Thursday, November 14, 2013

Ketoacidotic death in lactation!

Laura forwarded me the link to this epic study:

A gestational ketogenic diet alters maternal metabolic status as well as offspring physiological growth and brain structure in the neonatal mouse.

It has a very very clear message. This is the first paragraph of the results section:

"Lactation in KD [ketogenic diet fed] Dams Leads to Fatal Ketoacidosis. In the initial trial phase, 4 KD dams remained with their biological litters post parturition, and during lactation. However, lactation appeared to cause severe physiological strain to all KD dams. Soon after parturition they started exhibiting signs of high stress, as was also apparent by them cannibalizing their litter. Measurements of their blood glucose and ketone revealed elevated values (Glucose: ∼20 mmol/L and Ketone: ∼6 mmol/L), indicating development of ketoacidosis. This ketoacidosis rapidly progressed to a fatal metabolic state, leading to the death of the KD dams within a few days post parturition"

I hope that is clear. No beating about the bush.

These folks are cutting edge. They know how to get impressive results.

Take home message: If you wish to survive lactation do not, UNDER ANY CIRCUMSTANCES, base your diet on CRISCO. Do not do it.

My wife seems to have survived two ketogenic lactations in pretty good shape. Daniel's school is well in to spelling test this term. He is the only kid in his class to have made no mistakes so far. It doesn't look as if we have broken his brain. No Crisco.

Of course Sussman et al blame the ketosis. They keep very quiet about the Crisco:

TD.96355 Ketogenic Diet: "Vegetable Shortening, hydrogenated (Crisco) 586.4g/kg"

Want to die? Always ask for Crisco by name. Crooks.

Peter

43 comments:

karl said...

Link to paper
http://www.biomedcentral.com/content/pdf/1471-2393-13-198.pdf

link to transfat diet

http://www.harlan.com/download.axd/3097bc2daaab4784bc91f2153952d028.pdf?d=96365

Who is supporting this propaganda?

"The study was supported by The Hospital for Sick Children in Toronto, Canada. D. Sussman holds an Alexander Graham Bell Canada Graduate Scholarship (CGS) from the Natural Sciences and Engineering Research Council of Canada (NSERC). M. Henkelman holds a Canada Research Chair in Imaging Technologies in Human Disease and Preclinical Models."

I suspect there is some organized effort behind this that is not apparent.


Peter said...

Karl,

Big crooks, little crooks. Just crooks... These people disgust me.

Peter

tess said...

did it never occur to these people that MICE are not designed to thrive on a ketogenic diet? might as well feed cholesterol to rabbits -- oh wait....

Galina L. said...

I checked what the Crisco was made of, because I had no idea. I din't use it even during my low-fat/whole grains/buckets of vegetables days.
About.com says http://lowfatcooking.about.com/od/faqs/f/hydrogenated.htm it is not that bad " Crisco uses soybean oil, fully hydrogenated palm oil, and partially hydrogenated palm and soybean oils. To be clear: just because it is trans-fat-free doesn't mean it is low fat. One tablespoon of trans-fat free shortening contains 110 calories, 12g of fat, 3g of which is saturated. It is cholesterol free, however."

It is somehow trans-fats free despite containing partially hydrogenated oils, and hydrogenated palm and soybean oils are normal healthy fats because saturated fats and hydrogenated fats are basically synonymous " Full hydrogenation increases the amount of saturated fat, although much of it is in the form of stearic acid, which is converted by the body to oleic acid, a monounsaturated fat, which doesn't raise levels of bad cholesterol. This makes fully hydrogenated fats less harmful than partially hydrogenated fats."

George Henderson said...

So stearate, the "good" SFA, is not so good when it is making up a disproportionately large amount of the fat.
Maybe what we are seeing here is - palmitate deficiency.

George Henderson said...

Almost all the epidemiology about SFAs makes no distinction between animal and vegetable sources, and none distinguishes between natural and artificial sources.
Today, that epidemiology became even more worthless.

karl said...

