Playing with salt and water

While we're talking about the risks of low salt and high water intakes, this hit the news today: You want to try a "detox" diet?

Don't!

It's arguable whether a detox diet is more or less likely to precipitate a hyponatraemic crisis than either Ecstasy or psychogenic polydipsia (a psychosis). Never forget the massive press misinformation about Leah Betts. This is what really happened to her:

"Hyponatraemia is an uncommon complication of MDMA ingestion. Only a few cases have been reported. The death of Leah Betts achieved wide publicity in the popular press, and it became clear that fatal water intoxication can be precipitated by excessive water drinking in ecstasy users. Fifteen cases were identified between August 1994 and December 1995 by the National Poisons Information Service (London), with serum Na+ concentrations of <130 mmol litre–1. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed by drowsiness and agitation and, in seven cases, epileptiform convulsions. Drowsiness, a mute state and disorientation were observed for up to 3 days (Hartung TK, Schofield E, Short AI, Parr MJA, Henry JA, unpublished)"

Detox time or too much water after taking E at a party? Neither is beneficial and both can be fatal. Play safely!

Peter

Update

Well, here I am briefly. Things have pretty much ground to a halt on Hyperlipid. What has happened is that my boss has broken his little finger, in to lots of little pieces (pushbiking is pretty dangerous!). The steel pin, support dressing and full time sling don't seem to be doing much good so he's off work for 6 weeks and I've gone from working one day a week to working full time. Then our other primary surgeon is on study leave for his surgery ticket and our full time internal medicine slanted vet is off sick... So this is the first time I've logged on to do anything other than check work emails.

I'm just finishing week four out of six... By the time I get to answer comments people will probably will probably have forgotten they posted them! Still, it pays off a chunk of the mortgage.

So apologies for the lack of activity and replies.

BTW the off sick vet is really interesting. Anaemia to the point of hyperventilation after climbing the stairs and recurrent major infections. Ah, Weight Watchers and wholemeal bread! People love these wacky diets, play at your own risk!

Peter

AGE, RAGE and ALE; oxLDL

This is the abstract from a discussion paper, it's not in pubmed for some reason but I have the pdf lying around my hard drive. It's just an opinion piece but quite well referenced.


Oxidized Low-Density Lipoproteins and Atherosclerosis
S. Ylä-Herttuala1,2, T. Pakkanen1, P. Leppänen1, T. Häkkinen1

Basic research has provided strong evidence that LDL oxidation plays an important role in atherogenesis. Several mechanisms have been identified which can lead to LDL oxidation in vivo. Clinical and epidemiological studies have provided circumstancial evidence that oxidized LDL may be involved in the progression of atherosclerotic vascular disease. Better understanding of mechanisms that lead to LDL oxidation or protect LDL against oxidative damages shouldhelp the development of new strategies for the prevention of cardiovascular diseases. J Clin Basic Cardiol 2000; 3: 87–8.

Just look at this table of comparison between LDL lipoproteins and oxLDL lipoproteins.

If you are measuring the size and numbers of your LDL particles, you might also want to look at their oxidation state too. Perhaps it matters more? Are the small dense LDL particles so associated with atherosclerosis also the most AGEd and ALEd?

Here's the table, click to enlarge



If you had the choice between lots of minimally oxidised LDL and a small amount of highly oxidised LDL which would you choose? Low fat diet anyone, or maybe just more sugar on your soya oil fried donut? Mmmmmmm, yumeeee.

Peter

AGE, RAGE and ALE: The ALE of LDL

I looked at glucose reacting with amino groups of proteins in the last post on the formation of AGEs. Apart from protein, cell membranes and the surface membrane of lipoprotein particles contain lipids. These form the classical lipid bilayer of biological membranes. The lipids of the bilayer come in a mix of saturates, mono unsaturates and PUFA. The exact mix of saturates to monounsaturates is largely determined by stearoyl-CoA desaturase, the enzyme which puts double bonds in to saturated fats to give monounsaturates.

Interestingly this enzyme appears to be under the control of insulin and activity goes up in insulin resistant states. That's another subject.

The PUFA composition is largely diet determined.

While boiling sugar with butter gives toffee, the situation in vivo seems more complicated and the initial generation of damaged lipids (ALEs, advanced lipoxidation end products) seems to involve an amino group. These are freely available from molecules like phosphatidylserine in cell (or lipoprotein) membranes. They provide the nitrogen for the formation of that horrible unstable Schiff base and its subsequent decay. The decaying base triggers oxidation/reduction reactions which hit double bonds in surrounding fatty acids, leading to ALE formation.

