Wednesday, June 11, 2008

Breast cancer BRCA1 and metabolic syndrome

There is a breast cancer gene, the BRCA1 gene. It controls certain aspects of metabolism, it's not just some random gene=cancer mystery mechanism. It's to do with energy metabolism. Just look at what delays the onset of breast cancer in BRCA1 genetically prone women:

"Interestingly, physical exercise and lack of obesity in adolescence have been associated with significantly delayed breast cancer onset for Ashkenazi Jewish women carrying BRCA1 gene mutations"


Now look at the potential therapies being considered:

"Further clinical work may explore a chemopreventative role of "low-energy-mimickers" deactivating the ACCA-driven "lipogenic phenotype" in women with inherited mutations in BRCA1. This goal might be obtained with current therapeutic approaches useful in treating the metabolic syndrome and associated disorders in humans (e.g., type 2 diabetes and obesity), including metformin, thiazolidinediones (TZDs), calorie deprivation, and exercise"

What is the glaring omission, the raging silence????

What is most effective management of metabolic syndrome, diabetes, hypertension, central obestity, dyslipidaemia, hyperglycaemia? Just pretend breast cancer is really diabetes. Never mind metformin (good) or TZDs (bad). Do I hear carbohydrate restriction anywhere?

No I don't.

I should.

Peter (grinding teeth)

PS Never mind <10% of calories from fat and all of those fat calories to be from fish oil. What would that do for diabetes? (not a dig at you Gyan, the low fat mantra is ubiquitous and wrong).

54 comments:

Kevin said...

Isn't 'calorie deprivation' the same as 'carbohydrate restriction'? My wife had Hodgkins Lymphoma when she was in her twenties. She received a lifetime dose of radiation as treatment. Twenty years later she developed breast cancer. The oncologist says her radiation treatments predisposed her to breast cancer. With a mastectomy and chemotherapy she's doing well four+ years later. I don't know the details but tests showed gene mutations. Our 16 year old daughter had tests that showed she doesn't carry those mutations.

donny said...

http://www.jstor.org/pss/66150

Maybe that'll work. It's a study (at least the fragment I could look at in JSTOR) showing the stimulus of cell division by insulin in a particular line of breast cancer cells. It's done in the absence of glucose. The highest infusion of insulin caused a 69 percent increase in the number of cancer cells above controls in 24 hours. That's not a 69 percent increase in the rate of growth, but in the actual number of cells.
I have to wonder about bodybuilders who manipulate insulin levels, trying to promote muscle growth, and whether there'll be a fallout.

Peter said...

Hi Donny,

Link works fine (hurray). 1976 publication? The mechanism has been around for a long time! I found the BRCA1 link while hunting a paper from a group in Sweden who consider breast cancer to be just another aspect of metabolic syndrome...

Peter said...

Kevin,

I'm not sure calorie restriction and carbohydrate restriction are the same, and I'm even less sure that caloric restriction at a stable low weight is the same as caloric restriction with weight loss. What is needed is to feed the mitochondria on substrates which bypass complex I, the one which leaks the most free radicals to signal cell division. Glucose feeds reducing equivalents in to complex I, fat does some complex I and some complex II. Caloric restriction without being fat based will not spare complex I leakage, look at Walford (balanced diet, caloric restriction), ALS is a mitochondrial failure.

Caloric restriction with weight loss may do it as metabolism is then based on human adipose tissue as the primary energy source...

Fat based diets will probably induce uncoupling protein production, this decreases the leakage pressure for free radical generation in the mitochondria too. No one ever heard of sugar inducing uncoupling protein synthesis...

Having a mutation doesn't cause cancer without a mechanism. If Nick Lane is correct mitochondrial energy issues are the basis of cancer, which is probably a facet of metabolic syndrome.

Peter

Bruce K said...

I don't know if Walford ate a truly balanced diet. He was more low-fat, Ornish, as I recall. Check his book The 120 Year Diet or his website at walford dot com. Based on recipes I see on his website (egg whites, fat free yogurt, whole wheat pasta, and bread), it looks Ornish-esque.

http://www.walford.com/cronmeals1.htm
http://www.walford.com/kitchen.htm

Good point, that calorie-restricted diets with weight loss are high-fat diets by definition. The results of those diets might be different once weight stabilizes (as it eventually must unless you want to die). Would you also say that a fat decreases a person's nutrient requirements more than carbohydrates or protein?

These are ad-hoc theories, however. Go to a low-carb group and bring up calorie restriction, somebody will say that carb restriction and body fat are providing the benefits. Go to a raw-food list and they'll say it's because people are eating less toxins from cooked food. Go to the vegan groups and they will say it's because less meat and animal foods are being eaten. We need a lot more scientific evidence here.

Peter said...

Bruce,

My prime reason for believing that fat requires the least nutrient input per calorie provided is that fat is what we have evolved to live on when there is zero dietary nutrient input. We have access to bulk vitamin A, B12 and D, plus a few other odds and ends from the liver. If we needed lots of B3 etc to run our metabolism when fasting, we'd store it too. No science base here.

Walford's recipes look pretty awful. High protein, very low fat and enough carbohydrate to have you dreaming of food in the reactive hypoglycaemic patches. Those same hypoglycaemic episodes which might just trigger an energy crisis and failure of cellular integrity. Cells with no ability to burn fats would die first, could that be nerve cells? The choice seems to be between Alzheimers, Parkinsons or Motor Neurone Disease. Motor neurone disease it was. Ketones might just have saved the day, even on 1500kcal/d.

