Thursday, November 22, 2012

Are humans just multicellular yeasts?

Again via the Brent Kearney link on Stan's site.

discussing this paper

I especially like the last sentence of these two paragraphs:

These results are just the newest chapter in a "decade-old interest," according to Gottschling. He and his colleagues have made several landmark discoveries in the past 10 years, including finding that aging yeast cells exhibit the same genomic instability seen in human cancer cells and proving that mitochondrial dysfunction causes that instability. Gottschling's team also has developed innovative tools to leverage the power of yeast as a model organism, including a technique called the Mother Enrichment Program that makes experiments more efficient by enabling researchers to generate large populations of aging yeast cells.

"It's worth using yeast to study complex things like aging because a lot of person-years of research have gone into understanding the fundamentals. The genetic and cell-biology tools available for studying yeast are unparalleled," Gottschling said. "Having the proper tools is like having new glasses; you can see things you never could before, and once you start to see new things, you can dissect them to understand how they work."

The full paper is a Letter to Nature. That means it is technically very dense, but very interesting.

Caloric restriction to a yeast is, essentially, glucose restriction. In organisms with a circulation, an hormone system and a background FFA supply, caloric restriction at the cellular level (where it matters) is achieved by resisting the insulin mediated facilitation of glucose access, ie glucose restriction. Using superoxide.

Palmitate please, with just a very little glucose.



karl said...

Yeast are eukaryotic - they have the merged mitochondria, but they divide asexually - not sure it is correct to assume they represent human cells. They can respire AND ferment via glycolysis.

I'm thinking they may represent a degraded human cell - perhaps a model of cancer? (Most cancers don't respire - the marriage of mitochondria to cell seems to be broken (thus avoiding high BG appears to help avoid cancers - they have a hard time out growing our immune systems ))

This sounds like some of what Nick Lane was talking about in his mitochondria book: that ROS is not bad, but a part of the respiration control loop (and thus dietary antiox is doomed to fail as if it really works it can upset the balance - I can see the place where antiox keeps the level of ROS within the range of the control loop, but our bodies do what they can to get rid of excess antiox (vit C) - I wonder what C60 might do to the membrane of a mitochondria? ).

Purposelessness said...

Yeast can reproduce sexually, karl:

FrankG said...

I think it can help us to be suitably humble, realistic and useful to think of any complex organism -- including us lofty humans -- as colonies of ever simpler organisms.

I have heard biologists consider a termite colony (for example) as a single living organism.

Each sub-unit of the colony is relatively simple in that it has limited tasks and ability but the sum is far greater than the parts.

Think of a murmuration of Starlings (or a school of fish) where each is following a simple set of instructions to: fly as close as possible to the birds around you, while avoiding collisions and stay away from the edges (where the predators tend to attack) -- yet the end result looks to all intents and purposes like a single, complex organism that moves in concert.

This is one reason why I resits suggestion that our brain controls everything... doesn't that presuppose that the brain came along first? Whereas I think there is little doubt that our ancient and much simpler, primordial ancestors had established nutritional homeostasis (as but one example) before anything resembling a brain came along.

DLS said...

little glucose...what do you think about this? (copy-paste)

btw that guy is on a wheelchair..

Peter said...


The concept is of a mother yeast which ages, while budding off baby yeasts, which are budded off as young offspring. Division may be technically correct but this is nothing like the fairly even division of a bacterium.

The pH of the lysosome-like vacuole appears to control the mitochondria and determine the "age" of the yeast.

This is a very interesting idea.

But surely caloric restriction works through the mitochondria? Or does it work equally in a-mitochondrial yeasts, which depend fully on fermentation? Does the lysosome control the age of the cell even without mitochondria?


mommymd said...

Considering we all start out as single cell organisms that happen to be most successful in transmitting our DNA by asexually dividing and having our daughter progeny subsequently specialize into a constellation of cells in a larger organism, I think you are on to something in looking at the yeast model.

Puddleg said...

FrankG, good point.

Certainly before the adult brain develops...

original paper:

Gadfly said...

@ Pablo DLS:

That's great Pablo. You don't suppose that a big muscle-bound guy lifting weights regularly, operating a wheelchair and eating less than his BMR is going to lose weight over the long haul no matter what the macros? I'm an 11st.4lb guy who lifts weights regularly and plays drums for a living and I need a hell of a lot more than 1900 calories a day to keep my weight steady.

Stan Bleszynski said...