There's a good summary in this paper.

I just loved the chemistry in the introduction with stuff about electron spins, the pi antibonding level and other stuff that sounds really fancy. I think it means that molecular oxygen leaves PUFA alone without a transition metal or a pre formed free radical to get things going.

Until you add glucose that is.

Now I have two complaints about this paper. First is that some of the glucose concentrations used would make the ADA blanche. Not even an ADA diabetologist would suggest a blood glucose of 500mM (ie 500mmol/l). The 200mM used to oxidise the LDL particles would have had an intact human being in hyperglycaemic coma too. This is aggressive corner cutting on a time basis I guess. They did do some work down at 5mM.

Second is that they thanked Scott Grundy for helpful discussions. If you don't know who Scott Grundy is then you haven't read enough about the cholesterol con. Big black mark to the paper.

Third is that they used oleic acid for a lot of the work. They do comment that PUFA are 10-30 fold more oxidisable than oleic acid but PUFA didn't fit their protocols. They also forgot to mention that saturated fats just won't randomly oxidise at all in biological systems. No double bonds. But who would expect that sort of information from a cardiologist?

Did I say two complaints? Fourth...

So this paper is a bit rocky.

But what I do like about it is that it appears to show that glycation is what converts an LDL cholesterol particle in to an oxLDL particle. They're not the same. This is compatible with the recent study using low fat diets to (accidentally) raise the levels of oxLDL in intact humans.

Seems like sugar is what oxidises the PUFA in LDL to give oxLDL.

Avoid sugar, PUFA or both. Seems sensible to me.

Peter

Statin stupidity again

Read and cry.

Cure for C sections!

Perhaps a little less sugar might be a better approach!

I found this while searching for a snippet from Radio 4's Today Program announcing the recommendation from field leaders in the USA that children should start taking stains at 8 years of age, on the off chance it might eliminate all illness for ever. Happy happy happy I don't think. Couldn't find it on R4, but it'll surface soon in other places I guess.

Sigh.

Peter

Edit: You've all read Chris's post here? Never mind which end of life, you have a statin deficiency.

AGE, RAGE and ALE: The AGE of LDL

A glucose molecule can assume various shapes. If presented as a linear rather than a ring structure, one of the two end carbons will contain an aldehyde grouping. The C=O structure of the aldehyde can react chemically with an amino group on another organic molecule to give a Schiff base. This is a horribly complex structure where the carbon of the sugar is double bonded to the nitrogen of the amino group, which stays attached by its third bond to whatever structure it's part of. Classically this is a "free" amino group of lysine or arginine. Needless to say this structure is unstable and falls apart in various ways. The sugar can remain attached or break off taking the amino group with it. Either way there is damage to the protein and the potential for cross linkages to form. Lysine and arginine are, as I mentioned, the most susceptible amino acids. Glucose is one of the least problematic sugars, fructose is one of the worst.

The end result of this sugar driven reaction is the generation of Advanced Glycation Endproducts (AGEs). They're probably bad.

There is a section of the apolipoprotein B100 molecule (That's that sole protein on the surface of the LDL cholesterol particle) which is very prone to AGE formation. These people have looked at the process in detail. They have located, within the apoB100 protein, a distinct continuous sequence of 67 amino acids which are exquisitely prone to AGE formation. This section of apoB100 is probably not part of the binding domain for the LDL receptor, but formation of AGEs here does strongly influence the binding domain and effectively stops it working. So AGE formation in this area inhibits LDL particle attachment to its receptor, so reduces clearance from the plasma.

This is highly reminiscent of the situation in familial hypercholesterolaemia.

Why is apoB100 designed this way? Stuff doesn't just happen "accidentally" like this. Evolution has selected the sequence of apoB100 protein to provide a 67 animo acid section in which AGE formation inhibits uptake of the LDL particle in to cells which might want it.

Let's look at the logic.

During glycation conditions the LDL cholesterol particle stops sticking to its normal receptor. Why? My answer is that under these conditions it is more advantageous for the body to have the LDL cholesterol particle in the blood stream than it is to have it endocytosed by an endothelial cell.

Glycation is related to sugar concentration. Glucose is the sugar least prone to glycate anything to an AGE. Couple that with the tendency for humans, over an evolutionary time scale, to eat diets that rarely budge the blood glucose outside of a relatively narrow range, and I'm not sure hyperglycaemia is what the "switch" on LDL is evolved to look at.

