Monday, May 04, 2020

Surwit diet and derivatives (3) 5LJ5 vs D12330: Chow vs Surwit

TLDR: A "healthy", complex carbohydrate, low glycaemic index diet appears to markedly shorten the median lifespan of mice when compared to a diet of maltodextrin/sucrose with hydrogenated coconut oil, irrespective of obesity or insulin gene dose.

This is the second excellent paper from Jim Johnson's lab:

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

It is slightly different from the 2012 paper as these mice are full knockout for the Ins1 gene and this time it is the Ins2 gene that is present as a full complement or at half knockout, to adjust the insulin gene dosage.

The study was never intended to compare the two diets, the diets were simply intended to provide a fairly normal insulin environment using a rodent chow against an high insulin environment generated by a Surwit type diet. It was the insulin exposure which was the focus of the study.

But, ultimately, the study did compare the two diets and in some detail.

Just to summarise the diets. Both had 4% of calories as PUFA, primarily linoleic acid. The 5LJ5 chow used a slow release carbohydrate (as uncooked ground wheat) combined with a little extra protein from soybean meal. The D12330 (Surwit type) diet was the usual hydrogenated coconut oil with maltodextrin/sucrose plus casein as the sole protein source.

Maximum individual longevities came out as expected, with the 5LJ5 coming out best and the low insulin gene dose conferring benefit to both diets.

These are the mean lifespans of the four longest lived mice in each group (top decile) as shown by the open circles/squares on the bar chart, taken from the end stage of the survival curves as shown here:

That's relatively unexciting and no one would be surprised by it.

What surprised me was the longevity advantage to the Surwit diet groups when assessed at median life span. Not only did the Surwit groups both do a great deal better than the chow groups at median lifespan but there was only a very small improvement (about 3%) obtained by reducing insulin exposure. In fact the normal gene-dose, obese, high insulin-exposure Surwit diet group (purple) had a longer median lifespan compared to the reduced insulin-exposure group that was on chow. Which was better again than that of the ordinary mice fed on chow.

If we simply ignore the reduced insulin exposure groups we can also suggest, based on these data, that the unmodified Surwit diet produces a median longevity gain in the order of 16% over a top-of-the-range excellently formulated lab animal breeding chow.

If the Surwit diet was a drug it would knock spots off of metformin, rapamycin, ethanol, caffeine or glucosamine for median lifespan extension. These mostly gain around 10% in median life span extension.

I accept that, for the four mice which made it in to extreme old age, there is a small disadvantage to the Surwit diet, but this only becomes apparent at those lifespans at over 750 days of age, out of a max of just over 900 days.

A quick look round the literature shows us that feeding a 60% fat diet where the PUFA content comes out at around 15% of total calories (high PUFA lard as the fat source), combined with Surwit-like levels of maltodextrin/sucrose, is a catastrophe. As in this one using TD.06414.

At the risk of speculating; there may be a host of problems triggered by a wheat/soybean based diet which do not appear to occur with a casein/saturated fat based diet, certainly until extreme old age is achieved. Or there could be some specific advantage to a highly saturated fat based diet which over rides the problems provided by maltodextrin/sucrose. Lots of possibilities, no obvious answers!

Fascinating study.



ELau said...

Hi Peter,

I've been absolutely fascinated with what you've been putting out and trying to learn as much as I can on my own. While the evidence you've presented are not only intriguing but actually quite reasonable, I still find myself reluctant to jump in, whether it's due to fear of my individual circumstances being not applicable or bias or just not a good enough grasp on the data/science yet. Would love to hear your thoughts:

I have the E3/E4 genotype and high genetic Lp(a), with moderately high ApoB. Despite all that I'm quite healthy all around (I'm in my 30s). I have low body fat due to very frequent and intensive exercise regime. I tried the low-fat diet two years ago and it did very little to my ApoB numbers. Six months ago, listening to The Drive I got on the keto bandwagon using a "safe version" eg. zero sugar, mostly MUFA, moderate protein, high veg/fiber. ApoB again didn't budge much but glucose/glucose variability predictably improved. I feel more energetic as well. The one thing that was a bit weird was a dramatically lower neutrophil count, close to neutropenia. The fat composition and veg intake seem to be opposite of what you believe. Considering my personal predispositions, would you recommend that I give high SFA a shot in my next round of diet trial n of 1?