Peter

ItsTheWooo said...

kevin -
Calorie deprivation is very much like carb restriction, except much harder to stick with and it causes intolerable side effects (psychological and physical).
I've had a mild eating disorder, slightly worse perhaps than successful calorie restriction. It was physicially awful. I was cold all of the time and extremely weak and hungry.
Psychologically it was even worse. Even if I ignore psychological symptoms specific to disordered eating (such as dysphoria about myself, weight, and food) it was still very much intolerable because there are real neurophysiological consequences of starvation or semistarvation. I felt like an OCD robot, because of brain chemical depletion/imbalances.

There are long term consequences. Additionally, I have osteopenia probably caused by that few year stint of low calorie eating & being underweight and I am certain all CRONers also have it as well. Infertility is also a risk once a female drops below her set point weight (I remain infertile because I am still below mine).


CRON = SUCKS and the only people who promote it are either scientists who don't actually practice it or cultist weirdos who for all practical purposes have eating disorders because the thing has consumed them entirely.


Carb restriction is like living life! It is much more effective mentally and physically for moderate calorie very low carb and high fat. This avoids or minimizes the terrible side effects of calorie restriction while maximizing the protection against neoplastic growth.

For dinner I enjoyed a luscious chicken quarter, roasted crispy in chicken fat, with a reduced fat dressing caesar salad (I try to reduce superfluous plant fat oils since animal fat seems to agree better as an energy source). I feel so full right now. I almost never feel hungry anymore. My vitals and labwork are indistinguishable from a calorie restrictor. Perhaps better, because I don't show abnormalities associated with semistarvation like extremely low cholesterol (a risk for trauma/hemorrhagic death).

ItsTheWooo said...

Peter - I would think it does not matter if the calorie restriction does or does not involve weight loss. If the calorie restrictor is maintaining, we can assume they are in metabolic conservation, a state of functional hypothyroidism with low sympathetic tone... in which case their mitochondria are not making as much energy as normal. So, it no longer matters that they are not feeding the cells fat, because the cells are perpetually starved (eating neither glucose or fat). CR is like being half dead, your metabolism is funcitoning at a reduced rate... and half dead people don't get cancer. If you don't have the energy to grow normally (muscle/fat) or to reproduce you certainly don't have the energy to support reckless cell division and neoplasm.

Also, I would think that a very low carb diet with excessive calories (from dietary fat or protein) is not very effective. Both excessive fat and excessive protein intake will increase blood glucose, which increases insulin & IGF levels, a real risk for neoplastic growth.
Granted most people who consistently adhere to a very low carb diet won't eat excessive fat calories because their cells will receive adequate energy suppressing hunger (provided there is no defect in their satiety/appetite regulation system, the high fat low carb diet will energize cells consistently and suppress excessive appetite)

Bruce K said...

Gary Taubes pointed out that cancer does not occur, unless you eat PUFA oils. Fat produces 10% glucose, and protein 58%. The Eskimos ate a high fat, high protein, and high calorie diet. They never had cancers, until they started to eat the white man's foods - sugar, bread, flour, highly unsaturated oils, margarine... Gary Taubes mentioned that high-calories stimulate more cancer more than low calories. But that's in the context of diets filled with sugar, flours, vegetable oils, and other junk. The animal studies typically use casein powder. That's carcinogenic, esp in the context of sucrose, cornstarch, and corn oil - the typical rat chow used in these experiments.

For example:
http://jn.nutrition.org/cgi/content/abstract/121/9/1454

Bruce K said...

Peter: "We have access to bulk vitamin A, B12 and D, plus a few other odds and ends from the liver. If we needed lots of B3 etc to run our metabolism when fasting, we'd store it too. No science base here."

But how much do we require? Do you have any figures on this? Say if a person ate lots of coconut oil and macadamia oil, would they deplete their bodieso f nutrients quickly? Or would a few eggs and some liver and butter and stuff like that be enough to run forever on pure fat? The fat in muscle doesn't have too much Vitamin A or D. Do you think it would cause a deficiency to eat lots of beef suet and low protein and low carb? Thanks

ItsTheWooo said...

The connection between PUFA and cancer is immunosuppression. PUFA may be one risk factor for cancer development, but there are numerous others. A lot about our environment suppresses the immune system. A very high calorie diet that induces metabolic syndrome is by definition immunosuppressive, in addition to promoting cell growth/division (at least, early on, before your body really goes to hell and you develop diabetes).

Another, perhaps greater risk for immunosuppression is poor sleeping habits. Most of us think nothing of depriving ourselves of sleep chronically, our way of life almost necessitates it. Artificial lighting, technology, and capitalist culture (excessive work/production) all prevent natural amounts of sleep may be the biggest risk factor for immunosuppression there is. I am gaurenteed to come down with illness-like symptoms if I deprive myself of sleep. If I recover said sleep, all traces of the illness go away.
If I don't sleep, cuts simply do not heal well. If I catch up my sleep for 10 hours, any lingering cuts and poor skin quality goes away totally.


