Author Archives: Bill

3 strikes – funny

Posted on February 2, 2018 | 1 comment

Weight reduction does not induce an undesirable decrease in muscle mass, muscle strength, or physical performance in men with obesity: a pilot study (Kim et al., 2018)

Cut & paste abstract. Literally.

“To date, there have been no reports on whether weight reduction causes decreases in muscle mass, muscle strength, or physical performance that could lead to health problems. Thus, in this pilot study, we investigated the appropriateness of the changes in muscle mass, muscle strength and physical performance after weight reduction.

Obese men who completed a weight reduction program to decrease and maintain a body mass index (BMI) of less than 25 kg/m2 for one year were recruited for the study. One year after the completion of a weight reduction program, the participants’ muscle mass, muscle strength, and physical performance were compared with those in a reference group composed of individuals whose BMI was less than 25 kg/m2. Whole-body scanning was performed using dual-energy X-ray absorptiometry to analyze muscle mass. Handgrip strength and knee extensor strength were measured to evaluate arm and leg muscle strength, respectively. For physical performance, a jump test was employed.

The results showed that the biceps, triceps, subscapular, and suprailiac areas of professional fashion models were significantly thinner than those of women in general (p<.001), and that their waist size was also significantly smaller (p<.001). However, hip circumference showed no significant difference. Body mass index, waist-to-hip ratio, and body fat (%) in professional fashion models were significantly lower than those in women in general (p<.001), while the body density in professional fashion models was significantly greater (p<0.001).

Weight reduction participants showed an average reduction in body weight of -16.47%. Normalized arm muscle mass and handgrip strength were significantly greater in the weight reduction group than in the reference group; however, no significant differences were detected between the two groups with respect to the other variables. After one year, there were no significant differences between the two groups.”

Wait, wut

O_o

I’m blaming that one on the journal. They made a mistake — strike 1. I read it twice before laughing out loud.

 

Table 1.

Given the title of the paper… statistically significant reductions in all of the muscles they measured. Strike 2.

I reiterate: given the title of the of the paper, statistically significant reductions in nearly every measure of performance. Strike 3. Strikes 2 and 3 are on the authors.

You’re OUT hahaha

 

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20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

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Posted in Advanced nutrition, muscle, strength

Chronobiological theories of mood disorders

Posted on January 28, 2018 | 1 comment

Another comprehensive review article: Chronobiological theories of mood disorders (Zaki et al., 2017)

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Here is my summary and opinions about it.

Tl;dr: the authors cautiously explored the bidirectional and/or causal effect of sleep & circadian disorders vs. mood disorders. I appreciated their caution but a lot of the evidence presented suggested circadian arrhythmia as a causal agent.

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) don’t address underlying circadian and seasonal rhythm dysfunctions, so patients are usually prescribed these meds indefinitely.

In the future, they see light therapy and melatonin receptor agonists as better treatments. I’d say an outdoor walk sunlight exposure after breakfast in the morning, blue blockers or nix artificial light at night, and instead of melatonin agonists, consider serine.

“The master clock controlling chronophysiological rhythms of theand body organs is located in the SCN…” VIP and AVP are abundant in the SCN! I knew it! LOL

“Humans’ endogenous rhythmic activity has a period slightly longer than 24 hours, hence, it needs daily entrainment to 24 hours with zeitgebers.”

Translation: SUNLIGHT AND BREAKFAST IN THE MORNING

Evidence favoring circadian and sleep disorders as causal agents in mood disorders:

For the rest of this article (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month gets you full access and there are many other options.

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UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE. 

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else. 

calories proper

 

 

 

 

 

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, Dopamine, melatonin, sleep, Sun, Vitamin D

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It STARTS with Sleep

Posted on January 22, 2018 | Leave a comment

In Nedeltcheva’s notorious weight loss study, those assigned to shorter sleep duration (5.5 hours) lost more muscle and less fat mass than those assigned to adequate sleep duration (8.5 hours). Same diet + same calories + circadian arrhythmia = no bueno.

