Monday, October 22, 2012

Skirting around leptin

I've been wanting to post about Wallace and Gromit, Batman and ob/ob SCD1 k/o mice for weeks now and it keeps not happening. Before we go there, just a word or two about leptin and weight gain. You can't work through anything relating to ob/ob mice (+/- SCD1 k/o) without having to, finally, sit down and read something about leptin. Or at least ob/ob mice...

To me the core question to ask is whether ob/ob mice are gaining weight because they have a brain disorder giving overeating or an adipocyte disorder storing calories. As always, there is an infinite supply of data suggesting a brain disorder, there's no denying leptin does things in the brain. The question is: Are ob/ob mice in caloric excess as they gain weight? ie Do they eat too much so gain weight or do they primarily lose calories in to their adipocytes and so have to eat more to just meet metabolic needs?

We have various rodent models of obesity which have the common feature of reducing the sympathetic nervous system drive to adipocytes, so failing to oppose insulin's lipogenic action. These animals gain fat even if you calorie restrict them. I'm thinking about hypothalamic ice-picks, various VMH neurotoxins or unprotected free radical generation. But the common thread is the loss of sympathetic nervous system driven lipolysis, facilitating insulin driven fat storage.

When confronted with the overwhelming literature on leptin it's hard to know where to start, especially when people are not asking the sorts of question which interest me, looking at the data from my very particular perspective.

I accept that ob/ob mice get fat. So too do brain injured rats and mice. Is there a common mechanism here? The smoking gun would be a period of enhanced insulin sensitivity in adipocytes, due to decreased sympathetic tone, which allows both fat gain and the preservation of insulin sensitivity in the early weeks, until adipocyte distension induced insulin resistance kicks in for the swelling adipocytes and systemic insulin resistance develops.

Of course the easy part, with absolute leptin deficiency, is asking whether leptin increases hypothalamic sympathetic nervous system outflow. That took about 30 seconds on pubmed and this was the 6th or 7th hit.

Leptin increases sympathetic drive. I think it's reasonable to conclude leptin deficiency does the converse and reduces sympathetic drive from the hypothalamus. So I'll take that as a yes. Don't forget I'm biased.

Sooooooo. Does leptin deficiency defend insulin sensitivity during rapid weight gain? As it should if the mechanism is enhanced lipid storage. And weight gain in young ob/ob mice is, well, rapid. To say the least. There will only be a very narrow window to pick up preserved insulin sensitivity before adipocyte insulin resistance and hyperinsulinaemia set in. By which time researchers have a usable model of established obesity.

I'm interested in what goes on before the model becomes "usable". We know that by rewarding volunteers to overeat we can spike their insulin levels massively within three days, probably faster. Does this happen with ob/ob mice as they over eat?

I've been working through a whole stack of papers on ob/ob mice, FFA levels, insulin levels, ketogenic diets... All the usual stuff. I ended up in a review by Lindström, giving this little gem of a quote:

"The muscle insulin resistance is not observed in very young [ob/ob] mice, but develops after 3–4 weeks [131]"

The abstract of ref 131 supports the concept of preserved insulin sensitivity, looking at muscle rather than adipocyte insulin resistance. The papers on palmitoleate as a lipokine suggest that muscle insulin resistance is controlled by adipocyte insulin resistance, via SCD1 and palmitoleate. The paper is rather nice because it is looking at ob/ob mice as ob/ob mice, not as some completely inappropriate model for hyperleptinaemic obese humans. It was, after all, 1980 when it was published.

So to summarise:

Danish volunteers who are paid to overeat spike insulin from 35pmol/l to 74pmol/l in just three days. Mice with zero leptin overeat massively, but do not show the same insulin spike. The insulin spike signifies insulin resistance, that characteristic antioxidant defence response to an excess of calories in the metabolic milieu. This does not happen with the early overeating phase of ob/ob mice. They are in metabolic caloric deficit, which they make up by eating enough to remain vaguely functional.

Absolute leptin deficiency appears to be a very harsh driver of fat storage. Losing this many calories makes you hungry. I guess some bit of the brain is involved in converting this state of actual calorie deficit in to a feeling of hunger, but that's not what interests me nearly as much as what is happening at the adipocyte level of calorie storage.


Now we can get on to Wallace and Gromit and knocking out SCD1 in ob/ob mice.


karl said...

I'm looking at this as a quest to find the causation of the evolving pandemic of T2D.

If I have this correct - you are sorting out leptin resistance from insulin resistance. ob/ob mice can't make leptin - missing leptin can model brain damage or leptin resistance that breaks the response to leptin. But - we have no insulin spike in these mice?

Overeating on the other-hand ( due to a breakdown of modern ethics - as some would have it ) spikes insulin. Thus leptin is doing more than talking to adipose tissue via the brain. Is leptin involved in controlling insulin production? ( I read where insulin controls leptin - but not the other way round? - thus I'm confused. Is the arrow of causation backward?)

The other bit about leptin is the effect of trygly causing leptin resistance:

<a href=" > Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier </a>

I'm trusting this paper is correct - if so, then fructose consumption which spikes trygly production could produce leptin resistance.

The problem with this is if that was all of the story, then people could quit eating fructose, lose weight and no longer have T2D - but that does not appear to be what happens - something gets permanently broken.

I'm also reminded that looking at a broken window does not tell us what broke it - was it a rock or baseball?

ItsTheWooo said...

Within minutes of my first subcutaneous injection of leptin, my hands were sweating and I had an overwhelming urge to move. It was like being given a stimulant.

Sympathetic nervous system FTW.
It's not just central, but *peripherally* that leptin increases the SNS, directly telling your fat tissue to leave the fat cell to create energy.

I think any hypothalamic model of obesity is basically redundant with a leptin deficient model. Leptin sensitive neurons are housed in the hypothalamus. The overwhelmingly primary reason hypothalamic abnormalities do what they do is because you have ruined the primary site for leptin detection.

Basically your brain thinks you have no fat tissue and are in an extended starvation, and everything follows from there. Unfortunate if your leptin is very high but your hypothalamus is damaged or genetically abnormal (e.g. praeder willi).

ob/ob mouse is different from VMH damage mouse only in that the former can be cured with a leptin injection.

Regarding insulin/metabolic health, picture more murky. I suppose an extremely starved (i.e. normal size adipose) leptin deficient animal might show normal or improved insulin sensitivity, due to the supersensitivity of adipose to insulin. However, at the site of the liver, it's pretty clear leptin deficiency is like diabetes express train. Liver doesn't stop making sugar, doesn't listen to insulin w/o leptin. But yes, I suppose at a level of normal body fatness and leptin deficiency combined, the result is adipocyte supersensitivity to insulin thus improved fat uptake into adipocytes as storage and decreased resistance to insulin.

There are experiments where leptin injections are more effective to control diabetes than insulin in STZ diabetic rats.

In leptin deficiency secondary to adipocyte loss (e.g. lipodystrophy of antiretrovial therapy) severe insulin resistance is observed, but that's kind of expected. Leptin therapy hugely improves the insulin resistance in spite of absent fat tissue (which is sort of like being four hundred thousand pounds as far as metabolic health is concerned).

PS, I do miss leptin. Best antiobesity drug in the entire universe, assuming paired with insulin controlling dietary practice of course.

I think I miss the dopamine. Leptin makes dopamine in your brain, ya know. First 3 months off leptin felt like I was on antipsychotics... or like I was quitting stimulants.

ItsTheWooo said...

Main question peter seems to be asking is whether early phase of leptin deficiency mimics hypothalamic damage, meaning there is a period of improved metabolic health and supersensitivity to insulin which is secondary to the adipocytes being driven to grow secondary to neurologically mediated supersensitivity to insulin.

My guess: yes, but probably not as completely as a hypothalamic form of obesity, due to the confounding issue of the peripheral leptin detection in the liver (the liver, which will be partly regulated in a hypothalamic damaged rodent who still makes leptin...whereas, in pure leptin deficiency, the liver will be so abnormal right away this will partially counter act the insulin sensitizing nature of adipocytes driven to expand via a collapsed sympathetic tone. )

Is leptin involved in controlling insulin production: absolutely without question yes. Leptin therapy improves insulin resistance almost immediately . This is overwhelmingly because a lack of leptin turns your liver into that of a diabetic like right away. Leptin is also necessarily to normally use both glucose and fat for energy, lack of which promotes hyperinsulinemia to process nutrition.

The question is... the exact moment one loses leptin, when fat cells are relatively normal sized...what happens at the site of fat tissue? Supersensitive, normal, or resistant?

"something gets permanently broken"
Sometimes it was broken before you were even born, as evidence suggests examining offspring of mothers with higher than normal levels of glucose, insulin, leptin, cortisol, etc. The damage to endocrine system and metabolism might not have anything to do with what you ate after birth, FYI.

Had to belly laugh when carbsane wrote that article fretting about ketogenic pregnancies, and arguedt hat gestational diabetes is normal. This woman is a menace for sure, she has so many SAHMs reading her and she posts this kind of crap.

Nothing says "healthy and natural" like a 12 pound fetus which needs to be cut out of your uterus because the IGF1 excess secondary to hyperglycemia turned it into some kind of mutant. Or, as the medical peeps would say, it has macrosomia and polyhydraminos <---now super common among your average american pregnant lady growing babies on MacDonalds + soda and absolutely no micronutrients and being very obese.

But yea, that's totally normal and gestational diabetes = SKAM.

Peter said...

karl, leptin controls many, many things. Insulin secretion at the level of cholinergic innervation of the pancreas for just one. I think you are asking, through T2DM, questions about ageing, which puts you straight back to the electron transport chain and supraphysiological free radicals and what can or cannot be reversed. Tissue specific mitochondrial heteroplasmy tolerance, as in the last Nick Lane post, might be of interest too.

I'm thinking that after the linoleic acid obese mice we might go to cirrhosis again, this time equipped with an F:N ratio and superoxide, rather than simply accepting that fish oil is even more cirrhosing than corn oil. And the role of visceral fat perhaps.

Woo, I pick at these things. You have no idea how helpful it is to have input from someone who has really been there. Ta.

6.45am, time to go and feed eggs, cream and butter to the family.


Kindke said...

