Feeding into old age: long-term effects of dietary fatty acid supplementation on tissue composition and life span in mice
The researchers fed mice on chow until 450 days of age. For some they then started blending in sunflower oil (omega-6 based) and for others they added in fish oil to the same chow. The composition of the diets was sufficiently similar that there was no effect on lifespan found, either median or maximum. But there was an effect on bodyweight. I bring this up because, while sunflower oil would be reasonably expected to be obesogenic, fish oil certainly would not.
Unless you view it from the Protons perspective of course. Here the mitochondrial oxidation of omega-3 PUFA should be more obesogenic than omega-6, which is almost never the finding in rodent studies and which is why, over the years, I collect any studies which suggest this. To confirm my bias.
Crucially the people running this current study were interested in longevity, not obesity.
Despite this, not only did they weigh the mice weekly (which most studies do) but they also reported those weights in detail (which many don't).
"Mean body weights in all three groups (over the entire experiment) and SEMs were 30.9 ± 0.1, 29.9 ± 0.1 and 28.7 ± 0.09 for n-3 rich, n-6 rich and controls, respectively."
Graphically it looks like this:
If we take the rather crowded data points over in to PowerPoint we can crudely rough in some curves:
The red line is the fish oil group, yellow the sunflower oil and blue the chow.
Fish oil should make you fat. Confirming this bias is remarkably difficult, so you can imagine how I feel about these data points.
The red line is the fish oil group, yellow the sunflower oil and blue the chow.
Fish oil should make you fat. Confirming this bias is remarkably difficult, so you can imagine how I feel about these data points.
Quite how fish oil can be shown to be so beneficial most of the time is beyond me. I think the aphorism goes something like "current medical research reflects current medical bias". Possibly from John Ioannidis?
Peter
Of course the fish oil mice might have looked like Arnie* on steroids. Or they might not.
*Having had the joke explained to me in comments I can't look at this without giggling. C57Schwarz6 mice!
*Having had the joke explained to me in comments I can't look at this without giggling. C57Schwarz6 mice!
27 comments:
C57Schwarz6?
So what diet / feeding style gives the longest lifespan in mice? I would have thought someone would create a prize for this, or scientists would be competing with each other for this anyway, but I can't find much.
https://www.cell.com/cell-metabolism/pdf/S1550-4131(17)30490-4.pdf has a keto diet giving about 33 months on avg for c57bl/6 mice and there are various studies on calorie restriction, has no-one tried a combination? Or permutations of all kinds of diet to find the best for health / longevity?
C57Bl/6, schwarz is German for black...
Peter
Malcolm,
Not that I can find either. Saturophobia runs deep. If you showed palmitic acid was a longevity drug where would your next grant come from???
Obviously there is a prize but not diet specific and GHR k/o mice own it and nothing has come close to them in over a decade.
Peter
Re the subject of the original post, I sure wish they had done an arm with some sort of saturated fat.
At the risk of embarrassing myself by stating the obvious, I assumed that Passthecream used Schwarz as a reference to Arnie.
Cavenewt, yes. Mice with tenpacks.
The base diet is very high in carbs/sugars (nfe) at around 60% and then only 2% lipid so maybe there is an interesting lipid 'multiplier effect' that helps to give such an interesting weight signal but I'm struggling to decrypt the lipid breakdown data in the lower part of table 1. Perhaps there are some other interesting effects to sieve out from that?
Higher carb % leading to what might be a higher sensitivity to lipid quality reminds me of Brad's croissant diet.
The high pufa diets didn't turn out detrimental to mice lifespan : w-3 mice lived 890 days vs 880 days for control and 824 days for w-6 mice.
Doctor Harvey told William Banting to avoid eating salmon
The plot of weight vs lifespan isn't clear. What is being plotted?. The weight of mice on the day x? So the mice gain weight by day 650 and then lose it by date 850 or so?
What makes them lose weight? merely old age issues?
I think Peter mentioned some years back at being slightly overweight extended lifespan on standard diet. Isn't it the similar thing we are seeing here? the w3 being slightly overweight but also living longest.
So even Omega 3's are bad for me now? Oh dear. How are they obesogenic?
cave and Pass,
Peter creeps away, pink with embarrassment...
