Category Archives: Dietary fat

CICO and rant

“Wait… what?  nutrient partitioning?”

Calories In, Calories Out should not be interpreted as “eat less, move more,” but rather kept in its more meaningless form of: “if you eat less than you expend, you’ll lose weight.”  At least then, it’s correct… meaningless, but correct.  Eating less and moving more is no guarantee of fat loss, in part, because total energy expenditure isn’t constant and there’s that whole thing with nutrient partitioning.

For obese insulin resistant folks, this is Low Carb’s strong suit: it causes “eat less, move more”spontaneously.

For some obese insulin sensitive patients, for whatever reason, their adherence and success is greater with Low Fat.  You might say, “yeah, but those suckers had to count calories.”  To that, I’d counter with: “it doesn’t matter, THEY WERE MORE SUCCESSFUL COUNTING CALORIES ON LOW FAT THAN NOT COUNTING ON LOW CARB.”  The spontaneous reduction in appetite obviously didn’t cut it.  Do not be in denial of these cases.

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Ketone bodies as signaling metabolites

*non sequiter*

One of the ways dietary carbohydrate contributes to liver fat is via ChREBP: “carbohydrate-response element binding protein.”  It responds to a glucose metabolite and activates transcription of lipogenic genes.  Insulin helps.  Ketones do the opposite (Nakagawa et al., 2013), by inhibiting the translocation of ChREBP into the nucleus where it does it’s dirty work:

 

ChREBP

 

More interestingly, ketones are histone deacetylase inhibitors (HDACi)… this leads to more histone acetylation.  Benefits of fasting sans fasting?  Modulating of acetylation is a MAJOR regulator of circadian rhythmicity.

Butyrate is another HDACi, so have some fibrous plant foods with your red wine and dark chocolate.  Anti-aging (mostly worm studies, but still).

 

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Omega-3 Index

“Need” is a funny concept.  You don’t need to eat seafood.  You don’t need an appendix or legs, either.

An article about the Omega-3 Index was published in Whole Foods Magazine.  Scanning through the figures, I noticed a few interesting studies.

For example, Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease (Farzaneh-Far et al., 2010)

Telomere length is believed to be a biomarker of aging: the shorter your telomeres, the faster you’re aging.  In the study, they measured telomere length in white blood cells and EPA+DHA in whole blood at baseline and again 5 years later.

omega-3 intake and telomerase

Quartile 1: EPA+DHA = 2.3% of the fatty acids in whole blood.

Quartile 2: 3.3%

Quartile 3: 4.3%

Quartile 4: 7.3%

Potential confounders: quartile 4 was comprised of educated rich white old non-smokers with low levels of inflammation, but the statisticians assure us those variables were controlled for… so there’s that.

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Because chocolate

To improve a memory, consider chocolate –NYT

Dark chocolate could improve memory by 25%, but you’d have to eat 7 bars a day –PBS

Dietary flavanols reverse age-related memory decline –Columbia University Medical Centre

dark chocolate

 

The actual study: Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults (Brickman et al., 2014)

High flavanol group: 900 mg cocoa flavanols and 138 mg epicatechin (that’d be a LOT of dark chocolate).

Control: 10 mg cocoa flavanols and 2 mg epicatechin

Study duration: 3 months

Funding: NIH & Mars lol

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Vegetable oil fatty acids are not essential. 

They are conditionally essential at best, only if docosahexaenoic acid (DHA) is lacking.  We can’t synthesize omega 3 fatty acids, and indeed they do prevent/cure certain manifestations of “essential fatty acid (EFA) deficiency” (Weise et al., 1958), but DHA can do all that and more.  Not that I recommend this, but a diet completely devoid of 18-carbon vege oil fatty acids will not produce EFA deficiency in the presence of DHA. (“vege,” rhymes with “wedge”)

Essential fatty acid metabolism

 

The “parent essential oils” are linoleic acid (LA) and alpha-linolenic acid (ALA).  The others, which I think are more important and the truly “essential” ones are eicosapentaenoic acid (EPA), arachidonic acid (AA), but mostly just DHA.

