High calorie and BCAA/Isoleucine restriction for weight loss

[nigma]

Some relatively new research has shown that BCAA (leucine, isoleucine and valine) restriction is responsible for the weight loss seen in protein restricted (PR) diets. As opposed to calorie restricted (CR) diets, the metabolic rate doesn't decrease as happens in CR and in some cases it seems weight loss is accelerated when extra calories are consumed. Most of the studies are in rodents, but some are in people. Some very recent research (Nov 2023) has narrowed it down to just 1 of the 3 BCAAs, isoleucine.

Brad from fireinabottle.net and @exfatloss from Twitter/X have been covering the research. I'll summarize the research and relate it to Ray's general advice for weight loss.

Only BCAA supplementation for inhibiting serotonin has been advocated on the RPF. But maybe getting adequate calcium is as good for lowering serotonin. Without calcium, tryptophan goes to serotonin, with adequate calcium, it goes to niacin.

Its been known for a while that the obese have high circulating BCAAs. In studies comparing lean vs obese people under a weight loss protocol, the lean burn more protein as fuel than the obese. This is also seen in animals during torpor, where for months they will go without eating, but their lean tissue is conserved, they wouldn't last many winters if they didn't do this. Animals in torpor also have high blood BCAAs. So a hypothesis is that the obese are in some kind of torpor-like protein sparing state and it seems eating a diet low in BCAAs (around 8g a day) is enough to switch out of this state.

In the above clip Ray mentions tryptophan, cysteine, and methionine as amino acids that are only needed in extremely low amounts in adults, they are growth amino acids. BCAAs are also critical to growth, its no surprise then that milk has one of the highest BCAA to total protein ratios, ~20%. But perhaps in the obese these amino acids are inhibiting a higher metabolism and weight loss? Fruit is lowest in BCAAs.

This kind of weight loss diet, while not low calorie, is low overall protein, since theres no easy way to eat only low BCAA protein sources. Gelatinous cuts of meat are the best. In the PR rodent experiments, protein is 7% of total caloric intake, higher and the effect drops of quickly.

PR (10%) study in people from exfatloss link

The protein is not even that low when compared to RDA.

PR study in mice from exfatloss link

PR study in mice from exfatloss link

Eat more and move same, results in lost weight and "increased energy expenditure".

PR study in mice from exfatloss link

Interestingly, here added BCAAs lead to extra weight gain.

PR study in mice from exfatloss link. Bottom right graph is "calories out".


High resting metabolic rate is a goal of a bioenergetic approach to health. i.e. how to get maximal energy throughput. Is BCAA acting as a metabolic brake in some susceptible people?

Perhaps its not even genetics that makes people susceptible, but it is triggered by environmental factors like PUFA combined with stress? We might suspect that once someone follows a low BCAA protocol like this and then returns to a lean state, that they wouldn't have to stay on the protocol since the metabolic pattern has been shifted.

I'll be trialling low BCAA myself, both for the weight loss effect, and the increased basal metabolism. The big difference compared with Ray's advice for weight loss is the lowered protein (though he did point to lowering methionine, cystine and tryptophan as a good thing) and dairy in particular, since he seemed to connect high dairy consuming cultures with leanness, but maybe the picture changes if your already broken metabolically? Using egg shell powder for the calcium lost with the reduction in dairy might be a good way to execute this while still keeping to Ray's diet principles.

@exfatloss: Show me the (BCAA) studies

 

[revenant]

Great summary, I've been researching the same subject lately. Also giving the low-protein diet a go currently. I did a high-protein diet (aiming for ~150g per day) for some months before this, it did not result in any weight loss and in fact I gained a few kg, whether that was muscle or fat, I don't know.

 

[cremes]

Thanks for posting this. I follow those guys on X and Reddit too. With Drynuary around the corner I’ll be dieting with my wife. We are agreed on a HCLF diet and I requested that our protein be treated as the “side dish” and the veggie be the main part of the meal. Coupling that with No Fat soup from broth I am hopeful we can hit our caloric targets while also achieving low protein.

 

[Ras]

Reminds me of Kempner's Rice Diet.

 

[cremes]

Reminds me of Kempner's Rice Diet.