Interesting idea about the vacuola/lysosomes pH driving or correlating with aging as per that paper. I am more inclined to believe that it may be the other way around - as you suggested, vacuola pH increase being a side effect of breaking down of the mitochondria due to overfeeding, causing incomplete processing of glucose and flooding the cell with by-products of deranged metabolism. You had a discussion on this topic before and I also posted a summary here.
Stan (Heretic)

karl said...

I'm making a F:N ratio spread sheet

Not clear how to calculate odd numbers of Carbon?

For the even number I have:

where C = number of carbon

FADH2 = C-1
NADH = C*2+1

It appears to be correct?

And each double bond reduces FADH2 by one?

And anything over 0.48 seems to turn on inappropriate insulin resistance via FAS (via cell death? )

I'm interested in 17:0 ( in milk ) and 18:0

Longer fatty acids end up in peroxisomes chopped down to 8:0? ( wikipedia says "However, the oxidation ceases at octanoyl-CoA. It is believed that very long chain (greater than C-22) fatty acids undergo initial oxidation in peroxisomes.." So what happens to 20:0- and 22:0 ?)

18:2 ω-6 with two double bonds would be a F:N of 15:35? or 0.43, but I find papers showing oxidative stress:

Is there something else going on with PUFA? I looks like :

Odd-numbered double bonds are handled by the isomerase.
Even-numbered double bonds by the reductase (which creates an odd-numbered double bond)

Confused as always..

Then there is the trans-fat cases.. and CLA

SS Biker said...


I think you're confusing oxidative stress through metabolic processes (F:N ratio) with simple in-vivo oxidation of the labile double bonds in PUFA - 2 different processes.

PUFA are susceptible to simple lipid peroxidation hence ployunsaturated fats generally being promoted as a "rich source of vitamin E" - for the health benefits doncha know - not of course "to stop this crap going rancid within a week" ;-

SS Biker said...


I think you're confusing oxidative stress through metabolic processes (F:N ratio) with simple in-vivo oxidation of the labile double bonds in PUFA - 2 different processes.

PUFA are susceptible to simple lipid peroxidation hence ployunsaturated fats being a "rich source of vitamin E" - for the health benefits doncha know - not of course "to stop this crap going rancid within a week.." ;-)

DLS said...

Anthropic Principle

karl said...

@O Numnos

That is probably the case - I just don't think that the amount of 18:2 ω-6 linoleic acid in our diets is good for us long term and was hoping this explained it.

After I figure out how to calculate the F:N of the odd numbered FA - I want to calculate the weighted average F:N of things like corn oil, olive oil. It would not be likely that we were digesting just one type of FA at a time.

I think I once knew Yeast had a form of sex - I'm not sure how they manage mitocohndria inheritance - they can switch sexes anyway? Do they end up with both sets of mitocohndria when they merge?

Zorica Vuletic said...

Off topic question:

It's regarding the 'all potatoe diet'. I wonder if someone is financially strapped for a few weeks (approx. time one is supposed to stay on potatoe diet and no longer) Is it safe to do this? I understand a preliminary level on how it can end up supressing insulin secretion due to lowered FFA supply etc.

I don't need to lose weight at all. I would be concerned about returning to the usual ketogenic type diet I typically follow these days (which includes heavy seafood consumption). I would not want to a. lose dramatic weight and also wouldn't want to lose muscle b. I would not to come into a problem I didn't have before ---which would be rapid excess weight gain upon returning to regular menu ie. keto/seafood.

What is your opinion on this?

Zorica Vuletic said...

Another question re: potatoe diet...maybe it's not a great idea for people who wish to maintain brain health; as in they rely on heavy use of CO oil for nice ketone supply for specific brain requirements (not epilepsy per se...but along those lines).

So random of questions and my thinking out loud---so thanks in advance for any advice you can give.

karl said...

First attempt to calculate the total F:N of corn oil I needed to use %moles

(blogger won't let me use tables ) Do these numbers make sense? I got the molar values from


Jane said...

'..Is there something else going on with PUFA?...'

Yes, there is. The latest idea is that they get oxidised (well we knew that) and and the oxidised PUFA activate PPAR gamma. Ativated PPAR gamma explains a whole lot of stuff. For instance in Peter's earlier post, how the mice got fat on fish oil. PPAR gamma sensitises fat cells to insulin which is what Peter is saying about the PUFA except that he's talking about the F:N ratio which I've never really got my head around.

Peter said...