Using Crisco to deceive and confuse the public is fraud at some level. Does anyone here think they just are ignorant?

I think this is purposeful. I don't understand the motivation.

George Henderson said...

The diet: zero omega 3.
Recent research has established that the standard rat ketogenic diet, perhaps identical to this one, is deficient enough in choline and biotin to be pathogenic.

Chip Spitter said...

Possibly one of the very few semi-useful things to do with crisco - http://www.kier-cs.com/2009/01/calvin-and-hobbes-crisco-hair.html

Apart from poisoning mice, of course.

Peter said...

karl, it's very hard to understand. A LC diet is currently one of the few effective therapies for a stack of medical problems, but people go out of their way to trash it. Axen and Axen started off honest in their first "ketosis will make you diabetic paper", my only complaint was their abstract omitted the trans fats which where the core message in the actual text. Their two follow on papers omitted ANY mention of trans fats, by which time they were simple KD bashing. What changed and why???

Galina, Crisco has been many things at different times. I suspect Harlan stockpiled the trans fat version.

Trans fats and uncoupling are a very interesting subject from the delta psi, UCP1 and FADH2:NADH ratio point of view. Notice from karl's link that you need sucrose to make them obesogenic. Not that insulin matters of course!!!

Peter

hithaeglir said...

Ketogenic (CRSCO) diet link:
http://www.harlan.com/download.axd/64f4c886f5bf47a3924e0168402ee232.pdf?d=96355

Yum!

Galina L. said...

The research claimed its purpose was just "to fill this knowledge gap" because "The use of the ketogenic diet (KD) among women of child-bearing age has been increasing, leading to increased interest in identifying the diet’s suitability during gestation."

I don't know what motivates some scientists to scare as much people from ketogenic diet as possible. May be they are vegans trying to save planet from meat-eating practice? People who follow a LC diet are often perceived as members of some extremist group (unlike vegans), as opposite to normal ones who try to keep themselves in a more or less starvation state while trying to move more. I guess if more women in a childbearing age start using ketogenic diets, it would increase the general state of health in a population. They would get more nutrition from their food and consume less antidepressants and anti-anxiety drags, and probably less Accutane.
Many start limiting carbohydrates in order to get thinner, then find out that most of their other health issues get taken care off. Next step - people are getting scared into eating "more balanced" diet.

melchiormeijer said...

Peter, perhaps the most important bit of information I got from re reading Stephen Cunnane’s ‘Survival of The Fast; The Key to Human Brain Evolution’ was that ketosis is the sine qua nog for developing the sapiens brain. Near the end of the second trimester the healthy human foetus goes into moderate to severe ketosis and it will not come of out of it until the child is a toddler, no matter how many carbs it’s cretin parents feed it. Human brain development is utterly dependent on a steady supply of ketones. It cannot afford itself to completely rely on glucose. This makes me speculate that (intermittent?) ketosis is the default state for healthy humans. It’s hardly a coincidence that so many disorders – especially neurological disorders – respond so well to low carb diets and even to administration of MCT’s, ketone esters or ketone salts. It seems, to me, that ketone bodies are an essential substrate to humans. Many diseases find their origin in a neolithic lack of ketotic episodes. I suspect.

melchiormeijer said...

Survival of The Fattest, sine qua non, please don't mind the typo's...

karl said...

@petro
The diet data sheet calls it "Vegetable Shortening, hydrogenated (Primex)" I don't think you can hydrogenate with out making lots of transfats.. and vegetable shortening is just not lard..

..................................
This paper I also don't believe:
http://www.gastrojournal.org/article/S0016-5085%2813%2901040-8/abstract

Something is wrong here...

There isn't the expected increase in blood trygly from fructose..

I see the opposite in the isocaloric period??

There was a large change in leptin..

Insulin is Higher in the fructose group???

"During both intervention periods the monosaccharides provided 25% of the subjects' predicted total daily energy requirements and were consumed 4 times a day..."

Something has to be wrong with this paper?

If replacing glucose with fructose does not increase trygly it turns over a large body of evidence..