Also while we're at it, wanted to hear your comments on a couple of the more recent seemingly well-prepared papers that offer contradictory opinions:

Alex said...

Good one.

Peter said...

Hi ELau,

Welcome. Happily I am no clinician, I just look at stuff to see how it works. Sadly I consider lipid numbers irrelevant to anything, unless you fill your lipids with linoleic acid, in which case you’re in trouble. As always, people cite all sorts of lipid numbers to me but never cite HbA1c. How can anyone think about CVD without an OGTT with insulin measurements? As in Kraft. Fix the glucose-insulin axis and what ever lipids you are left with will be good, linoleic acid excepted.

The first study is interventional and groups were either left on a diet of utter crap, had some of the saturates removed but stayed on a diet of utter crap or got some real food but probably mostly still got crap. Some numbers changed and the researchers think they know what they mean. In the absence of glucose/insulin/HbA1c data who knows whether their “MED” group were better or worse off than the usual diet group?

The second study is based on the six countries study. That’s observational and also it’s Ancel Keys derived, the guy who killed people with corn oil then refused to publish.

Re genetics: having “bad” lipids, to me, means you have no leeway to develop metabolic syndrome or eat linoleic acid even without metabolic syndrome. If you want to know more about Lp(a) search the blog for Bantu.

Thanks Alex, I think there might be a lot in this study but the late longevity data don’t give obvious answers. Getting all of your proteins from lectins might not be a good idea if you want to avoid mid-life illnesses… But who knows?


ELau said...

Thanks so much Peter. My glucose-insulin axis is pretty avg at glu 4.7 (low-fat) 4.4 (low carb) and insulin results between 20 and 50 pmol/l during low carb. I also have always had healthy low triglycerides. Due to lifestyle I don’t see myself as very high risk so as much as I’m trying to learn and optimize diet I do want to be taking baby steps one at a time. You’ve certainly convinced me of the toxicity of PUFA so I’m really cutting back on walnuts and pecans which I use to eat a lot. But what is the pathological underpinning for MUFA?

Also the first paper if you look at the supplement you will see the average total LDL particle number did drop by 100nmol/L over a few weeks(MUFA replacing SFA) which is not insignificant. My understanding is particle number is much better associated with CVD than other lipid numbers. Would you care to comment on why you don’t consider lipid data as useful?

Thanks again

Peter said...

Again, you are assuming that lipids cause CVD. As far as I am concerned the lipid hypothesis was complete bollocks when it was developed in the 1950s. At some point people assume it stopped being bollocks… LDL particle count concern is a primary symptom of cholesterol psychosis. I would stress that you are talking about associations. If I had to guess I would suggest that both CVD and LDL particle number are both driven by hyperinsulinaemia. This common cause explains the perceived association, which gets wrongly assumed to imply causation. Also whether any sort of lipid number is associated with CVD in the absence of a substantial linoleic acid content is an open question.

Oh, MUFA facilitate excess insulin signalling (cf saturated fats) in the immediate post prandial period. That puts lipids in to adipocytes. No one will run a study to show this unless by accident, as in the Spanish study.


Tucker Goodrich said...

Yet again,

"Question: If you are in a position of power over innocent folks who are trying to eat healthy food, which fat would you ban?

"Answer: The wrong one!"

ELau said...

Hi Peter,

Read the Spanish paper. I don’t quite understand the ramifications or perhaps I’m misreading it.

“...subjects became less insulin resistant postprandially as the proportion of MUFAs compared with SFAs in dietary fats increased (VEFO > ROO > HPSO > Butter), and this effect was linear. Similarly, we discovered that when the early postprandial insulin response was used as a measure of β cell function, it decreased as the ratio of dietary MUFAs to SFAs increased.”

This appears to show that MUFA (cf SFA) increases insulin sensitivity (you’ve mentioned this for sure), and LOWERS insulin secretion. I can see how it will be obesegenic with carbs, but if consumed in the context of a ketogenic diet, can I infer that MUFA may be healthier than SFA?


ELau said...

As an aside, don’t beef drippings have the same amount of MUFA and SFA? Would love to know your thoughts on beef drippings vs. butter.

Jay said...