No time at the moment. Karl, I'll get back to you re F:N calculations. Odd chained FFAs are odd. Last cycle of beta oxidation produces proprionic acid, not acetic acid. Proprionate is converted to a succinate derivative which is, of course, the FADH2 generating component of the TCA. Or it's used for gluconeogenesis...


annlee said...

@ Gladina - there have been a couple of massive discussions of the potato diet as a hack on the nutritionfnutritionforum at Mark's Daily Apple. My net take is that those who don't do well on high fast low carb lose weight well and feel good during it on the 1-2 weeks of all potatoes. However, those who thrive on high fat low carb get nothing, and don't feel as good. Given that I'm in the latter category, I have no interest at all in trying it.

Zorica Vuletic said...

@annlee: Thanks for your response. Despite feeling a bit desperate financially a few days ago, I doubt I'll try the all potatoe (in my case would be sweet potatoe) diet. It is winter and it makes no sense now to eat in that style.

I am one of those who thrive on HFLC diet with emphasis on seafood. So this might not be a good idea for me anyway. haha. It was as stated before, only to see if it could be a 'cheap' way to eat. lol I am not that willing nor desperate enough to attempt that at this point.

I have never felt as good as I do now during this time of year (November). The first half was a bit rough, but not nearly(!) as bad as certain years. This is certainly a good sign.

I am complimented on looking radiant even, despite it being this time of year with less sun. *I sungaze every morning anyway though. But yes, my skin actually glows as if it was July (I just am not as dark as July).

Well, happy Sunday to all.

M said...

Hi Peter! I think you'll be very interested in this:

A visit to a typical Russian market. I think you'd never leave! I know I wouldn't.

DLS said...

skinny fat diet plan in not good. if you are strapped ... just stay chill and dot eat for a few days... if it gets though read a few books, movies, sleep, practice meditation, take cold showers, masturbate, or have sex if you have a partner. exercise, lots of things to . if it get -really- though and u are still strapped. get some cheap source of protein like tuna, chicken and do a PSMF
that or you could eat a lot of eggs... eggs are cheap. ... anything else > moon diet plan good luck!

Zorica Vuletic said...

I ended up watching the whole thing. What a great episode.

I notice how yes, they will eat potatoes and some pancake things, that the focus is FIRST on meat and fish (with it's accompanying fat). There's a lot of pickled dishes and many times as in the beef stroganoff, it's plattered without starch etc.

Looks like my style of eating for sure. I def. appreciate Russian cuisine. (I would not try the lampray though lol).

Ahhhhhh and banya I do this anyway without needing to be Russian. It really is refreshing.

Zorica Vuletic said...

@ pablo DS: I believe your response is to mine? Thanks for the tips. I don't know what 'moon diet' is...but I can guess that potatoes are too much like 'moon' (bland and gross).

In my experience I don't like to eat too little other wise it will affect my sleep, but other than that I am solid with 2 meals. I just make sure it's a decent amount for each. Breakfast is my most important meal and theoretically I could make myself live on that meal alone---but being female I just prefer a little bit more regular meals b/c our bodies seem to require a little bit more than male to eat more regularly (but of course not absurd 6 meals a day or some nonsense like that).

I have drawn up some solutions for December that I think will be more successful than the past two months, so I will go with that. For me to eat only potatoes in winter doesn't make the most sense (even if they are storageable.) I will increase my sardine intake I suspect since those are fattier therefore more satiating. I eat carrots and sqaush instead of a potatoe if I want more starch.


Galina L. said...

There are plenty of interesting items not available for sale in regular stores in an ethnic Russian store which could be in your own town.We have 3 in our obscure town in the North Florida in USA. I especially recommend to check fish counter and a deli department. For people who eat dairy, try ryazenka - full fat fermented baked milk. It is highly possible they also sell good quality sauerkraut.
I just come back from my visit to Russia where I had some quality time hanging out in Russian markets in Moscow(besides spending time with friends and family and going to theaters and museums). What a variety there!

M said...

Hello Galina. Here in Lisbon where I live I've only found one very, very tiny Russian store, with very few things on offer and nothing that one can't find every where else in ordinary butchers, supermarkets and health food stores. The ones in your town are much better!

John said...


I tried a sort of high potato diet one time, where I was eating sweet potato varieties and gelatin broths. My calorie intake was standard for me, ~4000, but I experienced a reduced sleep quality and chess performance. I also had lots of trouble recovering from physical activity, which is weightlifting and ballet. I constantly yearned for Sunday, which is my only day off.