I was most interested in the change of Il-6 and crp - but I don't trust this paper enough to believe any of it...

Tom of the Missouri said...

Wow, now I have a new substance to put on my mouse traps this winter. I won't even need to set the trap, just let them eat the Crisco. Someone should tell Home Depot so they can put Crisco in their pest control section.

Laura said...

After seeing the KD formulation these researchers used (and washing the resulting vomit from my mouth), I have actually written the lead author regarding the type of diet they are using in their studies and the fact that this does not correlate with the clinical scenario (we do not have our keto patients eating Crisco, but instead lots of saturated fats and MCT). We'll see if she deigns to respond...

These types of studies make me mad because they make people afraid of using the keto diet for therapeutic (and health maintenance, etc...) purposes. Not to mention those poor mice...

Galina L. said...

It makes me mad too. I remember how I failed to convince my friend that keto-diet would be a good diet to follow for her doter who sometimes had epileptic seizures.

Recently another friend whose mother was freshly diagnosed with a brain cancer found after one minute of Googling that level of carbohydrates in a diet had no influence on a cancer outcome, and it outweighed immediately whatever I was saying about benefits of ketones and even what she knew about Warburg effect.

People who produce studies about mortal dangers of ketosis rather effectively scary away from that diet approach very vulnerable part of population - pregnant woman, cancer patients, mothers of growing children.

George Henderson said...

Here we go:

1) the Harlan KD is probably choline-deficient:
"A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756977/
(wavy line) 300mg/Kg choline is similar to the amount in the rat paper.
"These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

2) Rodent (and infant formula) KDs underestimate biotin requirement (I think this might be worsened by lactation)
"the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement."

In both cases, eat your egg yolks as part of the KD and you'll avoid these problems.
http://www.ncbi.nlm.nih.gov/pubmed/24012088

So they know now this type of ketogenic diet is wrong for rodents.

The Harlan diet is free of omega 3, but a keto diet that includes omega 3 is well-tolerated by mice
"The ketogenic diet was well accepted by the KD mice"
http://www.ncbi.nlm.nih.gov/pubmed/18447912

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.

Stan (Heretic) said...

Hi Peter,

Classical case of bad science! You may find the recent post by Dr. Eades interesting:

http://www.proteinpower.com/drmike/lipid-hypothesis/cholesterol-heart-disease-science/

It illustrates this phenomenon even better. It's amazing that there are so many failed scientists occupying most of the prominent positions in the North American universities and top institutions!

Must have been some kind of negative selection put in place, in-breading among the elites, or what else? Hard to explain!

Different subject, very different subject: did you ever look into hydrogen-breathing cellular lifeforms, what would be their equivalent of Krebs Cycle? What would be the main metabolic by-product being expelled, methane? Would they also have a preference for glucose, or other form of carbon compounds? How about protein?

Best regards,
Stan (Heretic)

Peter said...

Stan,

Have you bee through Nick Lane's http://www.nick-lane.net/Sousa%20et%20al%20Phil%20Trans.pdf paper? He goes in to great detail about electron bifurcation and its core role in generating a sufficiently negative electron to reduce ferrodoxin. Ferrodoxin is then used to drive a sodium pump to maintain a Na+ based gradient which an ATPase uses to generate ATP, much as the mitochondrial ATPase uses H+.

The system of electron bifurcation is used in methanogens and acetogens which lack cytochomes. There is no electron transport chain, no CoQ couple, just molecular H2 being split in to 2H+ and 2e-. Either of these electrons alone has insufficient reducing power to reduce ferrodoxin but the energy released by the drop of one electron on to either NAD+ or the heterodisulfide CoM-S-S-CoB is used to "boost" the other electron to a potential where it can manage ferrodoxin reduction. Took some time to get my head around this.

Ferrodoxin is the main energy currency in these bacteria, particularly in the methanogens. The paper has interesting ideas on why ATP happens to be what appears to be a universal currency when ferrodoxin does an equally good job.