No, my guess is that fructose was the original lever to develop a glycation based switch on the apoB100 molecule. Just about the only time a human ought to get a big enough load of sugar to risk any damage to themselves is during late summer or autumn in temperate regions, the source would be fruit. Possibly large amounts during a short period. If this happens in autumn it's a good source of calories to convert to fat and not to be wasted. But fructose is ten or seventeen times as good as glucose at AGE formation, depending on which AGE you look at and which model you use.

Fructose appears to be bad news, especially if any gets in to the systemic circulation. I can see some logic in taking the LDL particle away from arterial endothelial cells, which can make their own cholesterol anyway, and having it handy in the circulation for other purposes, like patching up fructose induced damage. Bear in mind that, while fructose is only present in the systemic circulation in trace amounts (which are probably bad for you) it will be present in copious amounts in the portal vein from gut to liver after each fruit meal. Lipoproteins are present throughout the circulation. Fructose will meet LDL particles with head on impact in the portal vein. AGEs on apoB100 suggest AGEs elsewhere, which mean repair is going to be needed. The LDL particle is diverted away from the endocytosis receptor. This is probably physiological.

But raising blood glucose from below 6mmol/l to above 30mmol/l would allow glucose to become the primary glycating agent. For a diabetic on the ADA diet the glycosylation of apoB100 is probably a fact of life. This is not our normal autumn carb loading pre winter. It's more of a pathological process.

Finding high levels of LDL cholesterol is one of the more logical aspects of the hyperglycaemia of type 2 diabetes. Putting these patients on to LC diets usually drops their calculated LDL cholesterol levels along with their blood glucose levels. It probably markedly reduces AGE formation throughout their physiology. LDL can then get back to supplying normal lipid to normal cells through the LDL receptor.

Peter

Food, fremented cream and 85% chocolate

OK, another non technical post. I hit a patch of work so I'm just glad to have arrived home one day while Squiggs was still up and eating.

Voices are the neighbours... Except the lip smacking from Squiggs!




Peter

Opioid pictures

No, it's not Afghanistan, that's the A34 in the background. The NHS had (has?) a diamorphine supply problem since our foray in to the opium fields of Afghanistan. Now we're in to grow your own!




The surrounding fields are far less recreational but could be far more damaging!



No surprise people like bread, it's acting on the same receptors as the poppy juice....

Peter

Diabetes in Sweden update

Just an update from Nielson and Joensson, original comment here. Happened on it while chasing assorted lipoprotein numbers for another post.

HbA1c below 5% without meds is possible through diet. I wouldn't describe these people as cured, a pizza a week would have them in trouble, but with HbA1c this low I'd not be worrying about CVD too much.

"Of the total of 10 controls, who have switched diet, 2 persons after a weight reduction of 20 kg each are free of all signs of diabetes after 3 and 2 years respectively i.e. HbA1c below 5.0%, fasting blood glucose below 5.0 mmol/l and free of any blood glucose lowering medication"

Second comment is that, even with successful weight loss and diabetes imporvement, carb creep is real and hard to avoid.

"After 22 months 2 patients had resumed insulin treatment following an increase of carbohydrates."

I know that rye crisp bread was a feature of this diet. I wonder what would have happened in the complete absence of gluten? Or whether the problems of removing this potentially addictive carbohydrate source would just have sabotaged the initial compliance?

Peter

Gluten, thyroid and auto immunity

This an old press release, no longer available, sent to me by a friend from Dr Bernstein's forum. It appears to relate to this paper. Can't get the full text but the abstract and PR seems to sum up the results quite well.

There are three things of particular interest, one was the suggestion that coelaic disease patients develop other auto immune diseases. Second was that on withdrawl of gluten they not only loose both their anti endomysial antibody titers (traditional marker of coeliac disease) but they also loose their auto immune disease antibodies too. Third is that it's not overnight, 3-6 months is more like it.

From several people I get the impression that 2 weeks is often enough to see some change in an auto immune disease, a month is needed for convinving improvement and resolution needs about 6 months. There are good and bad patches in the process.

Nice to see a research group backing up the anecdote. Here's the press release:


"Dr. Tarcisio Not, of Clinica Pediatrica, I.R.C.C.S., Trieste, and colleagues, studied 172 patients with autoimmune thyroid disorders, and two control groups. The control groups comprised 498 patients with other diseases and 4,000 healthy blood donors. Screening was done with IgA-class endomysium antibody using immunofluorescence.