Besides that, I find it annoying to make lots of sweet potatoes. Eggs, butter, cream is pretty cheap and convenient. Making stews and stuff with bone-in cuts is also pretty inexpensive. Of course you may never get down to rice-diet prices.

Zorica Vuletic said...

@ John: Thanks for your response.

Yes, I think I decided to not bother with a potatoe diet after all. I drafted a very clever budget for December that will still have me eating very well according to nutrition that my body performs best on (both in sleep and in day).

After experimenting with an assortment of seafoods I have determined which ones I a. enjoy best and b. are still the cheapest. I shall include more bones from beef and/or lamb for variety and alternative affordability. I do enjoy eggs too.


Anonymous said...

I may just have a weird sense of humour, but if you type "" into this search engine - you get an interesting gangsta translation of Peter's writings.

Just one gem - "Edward busted mah crazy ass this paper. I think I did already gotz a copy on mah hard drive but yo ass can't straight-up start ta make head nor tail of what tha f..k is straight-up goin on until yo ass gotz a handle on F:N ratio n' tha physiological role fo' supaoxide."

And here I was thinking it couldn't get any harder to understand.

Tony Mach said...

Have you seen this?

A Decade of Misconduct

A senior cardiovascular disease and diabetes researcher at the University of Kentucky has been found guilty of falsifying data over the past 10 years.

A joint investigation carried out over the course of 2 years by the ORI and the UK found that Eric Smart, who studied the molecular mechanisms behind cardiovascular diseases and diabetes, had falsified or fabricated a total of 45 figures—mostly images of Western blots, a technique used to identify proteins—in seven grant applications, three progress reports, and 10 published papers, some of which were cited more than 100 times, according to Thomson Scientific’s Web of Knowledge. The notice says that Smart also reported experimental data from knockout mice that did not exist.

This is surprising and disappointing news to me,” said Philippe Frank of Thomas Jefferson University in Philadelphia. “Dr. Smart's papers were highly cited in the specific caveolae/cardiovascular research field.” William Sessa of the Yale University School of Medicine told The Scientist by email that he was “shocked at the extent of misconduct,” and that the reporting of data for knockout mice that did not exist in grant applications “is very problematic indeed.” But, he added, “since I do not know what aspects of the figures were incorrect or misrepresented, it is difficult to assess the impact on the field.

Yeah, how can one know which cardiovascular research to trust?

Tony Mach said...

Here is Retraction Watch on the topic of Eric Smart, with a (possibly non-exhaustive) list of papers affected:

karl said...

RE: A Decade of Misconduct

Sadly, we don't know how many papers are never exposed. There are a lot of papers written to support the status quo in order to keep the grant money coming.

I sadly think there could be 20% of the papers with fabricated data.

Makro said...

"Sadly, we don't know how many papers are never exposed. There are a lot of papers written to support the status quo in order to keep the grant money coming. "

Well, also, it´s just a fact of life that if you fake your way to publication in any field, you damn well better fake in support of the status quo.

People actually check 'novel' results sometimes, after all...

blogblog said...


millions of South Americans spend there entire lives on potato diets without health problems.

Unknown said...

Gottschling's team also has developed impressive tools to make use of the power of fungus as a design patient, along with a technique called the Mother Enrichment Program that makes tests more effective by allowing scientists to produce large communities of getting older fungus tissues.

Zorica Vuletic said...


Thanks for your comment. As I have stated above, I have created a workable budget for December that allows for me to continue eating foods which contribute to 'my' unique health demands. There are a few tweaks here and there, but overall I believe it will be more effective as a result.

SO yes, I've decided against investigating further at an all potatoe diet, despite what South American tribe may thrive on. I am not S. American tribe person and I don't share their epi-genetic effects. *It does interest me to see the variation in diets that work for large populations and individuals too. Luckily for me, I chucked my dogma out the window a while ago.

karl said...

@blogblog and Gladina

It seems to me that there is a lot of confusion over the point of "what is a healthy diet" vs "What is a healthy diet once your BG system is damaged."

We have a situation where 40% of the public has T2D - (If you think you know definitively what is causing this pandemic, it means you don't understand the question ).

Healthy people can eat potatoes and maintain BG below 110 - but close to half the US public can't.

I'm finally reading John Kudkin's Pure White & Deadly now that it is finally available as a reprint. He obviously suspected fructose containing sugar back in 1972, and was way ahead of discounting the cholesterol mantra of Ancel Keys that still has standard medical care quite bollixed up.