Yes, his rice diet, the potato hack, or a fruitarian diet are all going to be low in BCAAs.

 

[Elie]

what about the fat content? how much difference does that make in this case?

 

[Alpha]

This might be the most ridiculous thread I've seen here. Eat your proteins.

 

[cremes]

This might be the most ridiculous thread I've seen here. Eat your proteins.

Yes, many people arguing with this position on X too. Apparently they aren't keeping up with the latest research. Science!

Start here, @Alpha , and read.

 

[Alpha]

Yes, many people arguing with this position on X too. Apparently they aren't keeping up with the latest research. Science!

Start here, @Alpha , and read.

Unlike most people, I actually read the studies.

Let's go through them one by one. I'll make one post per study for time purposes.

Study #1:

Ferraz-Bannitz R, et al. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial. Nutrients. 2022; 14(13):2670. Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial

Both groups were placed in a hospitalized setting for 27 days, one group on a 2,000kcal/day diet (PR), the other on 1,500kcal/diet (CR). The Protein Restricted (PR) diet had RDA protein per day, in no way deficient. Yet both groups lost 8% and 6.6% of their weight respectively, how can that be?

The experiment design is flawed, it is missing a control group, one of the most important methods in any credible RCT. How much would have they lost if fed isocaloric 20% protein? Most likely the same as the 10% group. Both groups were hospitalized with controlled diets, which probably meant they ate much higher quality foods compared to what they were eating before, that could explain why their metabolic syndrome biomarkers improved in both groups, and why you saw a similar weight loss. This is why a control group was essential in the experimental design, the authors are incompetent.

Let's look at the data again, CR seemed to have lost significantly more waist and hip circumference, yet weight loss was the same, how is that possible? Simple, the starting weights are wrong. This is particularly evident in subjects #1 and #4 of the PR group when you cross-check with the bioimpedance data.

Furthermore, the PR group started out, and ended with an average 20% higher BMR, so that makes the difference between the CR and PR groups for calorie restriction only -5% less, not -25%.

The average weight and height between both groups are the same, 81kg 1.65m approximately. 5.4kg and 6.9kg were lost in both groups PR and CR respectively. That was achieved in 27 days. This means you had to go in a 1,500 deficit per day for PR, and a 2,000 calories deficit in the CR group to achieve that fat mass loss.

Notice that the difference is 500 kcal. That's right, that was the difference in weight loss between both groups. The other 5.4kg came from a combination of higher-quality foods, and a significant underestimation of maintenance calories of only 2,000/day.

 

[Alpha]

Honestly getting tired, I shouldn't be doing this. I'll go more quickly through them.

Study #2:
Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

’ll leave you with this amazing quote:

Despite consuming more food, mice on the 7% PR diet gained less weight than mice on the 21% protein control diet over the course of 2 months.

Body composition analysis suggested that while consumption of a low-protein diet slowed the gain of lean mass, fat mass accumulation was almost entirely blocked.

Mice eating the 7% PR diet had no change in spontaneous activity, but exhibited increased respiration throughout a 24-hr cycle and had increased energy expenditure at night

So the protein-restricted mice:

1. Ate more
2. Gained practically no fat
3. Didn’t have reduced activity levels
4. Burned more energy

Protein leverage me that!

Uh, no.

Fat mass was unchanged in the 7% protein group, they did gain less weight, but surprise surprise, this is the same ***t I see in all protein restricted studies, body compsosition was the same or slightly worse due to lower MPS.

Also he missed something, blood glucose markers were worse in the lower protein group in an insuling tolerance test.

Next experiment:

Oh look, extremely low AA lost more weight than a normal diet!

Oh wait...

Next experiment,

From the study "we observed that mice fed a Low Leu diet showed a trend toward increased adipose mass and decreased lean mass; further, the mice appeared fatty upon necropsy."

Low BCAA, more insulin resistance

Also there is no experiment design outlined anywhere that I could find, despite the flaws in the results, make all the results ambiguous at best.

 

[Alpha]

Study #3:

The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine

Another study with no methodology or design listed.

