Do you believe in MRI scanners?

I was thinking about mitochondria, but I got sidetracked when I remembered Ling and his opinion about ATP. Here's how it went:

The vast majority of the energy production in our bodies occurs in our mitochondria. These are the tiny powerhouses which generate most of the high energy adenosine tri phosphate (ATP) on which we ultimately run our metabolism.

NB an aside; Gilbert Ling does not believe in ATP as an energy source for cells (though he thinks it is a crucial molecule), any more than he believes in the lipid bi-layer cell membrane or the sodium/potassium ATP pump. He is truly out on a limb with his "Association Induction Hypothesis" of life at cell and below cell level. A fruitcake, obviously. Except his ideas on the localisation of cell water around proteins led to the invention of the MRI scanner. If MRI scanners work, that cookie Ling is right. And almost all of modern physiology is wrong.

It is, for me personally, MUCH easier to think within the "normal" physiology of my education. But, because MRI scanners work, this is the equivalent of thinking that the table in front of me is "solid" when quantum mechanics tells me that it is anything but solid...

Now there's a thought.

Peter

Dietary sins of Swedish children

Dr Haglund Garemo is a paediatric nutritionist at Göteborgs University in Sweden. She defended her PhD in December 2006. The abstract is available here. She studied the socioeconomic status, diet, weight and health markers in a group of 4 year old children.

The relevant quotes from the abstract are

"The energy intake/kg was according to Nordic nutrition recommendations"

"Most children had a higher intake of saturated fat and sucrose than recommended"

"A higher BMI was associated with lower fat and higher sucrose intake"

"A lower fat intake was associated with higher BMI and higher HOMA ß-cell function"


If you had to summarise these findings they would be, with a little license, as follows: Eating fat makes you thin. Eating sugar makes you fat. Eating sugar makes you hyperinsulinaemic.


Here are some interesting interview quotes from Dr Garemo in addition to her thesis abstract:

Food and Drink Europe quote her in an interview as commenting:

"analysis of the children's body build showed that weight increases was a result of the body storing more fat, but those who ate the most fat were not the ones who weighed most. Instead, children who ate less fat had higher BMIs"


News-medical have this quote. Odd way of phrasing it, "less heightened"!

"Insulin production was less heightened in girls who ate more fat"

"Such results would go against the common perception that fat causes increased insulin production as a result of insulin resistance"



Overall, eating fat came out rather well. Most of it was saturated. That is an understatement. Interestingly that last quote above is the explanation of the bizarre medical idea that eating fat raises your blood sugar level.

It's wrong, excepting the ideas in my post on physiological insulin resistance. I doubt any of these children were eating enough fat to be in ketosis! BTW if you ever come across a diabetic person having a severe hypoglycaemic episode, please do NOT give them butter to try and raise their blood sugar, they might well die. Try sugar.

That should tell you something. Duh.

Peter

Physiological insulin resistance

Back in mid summer 2007 there was this [unfixable link] thread on the Bernstein forum. Mark, posting as iwilsmar, asked about his gradual yet progressively rising fasting blood glucose (FBG) level over a 10 year period of paleolithic LC eating. Always eating less than 30g carbohydrate per day. Initially on LC his blood glucose was 83mg/dl but it has crept up, year by year, until now his FBG is up to 115mg/dl. Post prandial values are normal.

He wanted to know if he was developing diabetes.

I've been thinking about this for some time as my own FBG is usually five point something mmol/l whole blood. Converting my whole blood values to Mark's USA plasma values, this works out at about 100-120mg/dl. Normal to prediabetic in modern parlance. However my HbA1c is only 4.4%, well toward the lower end of normality and healthy. That's always assuming that I don't have some horrible problem resulting in very rapid red blood cell turnover. I don't think so...

I spend rather a lot of my life in mild ketosis, despite the 50g of carbs I eat per day. So I can run a moderate ketonuric urine sample with a random post-chocolate blood glucose value of 6.5mmol/l. What is happening?

Well, the first thing is that LC eating rapidly induces insulin resistance.

This is a completely and utterly normal physiological response to carbohydrate restriction. Carbohydrate restriction drops insulin levels. Low insulin levels activate hormone sensitive lipase. Fatty tissue breaks down and releases non esterified fatty acids. These are mostly taken up by muscle cells as fuel and automatically induce insulin resistance in those muscles. There are a couple of nice summaries by Brand Miller (from back in the days when she used her brain for thinking) here and here and Wolever has some grasp of the problem too.

This is patently logical as muscle runs well on lipids and so glucose can be left for tissues such as brain, which really need it. Neuronal tissue varies in its use of insulin to uptake glucose but doesn't accumulate lipid in the way muscle does, so physiological insulin resistance is not an issue for brain cells. However, while muscles are in "refusal mode" for glucose the least input, from food or gluconeogenesis, will rapidly spike blood glucose out of all proportion.

This is fine if you stick to LC in your eating. It also means that if you take an oral glucose tolerance test you will fail and be labelled diabetic.

In fact, even a single high fat meal can do this, extending insulin resistance in to the next day.

Here's a reference for this.

The general opinion in LC circles is that you need 150g of carbohydrate per day for three days before an oral glucose tolerance test. I did this carb loading thing, then performed my own OGTT. It came out very normal except for mild reactive hypoglycaemia.

So, I often walk around with a fasting blood glucose of 5.9mmol/l and in mild ketosis, yet have normal pancreatic and muscle function, provided I carb load before the test. 