The findings, reported in the February issue of Digestive Diseases and Sciences, show that the prevalence of celiac disease was 3.4% in patients with autoimmune thyroiditis, and 0.6% and 0.25% among the two control groups.

Moreover, the study found an association between untreated celiac disease, gluten intake and autoimmune disorders. The researchers write, "We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ-specific autoantibodies."

They add, "By following these subjects longitudinally, it has been seen that not only do the anti-gliadin antibodies and anti-endomysium antibodies disappear after 3 to 6 months of a gluten-free diet, but so do the organ-specific autoantibodies."

Given these results, Dr. Not and his team suggest that patients with autoimmune thyroiditis "may benefit from a screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders."

Dig Dis Sci 2000;45:403-406.(end)"


Peter

Gluten and gall bladders

Chris from Conditioning Research emailed this link to me, just before Troy asked about high fat eating after the surgical loss of your gall bladder. Many thanks Chris, immaculate timing. The main problem without a gall bladder is that there is no pulsatile release of bile acids to allow the formation of the lipid miceles needed for fat digestion and absorption. However, even without a gall bladder, there must be some on going bile secretion, even if there is no storage for a big release after a large meal. Is this enough? I commented that medium chain triglycerides might help, these are slowly absorbed without pancreatic lipase, but now I think about it, I'm not sure if this would work without bile acids to get the MCTs in to the enterocytes in the first place...

But there is a separate problem anyway. If you have coeliac disease you don't seem to produce cholecystokinin (CCK) when fat hits your small intestine. So under these circumstances, you may as well not have a gall bladder anyway!

There is obviously a trade off between the severity of the coeliac disease and the degree of cholestasis. The link above mentions active disease... I get the impression that villous atrophy is needed to get the blunted CCK response.

But then it's worth remembering that 1mg, that's one milligram, no typo, of gluten per day will sustain villous atrophy in unlucky individuals. They will be clinically and serologically normal under these conditions. I bet they don't make a lot of CCK though! Or get picked up by the average gastroenterologist.

So is subclinical coeliac disease any worse than having no gall bladder? Many many many people have sub clinical coeliac disease. Perhaps this is the wrong question. Maybe it would be better to ask whether THE reason you have had your gall bladder removed is that sub clinical coeliac disease was the underlying cause of your gall stone anyway. No CCK means no gall bladder contraction, which means no bile acid deposition, which means cholestasis, which means gall stones. Also means blunted fat absorption. Which means no CCK release... It's a chicken and egg situation.

Apart from coeliac disease and CCK, the other aspect which fascinates me is the effect of opioids on the sphincter of Oddi, at the end of the bile duct (includes the pancreatic duct in some individuals). Opioids spasm this sphincter. I know, I precipitated pancreatitis in a dog with a (big) dose of morphine once. It recovered.

So what does a continuous flow of gluten derived opioids through the gut do to the sphincter of Oddi? There's nothing I can find on pubmed directly related to this, but anyone with cholestasis problems or recurrent "idiopathic" pancreatitis wants to dump gluten big time. As if there weren't enough reasons to do this already.

So is anyone who is missing their gall bladder any worse off than someone eating to the food pyramid? Probably not. But who would want to be as dyspepsic as a food pyramid eater anyway???????? I guess the answer is dump the gluten, start with medium fat carried in real Food, dump the gluten, work up to higher fat loads, dump the gluten and try for 70% fat calories if any Olestra like effect allows, dumping the gluten. Whatever the outcome, sticking to Food and dumping gluten is the best you can do. Did I mention gluten?

Peter

PS at my time of peak gluten eating I was ultra sound scanned for gall stones. Negative, but that's just how it felt. Reading the celiac.com comments, it turns out you get that particular ache from gluten even after your gall bladder is removed! Maybe it's spasm in the sphincter of Oddi!

PPS When spell checking "Oddi" in google I found a host of support sites for people with dysfunction of this particular organ. Looks like it is coeliac disease rearing its head again.

And again, note the stupidity of ONLY biopsy sampling people who are anti endomysial antibody positive. Under diagnosis rules. As does 1mg per day of gluten induced, sero negative coeliac disease. Causing gall bladder disease. Or pancreatitis. You do not want pancreatitis. Honestly.

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).

Fruit and vegetables, WHEL study and McDougall

This was mentioned in the comments section of another thread. Needs its own post!