Hi BillyHW, well it's only one study, and there are an infinite supply of contradictory ones... The question which is hard to answer is which long chain omega 3s end up in mitochondria (obesogenic) and which end up in peroxisomes. ALA and EPA probably go to mitochondria but DHA may go to peroxisomes so be neutral or maybe even beneficial. That's before you start on the roll of VLC omega 3s as signalling molecules through G protein-coupled receptors. But core is that each double bond fails to input at the CoQ couple so will not generate satiety signalling ROS. Cells will over-accept calories, adipocytes included.
Gyan, yes old mice get thin. When you look through the measured diet composition there was remarkably little difference except small amounts of extra DHA and EPA in the fish oil group.
cave, yes, a beef dripping group would have been fascinating.
Galina, oh, I missed that. Interesting, especially as Banting's diet was nowhere near ketogenic so PUFA might have been important. Possibly cotton oil adulteration of lard was rare in the middle 1800s in London? Oily fish might have been a significant source of double bonds.
Pass, yep, the diet analysis, considering how well it was done, is very obscure/poor in the table!
Still embarrassed. My apologies.
Peter
Peter, never need to apologise. I was amused by the image of an Arny mouse, mus muscularis! And I am a fully qualified eedjut.
It's impressive how you spotted that lipid vs weight signal. The age vs weight plot in other ways is complicated to interpret. You say old mice lose weight but it's not a mouse continuum vs time, only age, so it is equally valid to say thinner mice get older, and the big peak near 600 days means the heaviest mice die younger. That increase after the lower death rate ( base rate?) for younger less heavy mice is curious.
Such a simple experiment reminds me that it's perfectly legal to have pet mice and feed them anything you like within reason and with kindness. (or even to set traps and lay poison to kill their wild cousins). When does that cross the boundary into being a fully fledged experiment? Probably when it needs to be published and peer reviewed, or grants and salaries need to be applied for and received.
(... experiment, requiring ethics approval ...)
Pass, absolutely. I have a post part written about OGTT and age in people which also illustrates this nicely... Maybe go dig it out sometime.
Peter
This confirms the aquatic ape hypothesis https://www.bbc.co.uk/programmes/topics/Aquatic_ape_hypothesis
Peter, you would laugh- Dr. Harvey allowed Banting to eat any meat except pork. However bacon was allowed. Go figure. I went to check here https://www.gutenberg.org/files/57545/57545-h/57545-h.htm
Thanks Galina, it's a very long time since I last read Banting! Happy days at the beginning of LC eating, you forget what a transformation it was. And must still be for newbies.
Ivo, I read Elaine Morgan's first book in the 1980s (back when you went to libraries and borrowed books for a few weeks). I liked the hypothesis but over the years I am less and less convinced. Partly because I'm not a much of a DHA-ophile and partly because the mammoth bones left behind by humans are not covered in fishbones.
Peter
I guess the counter-argument to the fish bones is that the mammoths had higher O3 back then. Or at least that's one theory.
But it becomes difficult to know what people ate back then, and what actually was in the fat of animals. For instance, I saw a post on Twitter from FireInABottle's feed, a study where they looked at what a certain people ate, which was pigs and chickens, quite a bit anyway. FireInABottle was discussing the high saturated fat in pigs, but I noted that the chicken fat was 77% saturated. Impressive!
I used to eat fish several times a week; now, rarely. I just wish things were more clear-cut, as in "I eat fish (or chicken) and I'm ravenous later". But, at least for me, it's not that simple.
I do note that if I eat a lot of saturated fat (eg, stearic acid enhanced ghee plus cacao butter), I do get less hungry, and that persists at least to and through dinner if I eat high sat fat at "lunch" (don't eat breakfast). In fact, I've had to stop eating very high levels of sat fat at lunch, because I want to eat dinner with my family, and I can't if I eat high sat fat.
But I have to "try" to eat this much saturated fat, and it's difficult for me to associate eating less sat fat or even high PUFA, such as in chicken, with increased hunger. It could be true, but it's harder to gauge. That is, eating "normally" (without adding high sat fat), it's harder to ferret out what's happening. I'd need two of me, and the money to run things like DEXA scans.
But if your theory is that PUFA = more hunger, then I think O3 should fit into that theory, as you've "shown" above.
Anyone know of a high fish eating (but not high coconut eating) population? Preferably low carb?