BTW my FBG dropped to 4.3mmol/l after three days of carb loading. That then raises the question as to whether Mark "iwilsmar" and myself are typical of LC eating people, or an oddity or two.

This brought to mind the self selected macronutrient study performed on mice by Ortman, Prinzler and Klause. They allowed mice to select their own diet and, lo and behold, the mice chose (by calories, not weight!) 82% fat and 5.6% carbohydrate. Sensible mice. NB These German mice should each be given Professorships of Nutrition at medical schools in the most obese nations of the world. Quite what we should do with the current professors I'm not sure, but I bet the mice could think of something.

Anyway, these mice are cool. The only thing that bugged me when I first read the paper was that they had a higher fasting blood glucose than those poor mice fed the normal junk which passes for laboratory mouse "chow". This now fits in to an overall pattern. Elevated non esterified fatty acids induce physiological insulin resistance and a higher than expected FBG level.

A simple switch to higher carbohydrate eating (in myself) allows the normal underlying pancreatic and muscle function to show. It also fits in with the FBG of 3.5mmol/l found in the carbohydrate fuelled natives in the Kitava studies. So do I worry about a FBG of over 5.5mmol/l? Not while my HbA1c is 4.4%.

Peter

Familial Hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a common genetic disease. That says something quite profound to me. If it is both genetic and common there cannot be too strong a disadvantage to it on an evolutionary basis. There are also lots and lots and lots of variants. All affect the LDL-C receptor. If you get one copy of any one of a large selection of defective receptor genes, you have quite high levels of cholesterol in your blood and... well, you know the story about clogged arteries and heart attacks. In fact, if LDL-C is such lethal stuff you would have thought that evolution would not have been so careless with the stability of the crucial piece of DNA coding for its receptor. But it wasn't careful and there are a myriad of FH variant genes. Oddly enough people in the 1800s with FH lived as long as, or even longer than, "normal" people, check out the Dutch pedigree and Utah pedigree studies.

Now this is interesting. In 1807 LDL-C at above normal levels was beneficial, particularly in Holland. In 2007 it is an automatic statin deficiency and don't try to get life insurance. What's going on?

If you ask a cardiologist about the function of the LDL-C receptor you will find that it is used by the liver to mop up that horribly artery clogging LDL-C before the patient secumbs. However, there are LDL-C receptors in other places than the liver. Such as on the endothelial cells lining the arteries. If FH sufferers have non functional receptors in their livers I am willing to bet they have poor receptors on their endothelial cells too. But wait a minute, this should be good! If you have reduced receptors you should have reduced stickiness and LESS clogging of the arteries.

But there again, the receptor is normally present and evolution does not go to the effort of building a complex structure just for the fun of wasting protein resources. No, that receptor is there for a reason, and that reason is to stick LDL-C to endothelial cells when they need it. Interestingly, isolated endothelial cells produce lots of LDL-C receptors, where as endothelial cells in contact with their brethren don't. The conclusion from this is that in areas of damage, the endothelial cells are isolated and express lots of receptors which cry out for cholesterol. In FH they don't get the cholesterol they need because the receptors don't work. Cell repair is difficult without a handy supply of lipids.

So, if you had to suggest what sort of problem might be caused by a defective cholesterol receptor, then vascular problems might be a good guess. Possibly heart attack.

NB What do you think might happen if you got two genes for a defective LDL-C receptor? This is homozygous FH. It's bad. You can see why.

So why wasn't heart attack common in FH carriers in 1807? How common was sugar in 1807? Not very. Perhaps there is a link here.

Just a minute. Where did all of that cholesterol come from in the arteries of modern sufferers? Well, you can stick LDL-C to vascular tissue with things other than the apoB-100 receptor. Try the LOX1 receptor for a start. This binds oxidised LDL-C rather nicely. Oxidised cholesterol is seriously nasty stuff. What oxidises cholesterol in your bloodstream? Try fruit and vegetables. Try sugar. Try a low fat diet. My guess is that these were thin on the ground in 1807 in Utah or Holland.

Peter

Niacin and beta hydroxybutyrate

There is nothing about antioxidants in general that affect lipoprotein levels. Niacin undoubtedly does have significant action on blood lipids so undoubtedly is more than an antioxidant. I find that interesting. Why should that be? Many biological processes act through receptors. The niacin effect on lipids, and the niacin flush (ever tried this? It's fun fun fun, not!), are receptor mediated. Clever people have found at least a couple of receptors. The first was HM74, now joined by HM74A. These receptors were not sitting there waiting for either psychiatrists or cardiologists to prescribe multigram doses of nicain, useful though that may be.

No, they have a natural ligand, beta hydroxybutyrate. Beta hydroxybutyrate is a substance dear to my heart, and your heart too, see here. It's a ketone body, naturally manufactured by the liver in times of starvation or carbohydrate restriction. Plus times of coconut fat consumption too, as medium chain triglycerides (MCTs) will produce ketone bodies even in the presence of carbohydrate. By the way, this is not my preferred fat, and it worries me a little that humans break down MCTs as fast as the liver can do so, plus they are shunted down the hepatic vein rather than the thoracic duct, minimising their access to the general circulation. It just reminds me of our metabolism's approach to fructose a bit. Still, coconuts have an excellent track record as a human food in the tropics, so I'm probably just being a bit paranoid here.