@ELau For what reason would it be healthier since in the context of a ketogenic diet you wouldn't be secreting much insulin anyway?
"This appears to show that MUFA (cf SFA) increases insulin sensitivity (you’ve mentioned this for sure), and LOWERS insulin secretion. I can see how it will be obesegenic with carbs, but if consumed in the context of a ketogenic diet,"

ctviggen said...

ELau, I wouldn't get too concerned with Lp(a). I have extremely high Lp(a) (300+ nmol/l or 125 mg/dl, depending on testing facility and other factors; "good" is <75 nmol/l or <30 mg/dl, and I'm 4-5 times that). I'm 55, got a coronary arterial calcification scan done last year and got a zero score. 90% of people my age scored higher. Been low carb/keto since 1/1/14. Lp(a) high for any test during that time, though I never took it before going low carb.

Now, no test is perfect and my zero CAC score doesn't mean I have zero risk of heart "disease". But based on that metric, Lp(a) isn't causing calcification.

If you're concerned about this, in addition to the excellent materials here, visit the following:

Malcolm Kendrick's blog (believes you have to protect the endothelium/glycocalyx, and whatever causes damage to those causes heart disease):

If you're lean and have high "cholesterol", you could be a LMHR:

Also, as an engineer, I've tested many, many different things during the last 6 years. Have thousands of blood sugar and ketone readings, bought my own CGM, etc. Just know that the testing tools aren't great (high errors) and designing a good test is...difficult.

Let's say you want to test higher "saturated fat". To do this, not only are you decreasing something else, but you may be adding other variables. For instance, to increase saturated fat, you might add dairy, say butter, sour cream, cream, cheese, etc. Is any benefit or detriment due to the "increase" in saturated fat, the decrease in whatever you're no longer eating, the foods that contain the saturated fat, or some combination of these? It is often a challenge to determine this.

karl said...


I got CAD - stents - CABG. Inspired me to spend quite a bit of time (totally too much time - years on end) looking at lipids/Lp(a) etc - finally realized it was a false narrative. There are about 16 drugs(and PUFA) that lower cholesterol numbers - but for some strange reason - only statins seem to have ANY effect of CHD. And that is a tiny effect - and only if the research is run by a drug company.

Most likely when they first saw the weak correlation between CHD and cholesterol they got the arrow of causation backwards - the cholesterol did not cause CHD - instead the CHD (the actual damaged blood vesicles) triggered a slight rise in cholesterol. ( burn patients get higher LDL numbers - but we don't assume that the LDL caused the burn)..

The false-narrative claims that LDL enters the intima wall and does it's damage - but several groups have tried to see this happen - with out luck.

Anyway - my quest has led me to believe that it isn't LDL - but instead disruption of the NO system that is the primary cause of CHD - nicotine/stress/PPIs/high Blood sugar - and hugely - low level lead exposure all mess with the NO system.

I think Kendrick has done a good job of exploring causation - it will take a long time for medical practice to change.

ELau said...

Jay: I guess what I meant was, if MUFA encourages insulin signaling & insulin sensitivity, and at the same time there is little insulin to be excreted, then under the context of a ketogenic diet MUFA (all other things being equal) is no less good / no more hazardous to you compared to SFA in terms of energy metabolism. This is something that could be meaningful to an E4 carrier who wants to be extra careful with reconfigurations to his diet (ie sticking with MUFA).

ctviggen: Thank you for sharing your experience. I don’t think I’m a “LMHR” because my ApoB and LDL-C numbers have stayed largely the same after going LC (ie. not much response). Would love to know what other insights have you found over the years of testing?

Karl: Also thank you for sharing. Regarding the misinterpretation of causality, are you basically saying that those who had a higher baseline lipid number AT BIRTH are not at higher risk- and those who are actually at higher risk (whatever their initial numbers may be, as long as it is not FH) get a raised lipid number OVER TIME - so on average, the at-risk group is associated with higher numbers? I’m surprised that there hasn’t been proper study done to follow a population from early childhood!

ELau said...

By excreted I meant secreted. Oops.

Peter said...

Hi ELau,

Yes, you can theoretically look at pretty well all lipids as equivalent under ketogenic conditions, from the obesity point of view. Though whether this applies at “normal” bodyweight, ie slim/no weight loss looks to be an open question at the moment.

However working at lipid numbers assumes we understand what those numbers mean, so working towards an insulin sensitising MUFA presumes we know what the outcome of this will be overall (and that it is good).

