Monday, January 27, 2020

Rory Robertson and Protein Restricted Longevity

I looked at this paper when it did the rounds a fair while ago, saw that the only fat source used was soybean oil and decided that living on soybean oil, sucrose, maltodextrin and wheat starch was not a good idea and so I binned it as the junk it is:

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

I missed the embedded problems which have since been brought to light by Rory Robertson, whose slightly over-the-top concerns are voiced here. I would perhaps disagree slightly with some of his opinions but, overall, he makes a rather good case. The first thing to note is that you have to go to the supplementary data to realise that a significant number of groups of mice were lost (and excluded) due to mortality problems. Table S1 describes all thirty of the diets which the study started out with. Five of these diets had to be discontinued because too many mice either died outright or (I suspect) were ordered to be euthanased on the authority of the supervising veterinary surgeon due to concerns about animal welfare. I'm assuming Oz has a Home Office much as the UK does which requires Named Veterinary Surgeons to be employed to supervise animal welfare in all laboratories.

We know this from the legend to supplementary table S1. Here is the last section of that legend (sorry that the small letter superscripting is lost, that's blogger for you):

"a Diets 2 low energy and 6 medium energy were discontinued within 23 weeks. b Diets 3 low energy, 3 medium energy and 6 low energy were discontinued within 10 weeks of treatment. These diets were discontinued due to weight loss (≥ 20%), rectal prolapse or failure to thrive".

Here is table S1 with the discontinued (and removed) groups outlined in red:

So, they started with 30 diets groups but five of them had such high early death rates that they were excluded from the study. This left 25 groups. Other than the legend to supplementary table S1 I am unable to find any reference to the loss of five diet groups anywhere in the main paper, which gives the distinct impression that 25 groups were all that were included from the start. So 17% of the mice died at under 23 weeks in to the study, many of those within less than 10 weeks, and you have to read the supplementary data to find out.

All of the high mortality groups were eating 5% of calories as protein.

Did you pick that up in the abstract? No, you didn't.

Is there any excuse for failing to discuss this crucial finding in the results and discussion sections of the paper? You can decide that. It's not exactly rocket science.

My feeling is that the authors could argue, if they were convinced that protein restriction was key to longevity (amino acids, cysteine, mTOR etc don'tchano), that studying early life mortality has no relevance to late life longevity. Why not leave early mortality to the paediatricians? That is a potentially arguable position and should, as it involved a huge chunk of the study mice, have been reported and been justified (if possible) in the results, discussion and especially in the abstract.

The other slight hiccup is this line from the main paper:

"Median lifespan was greatest for animals whose intakes were low in protein and high in carbohydrate... (Figure 2A)"

Figure 2A is not in a format which lends itself to simple interpretation and, obviously, excludes all of the mice which died or were euthanased at less than 23 weeks of age, all of which were in low protein groups. Anyway, you might want to see a simple table of median lifespan for each of the surviving groups. Like supplementary table S2. I've high-lighted the group which had the longest median lifespan in red:

Looks to me like the longest median lifespan group might have been eating 42% of it's calories as protein... Hmmmm. Worth repeating:

"Median lifespan was greatest for animals whose intakes were low in protein and high in carbohydrate... (Figure 2A)".

vs Table S2 giving 42% protein for longest median lifespan.


Let's make this crystal clear: The data demonstrating the actual outcomes are, absolutely, present in the supplementary data of the paper. It is also absolutely crystal clear that the paper itself, excluding supplementary information, does not accurately represent the the actual findings in the study.

If you had to summarise the paper in human terms you could say that applying severe protein restriction to your kids while topping up their calories with sugar and soyabean oil would hopefully result in them being taken away from you and placed in to care before they died.

Please don't try this at home.


My thanks to Rory Robertson for his attempts to have this paper retracted and more accurately rewritten and to Grant Schofield for tweeting about his efforts.


cavenewt said...

I took a look at those lengthy letters that Robertson wrote. He's obviously passionate and, as you point out, his criticisms are valid.

He just didn't do himself any favors in terms of the reception he received by writing such lengthy missives which, even to a sympathizer, look like diatribes.

Which makes it all the more impressive if they eventually will have the intended effect.

karl said...

One of the other bits that hasn't been well studied are chemically defined diets where the amino acids are modulated - one by one.

I think the reality is no one wants to look at this straight on. I don't think that there is much doubt that poor childhood diets lead to stunting - and particularly poor brain development - which appears to be a permanent problem - these children don't appear to recover even with a better diet latter in life. If they figure out that humans need a good source of protein and fats to thrive - they might also figure out there really isn't enough food for the world. Thus we have people getting large amounts of their calories in the form of sugar and PUFAs - as if it was a proper diet.

Stunting is common in places of the world where the poor have to eat a mostly vegan diet - yet they keep pushing this narrative.

Particularly for brain health - we are an unusual animal - a mouse model does not represent the huge demands for nutrients our brains make.

Peter said...

karl, I do feel that those pushing the veg*n narrative where there is any alternative should be in the dock along side the parents of those children who have died of malnutrition on veg*n diets. Veganuary is child abuse.

Cave, yes, Robertson goes way over the top but he correctly points out the data. I'm shocked that this got through peer review, without any speculation about motive for the way the results were presented.


Geta said...

The reviewers should have picked it up. It is inexcusable.

Shaza said...

Peter, this OFF TOPIC, the topic is VIRKON-S
Is there any news if the 'pink solution' kills nCoV-2019. I am curious as I have some in Hong Kong apartment and I am going across in March. I would be thinking of it to spray surfaces/ carpet. I have it there as my daughter's cat had feline Corona virus from a cat she rescued in a Macau shelter. (ANIMAS) The poor kitten had everything from ringworm to Feline CoV.

I read your blog all the time, thank you so much for all your writings. Sorry to present something so OFF TOPIC!

Peter said...

Hi Shaza, it's a single strand RNA virus. Almost anything will kill it, certainly I'd expect Virkon to do so but it seems a bit over the top when simple dilute bleach wiped on surfaces works...


Shaza said...

Hi Peter thanks so much! It is what is on hand in the apartment! But I can buy bleach when I get there! I think I will still do the bottom of shoes, esp in Macao, where my daughter lives!

There are lots and lots of nasty viruses in that area of the world. as you know!

I so appreciate your prompt reply. I am off again in March for a month so hopefully the virus and the hysteria will have calmed down!
Shannon ( shaza)

Passthecream said...

Peter, OZ experiments are overseen by an animal ethics committee convened by the organisation eg Uni, etc., and they are pretty tough. Then a Vet keeping an eye on things and the researchers themselves are supposed to treat the animals correctly, euthanase if needed, in accordance with their ethics approval and agreed criteria. Sometimes it all gets in the way of useful results when sick animals must be euthanased before the experimental endpoints. It is tricky.

Peter said...

Thanks Pass, pretty much like the UK then...


Passthecream said...

Some of these dietary experiments, makes you wonder what the ethics people are thinking to let them proceed. More cruel than pneumonia etc. trials imo.

Passthecream said...

.. and much less precise or useful endpoints.

tuul said...

The 60% protein group performed poorly too, perhaps also making protein look bad. Seems dishonest for them to conclude that the trend that "protein is bad" is linear or applies to any amount a human is going to eat.

The high-energy density diets were better than the low energy density diets (cellulose bulked). Curious that they didn't reach the conclusion that we shouldn't eat cellulose.

Frunobulax said...

@tuul Any nutrient following a U-shaped curve can be made look bad in studies by consuming too much or not enough. Humans don't do too well on lean meat either if they don't eat enough fat.

altavista said...