*I’d say 8.5 hours can be called in this context. I like saying, seasonally, 8-9.5 hours of darkness, most of which should be spent sleeping. Others say 7-9 hours is adequate and <7 is inadequate. I agree with that, too*

Similar outcomes are seen in any number of sleep restriction studies. Figuratively, everything goes down the toilet. But that’s only half of the story.

There are a couple randomized intervention studies on intentional sleep extension and the results are very cool.

 

 

The effects of extended bedtimes on sleep duration and food desire in overweight young adults: a home-based intervention (Tasali et al., 2014)

They recruited habitual under-sleepers (<6.5 hours), recorded their sleep behaviors for a week, then gave them individualized behavioral counseling on sleep hygiene with the goal of extending their sleep duration to 8.5 hours. It worked: they were less sleepy, felt more vigorous, and spontaneously ate less sugar and fewer calories. Had the intervention lasted longer than 2 weeks, we would’ve seen body comp improvements as per Nedeltcheva’s study results. IT STARTS WITH SLEEP.

Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction (Leproult et al., 2015)

Similar set-up as above: 2 weeks initial monitoring, then 6 weeks where they slept about an hour longer. It worked. Total sleep time positively correlated with indices of insulin sensitivity.

Feasibility and emotional impact of experimentally extending sleep in short-sleeping adolescents (van Dyk et al., 2017)

Kids who normally slept 5-7 hours a night increased that by ~70 minutes for 5 weeks. It worked: reduced symptoms of sleepiness, anger, and confusion! Seriously?

Seriously.

Most of these studies basically just told the participants to go to bed earlier (in evening chronotypes) or sleep a little later (in morning chronotypes). It was individualized and not pharmacological. That means you can do it.

Check it: Blocking nocturnal blue light for insomnia: a randomized control trial (Schecter et al., 2018) CROSSOVER STUDY. Tl;dr: it worked. Blue blockers, FTW.

If you like what I do and want to support it, check out my Patreon campaign!

UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.

If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

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Posted in chronopharmacology, circadian, Dopamine

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Start paying attention to REV-ERB alpha

Posted on January 17, 2018 | 2 comments

Hey team, remember when I was making wild predictions about REV-ERB alpha?

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“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells). Heme is degraded into bilirubin.  Elevated levels of bilirubin cause jaundice. A treatment of neonatal jaundice is exposure to blue light. Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game. The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb.  Cool.” (From HERE)

and statements:

“Pharmaceutical-grade circadian augmentation = unwittingly better-timed meals? Improved body composition? …they were eating more and moving less. … One possible mechanistic explanation comes from mice lacking Rev-erb in skeletal muscle (Woldt et al., 2013). Mitochondrial biogenesis was impaired and exercise tolerance was reduced in these mice. Spontaneous physical activity was lower; thus, it stands to reason that Rev-erb agonism may improve skeletal muscle mitochondrial function. This isn’t entirely consistent with the drug study, but pretty close.” (From HERE)

 

REV-ERB is really really good for skeletal muscle.

Beta-hydroxybutyrate inhibits activation of the NLRP3 inflammasome.

 

 

Well, so does REV-ERB alpha! In a new study, knocking down REV-ERB alpha jacked up NLRP3 and pharmacologically enhancing it attenuated NLRP3 (Pourcet et al., 2017). The consequence of this in REV-ERB KO mice injected with LPS was hyper-inflation. No bueno. Mice given the commercially-available REV-ERB alpha agonist “Stenabolic” were protected.

I’m geeking out about REV-ERB alpha & SR9009. And fwiw, I don’t think anything will actually fully replace the benefits from actual physical activity and/or exercise, although it’s very hard for some people; eg, COPD, CHD, etc. In those populations, if they can’t exercise enough to really improve their condition, something like this might help. But I’m sure perfectly healthy people are going to try it. If you do, let us know in the comments!

For more about this fascinating research and how it can work for you (or if you just like what I do and want to support it), head over to Patreon! Five bucks a month gets you full access and there are many other options.

It’s ad-free and you can quit if it sucks 🙂

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE. 

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else. 

