mehran et al., 2012)

The researchers generated a mouse with half as much insulin as normal mice.  Physiological insulin levels remain intact, but hyperinsulinemia is genetically inhibited.  For the sake of simplicity, we’ll call them “InsKO.”

When fed a high fat diet, normal mice become markedly hyperinsulinemic (pink line) whereas InsKO mice maintain relatively normal insulin levels (red line).  Blue lines are chow-fed mice; similar trend but less interesting.

divide and conquer

InsKO mice don’t get fat,

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Sir Philip Randle and the effects of blocking fat oxidation

The Randle Cycle, put forth in 1963, dictates that increased fatty acid oxidation inhibits glucose uptake and increased glucose oxidation inhibits fatty acid oxidation – it just makes sense.  Insulin enhances glucose uptake and oxidation while suppressing lipolysis; growth hormone, cortisol, and adrenaline enhance lipolysis and fatty acid oxidation which suppresses glucose oxidation.  Low carbohydrate diets reduce insulin, and the reduced glucose oxidation is metabolically irrelevant because of reduced glucose intake (by definition).  This is critical information.  And as a student of basic intermediary metabolism, I prefer the Randle Cycle over any number of alphabet soup recipes to explain metabolic phenotypes (eg, fat and carbs as opposed to IRS, Akt, Jnk, ERK, etc., etc.).  Many valuable lessons can be learned from understanding permutations of the Randle Cycle.

For example,

Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice (Keung et al., 2012)

divide and conquer

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The curious effects of calories in mice

What is the biological impact of a history of obesity and weight loss?  The metabolic trajectory of two calorically restricted skinny mice depends entirely upon whether or not they used to be fat.  The end of this story might be: ‘Tis better to have lost and re-gained than never to have lost at all; or it’s just an interesting new take on the body weight set point theory.

Caloric restriction chronically impairs metabolic programming in mice (Kirchner et al., 2012)

divide and conquer

Part 1.
Study 1. Calorie restricted lean mice: the effect of diet composition.

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Fish oil. Pills or directly from the source? Opus 118.

As a proponent of consuming fatty fish (sardines, salmon, etc.), I was interested to read the new fish oil study; as an opponent of meta-analyses, however, not so much.  A meta-analysis is a type of study whereby the researcher thinks of something they want to prove, then cherry picks studies that best support their point.  Or perhaps I’m just biased.  Nonetheless,

Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis (Chowdhury et al., 2012)

In brief, regarding whole fish consumption, 3 servings per week reduced stroke risk by 6% and 5 servings by 12%.  Surprisingly, there was no effect of fish oil pills that contained ~1.8 grams of long chain omega 3 fatty acids.  What this study lacks is any information about the dose of EPA and DHA (the major bioactive fatty acids in fatty fish); and with 38 studies analyzed, I’m not about to try to figure it out (sorry team)…  a serving of fish can have anywhere from 0 to 1 gram of EPA and DHA; 1.8 grams of long chain omega 3 fatty acids can have anywhere from 0 to 1.8 grams of EPA and DHA.  Therefore, I’ll resort to reviewing two of my favorite fish studies of all time: DART and GISSI.  For a more detailed review of fish oils and these studies, check out The poor, misunderstood calorie (chapter 9).

divide and conquer

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