The first manifestation of EFA deficiency is dermatitis (Prottey et al., 1975).  Some people say LA is necessary to prevent this, but it would be better phrased as “LA prevents dermatitis;” not “LA is necessary to prevent dermatitis.”  All of the evidence suggesting LA is essential is in the context of DHA deficiency.

Technically, we can convert a bit of ALA to DHA, estrogen helps, testosterone doesn’t (women have better conversion rates)… and I’d speculate that the reverse is probably easier (DHA –> ALA).

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Ketoadaptation and physiological insulin resistance

This is where the magic happens.

Rat pups, fed a flaxseed oil-based ketogenic diet from weaning onward – note the drop-off in ketones after 2 weeks (Likhodii et al., 2002):

flaxseed ketogenic diet

What happened on day 17?

Patient history: these rats have been “low carb” their whole lives.

Side note: flaxseed oil is very ketogenic! (Likhodii et al., 2000):

ketogenic rodent diets

Flaxseed oil-based ketogenic diet produced higher ketones than 48h fasting; the same can’t be said for butter or lard.  PUFAs in general are more ketogenic than saturated fats in humans, too (eg, Fuehrlein et al., 2004):Saturated polyunsaturated ketones

Crisco keto (adult rats) (Rho et al., 1999):

shortening-based ketogenic diet

suspect those two rogue peaks were experiment days…

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2 New Diet Studies

*ugh* journalists

I’m talking to you, Mandy Oaklander!

Regarding the new low carb vs low fat study, she writes: “Popular diets are pretty much the same for weight loss, study finds.

Effects of low-carbohydrate and low-fat diets: a randomized control trial (Bazzano et al., 2014)

Further, “An earlier study in Annals of Internal Medicine did find that low-carb dieters lost slightly more weight than low-fat dieters after one year. The study today reached similar conclusions, but the differences in weight loss were not significant.”

Perhaps Mandy just doesn’t realize there’s a difference between significant, as in “meaningful,” and significant, as in “P<0.05.”  Pro-tip: you can tell them apart relatively easily, because the latter is usually accompanied by a cute little asterisk.  For example, the differences in weight loss were quite statistically significant (P<0.05):

Bazzano BW
She goes on to say “After a year follow-up, some of those pounds crept back for people on both diets…”

To that I say: yeah, but fat mass continued to decline in those on the low carb diet, meaning some of that weight re-gain was muscle:

Bazzano FM

So, between 6 and 12 months, carbs and calories were creeping up in the LC group, yet fat mass was still declining.  Perhaps this way of eating improved their metabolism, or restored the ability to effectively partition nutrients.

***in real-time: at this point, I realize that Mandy was actually talking about the other study, which she was covering accurately.  Sorry, Mandy!***

Bazzano PA

…so maybe the low-carb (LC) diet improved muscle mass because it was also high protein? …perhaps, but 19% vs 24% (71 vs 85 grams) isn’t a very big difference.  Alternatively, since the LC group really just maintained absolute protein intake (86 grams at baseline, 85 at month 12), whereas low-fat (LF) dieters decreased (86 grams at baseline, 71 at 12 months); perhaps this is why LF lost muscle mass..?  Still, those changes in protein intake are small, and I think people can be too quick to chalk up the benefits of LC to “high protein.”

In sum, this is actually one of the more “pro” LC studies.  And it wasn’t even a huge difference in carbs: 198 vs 127 grams/d at month 12 (54% vs 34%).  Big difference in fat mass; and CRP, a marker of inflammation, even declined in the LC group.

Low fat diet advocates have been giving me headaches for years… the low fat diet caused headaches (P<0.05):

Adverse Events 1

 

 

Adverse Events 2

The study Mandy was actually talking about: Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis (Johnston et al., 2014)

It was a meta-analysis, which is just about the only type of study capable of taking down LC.

 

 

…but at least it had this cool chart (modified):

cool chart (modified)

cool chart (modified)

 

*ugh* scientists

crap

The macro’s in “Low fat” overlap with “Moderate,” implying “Low carb” is “EXTREME”  …the authors’ bias is subtle, I’ll give ‘em that, but I’m getting too old for this.