Because Stan (Heretic) visits some pretty weird places on the net, he led me astray to this bizarre commentary from some vegan low fat nut on the WHEL study. McDougall is a Dr no less. Here are some of the things he has to say:

"Breast cancer is a fatal disease and women will do almost anything to live. They will endure poisoning by toxic chemotherapy, burning with radiation, and mutilation from breast-amputating mastectomy; in the hopes of living a few more days. Obviously, if asked to do so, and given proper support from their doctors and dietitians, they would do something as simple, safe, costeffective, and enjoyable as eating oatmeal and bean burritos while avoiding beefsteaks and cheese omelets"

This initial quote from McDougall sums up what I imagine is the mental outlook of the WHEL study intervention group nicely. Women in the aftermath of breast cancer surgery DO want to live. As the dietary intervention tested in the WHEL study failed utterly to make an iota of difference to breast cancer recurrence, what is the explanation for its failure? This is how McDougall sees it:

"Data collected by asking the study participants about what they ate suggested they were eating more fruits and vegetables and less fat after being given instructions dictated by the study guidelines. But people don’t always tell the truth—they often want to please the investigators, so they tell them what they think they want to hear, which in this case was clearly inaccurate"

I'd summarise this as "the patients lied and the patients cheated". Now just try and reconcile statement one with statement two. Women will do anything to survive, statement one. Women will cheat and lie in a study which is trying to save their lives with vegetables, statement two. McDougall's answer as to what actually happened?

Statement one is correct, they cheated and lied. How can he tell?

Easy, next quote:

"Proof that the data collected from asking the women what they ate was inaccurate is shown in table 2. The women eating “a dietary pattern very high in vegetables, fruit, and fiber and low in fat” were reported to have decreased their daily calorie intake by an average of 181 calories (1719 initially, and 1538 six years later), yet they gained weight"

I hate to mention insulin, but ALL fruit and vegetables raise insulin levels. No one looses weight while insulin levels are high. Fruit and vegetables raise insulin. The only way that you can loose weight on a carbohydrate based diet is by caloric restriction to the extent that insulin levels fall between meals. The WHEL study was not a weight loss project, it was a "fruit and vegetables to save your life" project. Lack of weight loss can be taken as the removal of a variable extraneous to the study. It's a marked plus point about this particular study.

The increased weight in the intervention group, to my mind, is the clincher that the patients DID comply. They ate fruit and veggies, raised their insulin and kept any fat they stored post prandially.

I'd just like to point out that anyone on a vegan low fat diet who IS loosing weight is sourcing their calories from the ANIMAL fat on their own butt (this was a USA study, pardon the phraseology). Any health benefits claimed for veganism WITH weight loss has to accept this undeniable fact. Humans carry animal fat on their butt. Wasting muscles will provide animal protein.

I do have to thank Dr McDougall for one pointer.

Long term readers will know that I tend to believe people unless it's patently obvious that they're lying. The WHEL intervention group FAILED to maintain their fat intake reduction, and reported this truthfully. It was always below the non intervention group's fat intake, but it drifted up to 28.9% of 1538kcal, ie about 40g/d. The non intervention group ended up on 32.4% of 1159kcal (50g/d) of fat.

Why is this good? I was worried, at the back of my mind, that there had to be a reason why the death rate was identical in both groups. Given the background of the SAD, any increase of carbohydrate on top of the saturation levels of PUFA and sugar likely to be eaten routinely should have increased the death rate. The answer seems to be that the fat intake drop never really happened, so carbs never really increased and so luckily no one extra died in the intervention group.

This lack of compliance in dietary fat reduction occurred because the elevated insulin was locking energy in to adipose tissue and so energy had be sourced from the diet. That's called hunger. The effect on weight gain was small, in proportion to the small decrease in dietary fat.

The kindest thing I can say about McDougall is that he is a ranting extremist. He is stuck in his vegan rut and doesn't seem to understand how metabolism works.

The weird thing is that I believe he gets results! How come?

A real low fat diet will dump almost all PUFA. A real Food diet will eliminate all sugar. A hypocaloric weight reduction diet will both reduce insulin levels (a growth promoter for breast cancer) and switch metabolism to animal sourced saturated fat, the best source of calories available. Of course ketosis is out of the question, low fat veganism is a very limited approach.

Does McDougall know what he's doing, to get whatever results he does get?

No way.

Peter

Junk Food binge

My greenhouse is full of junk food, sugar ladened and delicious. Pretty hot on fructose too. These are gustatory recreation, not food. Going to live dangerously for a few weeks!





The weeds below are growing in an untended border outside my son's nursery. The unripe fruits are as big as they are going to get, though they too will go red and delicous in a week or so. They appear to be food, certainly better than starvation if hunting is bad. How long would it take to gather enough to keep yourself out of ketosis for a day?