It seems that, in addition to leptin potentiating the SNS outflow to adipocytes, that also leptin acts on the peripheral and in particular the liver to increase fat oxidation.

"I guess some bit of the brain is involved in converting this state of actual calorie deficit in to a feeling of hunger"

Peter just incase you are a *bit* interested, the model I have in my head is referred to as the hepatic oxidation theory in the literature. Basically it seems that hepatic oxidation of substrates is responsible for controlling hunger and appetite via the vagal afferent to the brain.

A drop in fat oxidation in the liver allows the vagal afferent to stimulate the orexigenic neurons in the brain and make you hungry. Many things control hepatic fat oxidation, like substrate availability from adipocytes, glp-1, ghrelin, leptin etc.

Most of the work is done in animals but im sure it applies to humans aswell!

Kindke said...


My feeling is that T2D is fundamentally something to do with impaired glp-1 secretion in response to oral glucose, since glp-1 activates glucokinase in the liver, ( probably also in the pancreas )

As to why that impaired secretion happens, no-one knows yet....

FrankG said...

@Karl: ...something gets permanently broken.

Type 2 Diabetes is a chronic progressive disease. It does not come on overnight but rather many months, years, or probably decades. It is only when the symptoms become overt that the individual seeks medical advice and a diagnosis is made... indeed the ADA guidelines are designed such that: diagnosis is held off until there is a higher degree of certainty.

Considering this, I fail to understand any logic that seeks to suggest that it can be "cured".

By the time symptoms become overt, it is likely that significant irreparable damage has already occurred...

If I hold my hand over a flame for a few seconds, my skin will go red but it will pass in a few minutes. If I hold it there long enough it will blister and may take several days to heal. If I hold it there even longer AND/OR repeat either of the above steps frequently enough, over many months, years, or decades I would expect to get scar tissue that will never heal.

Why does it seem hard for some to imagine that this same process can happen with repeated internal insults to the body?

karl said...

@FrankG said:
Type 2 Diabetes is a chronic progressive disease. It does not come on overnight but rather many months, years, or probably decades."

I quite agree - I don't see how anyone can claim that eating low-carb cures T2D - it only avoids stressing a broken system.

The bit I'm focused on, is that something has changed - this pandemic wasn't here 70 years ago. I would like to think it is fructose, but so many things changed at once that there are several possible things that could be causative in speeding up this aging. ( We are now even seeing a lot of adolescents with T2D ).

Eating low carb to prevent stressing the system suggests to some that it is the carbs that broke the system - I don't think that is true.

We have a broken window - cold air is blowing in - we can do things to slow the wind, but it would be an error to assume that the wind broke the window.

It could be fructose, refined vegi oils, excess O-6, trans-fats - but there are so many confounding variables:

Estrogen like plastics, dietary oxChol (found in large quantities in powdered-milk and powdered-eggs), 'natural pesticides' bred into plants, etc etc etc.

There is a phased in phenomena, where T2D is spreading to the third world - there could be some data that shows the timing of changes and T2D rates that might point to the real suspect.

Then there is the question of what exactly is broken: Pancreas, brain, liver, immune system.

I'm quite frustrated at not knowing the exact cause - really wish I could warn my children.

This paper:
Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier

Shows a suggests a possible way that fructose could cause leptin resistance of the brain via fructose effect of increasing triglyceride. I wonder if there is a similar bit going on in other tissues?

Leptin is also involved in the immune system via interleukins ( see :
leptin immune system

Leptin seems very similar in form (and function) to IL-6. So is the prime function of leptin weight regulation or immunological? ( Once again, biological reuse of design complicates our understanding ).

I like biological schematics like this:



Thinking graphically helps thinking about the subject.

FrankG said...

So we have a world-wide epidemic largely characterised by Metabolic Disorders including Type 2 Diabetes and Obesity, we have these same disorders rapidly spreading to the developing countries as (among other things) they adopt the "western diet", we have an effective way to control (stop, or even reverse) these disorders by means of adopting a naturally LCHF diet closer to that which was eaten by countless previous generations of humans...

So while I agree that we also need to question other things such as plastics, pollutants, vegetable oils etc... in the meantime I see no common-sense reason to dismiss the role of our western diet rich in refined starches and sugars as the likely culprit.

FrankG said...

My son (21 years old an University) acting on a synthesis of my life/health experience, my advice, his own reading and common-sense: cooks for himself, mostly real whole food, sourced locally and seasonally at the farmer's market -- naturally LCHF. Yes he still has beer and pizza on occasion but as I keep reminding him it is what he eats on a regular basis that counts.

Puddleg said...

In terms of reversing DM2, look at liver disease; you can reverse fibrosis by a stage or two, and even cirrhosis by a stage, if you get everything right. Take away the recurrent injury trigger (e.g. alcohol or virus), remove inflammatory diet components (0-6, fructose, gluten, etc), supply optimal repair diet (zinc, selenium,retinol etc).
If you're very lucky things might get clear again - if you didn't have cirrhosis, are young, and very lucky.
BUT the hepatic stellate cells will always be semi-transformed, i.e. you have an inflammatory memory of the injury, and it is easier to revive the inflammatory process than it is in someone who has never experienced it. A relatively short period of drinking or infection could see a return to significant scarring.
This might be a parallel case to DM2 and carb restriction.

Jane said...

Peter, I found this paper on white-adipose-specific inactivation of the leptin receptor

showing that yes indeed, leptin has important functions in WAT. The mice don't eat more but get fat just the same. They have lower levels of the beta-3 adrenergic receptor, meaning less lipolysis, and also lower adiponectin, meaning less fat burning in muscle and liver.

Puddleg said...

Indeed, the preadipocyte is a fibroblast, so the adipocyte is exactly the sort of cell to form an inflammatory memory.
So, what sort of factors dampen this "kindling" effect?
Once an engorged adipocyte, always a hungry adipocyte?
The parallel of the hepatic stellate cell suggests a wide range of influences; some (like curcumin) may well apply to both cell types.
if anyone wants to follow this up.

Puddleg said...

One for Jane:

Overall, the MetS group had significantly higher ferritin (260 ± 23 ng/ml vs. 185 ± 21 ng/ml, P < 0.01) and lower adiponectin (11.5 ± 1.0 μg/ml vs. 18.9 ± 1.9 μg/ml, P < 0.005) than the non-MetS group.

Jane said...

Wow! Thank you so much. I've seen some of this work before, in a PhD thesis, but didn't know there was a paper.

karl said...

@George Henderson
There are some papers that show an association between donating blood and ferritin levels - and others showing reduced 'events'

Not a huge effect - but there is one. Not a great study - you would have to select a group first and randomly select - etc..

The connection of adipose tissue with the immune system once again shows the insane amount of multipurpose in biological organs/tissues/proteins.

This multi-use reminds me that idea that lipoproteins exist to transport lipids to artery walls is quite silly - ignores the fact that LDL and HDL also have immune function.

I think some of the aging disease symptoms show that selection for competing roles of proteins end with a comprise that only multiplying the gene and then further evolution to select roles would cure. We are the result of selection rather than engineering.

karl said...

@George Henderson

Ran into a detail about zinc competing with copper and iron in one of Phinney's books ( which I recommend along with his other book).

I followed up with a little digging and found this paper

I'm wondering if taking zinc can reduce the oxidative stress of iron in the diet ( iron fuels the Fenton reactions which can be further fueled by excess vit C - (what makes something anti-ox vs pro-ox depends on cofactors - thus there is no agreed definition of an antioxidant. )

blogblog said...

you can gradually reverse virtally any cellular injury if you permanently remove the damaging stimulus.

humans evolved from fruit eating apes. Our nearest relatives bonobos and chimpanzees get up to 80% of their calories from fruit. They derive a miniscule 1-2% of their calories from aninal foods.

An ape diet contains negligible amounts of iron and massive quantities of antioxidants.

karl said...


The LCA of man and other apes was over 7-million years ago - time enough for large amounts of evolution.

Man has only been farming grasses for something around 4-thousand years, which is not time enough to evolve very far.

There is variation as to how tolerant people are to eating large amounts of carbohydrates. The fact remains that we now have about 40% of the public with some stage of T2D - a pandemic that did not exist in the 1950's.

Re: cellular injury - not sure that is what you want to really say? The body deals with damaged cells by killing them off on a regular basis.

The problem is senescent cells - That the body can not repair or destroy.


Also, we cannot remove some of the damaging stimulants - that would include things like oxygen. Aging is not avoidable on any diet.

Eva said...

Some interesting info I came upon. Ob/Ob mice can be made to become normal weight, not just by leptin injection, but also via using angiogenesis inhibitors: Fat cannot grow without blood supply, so the lack of getting fatter is not super surprising, but the angiogenesis blockers cause the mice to lose 2/3 of their body mass until they became normal sized mice but then they would not get any skinnier. They did not become emaciated but plateaued at normal. I'm going to have to do more looking into that one.

Jane said...

Have you come across something called autophagy? This is how cells repair themselves. It's a relatively new field and scientists are getting very excited about it. Here is a paper about autophagy in beta cells.

Role of autophagy in diabetes and mitochondria
Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic beta-cells producing insulin. Mitochondrial dysfunction may play a role in both processes of diabetes. Autophagy maintains cellular homeostasis through degradation and recycling of organelles such as mitochondria. As dysfunctional mitochondria are the main organelles removed by autophagy, we studied the role of autophagy in diabetes using mice with beta-cell-specific deletion of the Atg7 gene. Atg7-mutant mice showed reduction in beta-cell mass and pancreatic insulin content. Electron microscopy showed swollen mitochondria and other ultrastructural changes in autophagy-deficient beta-cells. Insulin secretory function ex vivo was also impaired. As a result, Atg7-mutant mice showed hypoinsulinemia and hyperglycemia. These results suggest that autophagy is necessary to maintain structure, mass, and function of beta-cells. Besides its effect on beta-cells, autophagy may affect insulin sensitivity because mitochondrial dysfunction has been implicated in insulin resistance and autophagy is involved in the maintenance of the organelles. Furthermore, since aging is associated with impaired glucose tolerance, decline of autophagic activity may be involved in age-associated reduction of glucose tolerance.