Holy canneloni. Despite continuing on the crazy Western Diet, restriction of all BCAAs, valine, and especially our favorite, isoleucine, caused the mice to drastically lose fat mass. Within 3 weeks, all of those 3 were leaner than the control-chow mice, who had never been obese to begin with.

And check that out: the restriction of BCAAs/Ile/Val also caused the mice to eat more - way more! The isoleucine-restricted mice ate nearly 2x as much as the control or Western Diet mice. Talk about a deficit - eat 2x as much, lose 2/3 of the weight!

This study alone proves that you can apparently “break the laws of thermodynamics” and double your food intake, while dramatically losing weight, just by doing this One Weird Trick: restricting isoleucine

So the TLDR is low Ile is significantly catabolic to lean mass and fat mass by blunting hepatic gluconeogenesis and induing a state of hypoglycemia. Why weren't the numbers listed out instead of a heatmap, no idea.

Then they try to replenish Ile to see the impact of a low PR diet without it.

They conclude only Ile attenuated the "beneficial impacts" of a low protein diet.

What they don't show you is the supplemental data that you have to download separately.

All combinations of a low AA, or BCAA, or individual AA diets led to same or worse body composition, except for low Ile.

But here's the kicker, despite a lower body fat percentage, they also lost significant lean mass in absolute weight.

 

[Alpha]

Study #4:

Ramzan I. A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes. Nutrients. 2020 Dec 30;13(1):95. doi: 10.3390/nu13010095.

"As expected, both the BCAA-restriction diet and control diet did not affect weight or body–mass index (BMI)"

I don't get how this supports low PR/BCAA diet.

"Although it was not the main aim of this study (i.e., underpowered to robustly detect effects on HOMA-IR), we nevertheless observed that BCAA restriction was associated with a decrease in HOMA-IR levels in healthy subjects assigned to the BCAA-restricted diet over seven days, with a p-value approaching significance."

Is that all they have to show for, a terrible p-value of 0.1, lol.

 

[Alpha]

Study #5:

Resistance exercise protects mice from protein-induced metabolic dysfunction

Nothing to see here. Low protein group had less weight gain but body composition deteriorated.

You get the idea.

I'm out.

 

[cremes]

Thanks for your time, @Alpha.

 

[Michael Mohn]

Recently I was looking into lowering serotonin and acetylcholine through diet and ended with a lower protein diet of gelatin and cheese plus fruit and starches. After a week I noticed reduced fatigue, less bloating and a flat belly.

A few years back my diet was low protein/BCAA too being at my lowest body weight but I had to increase my protein because I felt stressed out after a while and consequently I gained weight again. Low protein works for lowering body weight but it seems to be an impossible long term approach.

 

[cremes]

Low protein works for lowering body weight but it seems to be an impossible long term approach.

Correct, it’s an intervention while you work on improving and stabilizing your metabolism. Few are pitching it as a permanent dietary change.

 

[Michael Mohn]

A problem with these studies is the combination of low protein and low BCAA. A diet with normal levels of protein but low levels of BCAA would be ideal for a study. What are sources of proteins with low BCAA other than cheese and gelatin? Potato juice maybe?

 

[Alpha]

A problem with these studies is the combination of low protein and low BCAA. A diet with normal levels of protein but low levels of BCAA would be ideal for a study. What are sources of proteins with low BCAA other than cheese and gelatin? Potato juice maybe?

That's a great idea. If you want to lose weight fast through muscle, organ, and bone wasting, low protein, especially low BCAA is a great way to do that, the data is very clear.

The added testicle and inguinal fat deposits is a plus.

 

[Dutchie]

A problem with these studies is the combination of low protein and low BCAA. A diet with normal levels of protein but low levels of BCAA would be ideal for a study. What are sources of proteins with low BCAA other than cheese and gelatin? Potato juice maybe?

Is cheese (relatively) low bcaa? I've read somewhere else that dairy and (muscle) meat are the highest sources of bcaa

 

[Michael Mohn]

Is cheese (relatively) low bcaa? I've read somewhere else that dairy and (muscle) meat are the highest sources of bcaa

The BCAA is in the whey portion of the milk. Cheese should be low in BCAA but looking into some food lists it seems to be a mixed bag, some cheese are high other low in BCAA but also some meats have low BCAA.