Acetogens and methanogens both use versions of the Wood – Ljungdahl pathway. The subject is utterly fascinating. It annoyed me for some time that the two "early life" systems were based on Na+ pumping, not H+ pumping, but there are good reasons for this (in the paper). Of course the methanogens gave us the archaebacteria from which the "engulfer" in eukaryotes came from, and we still have a sodium pump on our cell surfaces, used for all sorts of functions excluding energy generation. The eubacteria, which provided mitochondria, came from the acetogens and it is a small step to go back to H+ pumping from Na+ pumping. No point trying to use a Na+ gradient when the surrounding methanogen has already dumped the sodium from its cytoplasm...

The paper is so good, on so many levels. There is much more to it than even the quite recent bioenergetic papers. Not read all of it yet but I really wanted to get electron bifurcation sorted in my head.

Peter

AlmondD'oh said...

@ Galina:

" I guess if more women in a childbearing age start using ketogenic diets, it would increase the general state of health in a population. They would get more nutrition from their food and consume less antidepressants and anti-anxiety drags, and probably less Accutane."

And thus would end the industry of Baby Vitamins, Baby Formula, Big Pharma... and the list goes on.

aaron blaisdell said...

I just returned from this year's annual Society for Neuroscience meeting, where 30,300 neuroscientists descended on San Diego to get their neurogeek on. I saw quite a few posters using a ketogenic diet in mice to show its therapeutic role in reducing neuro-inflammation and improving recovery from nerve damage (e.g., in spinal injury) and cognitive function. Nevertheless, the major component of commercial rodent keto diet itself is soybean oil. I didn't expect this to be all that therapeutic, and would be interested to see a whole foods keto diet composed of natural fats.

Laura said...

@Aaron,

My lab uses a keto diet primarily composed of lard and butter, so there are certainly better options for experimental diet chows out there in use in the scientific community.

aaron blaisdell said...

@Laura. That's good to know! Every time I look up the commercial rodent keto diet, it is invariably soy bean oil, or SBO + lard. Glad to see you are using lard and butter. Even I would sample that kind of chow. Could you tell me if it is a commercially available rodent diet, and if so, what is the manufacturer and product number? Thanks!

Laura said...

@ Aaron,

We use this one: F3666 from BioServ.
It is not perfect as it still contains corn oil, but its mostly lard and butter still :)

Stan (Heretic) said...

Peter, thanks for the pointers! I will read that Lane's paper. Fascinating!
Stan

aaron blaisdell said...

@Laura. Thanks! I'm currently studying the impact of a refined foods diet on cognition in rats. When it comes time to look at how much cognitive function can be rescued through lifestyle factors, such as whole foods diets (including HFLC), this may be a good off-the-shelf diet to use.

Vicki Higgins said...

An old paper on the adverse effects of a low carb diet on pregnant and lactating bitches
(Romnos et al, J Nutr 111, 678-689, 1981)made me wonder whether some of these adverse effects may be due to a lack of gluconeogenic precursors - fixed by feeding a bit more meat in essence! Maybe a bit like "ketosis" in high producing dairy cattle? Nothing wrong with the ketogenic diet as long as one recognises that certain high demand states like pregnancy and lactation require higher input of the right quality.

Jack Kruse said...

Peter, keep looking at Lane's work. Keep thinking deeply about electrons and transition metals. The more you do the more you will realize physics dictates biology. All biology happens at a molecular level and that world is controlled by quantum mechanics not biologic beliefs. I have mentioned to you long ago, to stop looking at food as metabolic fuel, and instead look at it as hormone information. It is electronic information from those electrons split from water. Light is part of the electromagnetic spectrum. It splits water into hydrogen, oxygen, and electrons. this is why your brain and spinal cord are covered with CSF and so is your inner mitochondrial membrane. These electrons electronically induce molecular changes in proteins to electrify the hormone cascade in the HPA. In the inner mitochondrial membrane they allow for the 150 millivolt electrical gradient that drives ECT. Light, by virtue of its electromagnetic force, turns off melatonin via the action of melanopsin. When this happens quantum sleep is induced. It is made most efficient when we are cold, ketotic, chemically reduced by these electrons. The cell becomes reduced by making large amounts of glutathione when melatonin is high in the absence of the electromagnetic force of light. Glutathione is the main chemical that provides for all redox reactions in the body. It is coupled to the electrons flowing in mitochondria. You see the biology in your ideas and I see the quantum physics......but we are seeing two sides of the same coin whether you know it or not.