Autophagy is controlled by enzymes which require manganese or magnesium, which also activate enzymes of DNA repair. The reason many people are not repairing themselves adequately may be because they eat refined carbs which have had the Mn and Mg removed.

Unknown said...

Regarding Karl's comments: Epidemics are not caused by genetics. This is also a clinical fact that gets lost in today's scientific literature, but you would never get that from reading the literature on diabetes.

Regarding blog blog on Where we came might want to read my series Brain but 1-5. It lays it all out in detail. I think BG 2 might really interest you. Fruit had nothing to do with us evolving from transitional apes. It was due to the environmental change in the Rift zone and a big change in our gut that made us susceptible to viral marketing Here ya go:

Unknown said...

Jane I fully agree with you on th eMn and Mg issue with autophagy. this is precisely why T2D is seen in cases where the Na/K ATPase is demolished. It causes a loss of energy in the brain and this degrades signal quality and its ability to be perceived in the cell. Iodine is the first micronutrient that gets disorders and causes Peter's icepick scenario.


When a person is iodine deficient, a person loses the ability to handle ROS (oxidation) optimally, and other organ systems have to offset those losses to protect the cell from more oxidation. When this happens we see a failure in their adrenal stress index because the cell is placed in a chronic survival mode. The person must rely on the "alternate biologic systems" built in to cells to handle these problems and they eventually become overwhelmed. That is the uric acid system, Vitamin E and C systems, and glutathione systems in humans. This often leads to a slow progressive decline in function on a physiologic basis of many organ systems in the body over time. It can occur in any organ system, but Hashimoto's has particular affinity to those two tissues in which iodine plays a critical role. The thyroid and the brain, especially the HPA axis in the brain. Loss of iodine degrades sleep and synaptic function as the first step in disease generation. this is where Jane's idea about Mn and Mg fit in. Anyoen with sleep disorders have horrible Mg and Mn because autophagy is most active in humans during sleep. This is why most T2D and T1.5 D have sleep apnea. Iodine is found in high concentrations in the synapse of neurons to optimize signaling. With more time for further iodine loss, it affects more epithelial tissues like the breast, ovaries, and testes to cause fibrocystic disease, cancer and infertility. It even can cause thyroid cancers. Once iodine goes, Magnesium is not far behind at the ATPase where energy is made. . This affects our cells ability to make energy from ATPa nd it cause a bio-energic deficit that further degrades autophagy. Our bodies ATPase is magnesium dependent. This is why diabetics and fat folks are so magnesium deficient; because they are energy inefficient because they live in the chronic oxidative pathway their entire life. Eventually this degrades their sleep and their ability to think clearly.
When cells lose iodine chronically and it is not replaced in the diet constantly, they lose the cellular ability to properly signal. Cells lose the ability to signal correctly and can not "chemically reduce" themselves at night when we sleep. This causes all organs to age faster with time because sleep is restorative by reducing our cells. It causes neolithic disease to happen earlier. This is precisely why bad sleep is associated with all diseases. Sleep is when we are the most chemically reduced in our entire life. When we do not sleep we are more oxidized or inflamed biochemically.

Unknown said...

When this chemical effect is CHRONICALLY present, the decision in the cell always has to be made between survival or reproduction based upon how the cell signals using its nuclear hormones. When we are oxidized we are using up are hormones. When we are reduced we are resupplying them in the great pharmacy in our brains. This means that all the LDL cholesterol that is normally made into pregnenolone will either go into cortisol OR to the progesterone pathway. If all the pregnenolone shunts to cortisol's path, it helps you survive life's oxidation. The shunting signal that determines that choice is the level of cellular inflammation that oxidizes the cell. When we measure cortisol in the plasma, saliva, or urine, it is often low when we are oxidized chronically. That is a sign the PVN nucelus in our brain is working over time, and this is sign you are oxidizing your cells. You are aging faster than normal. This is measured clinically in an adrenal stress index test and really accurate in a low salivary melatonin level. The result is all the hormones going the "other way" in the hormone synthesis chain are very low……..that is the "reduction path". Reduction means you are staying younger. If you re read Brain Gut 11 you will see what a chronic low cortisol buys us. Low cortisol = low melatonin = epithelial cancers = LR. We tend to get cancer as we age. It follows then that oxidation = Leptin Resistance and LR = aging. Low cortisol is not a good thing for a human long term. When the process first begins……ACUTELY, you will have hyper-cortisolism for a time, until you fatigue the output of your PVN nucleus in the hypothalamus. That PVN nucleus is just one of the major pharmacies that function in your brain. If you do that long enough, you oxidize (age) your body, while simultaneously destroying your sleep, to cause your body to slowly begin to fail while your body composition declines. For example, Hashimoto's disease is a disease of chronic oxidation for human nervous system. It depletes you of the life giving chemicals in the pharmacy that resides in your brain. This is why it is associated with so many other neolithic diseases.

Unknown said...

THE BRAIN AND DHA: Let us look deeper into the secrets of the neural lipid membrane for our health

DHA is concentrated in the brain and in neural lipids, especially cell membranes. The reason is simple. DHA allows for complex signaling that no other lipid can match from a chemical standpoint. Brain DHA concentrations are remarkably constant accross many terrestrial species irrespective of the diversity of the natural diets. This has deep implications for all of us with respect to health. Moreover, this finding is also found in many fish species living in environments over a very broad temperature ranges too. The colder the temperature of their environment, the more DHA the fish species tends to have. This is also true in sea mammals. The reason for this, is the more DHA a fish has the better fluidity is found in their cell membranes to allow for optimal cellular signaling of complex systems.

All of this data implies that DHA has a very specific molecular role in life. Many detailed studies show that omega 6 PUFA's can not replicate what DHA can do in the brain or in nerves. Vegetarians do not seem to realize this. The closest omega 6 PUFA is docasapentaenoic acid (22:5n-6, DPA omega6) which has the same number of carbons but only has one less double bond compared to DHA. Otherwise, it is bioidentical to DHA. Dietary deprivation of DHA in many species experimentally shows a rise in tissue DPA omega 6, and a big fall in DHA. This result than impairs cellular physiology directly, by altering signaling. This implies DHA has special cellular signaling properties that can not be replicated by any other lipid. The real interesting part of the story is that animal based omega 3 DHA is only found in the marine food chain.

Plant based omega 3 is called alpha linolenic acid (ALA). ALA in human systems is not well converted to long chained DHA in humans because of the enzyme biochemistry in humans is not well developed. This implies to us that DHA had to be present in abundance when we evolved to naturally select for our big brain. In humans, ALA is oxidized and used as a source of energy most frequently, and for carbon backbones to synthesize nonessential compounds like saturated fatty acids and cholesterol. We now know because of the work of Kaduce in 2008, that adult neurons can make DHA endogenously, but its ability is sharply limited. These facts are laid out in extreme detail in Cite 1. If you believe paleo is the solution for a mammal with a large brain, you better examine cite 1 very closely many times before you believe that meme. This new science shows you it is just not factual.

In adults humans, the DHA synthesis pathway is very inefficient and essentially stops at DPA omega 3, causing a sick brain to be dependent upon a constant source of new DHA. This is another reason why the Epi-paleo Rx is the best evolutionary answer for a mammal with a large brain. If that mammals brain is diseased for any reason at all it even becomes more critical for repair.

Unknown said...

The brain has massive concentrations of DHA in its foundational structure compared to other organ in the body. This suggests that it is indispensable for the special metabolic functions found in the brain. It also appears this was critical in overcoming the structural constraint of connect neurons to new places in the brain to develop new abilities.

Review cite number 1 below for this massively important insight to human physiology that many seem to be oblivious too: "These recent advances in understanding the influence of the highly unsaturated DHA molecule in the membrane phospholipids has fueled speculation that it may work as a metabolic “pacemaker” for cells, and perhaps influence the metabolism of the whole organism via an impact on the basal metabolic rate. This theory was tested by Turner et al., who demonstrated a positive linear relationship between the high molecular activity of the enzyme Na+K+ATPase (the sodium-potassium pump) and membrane concentration of DHA in the surrounding phospholipids in brain, heart, and kidney tissue of samples from both mammals and birds. Further, the highest concentration of DHA was found in the mammalian brain as was the highest activity rate of the pump. This is significant as the sodium-potassium pump accounts for some 20% of the basal metabolic rate but approximately 60% of the energy utilization in the brain." Here is why Jane's point about the Mg and Mn of Autophagy and the ATPase makes leaves us with a massive implication.........

Cite 1:

karl said...

@Jack Kruse
Iodine is quite interesting - in primitive organisms it served the function of thyroid hormone - in fact, we can think of T3 as being iodine that is enhanced via the attached protein.

People are avoiding salt and switching to sea salt thus no longer getting enough iodine in their diets. There is also the issue of carbohydrates causing the retention of salt vs someone on a ketogenic diet - thus people are told to avoid salt and may end up lacking iodine.

What is interesting, is that mild hypothyroidism is one of the most common diseases that people end up diagnosed with - and the medical community seems to not look at dietary iodine unless people present with a goiter. (restaurant food may be lacking iodine )


Of course cells perform autophagy - even DNA repair, but particularly when the mitochondria get damaged via ROS the cell removes them and the remaining ones split, but that only works so long for some subset of cells for which all the mitochondria will have accumulated enough DNA damage that the cell no longer function correctly. There is no way to move mitochondria DNA from healthy cells (there may be some ability for the cell to do mitochondrial DNA repair - but there is not much research on this). If the cell is beyond repair the cell hopefully performs apoptosis - but sometimes this programmed cell death fails and we end up accumulating senescent cells that appear to leak inflammatory interleukins. This is all part of natural aging.

T2D is claimed by some to be CAUSED by accelerated aging - I'm don't think that is true - if it was, children in high school would also be getting gray hair and old looking skin. ( This is likely a confusion of cause with effect - T2D does accelerate aging ).

So it is likely that what is causing the T2D pandemic is something specific to the BG system - some tissue in the Pancrease, brain, adipose tissue, or liver is specifically damaged. Afterwards, once BG goes out of control, symptoms of glycation damage appear. My quest is to know where/what/how the initial damage occurs.

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

de novo lipogenesis reduce SHBG in HepG2 cells ..