Sometimes I think sleep is just as important as carb restriction. Sleep deprivation can cause not just cancer, but metabolic syndrome & mental illness (dramatic increase in bipolar illness & depression is almost certainly linked to circadian rhythm disorders induced by modern living). I myself develop a form of mild rapid cycling bipolar when I do not keep a regular sleep rhythm (lately has been happening hardcore, haha). Birds chirp at night where I live. How unnatural.

ItsTheWooo said...

It is also important to remember that metabolic requirement determines what is and is not a high calorie diet. If I were living the life of an eskimo, doing hard physical labor in freezing weather, I would probably be needing a few thousand calories per day, too.

Metabolically and physiologically healthy people can only eat as much as they need over any continuum of time. It is abnormal not to; and even more abnormal to fail to grow fatter at all even with forced over eating.

Bruce K said...
This comment has been removed by the author.
Bruce K said...

Omega-6 is less immune-suppressive than omega-3, but both cause cancer beyond a certain threshold. Toxins, like pollution, increase this risk.

Lack of sleep is bad, of course. It still might not cause cancer if you avoid refined sugar, flour and high PUFA oils like the plague. (Studies should be done to isolate all these factors, as Taubes would say.)

Eades, Bear, and Taubes have argued that you couldn't gain too much fat by over-feeding low-carb diet. Some fats, like coconut oil, take weight off the more you eat them. High-fat and high-carb is definitely bad for most people. Esp when the carbs are from sugars and flours and the fats have more PUFAs than MUFAs/SFAs.

You've probably heard of people who ate a lot of calories on a low-carb diet, but failed to gain weight. It is a well-known phenomonenon. Eades mentioned some of his patients were eating 4000-5000 calories a day and that is what they self-reported, so it was probably more than that. Yet their weight was stable. Eating the modern diet is a commonality of all cancer. Sleep problems would rarely occur if people ate right, only ate when hungry, exercised, etc.

ItsTheWooo said...

I agree you can eat more calories and not gain weight on low carb, I've had this verified clinically in myself (actual intake: 1600-1700... RMR: 1000... no way I do 700 cal in activity!).
The metabolic advantage (or rather the disadvantage of carb) probably amounts to a few hundred cal... but not several thousand more. Eades' patients who were not gaining on 5000 calories were probably severely obese / metabolically active (meaning 5000 cal is really not that much for them and not that far away from default diets).
People do tend to lie about how much they eat... not because they're bad people but because we don't have the innate mental machinery to track such things. We can cultivate it via learning if so motivated, but our brains do not by default know exactly how much food we eat, for the same reason we don't know our average heart beats per minute or how many breaths we take. Our body handles it for us, we don't need to know the details.


I don't think it's possible to fail to gain weight eating 5000 calories of low carb food if your basal metabolism is normal/low. That would be diabetes, I mean, how could it be possible for a normal body to waste that much energy? Why would it? This would be evolutionarily counterintuitive. The reason we have conserved carbohydrate intolerance/weight gain is to fatten up for the winter as carbohydrate is a marker for nutrient and weather stress. Copious amounts of fat produced from other carb-intolerant animals snacking on the excesses of warm weather season should be another signal of the impending winter. Like a big cycle, carbs & body fat signal nutrient stress in the future. Genetically we are slaves to the sun. Obesity is when we are stuck in the pre-winter mode 24/7.



Eades, Taubes and (lol) Bear are just people... not father, son, or holy ghost... I take their opinions with a grain of salt, they're just opinions not gospel.


Sleep loss is immunosuppressive independent of diet... I'm evidence of that for sure. Most sleep loss is not caused by health problems, but by a lifestyle that prioritizes work to make stuff to buy stuff to use stuff over health and happiness.

Frank said...

My mother died from pancreatic cancer. She was a yoyo dieter, fat-phobic, and when she fell off the wagon binged on sugar and junk - so long as it was "low-fat" it was okay in her book. From diagnosis (they found liver mets before they figured out the primary) was only a few weeks.
It is claimed that a diet high in meat and saturated fat is correlated with pancreatic cancer, as is smoking - I think they are not considering confounding factors. It would be interesting to see what the rates were in LCs.

Frank said...

That sentence above should read from diagnosis to death - I should have previewed.

Peter said...

Hi Frank,

Sorry to hear that, at least with my dad it was random normal eating without any medical prompting that got him in to trouble.

I believe there are studies where they have managed to not associate sugar with pancreatic neoplasia, but most do. I had and have lost a paper from Canada, epidemiological only, which showed a marked protective association of saturated fat against pancreatic carcinoma. I've looked for it an many occasions (you can imagine why!) but have always failed to relocate it...

Peter

Dr. B G said...

Peter,

I love your posts -- I think you are discovering CURES for (all) cancers here.

Insulin derives from pancreatic cells -- and high carb diets over-rely on the function of the pancreas (as they do the stomach and you've discussed how H.pylori LOVES glucose/carbs to feast on -- which can lead to gastric cancer).

People (surgeons?) have been aware for decades apparently that diabetes predisposes to pancreatic neoplasia. See below (sorry -- how do you 'hyperlink'??)

Am J Surg. 1988 Jan;155(1):159-64
Influence of diabetes on susceptibility to experimental pancreatic cancer.
Bell RH Jr, et al.