Jack Kruse said...

There is only one issue with Nick's work I have. He still does not realize Mitchell was wrong and Gilbert Ling was right. I have a feeling when you get curious enough about all these ties to electrons and metal chemistry you will see association induction hypothesis is the big kahuna that modern biology is missing. Ling's work was the basis for development and formation of MRI and PET scanners in case you did not know. Mitchell's work has produced nothing. Ling also proved that the Na/K ATPase breaks the second law of thermodynamics by a 5 fold measurement in frog muscle. Exquisite work......hope you dive in when you get free. With your discerning eye you will be amazed at what he did.

Peter said...

Jack,

I am well aware that Ling's view is undoubtedly correct, I also view conventional physiology as a (useful) technique for describing the alterations in the molecular "state" Ling describes in manner which allows a more accessible (to my "process" ingrained outlook), if highly superficial, view of metabolism. I KNOW the electron goes through both holes (and the rest of the universe). I'm at the level of flicking a light switch or building a generator.

As you are well aware Ling has a very dubious view of the "high energy bond" concept of ATP. Nicely supported by the complete lack of any high energy bonds in reduced ferrodoxin, the core derivative of reduced FeS, the original hydrothermal vent derived energy currency before complex molecules got in on the scene.

Peter

Peter said...

Hi Vicki, couldn't get the paper to come up but, if it's the one I recall, the only issue was reduced litter size. That then begs the question of what is the "ideal" litter size in dogs. This looks at what label we might apply to a piece of information. Agriculture supports several billion humans. Rather a lot of us in hunger and poverty...

Peter

Galina L. said...

I am reading "Nutrition and Physical Degeneration" at the moment. Dr.Price recorded that many "primitive" societies tried to limit the amount of children per female by longer spacing between childbirths because they believed it resulted in healthier off-springs.

Vicki Higgins said...

Peter - so true that agriculture is a 2 edged sword - I acknowledge my fortune in having a choice about what I eat - low carb, high animal fat as I now recommend for my patients (I'm a vet too). And yes perhaps maximising litter survival is a mindset that needs to be reconsidered. I rather like this quote from a post graduate course from 1983 by DS Kronfield, " While eating raw meat we developed our minds and our nobler social instincts. Then suddenly about 10,000 years ago, God gave us dominion over the cereals. Our minds and nobler social instincts gave way to our bellies and pudendal pleasures. Our population explosion began. A century ago, we started to feed cereals to dogs, and their population explosion began. What had dogs done to deserve this?"
Thank you for your blog, I am learning a lot. Keep it up.

donny said...

Aside from the Crisco, I have to wonder how many protein and carbohydrate calories go into milk production for these mice? At 4:1 fat to (protein+carbs) ratio, pretty easy to see the animals getting into trouble. Even if ninety percent crisco calories was fine for these animals outside of pregnancy and lactation, the increase in need for protein and sugar for milk production might make it excessive.

Jack Kruse said...