What is interesting is that the amount of reduction is the same for fructose or glucose. I'm not
sure that the magnitudes of levels of fructose in this paper are similar to when someone drinks a
huge sugar soda and the liver gets backed up and goes into overdrive producing a spike in Trygly?

SHBG is confusing - increasing testosterone reduces SHBG ( I would have thought it would go up?) -
Increasing T3 in this paper also shows an increase in SHBG production:

But this paper shows no correlation:
Anyway - sugar can change SHBG via the liver.

I'm losing confidence in the idea that fructose is 'the' causative factor of the T2D pandemic -
there are a few counter examples of high sugar consumption with out knocking out BG control. Once the damage is done, avoiding sugars become pretty important - my quest continues for what is the likely cause (not symptom) of the T2D pandemic.

I'm now turning to O-6 over consumption and found a couple of graphs
and also this graph ( I can't find where the supporting data came from )

Insulin sensitivity is involved with HUFA on muscle cells - may get damaged by higher BG and O-6 - perhaps protected by some types of O-3?

This paper is interesting - seems counter to prevailing wisdom.

> Increased intakes of total omega-3 FAs were inversely associated with diabetes incidence [hazard
> ratio (HR) for the fifth compared with the first quintile: 0.78; 95% CI: 0.65, 0.94; P for trend
> = 0.02]. Omega-3 FAs from marine sources were not associated with diabetes risk, whereas
> nonmarine omega-3 FA intake was strongly associated (HR for the fifth compared with the first
> quintile: 0.79; 95% CI: 0.67, 0.93; P for trend = 0.004). Omega-6 and omega-6:omega-3 ratio were
> not associated with incidence of type 2 diabetes.

Much of the O-3 subject blurs the difference between Alpha-linolenic acid (ALA) vs DHA and EPA.

I saw here that Omega-3 eggs have less AA content.

blogblog said...

the problem with the paleo diet philosophy is that it is mostly based on old and largely discredited ethnography not hard science. It is NOT supported by the vast bulk of modern high quality peer-reviewed literature.

Contrary to what you believe our guts, digestive physiology and gut microbiota are those of generalist (mostly) vegetarian primates. In fact the only obvious genetic modifications concerning diet are a significant increase in salivary amylases and post-weaning lactose tolerance (in a small minority of people).

The vast majority of traditional socities have relied on high carbohydrate plant-based diets.

A century ago our ancestors were eating grain-based high-carbohydrate diets. There
was no obesity or diabetes epidemic.

The real reason for the obesity and diabetes epidemic in the developed world is TOO MANY CALORIES and NOT ENOUGH PHYSICAL ACTIVITY.

Jane said...

'...there may be some ability for the cell to do mitochondrial DNA repair - but there is not much research on this. ..'

It would be very surprising if mtDNA could not be repaired. It looks like manganese is critical here too.

'Manganese superoxide dismutase is a nuclear encoded primary antioxidant enzyme localized exclusively in the mitochondrial matrix. Genotoxic agents, such as ultraviolet (UV) radiation, generates oxidative stress and cause mitochondrial DNA (mtDNA) damage. The mtDNA polymerase (Polγ), a major constituent of nucleoids, is responsible for the replication and repair of the mitochondrial genome. Recent studies suggest that the mitochondria contain fidelity proteins and MnSOD constitutes an integral part of the nucleoid complex. However, it is not known whether or how MnSOD participates in the mitochondrial repair processes. Using skin tissue from C57BL/6 mice exposed to UVB radiation, we demonstrate that MnSOD has a critical role in preventing mtDNA damage by protecting the function of Polγ. ..'

Jane said...

@Jack Kruse
If you want me to comment on what you have said here, you will have to ask me very nicely. Every time I try to read your work I start out thinking 'that's interesting' and invariably before I've even finished the first paragraph I practically die of boredom. There are so many misunderstandings and mistakes I just can't face it.

Scott Russell said...

Autophagy definitely has some interesting potential as a curative. Although I haven't had the time to look at the article you posted, I'm wondering which specific form is Mg/Mn dependent. From what I've seen, there are three main types; macro, micro, and carrier-mediated. Are these all Mg/Mn dependent?

Macro-autophagy probably accounts for the benefits seen in intermittent fasting, whereas CMA probably explains some of the benefits of ketogenic diets, as ketones seem to stimulate CMA even with normal protein consumption.

I wouldn't generalize paleo quite so simply. Some are orthodox and dumb, some are much more nuanced and provide a valid approach to health. And generalizing our gut biota seems dubious, as the biggest determinant is what we put in it. Not to mention that a shift to a more protein and fat oriented diet wouldn't effect much of a change in type of gut bacteria, but rather mostly a change in absolute quantity.

Puddleg said...

@ Karl, thanks for the zinc paper. Have look at ways to moderate ferritin and don't like taking calcium which gets a bit neurotoxic.
I also hypothesise that taking supraphysiological doses of inorganic calcium is going to downregulate vitamin D - how else can the body compensate for the extra Ca migrating into the blood without D's assistance?

karl said...


Even within the cells own DNA there are some types of DNA damage that can't be repaired. From what I've read, the mitochondria hasn't the tools to repair it's own DNA - the potential repair is done by the cell.

What I find so interesting about mDNA is that it is reproduced asexually. Asexual creatures overcome the disadvantage by being quite prolific - large populations constantly dividing, less suited versions dying off in large numbers. The size of human egg cells limits the population pool.

Now realize that the entire variety of mDNA is contained in one-cell - the human egg cell which somehow is preserved in a dormant state - protected from damage in some non understood way. I think of it as an evolutionary choke point at every conception.

RE Paleo - I don't we can ignore what we evolved to eat.

My take is that our bodies are able to keto-adapt and carb adapt over a few weeks. IF our BG control is damaged it appears advantageous to eat a ketogenic diet. I don't think there is any doubt that at least some tribes ate mostly meat. I also don't think there is any doubt that eating mostly carbon that is derived from corn, soy, and wheat is a recent phenomena.

So there are two separate issues:

1 - What should we eat to manage T2D

2- What are we eating that is causing the T2D pandemic? ( Could even be some other environmental factor that is yet under the radar )

The problem is there are several changes that correlate with the pandemic of T2D - fructose consumption, O-6 consumption, trans-fats, plastics, disease exposure to new strains -- etc etc etc.

FrankG said...

@blogblog "you can gradually reverse [virtually] any cellular injury if you permanently remove the damaging stimulus."

Tell that to a burn victim with lifelong scars.

Or perhaps cite your own counter-evidence.

FrankG said...

"The chimpanzee diet consists mainly of fruit, but they also eat leaves and leaf buds, and the remaining part of their diet consists of a mixture of seeds, blossoms, stems, pith, bark and resin (Goodall 1986). Chimpanzees are highly specialized frugivores and across all study sites preferentially eat fruit, even when it is not abundant. They supplement their mainly vegetarian diet with insects, birds, birds' eggs, honey, soil, and small to medium-sized mammals (including other primates) (Goodall 1986; Boesch & Boesch-Achermann 1989; Isabirye-Basuta 1989). Their most common mammalian prey is the red colobus monkey (Procolobus badius), though they also eat blue duikers, bushbucks, red-tailed monkeys (Cercopithecus ascanius), yellow baboons (Papio cynocephalus cynocephalus), and warthogs (Boesch et al. 2002). Chimpanzees spend, on average, half of their days feeding, and much time moving from one food source to the next (Goodall 1986). The actual time spent feeding, though, is correlated with the amount of processing time required by the type of food being consumed."

I recall a BBC documentary based on the work of Professor Richard Wrangham. As part of the show they showed a group of human volunteers who set up home in a zoo alongside the Chimpanzee enclosure. They were given a diet of raw plant foods (fruit and veg.) designed by a dietitian to provide their individual nutritional needs for the duration of the experiment...

Two things were noted: there was not enough paper in the toilet for their frequent visits and there was not enough time in the day for them to eat the volume of food they were given.

We are not chimps. The fact that we don't have to spend all day either eating or searching for food could well be a major key to our differing evolutionary paths.

High-quality, nutritionally dense food -- made more readily digestible by cooking -- is very likely what gave us the time to devote to our culture, traditions and technology.

Modern "Western" food is no longer nutritionally dense; although it may provide a surfeit of calories.

Jane said...

I'm thinking of macroautophagy. There's a critical enzyme called Vps34, see this paper
'Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function'

Vps34 works together with mTOR, which you may have come across, and both are members of the PIKK family of which other members control DNA repair (ATM, ATR and DNA-PK). Most of them seem to be activated by Mn rather than Mg, but it's questionable whether this is physiological because very high concentrations of Mn are needed. In fact they all work at or in membrane-bound compartments (lysosomes, mitochondria or nucleus) which are known to concentrate Mn, so it may be true. Here are papers showing Mn dependence of mTOR and Vps34.

Mn dependence of mTOR (see Fig 2A):

Mn dependence of Vps34 (Fig 3A):

Jane said...

'.. From what I've read, the mitochondria hasn't the tools to repair it's own DNA ...'

If you read the abstract I linked, you will see that the DNA polymerase that replicates mtDNA also repairs it.

karl said...


Interesting - what we know about mDNA is changing rapidly in the last decade.

I found this paper - (search for: DNA Damage Processing in Mitochondrial )

This makes sense - with out a good repair system the dormant egg cells would accumulate damage.

I also read that there are 8? copies of the DNA in each of several hundred mitochondria.

Are you then saying that the levels of Mn involved are not practical as an intervention?

Puddleg said...

@ Kindke,

very interesting the HOT papers.
When you complain to a hepatologist that your liver hurts (or "hurts") they say, nonsense, there are no nerves in the liver.
Then you pick up a copy of Grays Anatomy and lo and behold, nerves in the liver.
Read a bit further and there are other cells that produce and process neurotransmitters.
The brain not having communication with the liver would be like a government being unable to communicate with the country's banks and heavy indistry.

blogblog said...
This comment has been removed by the author.
Jane said...

Thanks, interesting paper. Looks like all forms of mtDNA damage can be repaired one way or another. Yes, there are multiple copies, which I suppose means that some forms of damage can be repaired by recombination with an undamaged copy. Your paper does mention recombination.

