Thursday, February 16, 2012

NASH on a ketogenic diet

Just a brief post on the development of NASH in long term ketogenic fed mice because I've been side tracked by some other papers: Starvation (Ethan), metformin (tripped over this one myself, things are moving forward from PSS and Oxygen), UCPs and fat oxidation (kindke)...

NASH, it all comes down to this paper (thanks Liz).

Does sustained ketosis produce NASH? Well yes, or at least something like it. Just look at the picture:

The dark staining patch is made up of neutrophils. You don't want clumps of them aggregating in your liver.

That's what you get if you feed F3666 to C57BL/6 mice. It is, undoubtedly, intensely ketogenic. But is it anything else?

"These are typical amounts of nutrients calculated from
available information. Actual assay results may vary.
For more information contact Jaime Lecker, Ph.D."

The paper (and the F3666 pdf) specifies 16% of PUFA in the fat, which seems rather low considering that USA produced lard (the main ingredient) appears to have 32% PUFA (almost all omega 6) but, even at only 16%, these PUFA are 16% of 95% of your total calories. That's an awful lot of PUFA...

Do PUFA matter for the development of NASH? Probably. From this N and M paper:

"The lipid composition of the different diets which induce steatohepatitis (see Table 4) [19,20,51,52,54], were lard and corn oil, both oils rich in unsaturated fatty acids. We can observe that fat of all the diets inducing steatosis and inflammation (Table 4) were richer in MUFA and PUFA (>30% and >20% of total fat respectively) as compared to our diet (5% and 2%). The injurious effect of unsaturated fatty acids, and particularly n-6 polyunsaturated fatty acids, was associated with enhanced lipid peroxidation and decreased concentrations of antioxidant enzymes, implicating oxidative stress as a causal factor. Indeed, different studies showed the pro-inflammatory effect of polyunsaturated n-6 fatty acids which exacerbate liver oxidative stress [60,61] and promote the development of NASH."

So there is a message: If you are going to eat a very high fat diet in the long term, you should pay serious attention to PUFA creep. Having cirrhosis is not likely to help you make old bones in good shape. Perhaps go easy on the commercial mayonnaise and just spread some butter on your cheese... Actually I tend to add butter to my beef if it's too lean (only happens when eating out, no way we would choose lean beef to cook at home!)...

It makes me wonder about saturophobes who might be swilling PUFA to lower their LDL and triglycerides, with or without a LC diet... More potential victims of the cholesterol hypothesis I suppose.


56 comments: said...

I just bought a bunch of packages of "Wholly Guacamole," which lists the ingredients as Hass Avocados, Jalapeno Puree (white vinegar, jalapeno peppers, salt) Dehydrated Onion, Salt, Granulated Garlic.

Avocados are very high in fat. Should I be concerned?

ItsTheWooo said...

Bah who eats mayo? That's only useful for smearing on bread to choke down dry meat. Neither of these apply to a ketogenic diet where the meat is fatty and bread is not eaten. Mayo serves no purpose. :D

My take:
1) I doubt this is true at all in humans
2) who eats a 95% fat diet? NOBUDDIE except a poor lab animal. Poor lab animal :(

In humans eating people food promoting of ketosis, like fatty meat and dairy and avocados and macadamia nuts and cream, I sorta doubt this effect would occur.

@Jim Avocados are one of the healthiest things ever. I eat like an avocado every other day. They are mostly mosaturated fat. Fitday states they are 53% monosaturated, 10% pufa, and 12% saturated (75% fat total). The main problem appears to be inflammation from omega 6.

Unless you are planning on drinking a weird lipid emulsion from a straw and eating severely deficient protein and no carbohydrate at all, it is safe to throw this study in the waste bin of importance to humans following theraputic mildly or moderately ketogenic low carb diets. Even 10% pufa of an avocado is a whole lot less if fat is only 65% of total calories (vs 16% of 95% of calories which is a ton more).

blogblog said...

When I see the word "mouse" I know to read no further.

Mice can't tolerate a diet containing more than 6-8% fat. Feeding a ketogenic diet to a mouse is sheer lunacy.

blogblog said...

@Woo said:

"Jim Avocados are one of the healthiest things ever."

I couldn't disagree more. Avocados are little more than toxic waste. They contain (amongst other toxins) high levels of the potent fungicide persin which is toxic to virtually all birds and mammals. Persin is highly toxic to breast tissues and the myocardium and is used to treat certain breast cancers.