Clinical studies suggest that diabetes mellitus may predispose to the development of pancreatic cancer. The current study investigated the effect of experimental diabetes on the susceptibility of the Syrian hamster to the induction of exocrine pancreatic carcinoma by the carcinogen BOP. Diabetes was induced with the B-cell toxin streptozotocin. Three groups of animals were studied: nondiabetic control animals and animals with streptozotocin-induced diabetes, and a third group of animals in which the diabetogenic effect of streptozotocin was blocked with nicotinamide. Streptozotocin-induced diabetes significantly inhibited the induction of pancreatic carcinoma by BOP, decreasing the incidence of carcinoma to 24 percent compared with an incidence of 75 percent in nondiabetic control animals (p less than 0.002). In diabetic animals, the degree of inhibition of carcinogenesis paralleled the severity of the diabetes. Blocking the diabetogenic effect of streptozotocin with nicotinamide restored the incidence of induced invasive pancreatic carcinoma to that occurring in nondiabetic control animals. In the hamster model, diabetes appears to have a strong influence on susceptibility to the development of pancreatic carcinoma. PMID: 2963553

Neat how niacin (TRANSLATE= endogenous ketone bodies) can reverse/protect against carcinoma??


Here is only one case but alpha lipoic acid reduces metabolism and insulin resistance. Naltrexone reverse opioid actions, hhhhmmmm.... what's an opioid from our food??? gluten/casin opioid peptides?

Integr Cancer Ther. 2006 Mar;5(1):83-9.
The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol.
Berkson BM, et al.

This is what Bruce K is always railing upon... the dangers and toxicities of omega-6-laden 'junk food'. The lack and deficiency of EPA and DHA from pasture-fed animal milk, dairy and protein sources (and safe, mercury-free fish) also contribute strongly to pancreatic cancer, it appears.

Funahashi H, et al.
Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth.
Pancreas. 2008 May;36(4):353-62.
PMID: 18437081

Steve Jobs of Apple doesn't look too hot lately... he survived pancreas cancer several years ago (pre-iPOD days). I hope his nutrition includes:
--low carb (low GI) -- gluten free
--fats including high dose EPA+DHA and vitamins A/D3/E/K2
--healthy proteins
--insulin sensitizers (alpha lipoic acid, polyphenols, etc)

Thank you for your posts!

-G

Frank said...

Well I went searching for your paper and stumbled across this.
http://cebp.aacrjournals.org/cgi/reprint/4/8/895

What jumped off the page and blew me away was the HR for those eating fried food “very often” having a nearly 17-fold higher risk of pancreatic cancer! Can anyone say “rancid PUFAs”? Those who ate “salted food” very often had a greater than 9-fold greater risk! Rancid PUFAs in nutritionally devoid junk food and loaded with MSG?
I think this may be the one.
http://www.ncbi.nlm.nih.gov/pubmed/15685231?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Surprise, surprise!
“The results suggest that substituting polyunsaturated FAs with saturated or monounsaturated FAs may reduce pancreatic cancer risk, independently of total energy intake, particularly among obese subjects.”

Frank said...

Okay – I saw half the URLs fell off so here goes.
http://tinyurl.com/4k3vec
http://tinyurl.com/4s9s2d

Troy said...

peter,

i had a question that pertains to following the optimal diet for someone who has had there gallbladder removed...is it still possible? What are your recomendations?

Bruce K said...
This comment has been removed by the author.
Dr. B G said...

Good find Frank!

(why don't they ever look at carbs/insulin too?)

Dr. B G said...
This comment has been removed by the author.
Bruce K said...

Wooo: "People do tend to lie about how much they eat... not because they're bad people but because we don't have the innate mental machinery to track such things."

They also forget what they eat, but doubly-labeled water will show very clearly that they are lying or else having selective amnesia. The obese do eat more and move less. The thin have more thermogenesis, because of fidgeting and stuff like that. This is all well-established. Also, thin people have different gut bacteria, different hormone levels, etc.

"I don't think it's possible to fail to gain weight eating 5000 calories of low carb food if your basal metabolism is normal/low."

Think again. Lean people have tried to force themselves to gain, eating 4500-5000 Calories on low-carb, and doing no exercise. They failed. The critics of metabolic advantage like Anthony Colpo are careful to say it doesn't apply to weight LOSS, while saying nothing about weight GAIN or maintenance. Why? Because they know that it is very hard to gain weight on a high-fat diet with no carbs.

http://magicbus.myfreeforum.org/about846.html

"Eades, Taubes and (lol) Bear are just people... not father, son, or holy ghost... I take their opinions with a grain of salt, they're just opinions not gospel."

Their opinions are backed by a lot of experience and/or research. I'm not taking their word as gospel as there are many things they've said that I disagree with, or think are only half-true. I've pointed out a lot of these like Bear saying that animal fats are 90% saturatd and a lot of other silly things.

Frank said...

