The poor, misunderstood calorie

or nicotinamide mononucleotide (NMN)

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There is some banter about which is the better NAD+ precursor, but I don’t think it really matters. They are interconverted in vivo and cost about the same…

NR has been studied in both humans and rodents whereas NMN research is primarily rodents. I’m usually biased toward human studies, but again, I don’t think it matters in this #context.

Why NAD+ ?

Because OMG all of the animal studies! It’s like resveratrol all over again…

oh wait…

But seriously, old mice given either NAD+ precursor look like young mice by nearly every measure. NR and NMN have never been directly compared, but both produce equally positive effects in the various rodent models in which they’ve been tested.

And I’m fairly well-convinced NAD+ levels do decline with age…

Anyone gonna try NR or NMN? Let me know in the comments!

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calories proper

You can say that again!

Hot off the presses (Paoli et al., 2019).

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Good paper. Nice background with information about muscle protein balance, anabolic & catabolic factors, and signaling pathways.

At one point the authors seem to have confused a study on starvation ketosis with nutritional ketosis, but in all fairness they also acknowledged the study showing beta-hydroxybutyrate can inhibit AKT which is important for skeletal muscle hypertrophy (Yamada et al., 2010).

Let’s dive right in to Table 1 which is a summary of human studies on keto & lean mass:

Starting with the study by Wood and colleagues (2010), who studied: a low fat diet, low fat + exercise, keto, and keto + exercise. Everyone lost weight. The low fat group lost significantly more lean mass than any other group. The authors interpreted this to mean keto “had a protective effect on muscle mass.”

LFD+ex, Keto, & Keto+ex all lost the same amount of lean mass although the keto groups were getting 50% more protein.

Another interpretation, one could say that 50% more protein and even resistance exercise weren’t enough to prevent keto-induced muscle loss. They lost just as much lean mass as LFD+ex and Keto.

Jabekk and colleagues compared resistance exercise + usual diet with resistance exercise on keto (Jabekk et al., 2010).

The authors concluded: “a general conservation of muscle mass.”

That’s OK, but the control group gained lean mass! Thus, an alternate interpretation could be that keto blunted muscle gains.

Not acknowledging the control groups, as in Table 1, is a not-so-subtle-way of shifting goal posts imo.

Similar issues in the study by Paoli and colleagues (Paoli et al., 2010)…

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calories proper

text

outro2

New review out of Pittsburgh, Pennsylvania, gets some things right (Sherrier and Li, 2019).

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… takes some things out of context, too, like saying “beneficial effects of ketogenic diets on cancer,” as if that’s an established fact.

It’s not… but still, let’s focus on the positive

Some ground rules:

1. ketogenic diet =/= fasting
2. nutritional ketosis =/= exercise
3. carbs =/= obesity
4. the opposite of intermittent fasting isn’t diabetes

Another ground rule, or maybe a disclaimer: I’ve read and blogged about nearly every study on ketoadaptation & physical performance that’s out there. My 30000-foot view is: “it’s fine.”

Given adequate time to adapt (~3 weeks), keto doesn’t wreck physical performance. Some studies show a little positive, some a little negative; net sum = neutral.

Other energy systems kick in and performance is maintained. Any further gains from training are just that: gains from training (not gainz from moar ketoadaptation).

Keto isn’t muscle-sparing or anything like that, and you likely need more protein (not less) to maintain muscle, but this also isn’t really that big of a deal.

This article is pretty good, imo. Covers a lot of topics ranging from glycogen on keto to fat balance to exercise efficiency and more.

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calories proper

Three studies. Predicted effects on body composition & glucose tolerance?

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5/2 (Panizza et al., 2019): this is a form of intermittent fasting (IF). Two consecutive days you eat 70% less than usual; the other five days you eat at maintenance. It’s not ‘ad lib;’ there’s some calorie counting involved.

This study design was a little odd, but it’s cool that it came out around the same time as the other two (ADF & new eTRF) so we can cover a lot of ground in a short amount of time.

Is it fair to compare 5/2, higher protein, lower carb, Mediterranean diet to a lower protein, higher carb DASH diet? Predicted effects on body composition?

And I even say some nice things about fasting 🙂

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calories proper

The mystery of the ketogenic diet: benevolent pseudo-diabetes (Blagosklonny, 2019)

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“studies in rodents have found that the ketogenic diet causes diabetes”

Narrator: No, they don’t. In fact, rodent keto studies are all over the board.

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Sometimes glucose tolerance is up, sometimes it’s down, sometimes it depends on what you’re actually comparing it to — is the control group low fat or the notoriously misnamed high fat diet (it should just be called an obesogenic diet imo).

off topic — just found these and they’re awesome. Check out the digits.

OK, in some studies, keto mice are insulin resistant. Sometimes it correlates with body weight. See all the ‘somes’ here? You can’t make broad statements about rodent keto studies.