Low carbohydrate diets naturally produce ketone bodies. They will certainly elevate HDL cholesterol levels too. To which you may ask, "so what?". Well, elevated HDL cholesterol appears to be a marker of a high fat, low carbohydrate diet and its associated beta hydroxybutyrate. So it is a marker of good things happening in the metabolism. As such I welcome it, but not if it is an effect of some drug. Of course if your primary protection against heart disease is normal blood sugars and low insulin levels the elevated HDL-C is not essential, as seen on Kitava. On western food supply a little exercise plus LC eating seems to be the easiest way to maintain normal blood sugars, and coincidentally elevated beta hydroxybutyrate and so HDL-C. Statins and niacin may elevate HDL cholesterol but my guess is that their benefits (however small from the statins) are unrelated to their effect on HDL-C. And of course, once you are on a drug to elevate HDL-C, there is no way of telling if your metabolism is doing well or badly in terms of insulin sensitivity. If you combine a statin plus niacin plus the dreaded AHA Coco Krispies based low fat diet, you may well be on the road to a cardiovascular disaster, despite having the appearence of a "good" "good" cholesterol level...

Peter

Niacin and adrenochrome

We know that torectrapib was excellent at raising "good" HDL cholesterol, while simultaneously increasing the human death rate from heart attack to the point where it couldn't be ignored. We know that the Kitavans have low "good" HDL cholesterol and no heart disease. So we should forget good and bad cholesterol and concentrate on the things that really matter, which are probably hyperglycaemia, hyperinsulinaemia and wheat. Plus a few other things like trans fats. But the HDL as "good" cholesterol hypothesis will not lie down, although it seems to have been dead for some time. The statins raise HDL, but can be ignored due to their host of confounding pleiotropic effects, inseparable from their cholesterol effects. The current flavour of the month for raising HDL, since the demise of torcetrpib, appears to be niacin, vitamin B3, in multigram doses.

There is no doubt that niacin elevates HDL cholesterol levels and, according to those who follow these things, decreases overall mortality. Now niacin is a very interesting drug. Oh, at 2.0g a day niacin is a drug, not a vitamin. Its career began with Abraham Hoffer, who is still going strong, back in the 1950s. On the basis that "vitamin" doses of niacin had half emptied the psychiatric wards when the problem of pellagra was solved by Goldberger, Hoffer tried massive doses of B3 on schizophrenic patients. The idea was to see if they had a poor response to "normal" doses of B3 which could be overcome by high doses. It worked.

Hoffer's publication in 1954 was last-authored by Smythies, so I assume he was Hoffer's supervisor.

Smythies is also still going strong and has recently summarised the adrenochrome theory of schizophrenia in one of his many publications.

My guess is that niacin may be working by reducing adrenochrome in the brains of schizophrenics. I've no idea of how this works, but it is interesting to note that adrenochrome is an oxidation product and niacin is an effective antioxidant.

That dynamo of genuine cardiovascular research, Kummerow, has looked at adrenochrome in the blood of hypertensive patients. It's there and it mangles the vascular epithelium. Now, does niacin reduce adrenochrome in the blood stream as well as in the brain? It is, after all, a significant antioxidant and anti inflammatory agent. No one has looked at this as far as I know. I certainly don't know if this is the case, but I'm suspicious.

If it does, who cares about the HDL cholesterol effect? Like the statins, niacin appears to be a useful drug, possibly a very useful drug, chosen for the wrong reason. Unlike the statins, niacin has relatively little "badness" attached to it. The problem with torcetrapib was that it ONLY adjusted cholesterol levels. Whatever its associated "badness" or "goodness" might have turned out to be.

That's what happens when you spend millions or maybe billions of dollars developing a drug based on a wrong hypothesis.

Peter

The asterisk

The official title of the fruit and vegetable depletion study I've been discussing recently is this:

Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet*

Did you notice the asterisk? It got dropped from pubmed but is there in the full text pdf.

Why is it there in the paper title? It's there because a major funder for the research wishes to distance itself from the results! That's the EU for you. Fund the research and "IN NO WAY" (direct quote) use the results, as they do not fit your pre concieved ideas, to influence policy!!!!! This is the text associated with the asterisk:

* The study has been carried out with financial support in part from a Danish Food Technology grant (FØTEK2, ‘Antioxidants from plants’) and in part from the Commission of the European Communities, Agriculture and Fisheries (FAIR) specific RTD programme, CT 95-0158 ‘Natural Antioxidants from Foods’. It does not necessarily reflect its views and in no way anticipates the Commission’s future policy in this area.

Hats off to the Danish veterinarians who published this important piece of work and who probably have had their last ever grant from the EU coffers.

I don't think I have ever seen a comment like this ever before on a technical paper.

Wow!

Peter

Fruit and vegetables, last post (almost)

I've posted twice on the links between fruit and vegetables and oxidative damage to lipids, protein and DNA. This then begs the question as to why diets high in fruit and vegetables, on an epidemiological basis, are associated with less chronic diseases than diets deficient in fruit and vegetables. There seems to be a paradox here, fruit and veggies are repeatedly associated with oxidative damage, avoiding them is repeatedly beneficial, yet overall they look good for health when studied at the population level.

So, epidemiology finds fruit and veg are associated with better health. They shouldn't be. But epidemiology shows only shows association, never causality. Only interventions studies do that. On the basis of controlled intervention studies fruit and vegetable consumption shouldn't improve health, so there must be confounding factors here.