'.. Are you then saying that the levels of Mn involved are not practical as an intervention?'

Do you mean Mn pills? This is a difficult topic. I do believe Mn deficiency is a major cause of disease, but I don't necessarily think Mn pills would help. If people are deficient for Mn they will be deficient for other things too, and have been deficient for many years. There will be structural changes which might take some time to reverse.

There is also the question of whether your gut bacteria like pills of any kind. I doubt if they do.

Eva said...

Jane, I don't know about gut bacteria but I sure do better on magnesium pills. No more calf cramps and I sleep much better. How well pills work probably depends on what your probs and genetics are and what is in the pill. Of course, I'd like to get my mag from food but I have found these days I just don't feel like eating that much food all day and even the 'high magnesium' foods really don't have that much in em and there aren't many of them. I'd have to be eating something like salmon, bananas, and spinach at every meal to regularly meet the magnesium RDAs. Seems like most known vitamin needs are easily met by eating actual Food, but there are a few that are not, or at least not the Food we currently have access to. Yes, I agree that research behind most RDAs is flimsy and many paleo eaters assume that the RDAs they don't meet probably all are just wrong anyway, but there is no research to support that so may not be a good idea to blindly assume. And we all have different genetics and unhealthful living over the long haul may also have added additional stresses and needs. A damaged system often needs more support than a fully healthy one.

Scott Russell said...

Thanks for the refs, I'll start pouring through those pretty soon. Interesting that mToR is also Mn dependent, as autophagy and mToR are rather opposing processes.

karl said...

I've started Nick Lanes book:
Power, Sex, Suicide : Mitochondria and the meaning of life

Very interesting and well written. There is a huge amount of information that was not available when I was in school.

Turns out that the human egg may have up to 100,000 mitochondria. The mitochondria now only encodes for 13 of its own proteins - the rest of the m-proteins are now encoded by the nucleus. Absolutely fascinating the changes in what biology has figured out in the last decades.

The evolution theory of the mitochondria has changed - is changing.

@George Henderson

I don't think the liver has pain nerves - it has other nerves - sympathetic and Vagus . Pain in the liver area can be from gal-stones or connective tissue. The Vegas nerve can send back feelings of sickness - not perceived as pain - from what I understand.

Pain in that area should not be ignored - could be referred pain which is sometimes quite serious.

Hope you are OK..

Puddleg said...

Good thyroid-glucose paper

(Always impressed by the papers Hindawi publish. They've not disappointed me yet.)

Thyroid hormones have a large impact on glucose metabolism. A direct regulation on thyroid responsive genes at the target organ has been described and more recently an indirect effect involving hypothalamic pathways that regulate glucose metabolism via control of the sympathetic nervous system has been reported. Furthermore, thyroid hormone effects can be insulin agonistic, such as demonstrated in muscle or antagonistic such as observed in the liver. In hyperthyroidism, dysregulation of this balance may end in glucose intolerance mainly due to hepatic insulin resistance. In hypothyroidism the results are less evident. However, the available data suggest that insulin resistance is present mainly at the peripheral tissues. Possible explanations hypothesized to explain this phenomenon span from the dysregulation of mitochondrial oxidative metabolism to the reduction of blood flow in muscle and adipose tissue under hypothyroid conditions.

Puddleg said...

Karl, I am fine thanks, that was an old memory.
The liver "pain" of inflammation is like being kicked some in the solar plexus, the "sickness" you mention but also perceptible as ache.
The sharper pain, usually after eating, is the gall bladder (and this can get referred as far as the shoulder blade). Not necessarily stones (this is actually pretty common from gluten sensitivity diseases) but also cholecystitis, cholangitis, etc.
Nothing like saturated fat for keeping it all quiet.

Jane said...

I've just realised you won't be able to get the two papers on Mn dependence of mTOR and Vps34. Here are the titles. You may not be able to get them anyway and will just have to trust me that the figures show Mg doesn't activate them and Mn does.

Direct inhibition of the signaling functions of the mammalian
target of rapamycin by the phosphoinositide 3-kinase
inhibitors, wortmannin and LY294002
(see Fig 2A)

A human phosphatidylinositol 3-kinase complex related to the
yeast Vps34p-Vpsl5p protein sorting
(see Fig 3A)

Yes I agree, if they are both activated in vivo by Mn it's very interesting indeed. We now know that mTOR moves to lysosomes when it's activated
which means cell growth and autophagy and the switch between them might be controlled by lysosomes and the Mn in them.

Jane said...

There is certainly a lot of Mg deficiency around, but this is because people eat food that's had it removed, which I'm sure you are not doing. A wholefood diet should supply all the Mg you need, because the absorption systems in the gut are very flexible, and will upregulate in response to a low intake. But of course in response to a supplement they will downregulate, and then if you stop taking it you will get deficiency symptoms.

karl said...

Jane -

You might know about the ' Physician's Health Study' where they had doctors take ASA(aspirin) or placebo followed long term and then declared that taking ASA was a magic bullet. Only there was one detail - the ASA they used had magnesium in it.

That they wasted a huge amount of resources on a flawed experiment that had two variables instead of one is mind blowing. (If only the placebo also had magnesium ).

There is quite a body of work suggesting that magnesium reduces CAD - might via lowering BP plus other effects.

Gadfly said...

Good to see blogblog still proudly promulgating the bizarre and illogical notion that because we share DNA with chimps that our dietary needs are the same. We also share a lot of DNA with gorillas, but unless blogblog and Don Matesz have figured out how to grow hind guts, I don't think they ought to eat the same way. And just what ARE chimps are doing with their extra chromosome? Maybe they'll figure out how to make themselves talk and drive spacecraft like ours soon? Or maybe the devil is in the details. Either way, this nonsensical reasoning is ultimately an invitation to stroll down an infinite regress. And it's really no different than the poor argument made by some Paleo folks that 'because our ancestors didn't eat so-and-so, we shouldn't..." My ancestors will take our lactase persistence and raise you cooked starch to boot. Do chimps prefer their sweet potatoes baked or boiled?

Unknown said...

One of the main features of ob/ob mice is their hyoperphagia (as observed in the rare human equivalent mutants) where the defect is in the leptin gene itself. In both humans and mice this leptin deficiency can be successfulyl treated by injections of recombinant leptin. The main symptom to disappear is hyperphagia and the subjects (mice or man) return to a much leaner body composition over a few months/weeks of treatment.With the leptin restored these people are perfectly able to mobilise their fat stores once the appetite is under control.
A recent paper has studied conditional POMC mutant mice. Here the authors were able to reverse the POMC mutation that leads to obesity and they could control at which age they did so, i.e. they controlled how long the mice were obese before the POMC gene was reactivated. Interestingly enough in this case the longer the mice had spent as obese the less likely they were to retunr fully to a lean weight typical of the species (and this with the diet being kept constant and lab chow so no hyperpalatibility here. Hard to disentangle but could be a combination of both. Worth contacting Dr Friedman the Leptin discoverer.

Jane said...

Yes Mg deficiency seems to be just as important in heart disease as Cu deficiency. I expect you know that statins only work because they do what Mg does. Big problem for Big Pharma if the public decides to move on from Big Bank bashing.

I looked up the Physicians' Health Study and I'm not sure the amount of Mg was enough to explain the results. It seems to be pretty small - less than 30mg/day. But yes, the placebo should have had Mg too.

Jane said...

What did blogblog say that you didn't like? To my mind he talks a lot of sense. He and I used to have arguments but since then he's done his homework.

Eva said...

Jane, I eat 95% paleo, depending on what you call paleo Food style diet, very little processed. I do eat diary and whole fruits within reason. Sometimes I eat rice. Just crunch the numbers on the magnesium. The RDA for mag is 320 mg for women and 420 mg for men. Here is a list of 'high' mag foods:
Most of the highest are grains, beans, and nuts. I don't eat the first two (other than rice) and not much of the third. I tend to feel kinda icky if I eat a lot of nuts. SO what are you guys all eating every day that gives you RDA of mag every day? Just curious, but maybe part of my prob is eating paleo, I'm not that hungry and I don't eat much, maybe 2 meals per day, sometimes barely that. Plus I do better with about 500 mg magnesium daily. A whole food diet does NOT always give you full RDA on everything. It depends on which exact whole foods you eat. Does it matter if it doesn't? At least for magnesium and me personally, the answer is yes.

Eva said...

Karl, aspirin is a blood thinner (interestingly so is fish oil). I could see that for an overall unhealthy population of SAD eaters, a little bit of blood thinner might help blood pressure, etc. So I am not surprised if a bit of aspirin helps a lot of SAD eaters and that shows in research stats. I don't think we need to assume it is the mag, although that could be a contributor. The prob is when researchers assume that aspirin itself is good for everyone when really they should be looking at what aspirin is helping us with and why we need that help and how to get that more naturally. If your blood is already healthy, aspirin may actually (IMO likely) then be bad for you. What is good for one could be bad for another but you will see the stats usually lean towards the most likely scenario which in the US is SAD eaters.

Eva said...

Jane, forgot to mention, I had already switched to a diet of paleo style Food for some time before I figured out I also did better with mag supps. Eating healhy helped me in many ways but not everyone finds it fixes EVERYTHING that is wrong with them.

What I did was go to and see what (few) RDAs were not being met by my Food intake. Then I looked at common symptoms of lack of those vitamins. I was not meeting mag at all and common symptom of low mag was calf cramp, something I still had often. Took mag supps, calf cramp gone right away. Comes back if I forget the mag supps for a while. I am my own control group I guess.

I also don't meet RDA for calcium and E. Does it matter on those? Not sure. And although I eat meat at every meal, I often don't meet RDA on protein. I try to eat more but I get full and don't feel like eating. Maybe decades of bad eating have screwed up my system a bit. I am still working on final tweaks. I would like people to consider that eating Food is a wonderfully great idea but does not fix everything for everyone. Further tweeking is sometimes needed.

Also, my mag supps are only 300 mg a day, just under the RDA, not like a massive dose. I find it unlikely that I am causing some kind of massive down regulation in digestive uptake when my overall consumption is still not that much over RDAs and previous consumption levels were causing decades of calf cramps.