If you are genuinely concerned that you may have been dealt a bum deal genetically I don’t see how you can get away from the likely ancestral diet of large herbivore fat with some meat. Butter may well be perfectly alright but it isn’t the safety-default, being fairly neolithic. Though nothing like as neolithic as olive oil of course. I like Miki Ben-Dor’s take on this. Man the fat hunter.


Fred Lander said...

I would like to introduce the hypothesis ( I don't remember reading this anywhere ) that certain plants want us to eat them, and entice us to do so with a variety of ammunition, and the olive plant is a clear candidate. They do this as we contain a very valuable substance , equal to the weight of twelve elephants at the age of 70, and so , from the plants point of view, we are much more than good for just seed dispersal and they need to keep us alive as long as possible with their chemistry.

We release this substance in higher abundance in the vicinity of the plant, the longer we stay in that vicinity, and the plant helps us live longer and healthier so instead of depositing the weight of six elephants we deposit the full weight of 12 elephants, or more.

Other plants, like pomegranates, are also candidates with beneficial ( for us ) compounds in the peel and seeds. ( I take both with olive leaf extract and perhaps one liter of olive oil per week )

Olive plants may have evolved in our ancestral range, the rift valley or South Africa, but I have not searched for the origins of pomegranate plants. Been mulling over tea leaves and kiwi fruit some..... and turmeric and edelweiss and honokiol and even citrus pectin, modified for prostate health.

So prove this hypothesis wrong as it cannot ever be proven right. Gravity as a warping of the space, time continuum, has never been proven wrong, but they still keep trying. But is it right? Can quantum physics prove it wrong?

Passthecream said...

Fred Lander - symbiosis is common in the plant-animal dynamic. I'm reminded of this every morning when I clear the red peppercorn seeds out of our birdbath - schinus molle - only the thin outer fleshy layer is animal-edible, birds eat and digest the fruit and poop out the seed and the seed gets a germination boost. Some seed types need to pass through emu digestion before being able to germinate etc. I'm not so sure about coffee passing through civets .... olives however seem to be a more neolithic food ie requiring technology. Raw olives are completely, horribly inedible. Perhaps after floating in the sea for a while by chance they were sufficiently broken down, or perhaps by soaking in wood ashes? Like many toxic foods exterior agency is needed. Which raises the question about what is neolithic food exactly - many hunter gatherer groups seem use/have used food preparation technology to make plant foods mostly edible well before what we now call the neolithic stage. It is a lot of work compared to just spearing a lizard so this suggested human-plant symbiosis is a more desperate development.

ELau said...

Hi Peter,

Ben-Dor’s take is quite fun to read. I do think the evidence that he’s using is rather limited from a geographical perspective, however. I dug around some more and there are certainly quite a bit of conflicting views regarding prehistoric diet based on evidence ranging from gut structure comparisons to modern hunter-gatherer lifestyles. Could it be that there is a wide range of variations as a result of differences in seasonality (which would affect fat content of food and animal/plant availability), gender (women may be gatherers and ate more plant), geography (highland vs. tropics) etc., that it would actually make more sense to occasionally cycle to a more plant-based diet? (Certainly, even with cycling it would be much better to be utilizing ketones for longer periods than just glucose due to various other reasons.) That LCHF or the ketogenic diet is roughly as effective as LF or “mixed diet” in terms of energy utilization signals that one is unlikely to be exclusively preferable to the other?

If you’ll indulge me I just wanted to raise one other point regarding E4 genotype, SFA vs. MUFA. My understanding is that AD is sometimes considered a metabolic disease in the brain in that it is associated with insulin resistance in the brain. I think that the lack of suppression of FFA on ketogenic diets, which also creates insulin resistance, is irrelevant to the brain since FFAs do not cross the BBB. But SFA mediated insulin resistance may be relevant to brain health in this way? I would love to hear your thoughts on this speculative musing.


Peter said...

ELau, yes, there are many views on how we got to where we are and I certainly have a temporal climate bias. We all have to take our chance with what we feel most likely and what is possible. Hind gut fermentors have more PUFA in their fat than foregut fermentors. We ate them all.

The CNS and FFAs has to be considered carefully. FFAs are not oxidised by neurons but they certainly are by astrocytes which are ketogenic and can feed neurons. Also insulin has facilitated access to the CNS and large swathes of the brain have insulin receptors. Insulin-induced insulin resistance is clearly possible here. I might suggest that avoidance of hyperinsulinaemia might be a good idea if you wish to avoid AD...