Unfortunately health authorities have no interest in regulating existing foods.

LeonRover said...

"ASH on an old man's sleeve
Is all the ASH the burnt roses leave.
Dust in the air suspended
Marks the place where a story ended."

I believe similar happens with NASH.

Jim Purdy & blogblog

Re Avocado or persin

Paracelsus: The dose maketh the poison.

D1S said...

pino way we would choose lean beef to cook at home...

thats great and all - but what if all the meat available to u is 100% CAFO meat?... how do you suggest i should limit dat pufa overland intake specially eating a 60& fat diet?.. basically im eating this abomination
( observe the end)

so now im going for the absolutely LEANEST driest cuts possible + a shitload of butter
( not good for that 450 cholesterol )

your ideas? ( btw i dont know what to think about dat insulin theory... i ditched the lower prot idea @ ratios and im eating crazy amounts of prot a day ... and im leaner that evar? (65kgr) ex 180gr raw homemade cottage cheese , milk, sucrose, + the usual 140gr pastured yolks + lots of butter a day.

D1S said...

btw, 2:30 for the good stuff...
( video)

John said...

So with 95% fat, I'm going to guess "fatty liver" is unavoidable, as these animals are probably quite insulin resistant everywhere. With considerable PUFA, these mice have markers of excess "oxidative stress" and inflammation; this probably doesn't happen with butter?

With about 15% protein, as in the Mavropoulos prostate cancer papers, mice have low fatty liver [compared to Western and low fat/high sucrose] despite considerable PUFA. I wonder how these mice's inflammation/stress compares to the 5% protein+high PUFA mice and the [theoretical] 5% protein+low PUFA mice.

Moose said...

@ John, from the mouse paper:

"but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired."

Insulin-sensitive glucose intolerance...

But perhaps they just don't have enough glycogen/gluconeogenesis to recover from the insulin tolerance test... a false negative of sorts.

Nigel Kinbrum said...

I wonder how much choline there is in a diet consisting of 95% fat? Not a lot, I suspect.

@blogblog: Eat organic avocados.

@Jim: Don't worry, be happy.

LeonRover said...

Hey Petro


I'm guessing these guys are similar to the guys in your FIRKO-ise post.

The abstract refers to "distinctive nutrient milieu" and "unique signatures".

Are these similar to the "unique metabolic state" of FIRKO-ised?

(not prepared to pay for this one!!)

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

I would appreciate your comments on this paper

A 20 percentage point decrease in dietary fat (60%->40%), but higher sat fat, was apparently enough to wipe out the livers of these mice.

CharlesVegas said...

Also, if I may, in the Garbow paper the ketogenic-diet mice had "systemic glucose intolerance" yet had unimpaired "whole-body insulin responsiveness".

Is that a contradiction?

James said...

From your analysis of the Nash paper it's evident that high n-6 content was a likely candidate for the steatosis observed in the rats' livers. The Nutrition & Metabolism paper showed that rats fed high sat-fat (42 to 45% of calories) do not develop steatosis, but this does not regute the possibility that a 95% calories as fat diet may not be hard on the liver.

The reason i'm wondering about this is because i've been thinking lately about physical activity while on the KD. When you up the energy demands of your muscles, while they can only get energy from fat, is your liver going to be able to meet this demand? I'm not an expert on this topic but i guess what i'm wondering is if the liver would feel strained in producing such high levels of ketones long term.

James said...

Sorry in my previous post i meant to say "this does not refute the possibility that a 95% calories as fat diet MAY BE hard on the liver".

Tony Mach said...

With regards to n-6 PUFA excess I will through in one name: Bill Lands. (Just in case you haven't run across him yet)

His presentations may be awful, but he has a lot of material gathered on the health effect of the screwed up n-6/n-3 ratio. His singular focus on this may be a bit wrong, but I would suspect the studies he cites from are a treasure-cove on n-6/n-3.

Nigel Kinbrum said...

See The Sweet Truth About Liver and Egg Yolks -- Choline Matters More to Fatty Liver Than Sugar, Alcohol, or Fat

ItsTheWooo said...