I'm impressed at Kudkin's clear distinction of epidemiological vs experimental science - his reluctance to over state what is known. By 1972 there were several papers showing the marked increase in trygly with sucrose consumption.


Yet, I'm not sure that fructose containing sugars is the smoking gun - I'm leaning to thinking it is at least a two part poison. Vegetable oils + fructose?

Meanwhile, it appears difficult to determine if baby formula has lactose or sucrose - and they are not the same.

Galina L. said...

It looks like it is not necessary to be a diabetic of any kind to get an abnormal BS reading after eating carbohydrates. My mom who has a normal FBS and Aic got a pp BS around 170 mg/dL in one hour after eating a still-cut oatmeal prepared in a "healthy" fashion. I discovered it when I was convincing her to try a LC diet(I armed myself with a glucosemeter).
Many people who have no problem eating potatoes can't get it how it is possible that not every person around is like them.

karl said...

@Galina L.

IMO a "BS around 170 mg/dL" is not normal or healthy. Steel cut oatmeal has quite a bit of carbs - depending on how much you eat. I would say that if her BG system was not damaged she would have a postprandial of less than 110.

If you look at people eating primitive diets, they just don't get that high. I think anything over 110 is a result of damage or advanced age. ( My 88 year-old father can sat down and ate a potato as part of a meal and had a postprandial of 108. That is normal ..)

"Normal" BG is claimed to be the average - not what is normal for man eating foods we have evolved to eat. There are two ways you can look at the individual differences - that 40% have bad genes or 40% have damage. I think it is damage - 50 some years ago we just did not have the obesity rates that we have today - yet the same gene pool.

DLS said...

James Emmanuel Sisnett... 112 years old. he is currently the world's second oldest verified living man. here you have the man drinking orange juice and eating some kind of weird fruit

also, worked in a factory making sugar and syrup. explain that one,!
btw, me loves me tons of sucrose, bring it on!

Jane said...

Exactly. I suspect Galina's mother has a pancreas that needs to work very hard to keep her blood sugar stable, and doesn't quite manage it. Pancreatic beta cells are very sensitive to cellular stress, because they make large amounts of proteins for export which need to be properly folded, and protein folding is very tricky and stress-sensitive.

'The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes'
The endoplasmic reticulum (ER) is the entry site into the secretory pathway for newly synthesized proteins destined for the cell surface or released into the extracellular milieu. The study of protein folding and trafficking within the ER is an extremely active area of research that has provided novel insights into many disease processes. Cells have evolved mechanisms to modulate the capacity and quality of the ER protein-folding machinery to prevent the accumulation of unfolded or misfolded proteins. These signaling pathways are collectively termed the unfolded protein response (UPR). The UPR sensors signal a transcriptional response to expand the ER folding capacity, increase degradation of malfolded proteins, and limit the rate of mRNA translation to reduce the client protein load. Recent genetic and biochemical evidence in both humans and mice supports a requirement for the UPR to preserve ER homeostasis and prevent the β-cell failure that may be fundamental in the etiology of diabetes. Chronic or overwhelming ER stress stimuli associated with metabolic syndrome can disrupt protein folding in the ER, reduce insulin secretion, invoke oxidative stress, and activate cell death pathways. ..

karl said...

Interesting - I would suppose that after long term glycation damage there are a lot of senescence cells. I wonder if there is a way to push these into apoptosis? I've wondered if inducing senescence => apoptosis is how the hormesis of low level radiation, so-called-antioxidants, and perhaps C60 works?


That would be an example of anecdotal evidence -

I have no doubt that there are some people that can withstand a high level of sucrose in their diets - at least for a while. His long life may be a genetic difference that helped him prevent the glycation damage. The fact that he is an outlier in age makes him a poor representative of the average man.

IF that sucrose is elevating BG beyond 110 or so, I think it is doing damage - the rate of the damage may be slow and increases as BG control is lost.

I used to eat all sorts of sugar foods when I was young - I regret having burned by candle at both ends now that I'm 57 and barely survived CABG surgery.

Galina L. said...

@Karl, Jane, Blogblog,

My mom didn't commit usual offences to get to the unperfect metabolic state. She has being a health nut all her life and despised lazy sugar addicts. She is in a decent health for 75 years old, but carb-based meals give her a BS spike. May be more people should be aware of their numbers and make informed decisions based on individual differences rather than on the fact than some groups of people are doing fine eating mostly potatoes or Mediterranean diet or whatever .

Is any other food regiment that could have your approval and not based on eating mostly grains and drinking milk? Probably such foods contain all nutrients, but not perfect choices for everyone.

karl said...