You have to ask what the confounding factors might be. Is there anything about the sort of person who eats lots of fruit and veg, compared to those who don't, which might over ride the damage done by the vegetables?

Well, some factors come to mind.

Poverty has to be the first. Poor people do worst on a health basis on just about every measurement possible. They also don't buy much in the way of vegetables. I remember one study showing that poverty is associated with very poor outcomes in diabetes. The conclusion was that we should spend lots of money educating poor people to spend their limited resources on vegetables. You can guess what I think about that. The obvious solution is to give MONEY to those in poverty. When they are rich enough, their health might improve. They might even be able to tolerate eating vegetables with impunity. Of course the link between poverty and ill health is epidemiological. I haven't seen an intervention trial where a large group of impoverished people were give £100,000 each per year and the placebo group given a similar notional value in Enron shares. I'm waiting for that one.

The second consideration is to ask what vegetables might displace from the diet. That is, what do people eat instead of vegetables. Chances are it is sugar or high fructose corn syrup that forms a big chunk. In the fruit and vegetable wash out study a typical daily diet is given. The diet, including total calories, was very strictly controlled. The depletion diet was high in carbohydrate, but mostly from potatoes, rye bread and white bread. The only fructose in the menu was from sucrose in carrots (which are loaded) and in the cake. So this is a pretty low sucrose diet. Eating sucrose and high fructose corn syrup is like getting all the bad aspects of fruit and vegetables but none of the vitamins needed to process the sugars.

Vegetables are bad, but refined sugar is probably worse.

It is possible.

Peter

Vegetables damage your DNA, latest study headline!

Here we go again:

Less vegetables, less DNA damage, the key quote from this abstract is:

"African-Americans had ... lower self-reported intake of most antioxidants (than whites). Levels of oxidative DNA damage, measured using the alkaline comet assay, were lower in African-Americans than Whites"

I'll just repeat, plants make antioxidants to protect themselves from oxidation. They contain nasty pro oxidative substances, which drop on to your DNA whenever you eat those lovely plant based antioxidants.

The only lutein and zeaxanthin worth eating are from egg yolks!

Peter

Unpleasant lipid blockage, personal

There are some pretty nasty spin offs from eating a diet based around saturated fat. Over the last few days I've run it to a particular problem which is a direct result of my eating habits. It was very unpleasant and involved a serious lipid blockage.

A blockage of the main drain from my washing up sink, that is. Not the little U bend in the kitchen, I mean the outside drain, deep, dark, stinking and which must have been overflowing in to the gravel for quite some time. The water was disgusting. I had to hand bale it out down to a steel grid. This was stuck solid and I still haven't been able to remove it. But by slotting an aluminium blade through a gap in the grid and wiggling it back and forth I got the bulk of the water to slowly drain away.

Next move was a trip to B&Q for a large bottle of concentrated caustic soda solution. Sodium hydroxide reacts with fats to form soap, which is soluble, and so clears the drain. Unfortunately it also does the same to the lipids in your skin, so this stuff is not nice to handle. Goggles, gloves and great care are needed, and serious chemical burns result from significant skin contact. I followed it with a kettle of boiling water to speed the process up. Once the drain was clear I ran a large volume of very hot water through it. So far so good, it cleared and has stayed clear.

But it got me thinking. Why on earth have cardiologists not tried running hot caustic soda through peoples' coronary arteries? It should be pretty obvious that if the cause of clogged arteries and clogged drains is the one and the same devil, saturated fat, maybe the same solution should be applied. This is the level of thought that comes up with stupid comments about "artery clogging" saturated fats. Give me a break. Arteries are NOT NOT NOT drains. They do not clog with saturated fat. Do not accept a place in a trial of caustic soda angioplasty when offered it by your cardiologist.

Although my drains do block with saturated fat, my arteries don't. The occasional drain blockage is a price well worth paying for cardiac health.

Peter

Queen Hatshepsut

I've mentioned the health problems of the ancient Egyptians featuring ankylosing spondylitis and its associated IBS. Now add to that obesity, dental abcesses, diabetes and disseminated bone cancer. That was just one queen who ate to the USDA food pyramid.

I wonder how the tooth was snapped off. I wouldn't have wanted to have been her dentist!

Peter

PS Here's the quote as the NY Times link needs registration:

"CT scans led physicians to conclude that the woman was about 50 when she died. She was overweight and had bad teeth. She probably had diabetes and died of bone cancer, which had spread through her body"

and about the broken tooth from SAWF news:

"They said the final clue was a tooth found within a wooden box inscribed with the female Pharaoh's name, which matched exactly to the space of the missing molar and the broken root in the mummy’s jaw socket"

Ouch!

Cholesterol ratios through the looking glass

It is a foundation stone of modern cardiology that cholesterol causes heart disease. The roll of LDL-cholesterol is central. This is "bad" cholesterol. The cholesterol of the Dark Side. Then there is HDL-cholesterol, the "good" cholesterol. Feel the Force Luke.

You know the theory, people eat lots of fat and eggs, make lots of LDL-C. This sticks to the artery walls, bungs them up and a heart attack happens. You've seen all the ads on TV for cholesterol lowering by this or that health food.

But until the statin drugs arrived on the scene this theory was pretty well moribund. Every method of lowering cholesterol ever developed, from diet through cholestyramine to fibrates, had a nasty habit of leaving total mortality unchanged. In some studies it even went up, and almost always in unpleasant ways.