I don't think many hunter gatherers had greenhouses or ate strawberries!

Peter

Gluten Dr Briffa link

Not sure if this sort of thing has ever happened in the UK before, perhaps the parents and child discussed by Dr Briffa live in Nottingham. The case is highly complex, but here's the summary:

Wheat=diarrhoea

No wheat=no diarrhoea

Now, to assemble this Apollo 13 rocket, first remove all contents from packaging and make sure all pieces are present, locate an appropriately sized launch pad, take the first nut and an appropriately sized spanner (not supplied)...

The question is whether the dietitian and gastroenterologist can hide behind a negative coeliac antibody test (in a wheat avoiding, currently digestively normal coeliac) to justify their execrable behaviour.

I'm not much of a clinician nowadays, I'm pretty well ruined as far as belief structure in the marvels of the latest anti inflammatory drug or chemo protocol goes, but the one thing that I do still try very hard to do is to listen to my patient's owners. In their own way, from articulate to incoherent, these people are trying to tell you what the problem is. Relying on a set of bloods (normal) and an abdominal ultrasound (inconclusive) will miss you the opportunity to sort out an awful lot of problems.

Luckily the child's problems were limited to the superficial and highly responsive problem of diarrhoea in response to gluten. What if the presenting symptom had been gluten ataxia, hypothyroidism or systemic lupus. Scary.

Anyway, skip's arrived, time to shift some rubble!

Peter

IHD and ghee

Just while ghee is in focus, there's this abstract from Jaipur. There's a typo three lines from the end where the 1 is missing from the "greater than 1 kg". I've re checked the "greater than" sign in IBIDS and it is correct, the one is still missing.

So the ghee eaters were fatter, ate more calories, more sat fat and more monounsaturated fat. Same total PUFA as the low ghee eaters. Oh, they had less coronary heart disease too. The only serious potential confounder is that the ghee eaters were younger. With multivariate analysis to account for this, p was still less than 0.001. The odds ratio was 0.23. I think this means that they were less than a quarter as likely to have a heart attack. Eat your heart out statinators! Oh!!! That pun was NOT intentional. If only ghee were patentable!

Of course the dietitians probably forgot to ask about sugar consumption. If they did check, they're not saying. Certainly not in the abstract. This gets a bit tedious sometimes!

Fatty acid intake summary from the abstract:

"This group [ghee eaters] consumed significantly more calories, saturated and mono-unsaturated fats while the consumption of polyunsaturated fats was similar in the two groups"

"Fatty acid intake analysis showed that group 1 males consumed more mono-unsaturated (n-9) fatty acids than group 2. Intake of polyunsaturated n-3 and n-6 fatty acids was similar"

I take it from the second quote that the cardiologists are falling back on monounsaturates to save the lipid hypothesis. In their repetition, they forgot to repeat the higher saturated fat intake. Some people are just so forgetful!

But it looks to me to be more likely that you can eat extra calories and be fatter while being less likely to have heart disease, provided your excess calories come from non PUFA fat sources. The sugar intake? If anyone has the full text, and if it was even remotely enquired about, I'll bet it was lower in the healthier, heavier ghee eaters.

Peter

EFA deficiencies?

Arachidonic acid is essential. Apart from the fact that your brain is largely made out of it (I exaggerate here slightly) and it has a roll as a precursor to a myriad signaling molecules, there is a definite deficiency syndrome in the skin. The deficiency syndrome is a bit dubious in humans, especially adults, but pretty clear cut in lab animals, especially during growth. Chris Masterjohn covers this pretty thoroughly and it seems quite plausible.

In most adult humans there is enough linoleic acid stored in fatty tissue to act as a reservoir for the synthesis of arachidonic acid for a long time. Even after years on a PUFA free diet it is unlikely you could precipitate an arachidonic acid deficiency. Bear in mind that a completely PUFA free diet must be synthetic or largely so. No food, just a fat free protein source, sucrose, glucose and some multivits should cover it! Otherwise enough arachidonic acid would sneak in from meat and eggs to supply an adult's needs. Or maybe some linoleic acid from lettuce!

I suppose the flip side of this is that if you drop your PUFA intake deliberately it may well be quite a long time before you lower your blood linoleate levels. Obviously this depends on how much vegetable oil you've squirreled away in your fatty tissue, how much fat you (and your gut microbiota) actually own and if your hormone sensitive lipase ever actually gets working... And of course how low you think you need to get your linoleate level before a deficiency syndrome appears. No healthy adult has managed so far in the literature.