Galina L. said...
"My mom didn't commit usual offences to get to the unperfect metabolic state."

Could be genetic, or could be we don't know what is triggering the T2D pandemic - there are a lot of possibilities.

Gabriella Kadar said...

We're more like kefir grains. :)

DePaw said...

There is a doctor who says cancer is just candida and treats tumours very successfully just with sodium bicarbonate (baking soda) solutions.

Jane said...

Hi karl
I just looked up C60 and found it makes rats live twice as long. No toxicity! Then I looked up 'fullerene iron' and found it binds iron. I suspect it works by reducing the pool of free iron. Cool! I can't imagine just being 'an antioxidant' would give such spectacular results.

Hi Galina
What was the food you told me Russians ate during their economic crisis? I think it was home-grown potatoes, pickled cabbage, pork fat, onions and wild mushrooms. I thought it sounded delicious, and healthy.

Galina L. said...

Hi, Jane,
I always read your comments with respect. I am still under big impression of your story you told on the Scribble pad blog.
Sure, crisis Russian food is quite delicious,it also includes beets and fish. I brought to my Florida home some dried and pickled wild mushrooms from Russia, and sauerkraut is a fixture in my fridge.
However, people who live on crisis fare, do not look perfectly healthy, many has a middle-body obesity after middle-age and bad teeth. I didn't have a chance to check their pantries, but I know with certainty they also go heavy on a bread and cook mostly with sunflower oil. Sweet tea is also a part of their diet (not during a war, of course, but war was a long time ago). My mom used to eat rye bread with every piece of any food.

It looks for me you don't think that a daily consumption of any amount of meat and eggs is healthy.

karl said...


Re C60 - I think C60 might actually work via hormesis - some of the people taking it were talking about feeling tired - dosage may be critical - or might have side effects in humans - too soon to tell.

Jane said...

That's interesting. Actually I've been meaning to ask you something. I found some statistics for meat consumption in Russia, and sugar consumption, and both seemed to be much the same as here. But I have never been able to find numbers for white flour vs wholemeal flour. I imagine it's more rye than wheat, and I do know there is refined rye flour and whole rye flour. Do Russians eat a lot of refined flour? Are there white-flour cakes, pies, pastries, cookies etc? And is the rye bread wholemeal bread, or is it dark for other reasons?

About meat and eggs. The only reason I'm doubtful about meat is the potential for iron overload and manganese deficiency. I don't know how far eating organ meats can solve this problem. And eggs: I know there are studies showing they can increase diabetes risk, but I can't imagine they're a problem in the context of a wholefood diet. The Hunza didn't eat them according to one source, but that seems to be because they didn't like what chickens did to their crops.

Jane said...

I've been digging around and I found this paper

'Fullerene-based antioxidants and neurodegenerative disorders'
...Initial studies in two models of Parkinson's disease (PD) have been relatively promising. One study used intrastriatal injection of iron to produce striatal injury [6] and found that C3, when co-injected with the iron, reduced dopamine depletion. A high content of iron in the basal ganglia is believed to contribute to oxidative damage during PD, and to the vulnerability of this region in PD. C3 may bind to iron, so the ability of C3 injected to reduce injury in this model may reflect its ability to interact directly with iron, or its ability to decrease lipid peroxidation. ..

Jane said...

Forgot to say, thanks for the link, I read all the comments. People seem to be experimenting a lot with this stuff.

You might be interested to hear that manganese can do exactly what fullerenes do in models of Parkinson's. People thought manganese CAUSES Parkinson's, so this result is astonishing.

'It has been suggested that transition metals such as iron and manganese produce oxidative injury to the dopaminergic nigrostriatal system, which may play a critical role in the pathogenesis of Parkinson's disease. ... In contrast to iron's pro-oxidant effect, manganese (up to 30 nmol, i.n.) causes neither lipid peroxidation nor nigral injury/dopamine depletion. Manganese (1.05 to 4.2 nmol, i.n.) dose-dependently protected nigral neurons from iron-induced oxidative injury and dopamine depletion. Manganese also suppressed acute increase in dopamine turnover and contralateral turning behaviour induced by iron. In brain homogenates manganese (0 to 10 microM) concentration-dependently inhibited propagation of lipid peroxidation caused by iron (0 to 5 microM). Without the contribution of manganese-superoxide dismutase manganese was still effective in sodium azide and/or heat-pretreated brain homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate that iron and manganese are two transition metals mediating opposite effects in the nigrostriatal system, as pro-oxidant and antioxidant, respectively...'