Not so with the statins. The big plus side for statins is that they save lives. Ok, only if you have already had a heart attack first. And not many lives, but some. Being a bloke helps them work too, rather a lot. They do this, we are told, by decreasing bad cholesterol levels, particularly LDL-C, while increasing HDL-C, the good one. Yawn.

Now just imagine a "super drug" which could be added to the weakling statins to produce such a fantastic fall in LDL-C combined with such a rise in HDL-C that it is now possible to actually have an HDL-C level HIGHER than your LDL-C level. By quite a lot! This no minor feat. How good was the outcome? In this drug induced cardiological Nirvana, heart attacks must be banned for ever. Surely they must be. Please.

Except they're not.

The drug is (oops I mean was) torcetrapib and it's been pulled from development by Pfizer because adding it to atrovastatin doubles the cardiovascular catastrophe rate.

These two studies (RADIANCE 1 and RADIANCE 2) were published side by side in NEJM, to which I don't have access. Fortunately the nice people at the HDLforum.org do.

They give the cardiovascular catastrophe rate for torcetrapib combined with atrovastatin as 5.2% vs. 2.4% for atrovastatin alone from the RADIANCE 1 study. The same values from the RADIANCE 2 study are 9.5% vs. 5.6% respectively. These values are not in the abstracts for pretty obvious reasons!

So where does this leave torcetrapib? It appears to be in the rubbish bin, where it belongs! What about the good vs bad cholesterol hypothesis? This goes on as before, despite the increased heart attack rate in the subjects with deliriously high HDL-C and almost no LDL-C . I believe the usual phrase is something like "We wus unlucky, Guv" accompanied by head scratching.

Lowering LDL-C while raising HDL-C has been the Holy Grail of cardiology for some time. Now it's been done, with a vengeance, and it sucks.

The statins are the only lipid lowering drugs to decrease overall mortality in heart attack patients. Not by much, and you have to have had a heart attack first. They only work because they're anti thrombotic, anti inflammatory, anti proliferative, anti oxidant and anti a few other things too. Isn't the toxin (lovastatin) from a mould which grows on rice clever. Especially when compared to Big Pharma's torcetrapib! The cholesterol lowering aspect of lovastatin is an unpleasant and unnecessary side effect. Like the coenzyme Q10 depletion.

Your cholesterol ratios are useless. Thank you Pfizer for torcetrapib. RIP the lipid hypothesis. Again.

Peter

PS torcetrapib was doomed from the start because it had no X Y Z or V in its name. Blame the marketing folks.

Fruit, vegetables and DNA damage

I accidentally deleted this post by some strange miss click of the mouse. I'll re post the bare bones I get the chance. Sorry

Peter


Here is the re post

More from Kitava

Lindeberg and associates (as in the Kitava studies) postulated that elevated uric acid protected the Kitavans from heart disease (it's a good antioxidant). To check this out they compared the blood uric acid levels of these non westernised islanders to a Swedish population. Uric acid levels are basically the same, maybe 10% lower on Kitava. Conclusion:

"The rather similar uric acid levels between Kitava and Sweden imply that uric acid is of minor importance to explain the apparent absence of cardiovascular disease in Kitava"

Lets go back to the low HDL-C and elevated triglycerides levels on Kitava, which also were essentially the same as those in Sweden:

"the relationship between TGs and HDL-C (in Kitava) was similar to that observed in Caucasians"

Yet the conclusion was

"Evaluation of TGs and HDL-C as cardiovascular risk factors must thus be restricted to the study population"

These two papers and statements were written by the same research group. Let's clarify. Essentially uric acid, triglycerides and HLD cholesterol were pretty much the same in Kitava or Sweden. The conclusions from this group are that uric acid is unimportant in keeping the Kitavan's healthy but "bad" lipid levels are important in Sweden yet not in Kitava. Don't forget the levels of uric acid, triglycerides and HDL-C were the same in both populations.

I hadn't read the uric acid paper when I posted on the Kitava study and metabolic syndrome... Nobody will be upset by uric acid bashing. Not so the lipid hypothesis. It just strikes me that researcher's conclusions are determined by their preconceptions

And their future funding.

Peter

Heroin and IBS

Kurt Cobain, the late singer/guitarist from Nirvana, had a lot of problems. Both mental and physical. He self medicated with heroin, leading to serious addiction. On an archive BBC interview earlier this year he described the dramatic relief he got from his gut pain by using heroin. He freely admitted that he had multiple other problems leading to his addiction, but the relief from abdominal pain was a significant factor. No one believed him, this was just another junkie excuse. After all, none of the doctors he had consulted for years had an explanation or any therapy for the pain so it was all in his head, wasn't it...

I mention this because I read another account of a person with abdominal pain, this time there was a diagnosis, the label being IBS. This condition varies from modestly inconvenient through to unspeakably painful, with pulsing waves of cramping visceral pain going on for hours. This guy was posting on a discussion board specialising in poppy tea. Poppy tea is a morphine like opioid mixture reported to be more addictive than heroin as judged by withdrawl severity. It is 100% absolutely illegal just about everywhere in the world and DO NOT USE THIS. I only mention it because this poor guy posted to report the dramatic relief he had obtained from his severe IBS by drinking a cup of this poppy tea. The poppy tea board is a very easy going and very supportive place on the net for opioid addicts to hang out, but they all jumped on this guy like a ton of bricks. No one would remotely accept the reality of the relief he had obtained and the universal condemnation was centered around his using IBS as an excuse to consume the opioid tea, rather than coming clean and admitting he was a straightforward addict. I was shocked at the severity of the responses. Kurt Cobain must have gone through the same thing.