Interesting; I wonder if perhaps this substance is relatively non-toxic to humans? From what the internetz tells me, it seems quite toxic to animals, targets breast tissue leading to noninfectious mastitis in animals... but given the numbers of people eating avocados regularly I would assume we would hear at least some case reports of a toxic reaction.

Cancer cells are not like noncancerous ones so perhaps the substance only is toxic to these particular breast cancer cells. It appears to work through an estrogen receptor mechanism and there are some kinds of breast cancers which obviously are fueled by estrogen.

It seems to be the case most any plant food will have substances that can be toxic to animals or humans, stands to reason this is the case; mast plants have no other defense besides chemicals.

Unknown said...

Does that mean Fish oil is bad on a high fat diet ?

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vlprince said...

Interesting... I wonder how much of this is a liver-centric phenomenon and how much it is an issue that starts in the gut. Recent research exploring alcoholic liver disease suggests that the type of fat in the diet causes hepatic pathology by altering intestinal permeability.

It's interesting to have a suggested mechanism, as it's long been noted that saturated fat protects against ALD ( but without a clear mechanism (there has been some talk of an increase in adiponectin being protective).

So perhaps the hypothesis should be that an increase in PUFA (especially linoleic) causes an increases in gut permeability, leading to increased blood LPS and other substances that lead to inflammation and an inflammatory process in the liver. Of course, an overload of PUFA in the liver, with or without increased inflammation cause by gut permeability, is likely to cause inflammatory issues on it's own.

I wonder what role CYP2E1 plays in this pathology. The expression of CYP2E1 is induced by a high fat diet (as well as fasting, alcohol, and other processes) and CYP2E1 is involved in lipid peroxidation. Knocking out CYP2E1 attenuates alcoholic fatty liver (probably others too, I'm just aware of the ALD research). I'd think that a high fat/high PUFA diet which simultaneously induces CYP2E1 and gives it a heap of substrate (in the form of PUFA) to peroxidate would be a rather bad idea.

M said...

Hi, Peter. I wonder if you, or one of your readers, could answer this question. I'm having trouble keeping away from sugar. I try to stick to an OD diet, but every night I get cravings. No matter how tired I am, I find it very difficult to go to sleep unless I have something sugary. It is something of an addiction, isn't it? Is there some way of getting over it, or is it purely a matter of power of will, that is, forcing myself to not eat it, period? Thanks.

nancan said...

@M: Sugar is addictive for some of us, and you have to get it out of your diet or you will always have cravings. It only takes a few days for sugar to get out of your body, but it took me about a month before I finally changed my habits sufficiently to quit craving sugar. I substituted a nut butter treat made with equal parts Kerrygold butter, coconut butter/or oil, almond butter, with a handful of raw walnuts tossed in: pour in small container, score, refrigerate (or cool larder). A small square was just right to replace the junk.


nancan said...

New study on diabetes which may be developed in gut:

ItsTheWooo said...

@M Have you ruled out blood sugar instability? Take your blood sugar throughout the day, and take it at night when you get the cravings. If you are noticing that your blood sugar is changing a lot (e.g. it is 95 at all times but when the sugar cravings come you are 75) then the sugar cravings may be caused by hypoglycemic phenomenon.
Of course if your blood sugar is absolutely hypoglycemic at the time (<70) this would be an obvious cause of sugar cravings, however I specifically advice to monitor your sugar at various points in the day because absolute hypoglycemia is not as important as the steepness of the decline and where your relative baseline blood glucose is. The body produces reactions to hypoglycemia when sugar drops too quickly, too suddenly, or if the sugar is below the natural glucostat particularly if it occurs quickly.

Assuming you are sure it is not hypoglycemia, many people find low carb has a stimulating effect and sleep becomes difficult. You may be craving sugar to help calm nad relax you in which case I would advice to use other methods, like sleepytime tea, melatonin/5-htp so on. There are a lot of ways of suppressing the stress response without resorting to eating sugar.

CharlesVegas said...

@nancan: This paper has a similar theme:

The gut microbiota as an environmental factor that
regulates fat storage

Puddleg said...

In the World Book of Meat Dishes by Nina Froud, 1965, my best low-carb cookbook, any dish that calls for lean meat is prepared with butter or olive oil. If fat is cut off, then fat is supplemented.