Galina L. said...

What I am going to say is just my opinion based on personal observations, sort-off eye-witness account. I hope it will add to what you learned from statistics.

Traditionally people in Russia didn't appreciate much wholegrain breads, considered it of a low value, rye breads were mostly made from the grains with removed outer shell (most popular is"obdirnaya" rye flour , it literally means the flour is made out of grains which were scraped all over ). During last 15 - 20 years Russians started to catch Western food trends, there are a lot of commercials on TV for wholegrain and low-fat products, different sweet yogurts, "healthy"juices-based drinks. The society nowadays is more divided based on the income, and smaller well-off group is the group which follow Western-style food trends, while low-income people still eat traditionally, while statistically it looks the same. Many retires suffer financially and life on bread, potatoes,cabbage soup, gruel, milk and sweet tea. I guess both groups consume plenty of buckwheat grouts. I am sure that particular grain will meet your highest approval. The rye bread is the cheapest one, and people consider it more satiating food, it is more in a "food" category, while white bread is more in a "treat" category. I was basically forced to eat everything with rye bread in my childhood .Often it doesn't taste up to potential. When inviting guests in Moscow, I baked for them my own sourdough rye bread from local flour, and they were amazed how good it tasted compare to the store-bought one. Even refine rye bread prepared without molasses, only with salt and water, looks quite dark(hazelnut or walnut shell color inside, crust is much darker), while rye flour itself is just slightly grayish.

From what I saw with my own eyes it is difficult to believe that the consumption of meat in Russia is the same as in the US, where I live now. Russians in all social categories love fish, and in a regular grocery store there are more types of fish in more price range than good meat choices. Historically Russian authorities always messed up with statistics being oddly concerned with the country international image. However, it doesn't explain so high sugar consumption. As far as I know, there are still many people in Russia who make their own alcohol, many have black-market-made distilling devices, especially in a country, and sugar is the most convenient for it. Many people drink too much. However, fruit preservation with sugar is also popular, and almost everybody drinks sweet black tea.

Russian crowd so far looks 90% thin, but it is normal to have a high blood pressure after middle-age, diabetes is quite common as people age.

Galina L. said...
This comment has been removed by the author.
Puddleg said...

Here is my "big idea" for december.
Activity protects against metabolic inflexibility.
What is the "activity factor?" What distinguishes this state?
Lactate, or a higher lactate/glucose balance.
" The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion"

"he role of lactate for brain metabolism seems to be even more important at early stages of development (prenatal and early postnatal), with lactate at these stages having higher concentrations in body liquids, and being utilized by the brain even more preferentially over glucose.[13] It was also hypothesized that lactate may exert a strong action over GABAergic networks in the developing brain, making them more inhibitory than it was previously assumed,[17] acting either through better support of metabolites,[13] or alterations in base intracellular pH levels,[18][19] or both.[20]
A more recent paper by Zilberter's group looked directly at the energy metabolism features in brain slices of mice and showed that beta-hydroxybutyrate, lactate and pyruvate acted as oxidative energy substrates causing an increase in the NAD(P)H oxidation phase, that glucose was insufficient as an energy carrier during intense synaptic activity and finally, that lactate can be an efficient energy substrate capable of sustaining and enhancing brain aerobic energy metabolism in vitro.[21]"

The notion that lactic acid was bad took hold more than a century ago, said George A. Brooks, a professor in the department of integrative biology at the University of California, Berkeley. It stuck because it seemed to make so much sense.

"It's one of the classic mistakes in the history of science," Dr. Brooks said.

John said...


Lactate I think is correlated with glucose metabolism and carbohydrate intake, along with glycogen amount in muscles and muscle fiber type.

What are your practical ideas from your comment, or what do you think that quote about BHB, lactate, pyruvate, and glucose reveala about diet?

Jane said...

Thanks Galina, that's very interesting. So wholemeal bread was considered inferior, was it.

Karl said your mother's pancreas could not be healthy if she had such a high BG spike from eating oats, and I think he's right. If she's eaten refined rye bread all her life it's not surprising. Nor is it surprising that you had such good results from going low-carb.

Galina L. said...

It is also more difficult to store a wholegrain flour which could be important for mass-production. As I told before, I make a rye bread for my husband, and I have to store the wholegrain rye flour (the only type sold in stores in US, and it is ridiculously expensive even when bought on-line) in a freezer, otherwise it gets rancid.