What I find common on all nutrition groups is that people have strong opinions on what should and will work and not work. When evidence comes to the contrary, there is a strong tendency to ignore it or refute it without really checking into it first. But it's the stuff that does not fit that can give the most useful hints on where to improve. Always look openmindedly into that which does not fit preconcieved notions. Some of it will turn out to be crap but some will turn out to be golden.

karl said...

Laura McCormack said...

Interestingly enough in this case the longer the mice had spent as obese the less likely they were to retunr fully to a lean weight typical of the species (and this with the diet being kept constant and lab chow so no hyperpalatibility here.

This possibly makes sense - IF they get obese - end up insulin resistant => elevated BG and FFA - then I remember the graph from:

and damage to pancreatic beta cells.
No longer able to adequately control BG, we end up heavier?

Could it be that a similar situation is setup with O-6 producing Insulin resistance?

Jane said...
I expect you know that statins only work because they do what Mg does.

Not sure I would agree - statins are dirty drugs - I've read about 10 different effects other than lowering LDL (some may overlap). One effect is blocking LOX-1. They may also do some of what Mg does - but they do more. I think the LDL lowering is a side effect - not the way they work. (BTW I'm a CAD patient and I don't take a statin. Statins do not appear to lower oxLDL and appear to raise fasting BG - death by all causes is not impressive).

Re - the quantity of mg - the problem is we don't know if it was enough to matter - real science needs to change only one variable.

To be a real paleo one must eat bugs.. I was amazed at the amount of insects eaten by people in the tropical jungle.

Peter said...

Hi all,

Bit random on the replies front I'm afraid...

Karl, you need to read Oxygen too. It covers some areas in more depth than PSS and PSS does get rather lost when Nick Lane talks about insulin resistance. His website is excellent.

Eva, I think Mg is rather important too. It's lost through the kidneys under hyperglycaemic and hyperinsulinaemic conditions. I think I've got refs somewhere...

George, no nerves to the liver, wow. Some folks really do talk poop. Gastrocolonic fistula there, methinks! Thyroid paper is interesting.

Karl and Jane, mtDNA repair. The mitochondrial DNA is repaired by a nuclear coded mtDNA repair enzyme. Pubmed "mitochondrial mutator mouse", or read PSS. This area is as harmonious as Sheffield vs Nottingham for neurological manifestations of gluten toxicity. Controversy is not the word. Arguments are settled by researchers throwing house bricks at each other. Fun.

Laura, I would be interested in why you feel ob/ob mice, while hyperphagic, are not insulin resistant in early life (they're not). Are they over eating (this causes insulin resistance IMMEDIATELY in paid human volunteers or are they metabolically hypocaloric. The question is quite important as leptin clearly has effects on sympatheic innervation of adipocytes and directly on adipocytes themselves. This is a very fundamental question. Are ob/ob mice hungry because they have adipocytes which steal calories or are they hungry first and so have to stuff the excess calories somewhere, adipocytes being as good a place as any, better than most places. It is very difficult to over emphasis how important this dichotomy of point of view is.

Nice to hear that leptin doesn't work using food reward. Phew.

Gadfly, Jane and blogblog, You probably realise that I feel people can eat what ever they choose, I don't care. What I find scary is using Dandona's PMN model for decision making. He tested glucose, casein, cream, fructose and alcohol. All separately. We should live on a diet of fructose and alcohol, according to his PMN results. Well, vodka spiked agave syrup is a perfectly reasonable diet for anyone who so wishes to indulge. BTW he didn't look at uric acid. He should have done, certainly for the fructose group...

That leaves us with vodka. Hmmm, "The Vodka Diet", I could wite a book on that and become a diet guru, but Dandona has probably already beaten me to it!


karl said...

Petro said:
Are ob/ob mice hungry because they have adipocytes which steal calories or are they hungry first and so have to stuff the excess calories somewhere, adipocytes being as good a place as any, better than most places. It is very difficult to over emphasis how important this dichotomy of point of view is.

Exactly - is the dominant effect of leptin in the brain or adipose tissue? Or equally both?

Hmm - What if they turn off insulin so the adipocytes are not absorbing? Low carb diet? - except rats being herbivores don't like to eat that much fat. Remove their pancreas?

karl said...

BTW - already read Oxygen (Nick Lane) - excellent book, I would say the best I've read this year.

Eva said...

Yeah, I noticed this sentence from Laura as well, "With the leptin restored these people are perfectly able to mobilise their fat stores once the appetite is under control." I think there is an assumption there that the prob originates in the brain and fat mobilization is a side effect of what is eaten. But what if it is the reverse, that once fat mobilization is restored, then appetite is under control? The last one is actually more logical. If you can't access stores from fat cells, then you are going to HAVE to eat more in order to get energy.

Jane said...

Thanks Peter. Great stuff.

You eat meat at every meal? Hmmm. Have you considered the possibility that you have iron overload? I am not convinced that premenopausal women are immune from it. Iron overload would raise your requirement for Mg, and also for Mn and Cu. This may be the reason paleo eaters run into problems eventually. Much recent research indicates our ancestors ate less meat and more carbs than the paleo people thought.

I looked up and was not impressed. You would do better to read a short book called The Wheel of Health, available online. Despite being published in 1938 it contains the most advanced account of the causes of disease I have ever seen. It describes McCarrison's work on the Hunza, who 100 years ago were probably the healthiest people on the planet. I eat a Hunza diet myself.

Perhaps I should tell you about my background. I am a biologist, trained at Oxford and Cambridge, and have spent the past ~30 years studying the biomedical literature. I had an Oxford college research fellowship which was terminated in 1985 when my work led me to believe that modern disease is caused by nutritional deficiencies and not by genes. The biotech revolution was just starting and it was felt my work might make it difficult to get funding. I am not making this up.

Kindke said...

But what if it is the reverse, that once fat mobilization is restored, then appetite is under control?

I think this is more likely correct. With respect to the hepatic oxidation theory.

Puddleg said...

Chris Masterjohn talks about ROS and IR in cell signalling

Puddleg said...

@ blog blog

if humans evolved from fruit eating apes, why do both humans and apes have gall bladders?
How do we know what our LCA ate?
We're only just learning what apes eat, can't agree on what humans eat, and those are living examples.

Peter said...

Oh, re Dandona, I think maybe it was orange juice rather than fructose. Mmmmm, still chronic uric acid production...

BTW he has at least one nice article on insulin as an anti inflammatory hormone. Good on facts, not so hot on interpretation. I was going to post on it about 2 years ago! You know how life goes. Maybe when we get back to insulin and the ETC, which is interesting.


Eva said...

Jane, my hemoglobin still dips low enough after the time of the month to disallow blood donation (as per blood bank rules), so I don't think I have iron overload. Look at the whole picture of what I said. I said I eat meat at every meal but I also said I only eat 2 meals per day and my protein intake tends to be below recommended quite often. So that's not a ton of meat. Plus you are assuming it is all red meat. I also eat chicken, fish, shrimp, etc. Some days there is no red meat. As for iron overload, I have my suspicions that it may be more related to imbalance in the system and lack of proper excretion of iron than just eating too much red meat. Also, looking at the LONG list of iron overload symptoms, I have not a single one of them.

As for, I think it's a great way to tally nutrient intake and no book will do that for you so easily. Fitday gives you the raw numbers easily and it's free so no excuses for lazy or poor people! For instance, I had assumed I get plenty of protein but fitday informed me otherwise and I had no idea about my lack of magnesium intake until fitday.

Now as for interpretation of the numbers fitday gives you, that is another matter and I think I have already mentioned I feel that RDAs are not super accurate, sometimes probably too high and other times probably too low.

blogblog said...

@George Hendersen,

we have gall bladders because - like all primates - we evolved from insectivores. Biological structures don't disappear just because they lose importance.

Giant Pandas still retain a complete standard bear gut physiology and anatomy despite millions of years eating a 99% bamboo diet.

Anatomically the guts of polar bears and giant pandas are virtually identical. However they have a totally different gut microbiota.

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

before you criticise others you should get your facts right.

Gorillas don't have "giant" hindguts. They have relatively longer colons and shorter ileums than humans. Male mountain gorillas weigh up to 220kg - 3x the weight of a human male. If you adjust for body size gorillas and humans have similar sized guts.

Humans are far more closely related to chimpanzees and bobobos than gorillas. We have a very similar gut anatomy to bonobos when adjusted for relative size.

The human gut varies greatly depending on diet. Humans from socities that have very high fibre diets can have guts about 25% (1.5m) longer than Westerners.

The daily fibre intake in pre-industrial societies is up to 200g.

The REAL difference between carnivores and herbivores is the gut microbiota. eg Pandas and polar bears have very similar guts but radically different gut microbiota. The human gut microbiota is that of a typical (almost entirely) vegetarian primate and completely different to any true carnivore such as dogs or cats.

Jane said...

You said, perhaps you meant They seem to be different. It looks like wants to sell you a lot of stuff.

It does sound as if you have Mg deficiency. But that means you almost certainly have other deficiencies, and possibly iron overload. I say that because iron overload has been found in practically every disease you can think of. It often means copper deficiency, which is thought by some people (including most copper researchers) to be very common. Without copper, iron cannot get out of cells.

I see you don't eat grains or beans except rice. Is that white rice or brown rice? Some paleo people talk about white rice as 'safe starch', perhaps not realising it's had nearly all of its Mg removed.

The problem with eating meat instead of grains and beans is that you can get too much iron in relation to manganese and copper, which are needed to prevent/repair the damage iron can cause.

Scott Russell said...

You mention that human's gut biota is very similar to that of a vegetarian primate, but isn't this oversimplifying the data? You can dial your gut biota pretty radically with dietary changes, so saying humans have a vegetarian oriented biota really just means that the humans tested ate a fair amount of plant matter.

This also makes me think of the studies where they did fecal transplants to combat diet-induced obesity. Manipulation of the flora certainly has potential benefits, but I don't think we can state anything conclusively about what we should eat based solely on what biota we tend to have. And I'm highly skeptical that we can make categorical statements about what flora we have as a population.

Ken said...