Stan and Peter: The origin of steroid hormones in mammals is cholesterol that is metabolized by the mitochondrial CYP11A1 system. The cytochrome P450 is fed with reduction equivalents via a small electron transfer chain consisting of NADPH from the PPP, adrenodoxin reductase, and adrenodoxin better known as ferrodoxin-1 in humans. Modern research has extensively studied the redox behavior of the individual protein components, but they have ignored the kinetics of the system because they do not understand Ling's work. Ling called ATP an cardinal electron withdrawal protein. When a protein like cholesterol has its electrons stripped away.atom is called ionization. Even though an electron is stripped from atom, its mass is not changed since electrons have no mass. Electrons have a negative charge. Of course, when electrons are stripped from atom or proteins it becomes more positively charged than before since it lost an electron. Since ATP is electron withdrawing protein so its goal is to strip electrons to make proteins more positively charged. This single action makes them very reactive to the electromagnetic force in nature. It also allows the organism to control the magnetic part of the force using electronic induction. In regular magnetic tape drives in computers, they control the motion of magnetic domains by using a lot of power. This is a key technology in magnetic memory systems in a laptops hard disk. Biology contols the magnetic domains on cholesterol in neurons using no power source. It uses ATP actions to control the magnetic domains on cholesterol. This approach requires little power to write and no power to maintain the stored information in an excitable membrane. Biology controls magnetism by applying a voltage, rather than a magnetic field. Modern technology uses a magnetic field to do it, and as such is power expensive to maintain. Biology uses neuron membranes and intracellular water as magnetic storage devices in which data is written on "microscopic nanotubes or tracks", with magnetic “bits” of data hurtling along them like cars on a racetrack. This is why all neurodegenerative diseases are associated with altered hormone panels and an inability to make ATP. Carbs make less ATP than fat (36 to 147) hence their association with all these diseases. The same thing happens on the inner mitochondrial membrane.

Jack Kruse said...

Biology now has the ability to follow the reduction of each of the protein components of this system within one measurement when they simply mix all oxidized protein components with NADPH that is generated from the Pentose Phosphate pathway. These measurements have allowed them to determine the individual apparent rate constants for the reduction of all proteins involved in these reactions. Here is the key point: In addition, variation of the "ionic strength" IE the charge, in these experiments revealed different optimum salt concentrations for the reduction of adrenodoxin reductase and ferrodoxin-1. This result clearly links hormone panels to electronic induction to control the magnetic force. Moreover, it unravels the dramatic changing reduction rates of CYP11A1 by adrenodoxin/ferrodoxin. It is all buried in Ling's work. We just have to get more biologists realizing it by spending a bit of time understanding physics. The electromagnetic force is the most powerful of the 4 natural physical forces. They are marked by having strong power and infinite range.

Jack Kruse said...

Here is a thought meant to resonate and reverberate in your neurons to show you the power of the elctromagnetic force; a mathematician would say that an electromagnetic wave travels from Andromeda to your eye, and he would show you many equations to prove it true. A quantum biologist, like myself, says that it does even more than that..... that it also extends the power and information in Andromeda's light directly to your eye and brain to make some sense of it. Today, you can see Andromeda with your naked eye. It is 2.5 million light years away. When its light started heading your way to your eye, human beings did not even exist. Yet you are here now to see that light. This is by definition action at a spooky distance, showing you the power of the electromagentic force. It is, in fact, infinite.

Jack Kruse said...

http://www.ncbi.nlm.nih.gov/pubmed/8396893

donny said...

If they really wanted to study lactation on a very low-carb diet, they probably could have looked at various whales, seals and bears that sometimes go through pregnancy and nurse on a zero-carb program of total fasting.

Robert Andrew Brown said...

"karl said...

@petro
The diet data sheet calls it "Vegetable Shortening, hydrogenated (Primex)" I don't think you can hydrogenate with out making lots of transfats.. and vegetable shortening is just not lard..

..................................
This paper I also don't believe:
http://www.gastrojournal.org/article/S0016-5085%2813%2901040-8/abstract

Something is wrong here...

Full paper http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508513010408.pdf

Might the reported malabsortion of fructose have been a factor ?

and or does the gut bacterial population in the overweight increase the utilization of fructose in the gut by bacteria ?

It is a shame the fructose debate has become so polarised . . . but no question all empty calories are not good for human health . .

Great to have you back Peter (-: and may thanks for all your hard work - your blogs are always informative and thought provoking (-:

Cinnamonbite Zazzle said...

Even for making soap, you have to do a little digging to figure the fat to lye percentage with Crisco--it's Frankenfat.
EATING it? YIKES!
I'm curious why the basic processed food diet of most Americans isn't worse than Crisco?