Why on earth am I posting all of this?

Well, my disillusionment with the bulk of the medical profession and my journey in to nutrition began with a close friend who was suffering from severe gut problems without a specific label. Over a year or so the problem had been getting progressively worse. On medical advice she had been increasing her fibre intake. Food consisted of whole meal pasta, brown rice, lentils, chickpeas, whole meal bread and vegetables. Some meat and as little fat as possible completed it. During the final consult her doctor suggested increasing the fibre still further, without explaining quite how this might be achieved. My friend mentioned that she had found, quite by accident, that codeine produced dramatic symptomatic relief. After the doctor had been scraped off of the ceiling there followed a lecture on the constipating effects of codeine and the advice to use ibuprofen to control the pain. This was to a patient in whom a duodenal ulcer was high on the list of possibilities. Please don't do this at home either. Even if your doctor tells you to.

At this point I started reading the medical litterature for myself and we had my friend off of omeprazole and pain free within a month. She never went back to the medic, who is probably still recommending fibre and ibuprofen to her IBS patients and steadfastly refusing to think about why they don't get better.

What really struck me with all three stories was the absolute disbelief in all quarters that opioids could produce symptomatic relief in severe IBS. The impression is that people with severe gut problems are considered to use their "functional" problem as an excuse for recreational opioid abuse. Where is the "That's interesting" reaction from doctors? Nowhere.

The cure, by the way, is the elimination of almost all fibre, absolutely all grains and a marked reduction of carbohydrate consumption. She initially ate 20g/d of carbohydrate but currently anything under 70g/d seems fine for maintenance. Some people have to go a little further and eliminate starches and unfermented dairy too, but that wasn't needed in my friend's case. Grain ingestion, especially wheat, causes an immediate flare. No wonder the high fibre diet was a disaster.

So what is the link between IBS, opioids and especially grains?

Our bodies manufacture many short polypeptides for use as neurotransmitters. One specific group of them are the endorphins. These are naturally produced to control many biological processes. Gut motility and the limitation of both physical and emotional pain are two major functions under endorphin control. Morphine-like drugs, including its diacetylated derivative heroin, drop on to endorphin receptors and produce constipation and happiness. Withdrawl does the opposite. Badly.

Endorphins are produced by ourselves. Exorphins are similar peptides produced from our diet. Partially digested gluten from wheat is a major source. Eating a high gluten diet produces lots of exorphins. Constipation, often after an initial spasm reaction, is the result, just as it is from heroin. And pain too, because although exorphins do reach the brain, they never get there in the quantity needed to produce pain relief or happiness. In fact depression is common in IBS patients, but then chronic severe pain coupled with totally wrong advice tends to lead to depression!

When an IBS patient eventually has a bowel movement there is an immediate removal of the exorphins in contact with the gut wall. Acute opioid withdrawl produces diarrhoea. Remember the opening scenes of Trainspotting, with the methadone suppository and the worst public lavatory in Scotland?

So IBS is a functional problem of constipation with gut spasm alternating with diarrhoea. Eating grains is the commonest trigger. Wholegrains are the worst! Try telling that to your doctor.

BTW there are also exorphins in casein, haemoglobin and spinach but these do not seem to be as indestructible as the gluten derived peptides, although casmorphins do come a close second for many people.

Grains and heroin have a lot in common. Avoid both!

Peter

Living on the isolated island of Kitava

On the island of Kitava there are coconuts, sweet potatoes, yams, a few other starches and fish to eat. This leads to an interesting diet. The estimated percentages of energy from protein, fat and carbohydrates are 10%, 21% and 69% in Kitava. Most of the fat is saturated. Three quarters of the population smoke.

Obviously high carb eating should mean catastrophic blood lipids. You would expect low HDL cholesterol and high triglycerides. And this is exactly what you find. HDL-C down at 1.1mmol/l (some as low as 0.5mmol/l) and triglycerides up at 1.7mmol/l (some up at 3.0mmol/l). Not a good ratio. They smoke too. Must be a hotbed of cardiovascular disease. Especially as some of the total cholesterol readings were up around the (gasp) 7.0mmol/l mark. Pravastatin in the local well water is the obvious answer.

Except they have no heart disease. On a diet of 70% carbohydrate. Life expectancy, ignoring neonatal mortality which appears to be high, is around seventy years. That's without any medical facilities. How do they do it?

BTW there were two amusing comments in the discussion of this paper. The best was:

"Evaluation of TGs and HDL-C as cardiovascular risk factors must thus be restricted to the study population"

I'll rephrase that. In Sweden "bad" lipds (and smoking!) are BAD. Not so in Kitava, here "bad" lipids are not bad. They're a product of diet composition. As there is no heart disease they must be good!

So what's happening? Do horrible triglycerides block to your arteries like hot beef fat blocks a cold sewer in Sweden, but then by magic they become non sticky in Kitava? Go figure. Hint, maybe it's not the lipids that trigger the blocked arteries.

Second comment was

"our findings lend no support to the concept that a very high intake of carbohydrates (>60% of energy) increases the risk of cardiovascular disease"

ie living on low fat doughnuts is safe for everyone. Everyone. No suggestion that you have to live in Kitava for this to be the case. So if you eat a junk diet in Sweden and get Kitava lipids in Sweden plus smoke Kitava cigarettes, will you be OK? Somehow I doubt it!