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Regulation of Circadian Behavior and Metabolism by Synthetic Rev-erb Agonists (Solt et al., 2013)

Rev-erb alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy (Woldt et al., 2013)

SERcadian Rhythms

“Seriphos“

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Posted in angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, depression, Dopamine, Exercise, melatonin, muscle, sex, sleep, strength, Sun, vasopressin

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Breaking: Melanopsin Discovered in Human Adipose Tissue

Posted on January 14, 2018 | Leave a comment

PRELIMINARY FINDINGS. PRELIMINARY.

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“It is clear that centrally mediated circadian rhythms play an important role in human health and our results provide initial information about how appropriate sunlight exposure to subcutaneous white adipose tissue (scWAT) might act as a peripheral circadian sensor that contributes to metabolic health. In contrast, a lack of sufficient bodily exposure to sunlight may contribute to long-term scWAT dysfunction and the current epidemics of obesity, diabetes and cardiovascular disease.”

WUUUUUT

Melanopsin is the blue light photon receptor in our eyes responsible for relaying sunlight to the SCN to entrain the central pacemaker. Well, a group of scientists accidentally discovered it fat cells:

Subcutaneous white adipose tissue express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis (Ondrusova et al., 2017)

Figure “C” takes the cake. Electrophysiology studies show this receptor is highly sensitive to 465 nm blue/green, meaning it’s probably definitely melanopsin.

and guess what it does?

LIPOLYSIS — see Figure “E” above. Activation of melanopsin reduces the size of lipid droplets and lowers leptin. Interestingly, it also reduces adiponectin.

 

 

They also discovered this in mice, who are covered with fur and most of their melanopsin-containing scWAT is on their bellies which would never be exposed to the sun anyway. So….

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UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.
If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE. 

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else. 

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HAMMER TIME

Breakfast

Sunlight

The power of a good walk

Circadian rhythms: blocking the blues. AND THE GREENS

 

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Need vs. Optimization: Omnivores & Carnivores.

Posted on January 9, 2018 | 4 comments

Humans are omnivores but does that mean we need to eat plants AND animals?

To address this, we first need to ask 2 questions:
1) need for what?
2) need vs. optimization?

STORY TIME

Scientists were determining the amino acid requirements of cats by feeding them semi-synthetic diets with various levels of each amino acid, one at a time. Tedious. A lot of cats x a lot of amino acids x a lot of levels of each amino acid = a lot of work. What made it even more difficult (and equally more interesting) was that they didn’t know what they were looking for — this was long before we knew what we know now about biology.

Tyrosine

Funny thing, when they got to tyrosine: below a certain level and their black cats started turning red! At an even lower level, certain neuroloogical abnormalities set in. So, how much tyrosine do cats need? Enough to maintain their beautiful black coats? I think we can all agree that the level which induced neurological abnormalities was too low. What about fur color?

 

What if female cats prefer males with beautiful black coats? So the males have a better chance at reproducing if their diet is at the higher level of tyrosine. I’d say fur color is pretty important in this #context! [how ya like ‘dem apples]

Need vs. Optimization

Note: this occurred over the course of weeks-to-months, not hours-to-days.

Note (2): unlike humans, cats are obligate carnivores. Real, actual, carnivores.

 

 

Arginine

Below a certain level of arginine and the cats looked dizzy, wobbled around, and some of them died.

Not weeks-to-months. Hours-to-days. This is what it’s like to be a carnivore. They NEED to eat meat or die rapidly (this is one of the few examples of an acute nutritional deficiency causing severe toxicity in the entire animal kingdom).

Cats have an inability to downregulate protein degradation and need arginine to dispose of the nitrogens via urea cycle. Humans just reduce burning proteins when protein intake is low.

 

 

Part 2. Lobsters are omnivores and arginine is weird.

Lobster tail is rich in arginine (this might be what gives it a bit of a sweet-like flavor). If lobsters are fed an arginine-deficient diet, they go cannibal and eat other lobsters’ tails!

What does this say about lobster arginine requirements?

Need vs. optimization: they’re perfectly healthy, but is preventing cannibalism a “need?”

. .  .   .     .        .             .                     .

 

 

So, I ask again: Humans are omnivores but does that mean we need to eat plants and animals?

One retrospective study showed stroke victims who had consumed blueberries the day before showed significantly less cognitive decline post-stroke than those who hadn’t. Blueberries. Not green tea, blackberries, or dark chocolate. Blueberries. Do humans need to eat blueberries?