Nina Froud's Beef Stroganoff

750g fillet of beef (note: blade steak or rump is fine)
1 tsp salt
1/2 tsp pepper
2 medium-sized onions
125g butter
125g or 1&3/4 cups sliced mushrooms (optional, I prefer it without
these actually)
1 tbs tomato puree
1 tsp made mustard (English)
1 cup stock (or a tsp of fish sauce in a cup of water is fine)
1/2 pottle sour cream (original, not lite)
1 tbsp chopped parsley

Wash meat, trim away gristle, and 2 hours before cooking cut into
"straws" 1/4 inch thick by 1 inch long. Sprinkle with S & P and leave
to sit (or stand).

Slice the onions and fry in butter
Add mushrooms and fry together for 2-3 mins.
Add meat and fry together for 7-9 mins, stirring with a wooden fork.
Add tomato puree and mustard, dilute with stock, bring to boil.
Add sour cream, cover with lid, simmer for 15 minutes (30 mins if
using a cheaper beef cut)
Bring to the boil, sprinkle with chopped parsley.

(I leave out 1 tbsp flour, it doesn't need the aggravation)

Puddleg said...

Chromium piccolinate is the cure for sugar cravings. Marvellous stuff, just use a short course to get over the habit, repeat if necessary.

My (partial) hypothesis is that PUFAs in liver slow down beta-oxidation of MUFA by competing for saturase enzymes, causing both to accumulate. You do see the ratio of MUFA to SFA increase in these conditions.

M said...

Thanks for the replies!

Robert Andrew Brown said...

Tony Mach said

"With regards to n-6 PUFA excess I will through in one name: Bill Lands. (Just in case you haven't run across him yet)

His presentations may be awful, but he has a lot of material gathered on the health effect of the screwed up n-6/n-3 ratio. His singular focus on this may be a bit wrong, but I would suspect the studies he cites from are a treasure-cove on n-6/n-3."

Bill Lands is a genius before his time.

The Omega 3:6 imbalance is not the only health issue, but is way more important than most people realise.

Thanks Peter for another fascinating find and thought provoking commentary - great work (-:

CharlesVegas said...

Yet this AHA Science Advisory reads like a frigging testimonial for corn oil. I am utterly confused.

nancan said...

@George Henderson: What do you mean by a "short course" of chromium piccolinate? I've been taking as a supplement for years, and no doubt it helps with sugar-starch cravings, but to date nothing has stopped them totally, except a ketogenic diet.

Puddleg said...

@ Nancan, yes, but has M tried it?
I would suggest that if you were able to follow a ketogenic diet (which is of course the Gold Standard for all cravings) to begin with then sugar and carb cravings were not insurmountable.
Chromium at around 400mcg per day as piccolinate makes carbs manageable enough to restrict easily. Some people might need more, and co-factors like biotin and magnesium might also be needed.
The point is merely that chromnium is one of the more effective supplements for its intended use. If you didn't need it, you wouldn't notice.

CharlesVegas said...

Since I brought it up, I found an editorial commentary and a review paper by Ramsden that challenges the AHA Science Advisory:

British J Nutrition Vol 104 Issue 11 (not paywalled)

donny said...

Someone posted this on Active Low Carbers, yoinked from another forum.
Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

They have some numbers on liver triglycerides. Corn oil+sugar=fatty liver. Corn oil+protein doesn't seem to have this effect. A number of amino acids-glutamine, glycine, taurine, methionine, I'm sure the list goes on, have been shown to be important to fat metabolism, in the liver and elsewhere. Low methionine by itself can cause fatty liver. Omega 6's in large amounts suck, but we'd really better not be protein deficient at the same time.

Charles Vegas, that first study you posted, I can't see the full title. Probably my stupid browser's fault. Would you mind posting the study's title, so I can google it? Thanks.

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

@donny: The first paper I posted is

Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition

This link should work:

AJP - GI Nov 2011 vol 301 no. 5

Full article is paywalled.

D1S said...

lol Thanks!, regarding sucrose, just eat it first think in the morning. is mostly harmless, that is, if you are not a saggy bag of fat and bones!

Boomka Music said...


"Omega 6's in large amounts suck, but we'd really better not be protein deficient at the same time."

"Don't be a typical vegetarian", you mean?

Robert Andrew Brown said...
This comment has been removed by the author.
Robert Andrew Brown said...

Many thanks Charles Vegas for the useful links.

Thanks Donny - that is a really thought provoking paper. Thoughts arising . . .