So why are the Kitavans free of heart disease?

Their average fasting glucose is 3.7mmol/l and their fasting insulin 4.0 microU/ml. They do not have any features of metabolic syndrome! Except the lipids of course. Despite eating appalling quantities of carbohydrate. If we define metabolic syndrome as carbohydrate intolerance how do the Kitavans manage this?

I think that this goes back to the main limit on population growth, which is food. Daniel Quinn is the best source of information on this subject. As the Kitavans live with minimal Western food it seems they must be living within the food production capacity of their island. The basic principle is that populations grow to the limit set by their food supply. On Kitava you cannot make babies out of thin air. No extra yams means no extra people. The fluctuations in food and population must mean there are fluctuations in hunger and plenty, but if populations really do expand to the limits of food supply, the island location must ultimately apply calorie restriction. On average.

Ad lib food on a global basis has resulted in a population explosion. On an individual basis it results in a waistline explosion. As carbohydrate is cheap, addictive and hunger generating it is what usually fuels the metabolic syndrome, hence "bad" lipids are associated with metabolic syndrome as carbohydrates are the usual tool of excess calorie intake.

Calorie restriction, intermittent fasting and once daily eating all limit the development of insulin resistance and hyperglycaemia, pretty well independent of macro nutrient ratio. On Kitava there must be accidental calorie restriction as the population is in equilibrium with with a fixed food supply, hence no metabolic syndrome. Despite the "bad" lipids, which merely reflect the composition of their restricted diet.

Can we all do the same? Probably yes, but having read about life on the calorie restricted optimal nutrition (CRON) diet this is definitely not for me. Licking the plate clean because the sauce is delicious is one thing. Doing it because you are starving is quite another! No, there does appear to be a better way.

Eating a ketogenic diet appears to mimic calorie restriction. Ketosis limits appetite so allows modest calorie restriction without any hunger. Forget any drug which may be developed to mimic eating a high fat diet. Better pile on the lard, dump the "healthy" carbohydrate and generate a few ketone bodies. Enough to keep your energy intake reasonable without that desperate dreaming of food which is reputed to go with CRON.

Or you can starve on a balanced diet.

Peter

Paradoxes

Most of us have heard about the French Paradox, which basically says that the French eat masses of saturated fat and have a particularly low rate of heart disease. The usual explanation is that they are protected by all that red wine or their relaxed lifestyle or.... Unfortunately these do not protect the pasta based cuisine consumers of Italy. Quote "in contrast to the French Paradox, which examined how the indulgent French diet could produce favorable health outcomes, the studies of the Mediterranean diet has had the reverse effect in Italy". So do we now have a paradox within a paradox?

But then what about the

Spanish paradox Those naughty Spaniards are eating more fat and less carbs and getting LESS heart disease, now there's a suprise. Good job their medical system is so marvelous.

Sri Lanka paradox In Srilanka they eat <25% calories from fat and still get lots of heart disease. Tut tut.

Israeli paradox The Israelis eat buckets of polyunsaturated fat yet have a much higher heart attack rate than Europe.

Japanese paradox Not only are the naughty Japanese eating more fat, but it is RAISING THEIR SERUM CHOLESTEROL. GASP. So why is their heart attack rate dropping? Easy.

There is even an American paradox!

Particularly note the phrase in that last abstract

"a greater saturated fat intake is associated with less progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a greater progression"

The basic puzzlement in all of these is that the more fat, particularly saturated fat, a nation consumes the LOWER its incidence of heart disease. Low fat consumption, or increased polyunsaturate consumption, INCREASES heart disease.

Of course all paradoxes resolve when you realise saturated fat is not the cause of heart disease....

Peter

How to increase heart attack risk

The Women's Health Initiative was a massive study of the benefits of reducing the percentage of dietary calories from fat. It involved 48,835 women, so not a small study. Remember that small effects require large studies to detect them. Big effects will show in small groups, so I don't like this study. However it involved a massive input of money to produce a snippet of interest. It also kept 47 authors in gainful employment for over eight years. The women in the intervention group achieved intakes of saturated fat and cholesterol that were less than 10% of energy intake and less than 300 mg/d, respectively. The question is, does reducing your fat intake by 8.2% provide any benefit on cardiovascular disease risk?

The answer is "No", not if you were free of heart disease to begin with. Summary:

There is no benefit. I mean

*******THERE IS NO BENEFIT********

NONE.

What if you are already suffering from heart disease? There was a small subgroup (1,656 women) who had cardiovascular disease at the start of the study. This is what happened to them, and I quote

"The intervention was associated with increased risk in the 3.4% of women with baseline CVD; this may be a chance observation, or rates in this small subset may be confounded by concurrent therapy or comorbid conditions"

The hazard ratio was 1.26 for this group. That is, there was a 26% increase in risk of a cardiovascular incident. You notice from the quote that this "may be a chance observation". I'll translate this for you. What the authors mean is:

They found that reducing the amount of fat in your diet INCREASES your risk of cardiovascular disease. They've tried every possible way of explaining this away and have COMPLETELY failed. If you have already got heart disease you must not reduce your fat intake, unless you really want increase your risk of another heart attack.

You could call this a paradox. I mean yet another paradox.

Or just accept that fat is not the cause of heart disease.