What if this was confirmed in a double-blind RCT? Is preventing post-stroke cognitive decline a need or an optimization?

Which is more important to you?

I didn’t have it in me to put this behind a paywall because while I think the answer is getting simpler & simpler (eg, Sunlight, Hunger-Free Diet[s] and DietFits, hot Blue-Blockers, etc.), fad diets are getting weirder & weirder. Just eat like an adult.

That’s all for now!

For personalized health consulting services -> drlagakos@gmail.com

Check out my Patreon campaign! Full access for a five bucks a month and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

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Posted in Advanced nutrition, diet, mortality, Protein

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Is gluconeogenesis demand-driven? answer: it depends (#context strikes again!)

Posted on January 4, 2018 | Leave a comment

Context #1. The easiest way to explain gluconeogenesis (GNG) is how it relates to starvation. If you’re not eating food, your brain still needs a steady supply of fuel. Mostly glucose at first (ketones come later), but since you’re not eating anything, glucose comes from hepatic GNG (huge potential supply*) or glycogenolysis (limited supply). *One of the precursors for GNG, glycerol, comes from stored fat (which you’ll die of something else before you run out of stored fat bc GNG).

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In this case, it is mostly true that GNG is demand-driven.

 

If you’re interested in this, more HERE.

 

Context #2. Protein (which also contains GNG precursors) doesn’t acutely increase glucose. But you might think protein does convert to glucose via GNG but protein also induces a splash of insulin which is why blood glucose doesn’t rise. Read this blog post at least up to the awesome Fromentin study: “8% of the blood glucose produced under optimal gluconeogenic conditions came from dietary protein.” But also check out the Conn & Newburgh studies. And Gannon.

 

 

This is usually the reason recreational keto dieters say they can be high protein, which either ends up looking like PSMF or it’s probably not very ketogenic (which doesn’t really matter in this #context; protein is restricted in therapeutic ketogenic diets).

#BenignDietaryKetosis #BDK

 

 

For the rest of this article (or if you just like what I do and want to support it) head over to Patreon! Full access for a measly five bucks a month and there are many other options. It’s ad-free and you can cancel if it sucks 🙂

Also, I’m open to suggestions, so please don’t hesitate to leave a comment or contact me directly at drlagakos@gmail.com.

Affiliate links: still looking for a pair of hot blue blockers? Carbonshade  is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. TrueDark is running a pretty big sale HERE.  BLUblox just upped their game with their 550‘s.
If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE. 

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else. 

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Context #3. the mouse doctor is in 🙂

Context #3b. Chronic high protein.

Context #4. Random thoughts on animal foods.

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Posted in Advanced nutrition, diet, epilepsy, gelatin, gluten, insulin, Ketosis, liver, muscle, Protein, strength, TPMC

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Poor sleep, “dietary disinhibition,” and weight gain

Posted on December 30, 2017 | Leave a comment

“Dietary disinhibition”

In school, the concept was taught like this: recruit a bunch of people and tell them it’s for a cookie taste-testing project. Give them a form with a bunch of questions about cookie quality (taste, texture, sweetness, etc.) and a plate of cookies.

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SWITCHAROO!

They aren’t there for a cookie taste-test. It turns out that some people experience “dietary disinhibition” wherein if they eat one cookie, they think something like “well, I’ve blown my diet for the day, so might as well just eat the whole plate of cookies” (actually, I’m pretty sure it’s way more complicated than that, but I learned it in a nutrition class, not a psychology class).

It’s not a lot of people — most would just take a bite and fill out the questionnaire — but it’s been replicated in enough settings that it’s probably a real phenomenon.

Continue reading →

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Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, cancer, chronopharmacology, circadian, depression, diet, Dopamine, Energy balance, fertility, Fish, melatonin, mortality, muscle, Protein, sex, sleep, strength, Sun, vasopressin, Vitamin D

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Brain Health: Intermittent Fasting or Caloric Restriction

Posted on December 22, 2017 | 2 comments

Brief note: the definitions of IF and CR vary widely. For the sake of simplicity, in this article, if IF results in weight loss, then it’s also CR. CR, by definition, results in weight loss and typically includes ~3 meals a day. Neither diet specifies macros. Weight loss is a confounder to keep in mind.