So arachidonic acid deficiency in an adult human seems to be very, very unlikely. Especially if they occasionally eat items of food.


What about DHA? Amongst the many things which control elongation and desaturation of fatty acids I posted about recently, the parent molecules, linoleic acid and alpha linolenic acids, are effective depressors of the system. That is, if you eat a diet absolutely loaded with linoleic acid there is a down regulation of its conversion to arachidonic acid. That's logical. No one would want an unlimited supply of arachidonic acid. It does a lot of things to you, all of which would want to be done under careful control. It doesn't seem to be possible to down regulate to the point of arachidonic acid deficiency though, some will get through even under very high linoleate intake. Not so DHA.

Exactly the same elongase desaturase system used to manufacture arachidonic acid converts alpha linolenic acid to EPA, heading for DHA. Down regulating the system with linoleic acid, as above, will down regulate DHA production too.


Anyone on a "healthy" oils diet may well need to be getting preformed DHA. As DHA is only available from animal (or algal) sources, the problem person here looks to be the high PUFA eating vegan. That's fair enough, that particular diet choice comes with its own special consequences!

The quote below, which comes from this paper, seems to sum up the current state of unknowledge as to whether this problem is real:

"individuals who adhere to vegetarian and vegan diets do synthesize small amounts of DHA, and evidence to indicate deficits in brain development among vegetarians has not been published"

Of course there is plenty of evidence that being on total intravenous nutrition (TPN), based on linoleic acid as your sole source of lipid, means that you will require more than an absolute minimum of alpha linolenic acid before you actually get any DHA produced at all.

Under these conditions there could easily be an absolute DHA deficiency. There often is.

I think a strong admonition to avoid abdominal gunshot wounds, or anything else requiring years on intravenous feeding, would (if heeded) improve your DHA status. If you must do the iv feeding thing, adding some ALA to the lipid emulsion might be a good idea. Getting pregnant under these conditions might not be the best idea either, even if you felt that way inclined and were adult...

If you are a pregnant mother who avoids fish because of the mercury concern, avoids liver due to the vitamin A concern, avoids animal fats due to the cholesterol concern then your child's eyes and brain might be marginal on the DHA front. Pregnancy and growth seems to be when the body needs bulk DHA. Again, working through this review will fill in the background. Being DHA deficient in utero and during early post natal development seems to be bad news, not fully correctable by later DHA supplementation.

Of course, once you have started eating food as opposed to junk, dumped your heart healthy oils and are eating a little liver occasionally, the chance of developing any sort of PUFA deficiency seems rather small. Occasional fish or a decent amount of ruminant meat would eliminate the risk.

The problem is, how many people eat food and how many live on junk? If everyone were to switch to eating food, would DHA supplements be needed? If the intake of linoleic acid is low enough no doubt even the alpha linolenic acid from green leaf vegetables might end up as DHA.

So it looks as if there are certain circumstances, especially with those junk food based vegetarian diets easily achieved today, when DHA may not be available to meet foetal and neonatal needs. Taking a little DHA supplement may well be needed at this time or, better still, eat some food. Food's a good idea.

That seems to sum up the risk of deficiency to me, as far as I can see. We need some EFAs, more during pregnancy and nursing. Arachidonic acid is not a problem, DHA looks to be the weakest link. TPN is bad news (in case you want more bad news than whatever the reason is for your being on intravenous feeding).

So should we all be taking fish oil supplements, all of the time? Do we need to do anything except to avoid frank DHA deficiency as a foetus or newborn baby?

Maybe, maybe not. That's another post.

Peter

Casein, gluten and gastric pH

In a very interesting paper from Bloggeier on rheumatoid disease and multiple food allergies (worth a post on its own) there was this snippet:

"Thus infants are prone to develop cow’s milk allergy while their gastric acidity is pH 3–4 (compared with pH 2 in adults); at pH 4 the degradation of a-lactalbumin, BSA, and bovine IgG is markedly reduced in contrast to b lactoglobulin".

Following the ref gave this abstract. Just a pity that they didn't look at casein too. It brought to mind the idea that taking gastric acidity suppressing drugs is possibly the best technique we've developed to get ourselves a food allergy, obviously excluding wheat consumption. Of course the combination is probably a cracker.

Now, what does the cow's milk get poured over when weaning a child, who's gastric pH is 3-4?