Dear Obesity Researchers,

If you want to design a study showing a low fat diet is as good as low carb for fat loss, here’s your best bet: recruit young, exercise-tolerant overweight patients who aren’t on any meds.  PROOF (see Ebbeling study).  Or find 10 similar ones and write up a pro-LF meta.

If you want to show low carb is better, recruit patients with obesity.

 

calories proper

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Ketosis in an evolutionary context

Humans are unique in their remarkable ability to enter ketosis.  They’re also situated near the top of the food chain.  Coincidence?

During starvation, humans rapidly enter ketosis; they do this better than king penguins, and bears don’t do it at all.

Starvation ketosis

 

Starvation ketosis

Humans maintain a high level of functionality during starvation.  We can still hunt & plan; some would even argue it’s a more finely tuned state, cognitively.  And that’s important, because if we became progressively weaker and slower, chances of acquiring food would rapidly decline.

Perhaps this is why fasting bears just sleep most of the time: no ketones = no bueno..?

Observation: chronic ketosis is relatively rare in nature.  Angelo Coppola interpreted that to mean animals may have evolved a protective mechanism against ketosis (if you were following along, please let me know if this is a misrepresentation).

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Circadian phase delays and metabolism

Remember the “jet lag-resistant” mice?  Guess what: screw with circadian biology and metabolism pays the price.

In brief, vasopressin was classically thought of as an anti-hypotensive hormone.  The vasopressin analog Desmopressin is used to treat bed-wetting.  But vasopressin biology is much more interesting than that: mice lacking both vasopressin receptors require very little time adapting to large circadian phase changes.  And as with many fundamental concepts in chronobiology, this is intimately linked with metabolism.

People with certain polymorphisms of the vasopressin receptor, V1A, exhibit elevated blood glucose levels and are at greater risk for diabetes (Enhorning et al., 2009):

genotype

This risk is strongest in men in the highest quartile of fat intake, and is statistically more significant after adjusting for age and physical activity:

Fat consumption

This study wasn’t designed to be a very powerful indicator of diet-disease relationships, but a little speculation: some think higher fat [and lower carb] intake should be protective against diabetes… which may be true, for people who can tell time.  Alter one nucleotide in the vasopressin 1A receptor gene and the game changes.

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Protein “requirements,” carbs, and nutrient partitioning 

One way to determine protein requirements is the nitrogen balance technique.  If all of the nitrogen from dietary protein intake is equivalent to that lost via feces, urine, and sweat, then one is in nitrogen balance.  Growing children and pregnant women are usually in positive nitrogen balance, because much of the nitrogen is being invested in the growth of new tissue.  Cachectic cancer patients and sarcopenic elderly may be in negative nitrogen balance, because they’re losing lean mass.

Protein requirements to maintain nitrogen balance are largely dependent on total energy intake.  More calories in, less protein needed.  For people in negative energy balance (losing weight), this usually means more protein is required else muscle will be wasted.

Exercise lowers, not raises, protein “requirements,” because exercise is a potent anabolic stimulus; it helps preserve nitrogen at any level of dietary protein.  That’s not to say more won’t improve functional outcomes; just that it’s not “necessary” to prevent muscle loss.

Need =/= optimization.

Lastly, total grams, not percent of calories, is the most relevant way to talk about protein requirements in the context of nutrient partitioning and body composition.  This is just how protein operates.

Part 2.  The poor, misunderstood Randle Cycle

“The glucose-sparing effect of fat-derived fuels” …when you’re body starts burning more fat (and fat-derived fuels; ie, ketones), it’s use of glucose declines.  Thus, it’s “glucose-sparing” (spares glucose for the brain and obligatory glycolytic tissues, yada yada yada).

During starvation, much of that glucose comes from amino acids from skeletal muscle proteins, so it can also be phrased as: “the muscle-sparing effect of fat-derived fuels,”  which is equally biologically relevant, because similar to zeroglycemia, an unabated loss of muscle is incompatible with survival.