Purposelessness said...

fresh of the press (is that how you say it?), another piece of evidence that proves the Good Doctor's Food Reward TheoryTM and dismantles the dead insulin nail thingie. Or does it?

Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
"Thus, we provide genetic evidence that pathological circulating hyperinsulinemia drives diet-induced obesity and its complications."

James said...

Peter: I'd like to thank you for all the work you've put into writing this blog over the years. In all honesty, the knowledge and wisdom that i've gotten out of your writings has literally changed my life, and is changing the lives of my friends and family that are struggling with weight and diet issues. Keep up the good work!

Stipetic said...
This comment has been removed by the author.
Stipetic said...

Pureposelessness, I have a feeling Peter will enjoy Figure 7b with it's inclusion of Lipid Spillover (that's if I understand what he's talked about, which is not a given).

Makro said...

One of the researchers on the paper mentioned above in a tweet to Dr. Eades on their research:

"We are 1st to reduce insulin genetically and demonstrate lean phenotype in any mammal. New."

(Has the advantage of being a twitter-length abstract)

Puddleg said...

@ John,

At the moment it seems more of a mnemonic, something that make a useful educative soundbite.
In metabolic syndrome there is an excess of glucose and fatty acids in circulation. Would converting some of the glucose to lactate (by exercise) and/or some of the fatty acids to ketone bodies (by intermittent fasting and/or carbohydrate restriction) restore metabolic flexibility? This seems to be what happens.
What mechanisms might account for this in the case of lactate?

If nothing else it is a simple way to bring the benefits of exercise into the tent of basic metabolism, so is deserving of some investigation.

Incidentally, lactate is how muscle glycogen can be accessed by the brain. That amount that escapes into circulation and is not re-used by muscles can be converted to hepatic glycogen, or perhaps used directly.
Does lactate usage require less insulin overall?
Interestingly, the lactate receptor GPR81 is related to the ketone body receptor GPR109a.

Exercise might lower elevated FFA levels through this mechanism:
"Lactic acid is a well known metabolic by-product of intense exercise, particularly under anaerobic conditions. Lactate is also a key source of energy and an important metabolic substrate, and it has also been hypothesized to be a signaling molecule directing metabolic activity. Here we show that GPR81, an orphan G-protein-coupled receptor highly expressed in fat, is in fact a sensor for lactate. Lactate activates GPR81 in its physiological concentration range of 1–20 mM and suppresses lipolysis in mouse, rat, and human adipocytes as well as in differentiated 3T3-L1 cells. Adipocytes from GPR81-deficient mice lack an antilipolytic response to lactate but are responsive to other antilipolytic agents. Lactate specifically induces internalization of GPR81 after receptor activation. Site-directed mutagenesis of GPR81 coupled with homology modeling demonstrates that classically conserved key residues in the transmembrane binding domains are responsible for interacting with lactate. Our results indicate that lactate suppresses lipolysis in adipose tissue through a direct activation of GPR81. GPR81 may thus be an attractive target for the treatment of dyslipidemia and other metabolic disorders.";284/5/2811

Puddleg said...
actate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity.

More basal lactate from fewer mitochondria - a sign of over-reliance on glucose.
This all goes some way to explaining why exercise is not an easy fix for overweight.
However, lactate induces insulin resistance in muscle:

karl said...


You might want to check out what they were actually feeding the mice - is that the same paper where the hi-fat-diet had 20% sucrose? Best to start with the supplemental information to see what they don't want you to know.

Puddleg said...

Is this the difference a little lactate makes?

Our aim is to provide evidence that supports the hypothesis that physical inactivity per se is one of the primary causes in the development of metabolic inflexibility. This evidence will focus on four main tenants of metabolic inflexiblity: 1) insulin resistance, 2) impaired lipid trafficking and hyperlipidemia, 3) a shift in substrate use toward glucose, and 4) a shift in muscle fiber type and ectopic fat storage. Altogether, this hypothesis places sedentary behaviors upstream on the list of factors involved in metabolic inflexibility, which is considered to be a primary impairment in several metabolic disorders such as obesity, insulin resistance, and type 2 diabetes mellitus.

Makro said...

Bad news for all of you fat junkies out there:

Renaud said...

"Consistent with increased FOXO3A and MT2 activity, treatment of mice with βOHB confered significant protection against oxidative stress."

Sounds very good to me, for a bad news ;-)

karl said...

@ Makro
Why wouldn't the transcription of stress resistance inhibitors go down on a low-carb diet which reduce systemic inflammation?