Protein does not greatly increase fat deposition, due to metabolic costs / effects.

Improving the Omega 3:6 balance effects liver metabolism fat composition and content.

On the basis of the Omega ratio selected, Omega 3 had limited effect on the overall storage of fats, but increased omega 3 and decreased adipoycte omega 6 content.

The conclusions as to the effects of Omega 3 and 6 need to be pondered in light of a base diet that contained 70g per kg of soybean oil. Soybean as well as being high in Omega 6 contains some Omega 3. It would have been interesting to have had a group fed a very low Omega 3:6 as a base point, for a number of reasons including the saturation of tissue membrane at about 4% intake, and the very low levels, likely under 1%, needed to maintain essential health. Was Omega 6 intake already above its most sensitive range ?

I also look forward to reading the Ramsden paper, which looks even more fascinating.

Thanks again - highly thought provoking

Puddleg said...

I'll put the "substrate hypothesis" for omega 6 into clear terms. It is supplementary to insulin-signalling, LPS activation and other scenarios, but functions at a more basic metabolic level.
Long-chain, polyunsaturated fatty acids, when present as a significant % of calories, are ipso facto a calorie source, that is they must be catabolised via beta-oxidation to yield ATP.
They may even be prioritised as substrates over MUFA and SFA because this would tend to protect the cell from peroxidation and other consquences of high PUFA.
PUFA may compete for, or inhibit, enzymes (enoyl-CoA-isomerase and 2,4,dienoyl-CoA saturase) also needed for the saturation and of MUFA (this may also be part of trans-fat toxicity as metabolising trans fats would presumably require the same enzymes).
Different rates of PUFA clearance due to different genetic expression of these enzymes or availability of micronutrients required for PUFA clearance might account for variations in human responses to PUFA, for example PUFA from a nut or fish diet might be cleared faster than pure oil because of appropriate micronutrients for PUFA processing (including selenium and tocopherol) being present in the foods.

Puddleg said...

Here are some papers which either contradict or support the substrate hypothesis, and certainly complicate it enough for a make-over.
They show different ratios of MUFA/SFA related to steatosis - mostly less MUFA - and the mechanism is reduced desaturase activity. There are also variations in PUFA.
In this paper (steatosis in chonic hep C) there is more MUFA and PUFA, less SFA associated with steatosis.
In this mouse model (high-fat feed and Carbon tetrachloride), less MUFA and more SFA (due to less activity of stearoyl-CoA desaturase-1 (SCD1))

This is a very interesting review of the literature:
Though I suspect that their conclusions are not justified by the data, they have pulled together a lot of interesting papers.

Animal studies have pointed out that, after intestinal absorption, monounsaturated fatty acids (MUFA) and PUFA produced a higher thermogenic effect (16) and higher oxygen consumption (17) when compared to SFA. However, when PUFA were added to a high-MUFA diet (high PUFA/SFA ratio) for 8 weeks, the expression and activity of hormone-sensitive lipase (HSL) was up-regulated and adipose tissue peroxisome proliferator-activated gamma (PPARγ) was reduced when compared to a high-MUFA diet, which significantly elevated de novo hepatic lipogenesis (18).

Puddleg said...

Carbon tetrachloride mouse model:

Unknown said...

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Puddleg said...

Unknown writes "Does that mean Fish oil is bad on a high fat diet ?"
I'm coming round to the view that a higher intake of animal omega 3s such as EPA and DHA may be desirable on a ketogenic diet.
This is based on the thyroid-enhancing effect of these lipids, which may be the answer to the "euthyroid sick syndrome" panic, which is fuelling the current "safe starch" craze among low-carbers.
If VLCKD decreases thyroid activity, fish oil n-3s enhance it in many tissues such as liver; if VLCKD (in this scenario) can elevate LDL, fish oil n-3s lower it.

Note that in the example below, soy bean oil, a purported "source" of omega 3, was used as the placebo control substance.

Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms

n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oil (FO) exert important lipid-lowering effects, an effect also ascribed to thyroid hormones (TH) and TH receptor β1 (TRβ1)-specific agonists. n-3 PUFA effects are mediated by nuclear receptors, such as peroxisome proliferator-activated receptors (PPAR) and others. In this study, we investigated a role for TH signaling in n-3 PUFA effects. Euthyroid and hypothyroid adult rats (methimazole-treated for 5 weeks) received FO or soybean oil (control) by oral administration for 3 weeks. In euthyroid rats, FO treatment reduced serum triglycerides and cholesterol, diminished body fat, and increased protein content of the animals. In addition, FO-treated rats exhibited higher liver expression of TRβ1 and mitochondrial α-glycerophosphate dehydrogenase (mGPD), at protein and mRNA levels, but no alteration of glutathione S-transferase or type 1 deiodinase. In hypothyroid condition, FO induced reduction in serum cholesterol and increase in body protein content, but lost the ability to reduce triglycerides and body fat, and to induce TRβ1 and mGDP expression. FO did not change PPARα liver abundance regardless of thyroid state; however, hypothyroidism led to a marked increase in PPARα liver content but did not alter TRβ1 or TRα expression. The data suggest that part of the effect of n-3 PUFA from FO on lipid metabolism is dependent on TH signaling in specific steps and together with the marked upregulation of PPARα in liver of hypothyroid rats suggest important in vivo consequences of the cross-talking between those fatty acids and TH pathways in liver metabolism.

Renaud said...

Thanks for your blog Peter, i realy like it.

Some comment about this abstract ?

szielsdorf said...

Bottom line, what is the correct ratio of fats to eat in NASH liver disease?

Peter said...

Bottom line: Butter but with restricted carbohydrate.

Renaud: Missed this one, if you have marked to be updated I would comment that PUFA intake during pathological insulin resistance improves matters temporarily by increasing insulin sensitivity in adipocytes, hence the muscles, so will lower insulin levels, at the cost of increasing adipose depots (or hunger if calories are limited). Many of the ideas based around F:N ratio of PUFA indicate a failure to develop the insulin resistance appropriate for a given level of fat in the diet. The effect on the liver in the longer term is cirrhosis, ie the pathological response to caloric overload of hepatocytes with calories to which they fail to say no to. Excess electron transport in the absence of demand = pathological free radicals. I'd need the full text to see how they loaded the deck in this particular study to not find this...


Puddleg said...

Very interesting; this might help to solve the mystery of the metabolic push-me-pull-you, the diabetic hepatocytes that emit both glucose and triglycerides simultaneously

That krill oil at low doses, but not fish oil, can dampen both outputs is also interesting:

Renaud said...

Thanks Peter. Interesting, as allways.

I'm nearly certain that a high fat diet is better with low PUFAs. That's what i've done for a while. But i'm trying a higher carbs diet, and maybe in this context PUFA are more welcome, relative to SAFA... as long as total PUFA calories stay relatively low.

Peter said...

George, when we get back to cirrhosis I have some ideas about iron overload that may need some kicking around. Or kicking out. The line of thinking goes along as: PUFA + carbs w/o insulin resistance = hepatocyte caloric overload = enough free radicals to trigger necrosis, let alone apoptosis. How do you avoid this? Maybe some heavy metals to generate free radicals enough to provide an emergency supply of superoxide w/o going over the top. Cirrhosis is the end result of this elastoplast on corn oil toxicity, or possibily the result of this elastoplast failing. Low dose fish oil seems fine, 40% of calories as fish oil is catastrophic...

Renaud, just be careful. LC is a starvation mimic. It's physiological. There is nothing physiological about using PUFA as a metabolic tool. They might help some aspects and yet trash others. The Law of Unintended Consequences is a harsh mistress!

I tend to leave the increase in carb intake to people who think the increase in mitochondrial numbers produced by palmitate during LC has cured them, and they can stay cured using exercise as a substitute for palmitate free radicals. Let's look at them 10 years down the road before deciding it's OK to mainline glucose.


Puddleg said...

I'm thinking, insulin sensitivity at the cell surface caused by excess PUFA meets insulin resistance in the nucleus caused by ROS>Fox01, resulting in an overfed hepatocyte that has to export both lipids and glucose...

Peter said...

Hmmm, I'm still thinking about PUFA failing to generate superoxide as a problem at the mitochondrial level, certainly if provided in bulk... We'll see how things pan out. I haven't really started to pick at it closely. It may turn out to be in the same line as the brain generating canabinoids from AA as signalling molecules but the basis appears to be that the parent molecule, LA, is intrinsically fat storing at the adipocyte mitochondrial level and it's derivative fine tunes this through the brain. Lots to think about. Both ideas may be wrong!