Dr B G - some did look at carbs but depending on the study the results were inconsistent. Some found increased risk, some found decreased risk. Might I say "null hypothesis or confounders?
Bruce K - I have always struggled to maintain a normal weight - my BMI hovers around 18-18.5 kg/m2 (after children it went down to 15.5 kg/m2 because they were both greedy breastfeeding buggers!) and while I realise most women would spit on me for saying so; after I had my children 20-21 years ago I tried "Body Bulk" type protein drinks on top of my normal calorie intake and I didn't gain a damn ounce. Hmm, could it be that since leaving home I have always eaten a high-fat diet?
It's ironic - I tried to gain weight for years by eating high fat, when all I needed to do was eat high carbs.
The only time I went higher carbs was when my partner (of 12 years) moved in I made an effort to cook "healthier" because he was overweight and for the one and only time in my life achieved a BMI of 20!
Unfortunately, I will prise him from his potato habit (he's Irish) over his cold, dead body.
I should have added re my mother's death - it wasn't just fat phobia. She started on NSAIDS for early arthritis, followed by a proton pump inhibitor for the side effects of the NSAID, followed by HRT, then a Fosamax-type drug, an antidepressant and in fact she ended up on 8 prescription drugs. I had limited input because a) I'm "only" a nurse and b)I live on the other side of the planet.
I do think PPAR is a major player in cancer (as it is in weight and type 2 diabetes). From my readings we constantly hover between susceptibility to infection and cancer.

Peter said...

Hi Frank,

The second study was the one, thanks, at some point it will appear as a post. The list of drugs for your mother is very logically self consistent for someone eating wheat and avoiding fat. Agree re PPAR, so will g!

Need time...

Peter

donny said...

http://cebp.aacrjournals.org/cgi/reprint/4/8/885?ijkey=f5074a3daf84977a332b49a4201dd22a68490dae

http://cebp.aacrjournals.ort/cgi/reprint/4/8/885?ijkey+f5074a3daf84977a332b49a4201dd2a68490dae

I typed the second one instead of pasting, in case that's what works.

This is an epidemiological study in China on diet and pancreatic cancer. After correcting for a zillion things, higher protein as well as higher fat seemed to decrease pancreatic cancer.
They managed to find that increased fat or protein decreased cancer, without showing that increased carbohydrate had any effect in the opposite direction. Unless there was some heavy drinking involved, that's some mighty fine correcting.
They even found less cancer with increased calorie consumption.
Too bad studies like this don't prove anything.

Stan said...

Off topic:

Re: last message link.

When quoting studies' URLs you can skip anything including and following a question mark.

For example:

http://cebp.aacrjournals.org/cgi/reprint/4/8/885

works just as well.

ItsTheWooo said...

Frank - I'm curious because your problem of not being able to gain weight is 180 degrees of the problem I have. I most definitely can gain weight on low carb (<60 carbs daily, high fat) unless I control calories. There have been times I've eaten almost no carbs and nothing but meat, and I find it easier to avoid weight gain then... but I'm DEFINITELY certain I could gain weight eating 3000 calories of ketogenic low carb.

So, like, how many calories do you eat daily?

I admit, whenever a naturally thin person says they can't gain weight, I automatically assume they have physiologic anorexia and are unable to eat more than a few hundred calories per day, believing they are gorging themselves because their appetite is so low.

This would be the opposite of the problem most obese people have - constant hunger and mistakenly believing they eat less than they do.

ItsTheWooo said...

Frank - I love how the association between sugar and cancer is so clear, yet somehow splenda and aspartame get the wrap for being cancerous dangerous chemicals. LOL. You would think that artificial sweetener companies would run campaigns to fight this ignorance, but I suppose the corporations who make these products have a vested interest in keeping people eating sugar in other products, with no gain in sales of artificial sweetener (those who eat artificial sweeteners do so mainly because it is low calorie, not healthy; those who avoid artificial sweetener because it is unhealthy are behaving irrationally, so there is no point in appealing to rationality as their purchasing decision comes from an unfounded feeling that "natural" = safer).

One small argument, the paper finds the highest risk from fried foods was from fried meat; this was seen also in grilled and smoked meats. This type of cooking may create carcinogens which can initiate cancer. Fortunately, eating a low carb, moderate energy diet should protect people from cancer initiation (like an experiment where people are exposed to the cold virus to see who gets sick, it is ultimately the immune system that determines who does and does not get sick... and indeed studies show not sleeping significantly increases the risk of developing symptoms after exposure to the cold).

ItsTheWooo said...

Bruce K- I'm not adverse to believing that for SOME people the metabolic advantage can be several thousand calories... however I haven't seen many well controlled studies or anecdotal evidence. I do know there have been some people who were not able to gain weight even after massive overfeeding, even mixed diet overfeeding... but my intuition says this can not be common, and it is likely a marker for greater adaptation to a constant-food supply agricultural society as it would surely be death in any hunter-gatherer society that lives by the seasons and the sun and unpredictable food supplies.

Peter said...

Hi Bruce,

Re vits B12 and A, no, no idea of requirement, and obviously stores are variable and related to previous diet... Yes, I think it might be possible to get a deficiency, though 6 eggs a day gets you close to the RDA for B12 and A, and D too if you believe it. Obviously no where near the vegan risk for B12 def. It does seem to be the chilfren of vegans that are most at risk, the adult requirement for survival seems quite low.

Re ovefeeding... It does seem likely that overfeeding would produce weight gain, it might be hard for "skinny" types to do sustained overeating, but I think it's possible. What looks to be interesting is whether this LC overfeeding produces visceral or peripheral fat accumulation, with the variable this represents for hepatic insulin resistance. I realise that not everyone agrees that the visceral vs peripheral fat dichotomy is real...

Re PUFA and immunosuppression. Been reading re Eskimos and I'd agree they were cancer free 100% as far as could be determined on detailed searching. They seem to eat approx 13g/day fish oil and LC. How much fish oil do you think we need for significant immunosuppression on LC. Using 13g per day is far more than is used in the management of rheumatoid disease with fish oils. So 13g must be immunosuppresive, yet no cancers. Are fish oils safe in the absence of sugar and flour?????