I'm guessing there was plenty of O3 (DHA) in mammoth brains.
Hi Steve and ctviggen,
Let’s assume a mammoth had a brain the size of an elephant, 5000g (https://pubmed.ncbi.nlm.nih.gov/16782503/). Let’s assume it provides the same DHA as modern cow brain (https://nutritiondata.self.com/facts/beef-products/3461/2), 1g/100g, 50g DHA in total per mammoth brain.
An elephant also provides approx 200,000g (https://pubmed.ncbi.nlm.nih.gov/22174868/) of other (precious) edible fat.
So our “mammoth” would provide 50g of DHA in 200,000g of total fat, shared equally among the tribe.
Assuming any sensible HG eats 200g/day total fat this gives us 50/200,000 X 200g/day DHA
ie 0.05g, or 50mg. I’ve rounded numbers up throughout the assumptions.
50mg/d seems about right to me… It doesn’t strike me as a particularly large amount compared to a tablespoon of fish oil. Or 10% of calories as fish oil.
Maybe mammoths had twice as much DHA when purely grass fed. Say 100mg/d per person?
Peter
No need to speculate about mammoths and fat:
"The Fat from Frozen Mammals Reveals Sources of Essential Fatty Acids Suitable for Palaeolithic and Neolithic Humans"
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084480
And no need for fish.
Tucker, interesting!
Peter, they aren't Arnold mice at all but Arnettes, all female, which might have some bearing on the 600 day mortality peak. C57bl6 are not fertile much after 400-500 days. There could be weight gain associated with reproductive hormone changes in some of them. On top of that these are already mice with base metabolic problems so probably a mix of genotypes, some which gain weight and experience higher mortality versus a leaner longer living type -- lower insulin dynamics maybe leading to lower weight and fewer metabolic issues???
Ha, I'm so ruminant-centric. It's too easy to forget that mammoths were monogastric! I carry the bison paper around in my head where PUFA were deemed "inadequate" (assuming 50g/d of fat ingested!) for optimal human health... But saturates were very high so conversion to DHA should have been good. https://pubmed.ncbi.nlm.nih.gov/25604079/
Thanks
Peter
From your link:
"As demonstrated in this work, the subcutaneous fat of bison consumed by Mesolithic hunters contained amounts of n-3 fatty acids in higher quantities than those found in current bison; thus, the subcutaneous fat of bison could have contributed to meet today's recommended daily intake of essential fatty acids for good health..."
Peter—while looking at the bison article you linked above, an item in the list of similar articles sounded promising: "Evolutionary aspects of omega-3 fatty acids in the food supply", dated 1999. Here's the abstract for your perusal and enjoyment (emphasis added).
"Information from archaeological findings and studies from modern day hunter-gatherers suggest that the Paleolithic diet is the diet we evolved on and for which our genetic profile was programmed. The Paleolithic diet is characterized by lower fat and lower saturated fat intake than Western diets; a balanced intake of omega-6 and omega-3 essential fatty acids; small amounts of trans fatty acids, contributing less than 2% of dietary energy; more green leafy vegetables and fruits providing higher levels of vitamin E and vitamin C and other antioxidants than today's diet and higher amounts of calcium and potassium but lower sodium intake. Studies on the traditional Greek diet (diet of Crete) indicate an omega-6/omega-3 ratio of about 1/1. The importance of a balanced ratio of omega-6:omega-3, a lower saturated fatty acid and lower total fat intake (30-33%), along with higher intakes of fruits and vegetables leading to increases in vitamin E and C, was tested in the Lyon Heart study. The Lyon study, based on a modified diet of Crete, confirmed the importance of omega-3 fatty acids from marine and terrestrial sources, and vitamin E and vitamin C, in the secondary prevention of coronary heart disease, and cancer mortality."
Absolutely Tucker, it was the word “contributed” which niggled me. Just “met” would have been better.. It leaves the door open for piles of fish bones. Of course no one could be healthy just on bison fat and meat…
cave, the (excellent) Lyon Heart study changed many, many, many things. Some were more important than others and we will never know which did what. Ultimately it was a secondary prevention trial so the study population had already had a heart attack so by definition their baseline diet was probably execrable. They then stayed on a “prudent diet”, equally execrable as control diet or switched to something resembling Food for the intervention group. Excepting that awful margarine included.
Peter
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