By the way, none of this made it in to the abstract, you must access the full text of the JAMA paper, where you have to trawl through the results to get the Hazard Ratio number.

Funny that!

Peter

Which drink causes gout?

Uric acid is a breakdown product of the purines, adenine and guanine. These compounds are found in relatively high amounts in meat, especially organ meats. Obviously, anyone with gout should avoid dietary sources of purines. Ah, if only life were so simple! It reminds me of the truism that eating fat makes you fat... If that were true your average dietician would have cured the current obesity epidemic easily by now.

No, gout is much more interesting.

Gout is triggered by the presence of crystals of uric acid in your joints. It extremely painful. Many people with gout have high levels of uric acid in their blood stream. Oddly enough some people with gout do not have high levels of uric acid in their blood. Dig deeper.

Fructose is an unusual sugar for humans to eat. We have no system to break down fructose polymers. The only sources of fructose we can use are the simple sugar in fruit or honey and as the molecule combined with glucose as sucrose, ie table sugar. Drenching your metabolism with fructose is a recent innovation for humans. The current preferred sweetener for soft drinks is "high fructose corn syrup", a product of our dearly beloved food industry in the last thirty years or less.

What happens when you drench you metabolism with fructose? It enters the metabolic pathway of carbohydrate below its main control step and is immediately converted to fructose-1-phosphate. Quite why evolution has arranged things this way is a mystery, but my suspicion is that evolution does not like free fructose in human metabolism. So drinking a small bucket of cola will put 100gm of fructose in to your liver. This will require a large input of phosphate to for the fructose-1-phosphate, leaving very little for the generation of adenosine tri phosphate (ATP), the primary energy currency of our cells. A lack of ATP triggers activity of the degradation system for adenine and the production of, guess what, uric acid! Gout, and not a serving of kidneys in sight. Until 100 years ago only the rich could afford enough sugar to get gout, now it is a feature of metabolic syndrome and available to all.

Incidentally the fructose has to be "put" somewhere, and that is in to fat for storage, via elevated triglyceride levels in the blood. It causes insulin resistance too. Even the full metabolic syndrome!

In fact, probably the truth is that fructose causes insulin resistance, which causes gout. The hyper uricaemia and the fact that the joints produce uric acid crystals do not have to be causally related. I'd say they're not.

Incidentally, these bright researchers are looking for ways to minimise the self poisoning caused by fructose. They are actually suggesting looking for a drug to allow you to drink high fructose corn syrup without the rise in uric acid.

A drug for life to enjoy your cola. But of course that won't stop the insulin resistance from fructose, so......

Peter

Cholesterol Bogeyman

I was going to suggest it is currently accepted wisdom that an elevated blood cholesterol level is a "risk factor" for heart disease. That is not strictly true as there is a small group of medical practitioners who object to the idea that elevated cholesterol is a cause of heart disease. This even applies to those doctors who are so enthusiastic about cholesterol lowering drugs (statins) that they preach that everyone should take a statin IRRESPECTIVE of their cholesterol level. I find it hard to find a more convincing argument that cholesterol is irrelevant.

Anyway, let's look at one of the few reasonable cholesterol lowering trials ever completed. It was done in Japan. It simply involved taking 47,294 men, all of whom had a total cholesterol level above 240mg/dl (that's 6.15mmol/l in new money, but the paper is written in Noddy units). Everyone got either 5mg or 10mg of simvastatin per day (I presume based on body weight, the authors forgot to say how they decided!). They followed them for six years, then looked at death rates.

Now one strange thing about humans is that we are all different. If you give a big group of people the same dose of a drug most people will respond to it. Some by a lot, some by a little, a few not at all. That's exactly what happened. So now we can split those 47,294 men up in to those who lived with high, low or medium cholesterol levels for six years, all of whom had the same dose of simvastatin kicking around in their blood stream.

What do you get? I like death rates as a measure of outcome. There is no arguing with an outcome of being dead or a live. It's pretty clear cut. Even to a cardiologist. So what happened to death rates?

Those men who's cholesterol level ended up between 200 and 219mg/dl had the lowest risk of dying. In fact if the value ended up anywhere between 180mg/dl and 259mg/dl the risk of dying was pretty much the same as in the lowest risk group. Anything above 260mg/dl was associated with increased mortality. Above 280mg/dl the effect was most marked. Mostly heart disease. I'll write about inherited familial hypercholesterolaemia another day.

Wow, cholesterol must be really bad for you! Except there were a number of men who developed cholesterol levels below 160mg/dl on this dose of drug. Now this is a cholesterol level which would might once have made a cardiologist very happy. I believe they are harder to satisfy nowadays. How good for your overall health is a cholesterol level below 160mg/dl? Well, in this study, by six years later you are considerably more likely to be dead than if your level had only dropped to 210mg/dl. In fact you are 2.76 times more likely to be dead. This is actually a marginally higher death rate than if you had failed to respond to the drug at all. But your cardiologist would still be happy because the excess death rate is not due to heart disease.

The men who dropped their cholesterol below 160mg/dl tended to died of cancer.

Imagine going to your doctor and being offered a pill which would switch your future life from one ending in heart disease to one ending in cancer. Well, we've all got to die some time. Which disease would you prefer? Go on, really. A quickie heart attack or the big C?

By the way the Japanese appear somewhat more clued up about heart disease that the West. A nice commentary here. Pity the free full text is in Japanese!