Hi ItsTheWooo,

For me sleep deprivation seems to be significantly immunosuppressive. Cannot remember having as many colds as I've had in the last year or so, combination of a max of 3h sleep at a time, hours awake in the middle of the night and nursery as a source of bugs. Combination of effective sleep training for Squiggs, some D3 in Winter and now lots of sun and colds have stopped.... Might be random, Autumn will tell.

Eskimo seemed to run on about 2500-2800ish per day from the paper I have. Not sure if you would call this high calorie or not. Stephansson was very very adamant that they did NOT live in a cold environment, in fact topless was de riguer throughout the winter. There was a rough patch temperature-wise in spring as the snow cover on the stone houses thawed, summer was OK and autumn not too bad if there was a rapid drop in temp to get the snow on to the houses and keep it there. Their clothing effectively isolated them from their environment. One of his pet theories beyond diet was that the high rate of free sweating in their lifestyle was in some way protective against cancer. Email me off blog if you'd like a copy of his "Cancer, Disease of Civilisation?" in pdf form.

Hunger was occasional for the Eskimo but as far as I can see famine is the product of agriculture.

Re diabetes and overeating, the phrase is diabetes lipidus, it's in common usage in some research groups, obviously the low fat type.

Hi Donny,

Amen re the proof from studies like these! Hypothesis generation it is...

Hi Stan,

I tried to sort out a post to explain how to make hyperlinks but it keeps trying to make to explanation typing in to a hyperlink... Duhhh. I found out how to do it by looking at the source in "view source" and seeing what someone more net savvy than me had done, then copying!

BTW, if anyone posts long links and gets them truncated, if you click on the title bar at the top of any given post you get directed the whole post and and comments in a form where the comments have the full length of truncated web addresses. The post looks identical but the comments get reformatted.Then copy paste is easy.


Phew, that's a bit of a catch up, just the more random bits to sort....... Life is too frantic!

Peter

PS apologies for what I suspect will be millions of typos in this!

Peter said...

Hi Troy,

I really don't know.

It might be possible, I've never spoken to anyone who has tried and a similar query on the AHOA board got no replies that I can recall. Ultimately, if you can eat the occasional meal high in fat without getting the Olestra effect, I don't see why you shouldn't work up to a genuine high fat diet. The other option here would certainly be to consider medium chain triglycerides (coconut oil derived) as the primary source of fat. Not the sole source, and make sure you get on with them first. There are transported to the liver directly and may well not require chylomicron formation, so may be the preferred option.

Peter

BTW gall bladder disease appears to be a facet of coeliac disease. Now there's a surprise.

Troy said...

THanks peter,

as always, the blog is awesome! I learn so much in your commet discussions!

Anna said...

Itsthewoo: Just curious, are you reading or have recently read Lights Out (Wiley & Formby)?

Bruce K said...

"[Eskimos] seem to eat approx 13g/day fish oil and LC. How much fish oil do you think we need for significant immunosuppression on LC?" (Peter)

Don't know about low-carb. I saw an immune-suppressive effect from less than 1 tbsp of raw flaxseed oil, on a raw animal food diet. I had a dry sore throat for a month which began when I added flax oil, and ended as soon as I removed it. I was reading about experiments on cold exposure, how winter swimming gives benefits, as do cold showers, etc.

"Using 13g per day is far more than is used in the management of rheumatoid disease with fish oils. So 13g must be immunosuppresive, yet no cancers. Are fish oils safe in the absence of sugar and flour?????"

The Eskimos lived in a non-polluted area and probably had less stresses than modern people. The combination of stress and pollution (city life) changes the situation. So I tend to want to limit fish oils, unless you can get "high-vitamin fermented cod liver oil", like Blue Ice. I'd only take 1/5 to 1/2 tsp (1.0-2.5 g) per day, or 1 tsp every 2-3 days.

It's probably best not to mix carbs and PUFAs (including lard, chicken, turkey, oily fish, most nuts/seeds, etc). I think saturated fat is best with carbs, like butter, ghee, beef suet, cocoa butter, or coconut oil. Low-PUFA oils like mac nut, olive, hazelnut, and avocado might be OK. Don't eat whole avocado with carbs, because it has a sugar (heptulose) that makes you an instant diabetic, temporarily shutting down insulin.

Bruce K said...

ItsTheWoo: "I'm not adverse to believing that for SOME people the metabolic advantage can be several thousand calories... however I haven't seen many well controlled studies or anecdotal evidence."

I think Eades is right. There is an advantage for weight loss, but this is small and variable. There's more an advantage for maintenance (as in resistance to creeping obesity with age). The hard part is getting down to ideal weight, since many people have messed up their bodies greatly with the modern diet - toxic sugar, flour, and oils. Like I said, those who rant against the existence of a metabolic advantage are careful not to say weight gain, or maintenance. They know that over-feeding fat has never been proven to cause a weight gain, but overfeeding carbs and fat has, or processed carbs with no fat (like Snackwell cookies).

"I do know there have been some people who were not able to gain weight even after massive overfeeding, even mixed diet overfeeding..."