Well, in this house the wheat is notably absent! Actually so is the cow's milk pretty well and weaning, what there is of it, seems to be going fine on beef and pork purees with some root veggies (plus a little vitamin C to be on the safe side) thrown in.

Peter

Dr Davis links

I browse Dr Davis' blog occasionally. Although Dr D seems to be a total cholesterol believer and has his sights set on 60:60:60 for HDL, LDL and Trigs (and goes with the drug therapy needed to get there) he does have very extensive experience of getting people to change their eating habits. His dislike of wheat seems to come more from using it as a metaphor for junk food, but the addiction aspect is clearly up there too. This post and this one drop in to that last category.

I really like this one too. Been reading Sholokhov's "Virgin Soil Upturned". I'm thankful to be able to make food choices. I'm never hungry. I am grateful.

And then we have this one too. The beginnings of saturated fat acceptance!!!! Woo hoo. Here's the bit I like:

"Adding back saturated fat. I say "adding back" since most of us (including myself) went too far down the "saturated fat is bad" path over the past few years. While I do not advocate a carte blanche approach to saturated fat, I believe that adding back eggs (preferably free-range and/or omega-3 rich), lean meats, and hard cheeses is a good idea"

Okay, it's cautious, but its a shift in the right direction. Bring on the carte blanche and let the chickens choose their own weeds. Of course there's not a lot of saturated fat in eggs, so here we have cholesterol acceptance too, if only dietary... That's nice to read.

Peter

Metabolism nuts and bolts PUFA

This post is basic biochemistry that we probably all know. I've just stuck it down as I've slogged through it while I've been working through Chris Masterjohn's treatise on PUFA, it seems a waste not to use it. Ignore if you're happy with elongase and desaturase enzymes.

Omega counted double bonds are very straight forward, they are counted from the methyl end of a long chain fatty acid. Because mammals can't add extra chain length or desaturate at the methyl end, these bonds are "fixed" in their identity. So mammals can pop a double bond in to stearic acid in the omega 9 position to give oleic acid and that's it as far as the methyl end is concerned. Double bonds at the omega 3 and 6 positions are also fixed and come from the diet (mostly, there may be an exception). No chance of elongating at the methyl end, so the 9th/6th/3rd will always be the ninth (or 6th or 3rd) bond down from the omega end of the chain. So oleic acid is an omega 9 fat and all of its derivatives are too. Whatever elongation/desaturation happens, it happens at the carboxyl end. Ditto omega 3s and 6s.

Delta refers to desaturase enzyme's ability to change a single bond to a double bond, extracting two hydrogen atoms in the process. So delta 6 desaturase pops a double bond in to the place of the 6th carbon-carbon bond, counting from the carboxyl group end of a fatty acid. This number is the alpha number, as it's counted from the opposite end to omega number. The desaturases mostly don't care how long the fatty acid is, they just grab the acid end, count six (or seven or nine or five etc) and stick in a double bond.

We definitely have a delta 5 and a delta 6 desaturase. Oddly enough we never put double bonds in to adjacent locations in our fatty acid carbon chains, there is always a gap. The pattern goes double bond, two singles, double, two singles etc, as far as I can see. That is if you want extra double bonds at all.

Fatty acids get elongated. This always happens from the carboxyl end, and always involves adding two extra carbon atoms, using single bonds only. In mammals anyway.

So when the fatty acid with a recently added double bond placed in the alpha 6 position by our delta 6 desaturase gets elongated, that new double bond gets promoted from the alpha 6 position to the alpha 8 position.

To keep the pattern we want two single C-C bonds then the new double. That mean going for the 5th C-C bond using delta 5 desaturase.

This neatly gives us the end product of arachidonic acid from linoleic acid.

We also get to eicosapentaenoic acid (EPA) by the same pathway if we start from the alpha linolenic acid parent. Then a simple elongation and a delta 4 desaturation gives docosahexanoic acid (DHA). If your delta 4 desaturase doesn't work you can try this:

Double elongation w/o desaturation to 24 C chain with first double bond now pushed to the 9 position from the carboxyl end. Delta 6 desaturase places an appropriate double bond at the 6 position, as it always does. This weird fatty acid is then shortened by two c atoms (off of the COOH end of course) to give DHA, the new double bond thus ending up, as it should for DHA, at the 4 position (from the 6 position where it was placed by delta six desaturase).

That last paragraph is from Mary Enig's book "Know Your Fats". The rest is general biochemistry.

There is no arguing with the essentiality of arachidonic acid and probably the same goes for DHA. If we don't get them pre formed in our diet, this is how we make them.

Peter