And you definitely can’t use them to support recommendations for human diabetes/obesity.

this probably isn’t even keto’s strongest suit anyway…

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calories proper

SMH

Time-restricted feeding plus resistance training in active females: a randomized trial (Tinsley et al., 2019)

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Hate to be a buzzkill because this was actually a well-designed and well-conducted study.

I’m not a huge fan of intermittent fasting (IR) because it’s usually shown to be no better than continuous energy restriction (CER) yet also require prolonged periods of severe energy restriction.

Also, if forced, I’d recommend starting with eTRF or an early dinner; the point being to extend the fasting window by starting it earlier in the day rather than ending it later — there might actually be some metabolic benefits of this over isocaloric CER.

And in this case especially, athletes, who benefit from increased protein-feeding frequency which is removed from IF by design (although the authors attempted to partially bypass this by adding some HMB to an IF group).

#context: this wasn’t eTRF. It was skipping breakfast. These weren’t older insulin resistant people. They were young females with resistant training experience.

So, tell me again, how fasting induces growth hormone secretion which promotes the anabolic potential of skeletal muscle?

Breakfast and a late lunch instead?

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calories proper

The energy expenditure and food intake of individual men.

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So, this study has been making the rounds: Skipping Breakfast Before Exercise Creates a More Negative 24-hour Energy Balance: A Randomized Controlled Trial in Healthy Physically Active Young Men (Edinburgh et al., 2019)

I didn’t want to comment on it because critics could easily say I was just biased (many studies support breakfast from a variety of angles therefore so do I).

Does skipping breakfast allow your to maintain an energy deficit and lose excess body fat? If so, GO FOR IT. Skipping breakfast may not be optimal long-term wrt health & general well-being, but it’s better than carrying around excess body fat for decades.

I don’t buy intermittent fasting does much beyond that — with the exception of a few studies on eTRF (early Time-Restricted Feeding) which showed favorable effects on weight loss, insulin sensitivity, and fasting blood glucose. Not entirely sure why this happens with skipping dinner and not skipping breakfast but it is what it is. Probably has something to do with, ya know, circadian rhythms.

Regulation of energy balance –

1) I think the Edhold 1955 study on the short- vs. long-term regulation of appetite is great. Both what they did and their discussion.

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calories proper

Ask almost anyone who experiences chronic migraines and they’ll almost always say their latest attack was preceded by a period of poor quality or short duration sleep.

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That, in itself, is a hint circadian rhythms may be involved.

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Can circadian dysregulation exacerbate migraines? (Ong et al., 2018)

In this study, sleep characteristics and circadian rhythms were evaluated in 20 chronic migraine sufferers and 20 healthy controls.

They found that, despite similar sleep duration, later sleep timing and circadian dysregulation (as per salivary melatonin) were associated with higher migraine frequency and severity.

It is seriously unpleasant, but migraines can be experimentally induced in otherwise healthy people (eg, Amin et al., 2012).

PACAP. We’ve talked about this before. It’s a pretty big player in regulating circadian rhythms.

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calories proper

ApoE4: The door to insulin resistant dyslipidemia and brain fog? a case report (Stoykovich and Gibas, 2019).

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A retired business who was exposed to artificial light, day and night, his entire adult life. Insomnia. Last 15 years had T2D. Now, foggy thinking, forgetfulness, and impaired verbal fluency.

We aren’t given many details about his 10-week hypocaloric ketogenic diet but that’s OK in this case, as ‘hypocaloric’ was confirmed via weight loss, ketosis was confirmed via ketometer, and, well, this:

A little weight loss goes a long way. And those ketones may have helped, too…

Flash forward and we get this:

Ketones improves apolipoprotein E4-related memory deficiency via sirtuin 3 (Yin et al., 2019)

Wait, is it Sirt3 -> ketones or vice versa?

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calories proper

40 years late, sue me 🙂

These small, short duration studies suggest switching people from an ADA diet to a high carb, high fibre, whole food-based diet (HCF) would be of benefit in T2DM (Kiehm et al., 1976 and Anderson and Ward, 1979) (and longer-term follow-up with similar results).

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These studies have been blogged about. Like, a lot.

The diets were approximately isocaloric (not much weight loss on either); lower protein in the first study, same protein in the second.

Study design: relatively weak — 1 week on ADA diet, followed by 2 weeks HCF.

Strengths: the second study was in a metabolic ward and controlled for protein, and the long-term follow-up was at 15 months. Weight stable for the most part.

Here’s the rub:

1. HCF didn’t work in the most insulin resistant group. Fasting glucose actually seemed to improve a bit on ADA and then appeared to deteriorate in some individuals on HCF.

For the rest of my take on these studies and more, head over to Patreon! Join the community for up-to-date information about a variety of topics in the health & optimizing wellness space. Five bucks a month for access to this and all previous articles. It’s ad-free and you can cancel if it sucks  

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calories proper

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