Peter, Karl et al,
Here's a 1966 (pre-leptin) paper I came across, and filed under
"Carbohydrate Metabolism":
I think many will recognize some authors and others whose research is cited in the paper. The sentence that most grabbed me was this: "If these results are subsequently confirmed, they would suggest that hypertriglyceridemia can only develop in patients who have BOTH hyperglycemia and hyperinsulinemia."
I believe that this conclusion has stood the test of time, and surmise that it can be extended to include CVD (atherosclerosis).
That is, neither hyperglycemia nor hyperinsulinemia alone can explain
accelerated (beyond that attributable to aging alone) CVD.
What does the combination induce? I suggest excessive intracellular
fuel (in the form of glucose) in the endothelial cells (especially
with greater genetic susceptibility and/or lack of adaptive IR in these cells), leading to semi-permanent damage to DNA (nDNA, mtDNA) and then all the things that follow (as pathological adaptations, I believe): plaques, oxLDL, inflammation, ischemia, etc. Excessive ROS and so forth presumably provide the mechanism for damage. Chronic DNA damage accumulation (at any age) provides the setting whereby the body's rate of repair falls behind its need for repair, no?
Of course the other ingredient is oxygen to burn the excessive intracellular glucose. Atherosclerosis does not occur in veins. But it also seems to occur in arteries more commonly near the heart than peripherally. There is a lot of oxygen supply there.
In the context of hyperglycemia, hyperinsulinemia and CVD, study of individual type-1 diabetics (rather than averages of large cohorts) is fertile ground; T1Ds inject insulin (in widely varying amounts) peripherally but endogenously produce almost none, and have varying diets (from that of R. Bernstein to those w whole-body IR).
I suggest that all chronic/Western/civilization diseases have a root cause in damage to a central tissue type. For DM (both/all types) it's the islets (e.g. onset of frank T2DM requires ~80% loss of beta-cell function, regardless of whether pre-diabetic pathogenesis is partially whole-body IR-driven, as in IGT, or not at all, as in iIFG), for CVD it's the endothelium, for neural diseases it's one of the neural tissues. All sorts of complex pathological adaptations such as lipotoxicity, plaques (in various tissues w various diseases), glucokinase dysfunction (search research by L. Perreault),
inflammation, obesity, hypertension, etc. can be confused as etiological, but I think are probably not in general.
Bioenergetics probably IS key to all modern chronic diseases. Endocrinology beyond what we are evolved to handle w/o damage, resulting from a modern diet, is the precursor. But at the cellular level the primary damage involves energy production (as a cause or
effect), no?
Anyway, sorry for the diatribe -- I like the old paper/study and hope others find it interesting. Research and researchers were markedly different back then.

Eva said...

Jane you are right, Fitday.COM (not org) is the right one. THe other one looks fairly useless. SORRRYYY!! However, I still don't quite get where you are sure I don't have mg deficiency when I have already said I don't meet the RDAs at all and have muscle cramps UNLESS I supplement. Obviously, once I supplement, then I am meeting RDAs and a not deficient. That's the whole point of supplementation.

If your argument is that almost everyone has iron overload, despite not eating a lot of it according to RDA and despite not having any symptoms of it, well there is not point arguing with you about it. But you might want to consider that although iron retained in tissues is correlated with some illnesses, that does not automatically mean that iron caused it. Correlation does not imply causation is a basic tenant of science. The tissues and body are normally able to excrete iron. YOu could argue that they can't excrete enough, but then you would have to explain why the Massai are not all terribly ill with iron overload.

Blogblog, you can't have it both ways. You can't argue gut morphology proves that humans are plant eaters and then turn around 5 seconds later and say that gut morphology does not actually matter and it's really mostly only gut microbiota that matters. Which one is it?

karl said...


I disagree with the mainstream medical advice that only Trygly levels over 150 are abnormal.

Healthy children, athletes that are not gobbling sugar have Trygly of around 50-60. I don't understand the thinking that it is natural to double or tipple the that number. (Perhaps it isn't as important without the historical increases in dietary O-6 ).

If we go back before trade in sugar cane - I think it would be almost impossible to have a fasting Trygly of over 100 - even if eating rice. If we go back before man started growing and eating grass crops, a level of 100 would be quite rare.

My hunch is that elevated ( over 75) Trygly are a surrogate marker for FFA produced from fructose consumption or over consumption of other carbohydrates.

Once we add increased O-6 to induce insulin resistance we have FFA and high BG which start the accelerated aging of T2D.

@Eve and Jane
Irons ability to fuel Fenton reaction to produce ROS is probably mostly mitigated if postprandial BG stays below 110. I haven't had time to find out if anyone has looked at using zinc + magnesium to reduce iron absorption - I think that would likely do the trick.

There are two things I keep in mind when weighing dietary risks:

1 - What is the relative risk? Is it important to do more than eliminate the biggest risks? (One can end up with very few food choises in a hurry.)

2 - Does the risk apply to ME? Is eating sat fats important if my postprandial BG is below 110?

Most of the demographic information collected now has 40% of the public with either T2D or impaired BG regulation. That epidemiological data has problems to begin with ( epidemiological only suggests where to do a real experiment - and then only when they used tested and valid methods of collecting data (diet surveys are not valid)). If we remove the people that are failing GTT(Glucose Tolerance Tests) or have elevated HbA1c (I don't know if I trust HbA1c 100% ? ) what happens to their 'correlations'?

You are still ignoring the 7 million years that have passed from our LCA - which is more than enough time to evolve from a herbivore to carnivore and back again. On what basis can you ignore this?

Ken said...

P.S. BOTH Hyperglycemia and Hyperinsulinemia
I can't help but look at anecdotal evidence in myself and others with similar characteristics in forming hypotheses. I have had hypercholesterolemia (like Peter) since being on a ketogenic diet, but I also have a coronary calcium score of zero (at 54 years old, male). I am also borderline pre-diabetic with iIFG -- various different markers (including HOMA-B%, fasting BG and OGTT results) all indicate my beta-cell function is ~40%. Most are not familiar with isolated fasting hyperglycemia, but I have read almost all of the related research. There is no insulin-secretion "compensation" (and hence no "decompensation") stage in this form of pre-diabetes (which accounts for ~1/3 of pre-diabetes in the population -- it is common); beta-cell function heads straight down (but slowly, taking many decades before overt T2DM occurs) and never increases.
Whole-body insulin sensitivity is normal (on average) in iIFG. I have never experienced a hypoglycemic reaction in my life (although I have relatives who do all the time) -- my pancreas was always too weak, I think (and my HG relatives are not genetically susceptible to T2DM at all, like most of the population -- they have huge IR and over-sized islets).
For the same reason, I think that my form of susceptibility to T2DM has prevented me from developing vascular plaques. Before a few years ago my diet was the SAD, more or less. I had symptoms of IR/MS, I became increasingly overweight through middle age. I had all the ingredients (for development of atherosclerosis), I think, except the ability to produce compensatory hyperinsulinemia postprandially.
I am not unique; lots of statistical studies of pre-diabetics consistently indicate that there is NO increased risk of CVD associated with iIFG, whereas there is a large increased risk of CVD with iIGT and larger still with CGI. iIFG produces the lowest postprandial BG peaks (although higher than in normoglycemia), then iIGT, and CGI produces the highest typically. The same is generally true for postprandial insulin secretion during the pre-diabetic stage (i.e. before overt T2DM).
Another interesting difference between forms of pre-diabetes is that in iIFG there is an adaptive supra-normal secretion of GLP-1, whereas GLP-1 is sub-normal in IGT (accounting, it is believed, for many of the differences in postprandial response between IFG and IGT). But there is now huge interest in incretin drugs for prevention of CVD, especially in diabetics, and these drugs are mostly GLP-1 equivalents and mimetics. They appear to work for this purpose in addition to BG control. So could my extra GLP-1 secretion (at the most protective times, i.e. postprandially) also factor into my zero calcium score?
Put that in your pipes and smoke it, lipophobes!
Of course, I believe that various serum lipids are nothing more than markers for processes that relate to postprandial glucose and insulin and have nothing etiologically to do with CVD. LDLs end up in the vascular plaques -- granted. But so far, none of my many LDLs in my few plaques (well OK, none). Mine must be very frustrated LDLs indeed -- nowhere to hang/hide out avoiding the slaughterhouse (liver).

Ken said...

I completely agree with you about normal Tg levels. Those levels in the old paper WERE screamingly high, weren't they? It's neat that they included the data for each individual separately, though.
Incidentally, incidence of death by MI peaked around the same time as the paper (sixties). Coincidence?
I think even the current mainstream mostly recognizes that 150mg/dL is not healthy. But statins don't lower Tg's (much, if any), and nothing (except LC diet) else works very well either. So what's a drug-pusher to do? If mainstream medics suggested to us regular folks that Tg's should be in the double digits, millions might drop their statins (realizing that they do nothing for IR/MS) and millions more might stumble into carb-restriction for lack of a pill to pop.
Btw, I (obviously) share your interest in cause of DM. I am trying to reverse my hyperglycemia, and I believe this requires actual recovery of beta-cell mass/volume/granules/function. I know of NO anecdotal cases of this for iIFG. For IGT and T1DM I know of a number of anecdotal cases (all based upon LCD). So I am hopeful, but have no ideal model to emulate. Somewhat discouragingly, iIFG does not respond to any known interventions -- diet, drugs, exercise, etc. whereas IGT and CGI do. That's why there is almost no research on it -- no interest from the drug companies, and even the big government-sponsored studies like DPP screen out iIFG from their cohorts.
I just became aware of my hyperglycemia in Aug. 2010. My doctor thinks it's a big yawn -- he's totally dismissive. But boy was he concerned about my LDL-c of 270mg/dL!
Are you diabetic, or pre-dibetic, or just intellectually interested yourself?

LeonRover said...


"Blogblog, you can't have it both ways."

Oh, I don't know about that:

"‘When I use a word,' Humpty Dumpty said, in rather a scornful tone, ‘it means just what I choose it to mean—neither more nor less.'"

Blogblog may have it as many ways as Blogblog chooses.

You may observe: Well, today I'm Alice - one of my Three Faces - and ignore you.

Puddleg said...

@ blog blog, pandas have been observed to eat sheep, goats and cows.

Obviously the evolutionary record favours eating insects. That is man's true diet and Bear Grylls is our new guru.