I would also comment that there is a world of difference between acute physiological insulin-induced insulin resistance in the aftermath of a meal and the same phenomenon applied long term with continuous exposure to hyperglycaemia in the presence of inappropriately elevated FFAs. How the two are related is something I spend some considerable time thinking about nowadays.


ELau said...

Hi Peter,

From reading your blogs, I’ve certain got an inking that this relationship has been on your mind. There’s no doubt here that carbohydrate restriction is vastly preferable for metabolic health. In this case, can continuously elevated FFA on the ketogenic diet (without hyperglycemia) be considered “inappropriate” and pathologically insulin-resistance inducing, in both CNS and periphery?


Ps. This was an interesting read as well.

Fred Lander said...

Passthecream I had almost dismissed the theory once somebody told me how insipid raw olives taste, but you know how it when you think you have a novel idea. LOL.

I also remembered reports by the chimp scientists that the vast majority of the fruit they eat is insipid and stringy and inedible for us.

So I started thinking about those underground tubers the Hazda seek almost every day, and that westerners say are like eating some moist tree bark. Hmmmm...

Can the chimps and Hazda be getting a meaningful proportion of energy from fiber due to the more sophisticated microbiome?

I was expecting to find some evidence that the enterocytes or the bacteria gobble up all the fatty acids, but that is not what I found, so the hypothesis is resisting destruction, so far:
"Significant VFA, however, are now known to be produced in omnivorous species, such as pigs and humans. Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases"

1990 Apr;70(2):567-90.
doi: 10.1152/physrev.1990.70.2.567

This publication from 2019 had the above reference;
"Perspective: Physiologic Importance of Short-Chain Fatty Acids from Nondigestible Carbohydrate Fermentation"
"Most SCFAs that are not metabolized by the microbiota are absorbed by enterocytes via passive diffusion or monocarboxylate transporter 1–mediated transport and into the circulation via solute carrier (SLC) family transporters, SLC5A8 and SLC5A12 (17). Once absorbed, SCFAs may be used by the enterocyte for energy or released into the portal circulation for utilization by peripheral tissues"

So our large brained ancestors may have savored the olive fruit, despite the flavor we ourselves experience.

Rocksolid said...

Here’s a just submitted paper from NIH that’s interesting:

A plant-based, low-fat diet decreases ad libitum energy intake compared to an animal-based, ketogenic diet: An inpatient randomized controlled trial

Passthecream said...

Fred Lander I think we have nearly opposite understandings of the word insipid! It usually means bland and tasteless. Olives are definitely not bland, you might say they are full of flavour but mostly full of bitterness and horror and will make you feel quite ill. There is wildlife which eats the fruit though, parrots or other large birds and they spread the seeds far and wide.

Fred Lander said...

Passthecream making one feel quite ill is a different story and I had not considered very large birds eating the fruits. There were three wild cherry trees in my neighborhood, possibly originally domesticated, but very bland, insipid. Within three days the local birds stripped the trees clean and I got a picture of a robin working on its second cherry, with the goo dripping off it's beak:

Also of note the northern flickers would gorge on poison ivy berries in November and it is quite a sight to see them fluttering from vine to vine up in the height of the trees, looking like giant butterflies. I did get one picture of this bird eating a poison ivy berry:

But Passthecream what about the whole concept of certain plants finding a way to induce animals to leave their droppings in the vicinity of the plant, or at least leave this fertilizer, more, in the vicinity, due to the intervention of the plant?
It does make sense as a concept, no? Rather than selecting likely candidates, like olive trees or pomegranates, perhaps we can just consider this as a concept, in general?

Passthecream said...

Fred, yes certainly. That's why I mentioned the red peppercorns as an example. The flesh is edible even by humans, the seeds are toxic. And I have read of certain Australian plants which will not germinate at all unless they have been through some specific bird's digestive system.

It doesn't take a lot of work to make olives edible only very simple technology: long soaking in salt water; anaerobic fermentation in salt water, drying in excess salt (like the Sicilian dried olives); water and ashes. The standard commercial method now is to soak in alkali before salting. Using ashes, fermentations, or soaking problematic foods in running water are very old food preparation techniques.