That is, in starvation, where the “protein” is skeletal muscle, not dietary (because starvation)… but what about when following a low carb or ketogenic diet – do ketones (fat-derived fuels) exert a muscle-sparing effect in this context?

One study compared the impact of two isonitrogenous diets, low carb (Diet A) vs. high carb (Diet B), on nitrogen balance and showed that, except at very high levels of energy intake, nitrogen balance was consistently better on high carb.

carbs vs protein req

 

However, 51 kcal/kg is the textbook number of kcals “required” for young, moderately active adults.  With this understanding, it could be interpreted to mean that nitrogen balance is better with low carb (Diet A) for people in energy balance; and better with high carb (Diet B) if energy deficit.

edit: 51 kcal/kg is for athletes; probably about 20-25% less for non-athletes.

Or not: in another study, a low carb diet promoted better nitrogen retention albeit less weight loss than an isocaloric low fat diet.  The low carb group lost slightly more fat mass, which, combined with nitrogen balance data, suggest modestly improved body composition.  The differences were small, because this was a “non-ad lib” isocaloric diet study.  In the absence of large differences in intake, the most we can expect from such studies are subtle alterations in nutrient partitioning (which are usually difficult to detect).

Cancer cachexia is a condition of severe muscle wasting, and one study set out to determine, more directly, if ketones spared muscle in this context.  The study only lasted one week, but I suspect a certain degree of expedited ketoadaptation because: 1) it was very low in carbohydrate; 2) the fat was primarily MCTs; 3) they supplemented oral ketones; and 4) energy expenditure is elevated in this population.  Both the control and ketogenic diets were modestly hypercaloric, but nitrogen balance was more favorably improved by the high carb diet, in contrast to the above studies.

Thus, ketones don’t work in the context of a hypercaloric diet; however, pharmacologically elevating ketones via intravenous infusion in fasting subjects does work (because it’s more like starvation).

The muscle-sparing effect of fat-derived fuels is conceptually and physiologically more relevant to starvation, not nutritional ketosis.

Part 3.  Protein “requirements”

Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial (Pasiakos et al., 2013) 

Protein intake was 1x, 2x, or 3x the RDA; fat was 30% of calories, and carbs made up the rest; on a weight maintenance diet and again on 30% calorie restriction (it was technically a 40% energy deficit, because they tried to ramp up energy expenditure with exercise).

RDA

All groups lost weight, but the ratio of fat to muscle loss was significantly higher in the 2x and 3x RDA groups, which amounted to ~120 and 185 grams of protein per day, respectively.  The 3x group didn’t fare as well, possibly, because that much protein induces a high degree of satiety – this group ended up consuming significantly fewer calories than the 2x group.  So the interplay between energy intake and protein requirements is back on the table: the added energy deficit apparently increased protein requirements to some level above 185 grams per day.  Not much, given the small difference in muscle loss, but increased none the less.

Side note: be cautious when interpreting a study about the amount of protein required for xyz endpoint, because such studies usually only measure one of many important markers, and they don’t report absolute changes in size, strength, etc.  Also, context matters.

For example, Moore and colleagues (2014) showed that 0.24 g/kg (17 grams for a 70 kg adult) was enough to maximally stimulate myofibrillar fractional synthetic rate (mFSR):

mFSR

However, in the contexts of three square meals and energy balance (or deficit), 0.72 g/kg (50 g/d) is woefully inadequate.  Point being: mFSR (in this case) is only one measurement and shouldn’t be extrapolated to total daily requirements.  Perhaps you could eat six 17 g servings in order to fully maximize 24-hour mFSR, or you could realize that going above what saturates mFSR isn’t a bad thing, or wasteful.  mFSR is just one of many measurements of muscle protein balance.

My opinion

For those who need exact numbers, hopefully one point I’ve made is that there’s no answer to this question.  I’d guess that most people “need” 100+ grams of protein per day (more if losing weight), and 100 grams is probably too much in one sitting.  Also, need =/= optimization, and context matters.

Nutritional ketosis doesn’t appear to reduce the amount of dietary protein necessary to maintain lean mass.  The muscle-sparing of fat-derived fuels works during starvation; in other contexts, all bets are off.

calories proper

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