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For example, in this 3 month-long study, 30% CR was compared to an increased unsaturated fatty acid group and a control group (Witte et al., 2009). CR group lost weight whereas the other two groups actually gained weight (unintended). In this study, 30% CR resulted in an apparently pretty impressive improvement in memory:

 

 

HOWEVER: The actual dietary changes in each group were… interesting (see Table S1) — the control group ended up doing dietarily almost exactly what the CR group did… so why didn’t their memory score improve? Why didn’t they lose weight? I don’t know, but something seems fishy.

CR garners zero points for this.

 

 

Next on the docket is a systematic review (Benau et al., 2014), which concluded: “The combined results are equivocal: several studies report no observable differences as a result of fasting and others show specific deficits on tasks designed to test psychomotor speed, executive function, and mental rotation.” That was based on 10 studies. Given the nature of human biology, “no effects of IF” would not have been unexpected. Kinda surprised at all of those negatives.

The ice age fairy tales go something like this: no food for a day or two improves your cognitive capacity, makes you sharper so you can get your next meal (be it via hunting, gathering, or whatever).

I’m not anti-IF; in fact, I think everyone in weight maintenance should be able to go through the night without the need to wake-up to eat. I’m just commenting on the available studies by people who aren’t selling books on the topic.

For the rest of this article or if you just like what I do and want to support it, head over to Patreon! Five bucks a month for full access. It’s ad-free and you can cancel if it sucks 🙂

Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. TrueDark is running a pretty big sale HERE. If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. (I recommend Lion’s Mane for the brain and Reishi for everything else). 

 

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Posted in Advanced nutrition, diet, Energy balance

Intermittent fasting is nothingsauce

Posted on December 18, 2017 | Leave a comment

So Twitter got supermad when I said the human studies on intermittent fasting are not compelling. Not the anecdotes or n=1’s. The actual human studies.
And instead of “not compelling,” I may have said “nothingsauce.”

Hilarity ensued. I was bombarded with
ALL.
THE.
ANECDOTES.

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Someone was kind enough to send me all the proof that I was wrong. Here are the 5 non-Varady studies, reviewed.

Tl;dr: as long as you’re not eating like a child, “Eating > not eating. QED.”

 

 

Alternate day calorie restriction (ADCR) improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma (Johnson et al., 2006)

Study design: n=10, 8 weeks, NO CONTROL GROUP. Every other day they ate 20% of normal and ad lib the other days. This would’ve been much cooler if they included a 40% caloric restriction and weight maintenance (WM) control groups. The former to see if ADCR was superior to a similar reduction in energy intake and the latter because people behave differently when their being observed (regardless of which group they’re in) (few studies include a WM control group).

Result: body weight declined by 8%. Is that worth having nothing but a snack every other day? How about compared to 40% CR? Nothingsauce?

Oh yeah, uric acid increased and BDNF decreased. So, gout, kidney stones, and cognitive deterioration. Yummy nothingsauce.

 

The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women (Eshghinia et al., 2013)

Study design: similar to the above, and also lacking a control group.

Result: BW declined by 7%.

Critique: same. No control group. Would this have been better than CR or anything else? They basically just say “it’s relatively safe;” but it’s not, really… and some forms of intermittent fasting can have harmful side effects.

 

For the rest of this article (including some LOLZ & facepalming), head over to Patreon! It gets better (or worse, depending on how you look at it): metabolic mayhem, rebound hyperglycemia, some circadian chicanery #eTRF, and much more.

And stay tuned: since BDNF actually declined in the Johnson study, I’m following up with a review of intermittent fasting vs. various aspects of cognition, memory, mood, sleep, etc.

On Patreon, five bucks a month gets you full access. It’s ad-free and you can cancel if it sucks 🙂

UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade and TrueDark are offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE.

If you have no idea what I’m talking about, read this then this.

20% off some delish stocks and broths from Kettle and Fire HERE.

If you want the benefits of  ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.

Join Earn.com with this link. 

 

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Posted in Advanced nutrition, diet, Energy balance, insulin, Ketosis, muscle, Protein

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