It's because they have a better mix of gut flora, hormones, genes, etc. Animal studies have found that when you take the bacteria out of a lean animal and put them into a fat one, using antibiotics to wipe out their existing gut flora, they will lose weight. Evidence suggests that this works both ways. The bacteria makes you fat, and getting fat shifts the bacteria population to bacteroides, which help keep you fat.

http://cmr.asm.org/cgi/content/abstract/20/4/593.

Frank said...

Itsthewoo - Interesting exercise – I don’t normally count calories so I wandered over to mypyramidtracker.gov to work it out – according to their calculations I’m eating 200 calories over my recommended daily level on yesterday’s “menu” which wasn’t typical. I almost freaked when I saw the carb level, but then realised it had included the alcohol in my red wine as carbs (how rude). I ran it again with a more typical day’s fare and that puts me as 300 calories over – why am I not as big as a barn? I’m partially disabled and very sedentary so it isn’t output. Could it be that a calorie is not a calorie is not a calorie? Incidentally I avoid artificial sweetener because a) I’ve never had a sweet tooth and b) it tastes horrible. But I don’t consider sugar “natural” anyway.

When there are so many confounding factors it’s hard to take anything concrete from such studies – when they “adjust” for other factors they themselves decide what weight to give the other factors – without ever knowing they were right about the correlation of those factors in the first place.

The other issue is how immunity and cancer tie in. One eminent virologist has pointed out that there are no antigenic markers on tumour cell surfaces to alert “the immune system” to their presence. Only a fraction of human immunity is understood (or misunderstood). Reductionist science is too linear and doesn’t consider the vastly complex interaction between thousands of processes. I’m not sure they will ever fully understand it.

Frank said...

Bruce - I wasn't aware of the heptulose issue in avocados. It's quite a concern because type 2 diabetics are advised by the various diabetes associations to eat avocado. Nachos and guacamole would be hell in a handbasket for a type 2 diabetic!

ItsTheWooo said...

Peter - I've seen studies of eskimo which imply they have adaptations to deal with cold stress (such as that they rewarm more quickly than caucasians, due to greater peripheral blood flow). I agree they probably aren't completely exposed to freezing temps due to clothing adapted for protection, but I think it is unrealistic to assume that their environment requires no additional energy expenditure. Living in new jersey, which gets quite cold, I know my metabolic needs increase a few hundred cal in the winter so I would assume an eskimo is at least that much more than a temperate environment. 2800 or so sounds about right, I wouldn't consider that high calorie at all given their environment and lifestyle (hunting, moving & maneuvering through snow which offers resistance, so on)

I would be very interested in seeing it, if you don't mind mailing it to withthelightsout00-at-yahoo.com




Anna - Yep did read it, thought it was a great book.
Though I admit I don't practice it nearly as diligently as I do low carb, I completely agree with the author that technology, lighting, and lifestyle affecting sleep is a crucial key in understanding why we have the modern diseases we do (immune/stress/circadian rhythm diseases)
Most of us would avoid all disease if we slept 8-9 hours per night the way we were genetically prepared to. We wouldn't have to worry so much about carbs, either (obviously terribly maladaptive foods are verboten but we could probably handle fruits and moderate carbs if our stresses and sleep were genetically normal).
Speaking personally I can tolerate a LOT more carb when I sleep appropriately, and if done consistently my moods are much more balanced. Studies have repeatedly demonstrated clear causative links between diabetes, mental illnesses (particularly depression/bipolar) and sleep.
Sleep is as important as understanding carbohydrate.

I also agree with the author and believe that carbohydrate causes fattening because it is a seasonal marker which suggest nutrient/cold stress in the future. Taubes believes it is just a food we have not designed to process. I agree with this point of view when it comes to highly concentrated carbohydrate that is only capable of causing wanton and disregulated fat retention. OBESITY is the result of an intolerance to concentrated carbohydrate.
However, all carbohydrate, even small amounts, promotes moderate insulin resistance and situationally healthy adaptive weight gain... we must ask why this is, when we have evolved eating moderate amounts of carb.
So, we must look at our inability to metabolize carb not just as a byproduct of being naive to massive high carb/high fat diets... but as a byproduct of an adaptive trait that is being thrown off by a novel dietary substance (high carb, high fat food year round).

Higher fat intake with higher carb intake = warm weather = cold weather comming in 3-6 months = slight trend toward insulin resistance = storing fat in white adipose, and especially in the visceral organs to protect them from cold, higher blood sugars to keep warm, sedation and inactivity to promote sleep and conservation (which is why carb is exploited as tranquilizers by people with high stress & food addiction, and why it causes depression in the depression prone).
Obese people with thick slabs of visceral fat and diabetes are stuck in the pre-winter fattening mode constantly. They need a low carb diet to simulate the winter season, thus the end of preparative inflammation and fattening.

This is why I have *so much trouble* believing that a high fat diet without carbs cannot cause weight gain. Dietary fat is a marker for carbohydrate, as animals lay on fat when eating carbs just like we do (because animals, like humans, evolved with the sun controlling fluxes in nutrient availability). Sugar is plant fat; fat is animal fat; all come from the sun. Eating lots of fat is very little different to your genes than eating lots of sugar. Sure, sugar is a much more certain indicator (because, after all, fat is present when sugar is not, because fat is last months sugar, so fat can exist without the sun, so fat is not AS SURE of an indicator of the sun as carb is). But I would think a 2000 metabolism person downing 5000 calories of fat is going to tell their genes "holy crap, look at all this buffalo fat, it must be the warm weather season, better raise insulin and get ready for cold weather!"