If Bonobos eat bananas and have no hangups, and humans eat meat and have hangups and ipods, that just goes to show how far evolution can carry two related species from an ancient LCA.
We have closer ancestors we didn't share with the Bonobo. They wiped out the mammoth and the moa.

Pandas - not doing too well lately. Probably not a great role model for evlotionary success.

Gadfly said...

@blogblog: What "facts" do I need to get straight, exactly? Gorillas have hind guts. That's a fact. I also didn't say "giant", so perhaps you need to do the fact checking.

Similarly, your foray into panda physiology is comical because it simply demonstrates that similarities (or even identity) of gut construction doesn't dictate optimal diet.

Lots of "facts" in your reposte; very few of them relevant. Your position that chimps and bonobos have anything to do with human dietary needs is an invalid inference.

Eva said...

If you want to eat like a chimp, better brace yourself. During the season when fruit is scarce, plan to eat dirt, toxic (to humans) leaves like ficus, bark, pith, and baby chimps (I guess for humans that would mean you would be eating baby humans) Chimps like meat but they are limited to how much they can successfully hunt and they are not as good at hunting as we are with our big fat sneaky brains. Maybe taste for meat is why they sometimes resort to cannibalism. And when they kill, they eat all consummable parts of the animal.

YOu want to eat like a chimp? Try it and you will be lucky to stay alive long. Chimps can digest food that we cannot because their system is designed for a more plant based diet than humans. I don't want to hear anyone saying that chimps are an eating role model until there is some evidence that we can digest large handfuls of ficus leaves and bark without getting sick..

LeonRover said...


"I don't want to hear anyone saying that chimps are an eating role model until there is some evidence that we can digest large handfuls of ficus leaves and bark without getting sick."

You do not want to HEAR?


Others have to keep quiet, or not write!

You jest.

Surely you mean you do not want to LISTEN.

In which case just put your hands over your ears.


Jane said...

'..I still don't quite get where you are sure I don't have Mg deficiency..'

Hmmmmmm. I actually said it sounds as if you DO have Mg deficiency.

Christopher said...

Didn't CarbSane debunk most of this already??

Puddleg said...

I do want to hear more about blog blog eating ficus leaves and bark.
In fact, I want to watch it on YouTube.

John said...
This comment has been removed by the author.
Eva said...

Leon, you are quite right I do NOT want to hear anyone say how I should be eating leaves, bark, dirt, pith and baby humans as part of my diet. Do I REALLY need to explain why?!?!! LMAO! Seems like productivity of this conversation continues to degrade.

Actually, I also do not want to ever hear another political robo call nor another blue jay screeching on my window at the crack of dawn nor any other irritating thing either. Not wanting to hear something is a far cry from actually demanding it never happen again with any reasonable expectation or enforcement of it happening. One thing is not the other.

Gadfly said...


And here I thought Carbsane was busy mocking other fat people for being fat.

John said...


Where is the recent evidence that "paleos" ate more carbs? Would you please post or send to me? Where were they living?

Christopher said...

CarbSane exposed Jimmy Moore and Gary Taubes - among others. For that alone she's done yeoman work in the field.

Puddleg said...

Here is an excellent detailed account of what the most unspoiled and traditional hunter-gatherers of today, the Andaman Islanders, eat:

The amount of fatty meat consumed daily during the rainy season when pork was at its fattest was large and could on occasions rise to the truly gargantuan. People with an average adult body weight of around 40 kg (88 lb.) could, on occasion, eat up to 1.8 kg (4 lb.) of food. This could rise to a staggering 4.5 kg (10 lb.) during a 24-hour period on special occasions. At major feasts , during colossal honey-and-pork orgies, participants stuffed themselves to bursting point, leaving everyone barely able to walk and with severe indigestion for days. Such "food pig-outs" are known from many primitive societies that are precariously dependent on an insecure food supply.
Eggs of all kinds, but especially turtle eggs, were a favourite treat. Turtle eggs were searched out so avidly by man and beast alike that one observer thought no clutch laid on Little Andaman could possibly have a chance of surviving. The Onge even took to visiting the small islands between Little and Great Andaman such as the Brothers, Sisters and Cinque islands as well as South Sentinel and Passage island. Even if this improved their chances to find such eggs, it remained a rare and special treat. The Andamanese regarded any eggs as edible at any stage of development; if an embryo was already developing it was regarded as delicious. Undeveloped eggs were boiled and the yellow eaten (the white of turtle eggs does not congeal however long it is boiled) but sometimes entire eggs were eaten raw.

Mussels, collected by women were so low on the ranking of food animals that their very mention was enough to bring up thoughts of famine and hunger. The Andamanese only touched them when there really was nothing else to eat. Something like that also seems to have happened to birds, snakes, frogs, rats and monitor lizards, all of which were eaten only during times of famine.

There were considerable differences between the groups: the Jarawa occasionally eat monitor lizard while the Onge never do; the Great Andamanese accepted eel as food while the Onge do not. Birds, despite their abundance, are very rarely eaten by any group, probably for religious reasons.

A diet rich in animal fats together with the occasional over-indulgence cried out for a counter-balance in the form of starchy roots, vegetables and fruit. These were available throughout the year but most abundant during the dry season. Gathering the unglamorous but necessary supplements was left to the women. If an all-male hunting party, especially an unsuccessful one, happened to come across such items, they might stoop to gather and bring them home.

Jane said...

Hi john
Lessee now. Well Stephan has discussed recent evidence that we are descended from middle eastern agriculturalists as well as from northern hunter gatherers.

Then there's this paper from 2005.
'Mousterian vegetal food in Kebara Cave, Mt. Carmel'
'...Plant remains are rarely found in Paleolithic excavations. The prevailing site formation process in most caves and open-air sites did not encourage the preservation of these kinds of organics. ... the large Mousterian carbonized plant assemblage retrieved during the excavations at Kebara cave fills a major gap in our knowledge of Middle Paleolithic gathering... It also provides critical missing information about subsistence strategies that often are reconstructed solely on the basis of animal bones. ...'

They found ~4,000 seeds of which ~80% were legumes. '..we assume that the main source of energy in the diet of the Kebara inhabitants was the legumes, as their seeds form the vast majority of plant remains found in the cave.'

See also 'Starch grains found on Neandertal teeth debunks theory that dietary deficiencies caused their extinction'.

Peter said...


Without any wish to add anything to what Neanderthals ate (not something I've read much about), that article amused me a little when I read it some time ago. The Neanderthals are extinct. There may be many reasons. Maybe eating barley was one!

Well, the idea made me giggle anyway.

The article also left me wondering what dietary deficiencies come from eating meat??? Amanda Henry, file under idiot.


Jane said...

Yes! They probably made beer from it and drank themselves to death.

I wondered that too. I can't imagine she knows meat is very low in manganese, or would think it mattered if she did.

I suppose she might know about the atherosclerosis and osteoporosis in ancient Inuit mummies. I've only just found out about this, I thought they were very healthy. I did wonder how they avoided iron overload, and it now appears to me that they didn't.

Peter said...

Jane, don't forget the severe anthracosis of the lungs and very high PUFA content of the diet. I am still very interested in PUFA and iron absorption.

I'm assuming you are looking at Zimmermean's 1993 paper. It worries me a little that the arteriosclerosis diagnosis is supported by a pair of b/w H&E stained photomicrographs which I have much trouble interpreting. Certainly modern human neonates show arteriosclerosis which can be demonstrated far more clearly, and this is much more obvious if you stain with PAS rather than H&E.

But interesting never the less and on file for further thinking.


Jane said...

Ahem. It's saturated fat that promotes iron absorption, not PUFA. It also inhibits manganese absorption.

'Manganese absorption and retention in rats is affected by the type of dietary fat'
'..There is evidence that manganese (Mn) metabolism may be altered by the form and amount of dietary fat. Also, iron (Fe) absorption is greater with saturated fats, as compared to polyunsaturated fatty acids (PUFAs). The absorption of Fe and Mn are interrelated in many aspects; therefore, the form of dietary fat may indirectly alter Mn absorption. ..'

I know, it's rotten. I eat lots of saturated fat. It also inhibits copper absorption.

Gadfly said...

@ Christopher - You mean she "exposed" that Jimmy is still fat after lots of different diets? That's about all she's ever really pointed out about him. As for Taubes, if her exposure of him to her relatively tiny audience meant anything, I'm not seeing the signs. She barks and the caravan passes.

Peter said...

Jane, I have a great deal of reading to do on this subject but want to get the last 2 posts on beta cells and omega 6 obese mice out of the way before letting myself wander off in to hepatic insulin resistance and iron. My wife has just had another end stage liver disease biopsy with special-stain confirmed copper overload which she feels (for reasons best konwn to the pathologist who has looked at the sections) to be secondary copper overload rather than primary Wilson's Disease.

There is a lot to heavy metals in the liver which the mainstream does not address well, I'd like to get time to think about it.


BTW, Gadfly, while I agree with your comment whole heartedly please don't encourage poor folks like Christopher to continue to make fools of themslves by responding. They're hopeless, ie there is no hope for them. Best not waste your time!

Jane said...

Peter, yes of course. I do hope I'm being more of a help than a hindrance. I'm shocked to hear about your wife.

Peter said...

Jane, sorry sorry sorry!!! My wife IS the pathologist! She has the joy of trying to tell clinicians whether the copper accumulation in a given canine liver biopsy is indicative of a primary copper storage disease or is the common finding of copper rather than iron accumulation in cirrhosis. Not sure if the dog (my wife is a veterinary pathologist) had iron overload as well as copper overload.

Again, sorry for the crossed purposes. I forget how little day to day stuff gets on to the blog!

Needless to say I have a lot of interest in liver pathology.


Jane said...

Oh! What a relief. Of course, I should have realised. I KNEW your wife was a pathologist. And I knew she had said things about copper accumulation in cirrhotic liver.

Anyway, let's talk about this again when you've done the posts you're thinking about. They sound very interesting and I don't want to distract you.

Peter said...

Oh, and I really must stop calling Fe and Cu heavy metals. Duh.


Jane said...

Please would you give my best wishes to your wife and tell her how delighted I am she doesn't have end-stage liver disease.