ItsTheWooo said...

Bruce - I'm curious... have studies been done where all, or even most, were not able to gain weight with a high fat diet? If so, how low of a carb intake is required for this? I eat very low carb, <60, most of my cals are from fat, and I quite easily gain weight if I eat more calories. It is true that I gain weight much, much easier with more carbs, and it is more difficult if I eat ketogenic... but I do not think it is possible for me to not gain weight eating high calories.

My basal metabolism is very low, due to the effect of having lost 160 lbs of weight (present weight 121, 5'5). I think if I were at my set point weight this might be reasonable... but my set point weight is probably overweight or obesity (thanks to adipocyte hyperplasia from being exposed to so much insulin during my formative years). I believe obesity is a permanent disease, especially if aquired early in life. Insulin doesn't just put fat in cells, it makes new fat cells grow - lots of them - and those fat cells require fat be put in them for them to work right (i.e. to make leptin and other adipocyte hormones).

Do you have a link to any study which has failed to make people gain weight eating massive amounts of fat with low carbs?

I know, for me, this is definitely not possible, but then again I am not metabolically normal because of my obesity damaged body.

Bruce K said...

"I ran it again with a more typical day’s fare and that puts me as 300 calories over – why am I not as big as a barn?" (Frank)

This is a fallacy of the mainstream calorie dogma. Gaining weight makes you burn more calories, because the body has to carry extra weight, and some of the excess calories will go to muscles. (Obese people have huge muscles, esp the legs, but they are covered with fat.) The fallacy says that "eating just 10 extra Calories a day will make you gain a pound of fat every year."

I read this ludicrous theory stated almost verbatim in The Origin Diet, a book that takes the food pyramid, and dresses it up as the paleo diet (quite a laugh). Many people assume the body is just some dumb machine, that gains weight because we simply add a couple calories to our diets. They actually argue that the 10 lbs most people gain every decade comes from eating 10 calories too much. I think most people here realize what an absurd theory that is.

Bruce K said...

Wooo - "sedation and inactivity to promote sleep and conservation (which is why carb is exploited as tranquilizers by people with high stress & food addiction, and why it causes depression in the depression prone)."

I don't feel tired after carbs, but most of them are paleo (fresh honey and fruits, roots, tubers). I don't feel depressed, either. I think the refined carbs, PUFA oils, and dairy proteins/sugars are mainly to blame for depression and sleepiness. If I eat something like ice cream, I may get sleepy. There you have lactose, casein, and refined sugar. A deadly mix. Add some grains/flours and the high PUFA oils, you could be on the way to clinical depression.

BTW, Peter, can you send me the PDF of Stefansson's book? My email addy is "r en sie lk (a t) gm a il (dot) co m". Remove spaces and substitute signs for the words in parenthesis. Thanks, Bruce

Anna said...

itsthewoo,

I'm curious, have you looked into the issues that "broke up" the writing relationship of T.S. Wiley and Bent Formby when their second book was published? Or some of the controversy surrounding T.S. Wiley and her "Wiley Protocol"?

Jason said...

There is a lot of information that correlates breast cancer to iodine deficiency.

The breast holds the second largest concentration of iodine, second to the thyroid gland.

http://www.iodine4health.com/body/breast/breast.htm

Peter said...

Hi Jason,

Just got a chance to have a brief scan through the link you posted. The thing I find strangest is that I know of one near-OD eater who had two sessions of surgery, each to remove a benign breast cyst and who lived with persisted fibrotic changes for years. They cleared within a year of taking up high fat eating. Now I'm just wondering about the food choices involved (she's still vegetarian) or the roll of hyperglycaemia and/or hyperinsulinaemia on urinary loss or intestinal uptake of iodine... Have to have a look at that. The trouble is always that taking up high fat eating always changes far more than one aspect of diet. The iodine studies control for this but continue with a diet which predisposes. The question then is whether humans are adapted to central continental areas well away from coastal sources of iodine, or whether iodine deficiency is a marker of modern diets....

Peter

Bruce K said...

Jason, I think you have to consider what causes iodine deficiency. One factor is eating high-PUFA oils, as most people do if they eat cooking oils, restaurant foods, mayonnaise, salad dressing, etc. PUFA oils will absorb several times their own mass in iodine, while saturated fats do not absorb any. So, if you eat lots of PUFA, you need lots of iodine or you will have thyroid problems. The Eskimos had very high iodine intake and they needed it with all of the omega-3 fats in their diet. I think the better strategy is to minimize PUFAs equally from all sources.

Anna said...

ItsTheWoo:

Did you do any followup on the Wiley - Formby split? They apparently don't collaborate anymore after a disagreement on the Appendix contents of their second book (about female hormones). And Wiley got in a heap o' trouble with her Wiley Protocol of high progesterone supplementation. What I read about her "credentials" and her bioidentical hormone business made me start to question some of her assertions in Lights Outs.

Big Fat Keto Girl said...

Can you do me a favour Peter and email a copy of Stefansson's "Cancer: Disease of Civilisation" in pdf?

Thank you.
bigfatketogirl at gmail dot com

Peter said...

Hi BFKG,

Just need an email address...

Peter

Peter said...

Ah, got it!!!! Oops!

Peter

Big Fat Keto Girl said...

Thanks heaps!